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Valluri AR, Carter GJ, Robrahn I, Berg WA. Triple-Negative Breast Cancer: Radiologic-Pathologic Correlation. JOURNAL OF BREAST IMAGING 2025; 7:331-344. [PMID: 39801352 DOI: 10.1093/jbi/wbae085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Indexed: 05/20/2025]
Abstract
Triple-negative breast cancers (TNBCs) are invasive carcinomas that lack ER and PR expression and also lack amplification or overexpression of HER2. Triple-negative breast cancers are histopathologically diverse, with the majority classified as invasive breast carcinomas of no special type with a basal-like profile. Triple-negative breast cancer is the most aggressive molecular subtype of invasive breast carcinoma, with the highest rates of stage-matched mortality and regional recurrence. Triple-negative breast cancer has a younger median age of diagnosis than other molecular subtypes and is disproportionately diagnosed in Black women and BRCA1 germline pathogenic mutation carriers. On US and mammography, TNBCs are most often seen as a noncircumscribed mass without calcifications; TNBCs can have circumscribed margins and mimic a cyst or have probably benign features that may result in delayed diagnosis. MRI is the most sensitive modality for detecting TNBC, with rim enhancement being a common feature, and MRI is also the most accurate imaging for assessing neoadjuvant chemotherapy response. Understanding the radiologic and pathologic findings of TNBC can aid in diagnosis.
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Affiliation(s)
- Amrita R Valluri
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Gloria J Carter
- Department of Pathology, UPMC Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Inna Robrahn
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Wendie A Berg
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Andour L, Hagenaars SC, Vangangelt K, Aalberts J, Rebattu V, van der Meer DMAB, Kranenbarg EMK, Gaarenstroom KN, van Asperen CJ, Tollenaar RAEM, Mesker WE. The TESTBREAST journey: Revisiting the importance of early detection by frequent screening of women at high risk of breast cancer. Int J Cancer 2025. [PMID: 40232159 DOI: 10.1002/ijc.35444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 03/13/2025] [Accepted: 03/26/2025] [Indexed: 04/16/2025]
Abstract
Women with an inherited pathogenic variant (PV) in a breast cancer (BC) susceptibility gene, or familial predisposition (FP) have an increased risk to develop BC. There is a need for improvement of screening methods due to interval cancers and radiation exposure. The aim of the TESTBREAST study is to develop a blood test suitable for early diagnosis. Here, the clinical composition of participants is provided. From 2010 to 2022, 1108 women were included in the TESTBREAST study, with currently 750 participants suitable for serum analysis. The median follow-up was 7 years [1-14]. Of the 1108 participants, 70% (n = 728) had a PV. BC was diagnosed in 16.5% (n = 124), mainly stage I-II (68.5%), and mostly BRCA1 (n = 47, 47%) and BRCA2 (n = 29, 29%) carriers. Invasive cancer was diagnosed in 100 cases: 76% (n = 76) had a PV with a median age of 49 [26-68] at diagnosis, whereas 24% (n = 24) had a FP, with a median age of 51 years [25-65]. The general population (the Netherlands) is aged 61 years on average at diagnosis. Triple negative breast cancer (TNBC) occurred in 51% (n = 39) of the TESTBREAST women with a PV, whereas this was 11% in the general population. Within the TESTBREAST cohort, BRCA carriers were younger at diagnosis and often had the aggressive TNBC subtype. Improvement of current screening methods for early detection is especially important for this group of high-risk women to reduce interval cancers, exposure to radiation, and to improve survival.
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Affiliation(s)
- Layla Andour
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Sophie C Hagenaars
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Kiki Vangangelt
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Janneke Aalberts
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Valerie Rebattu
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Katja N Gaarenstroom
- Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands
| | - Christi J van Asperen
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
| | - Rob A E M Tollenaar
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wilma E Mesker
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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Thongheang K, Pamonsupornwichit T, Sornsuwan K, Juntit OA, Chokepaichitkool T, Thongkum W, Yasamut U, Tayapiwatana C. Potentiating Antibody-Dependent Cellular Cytotoxicity in Triple-Negative Breast Cancer via the Humanized Anti-CD147 Antibody. Antibodies (Basel) 2025; 14:36. [PMID: 40265417 PMCID: PMC12015854 DOI: 10.3390/antib14020036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/29/2025] [Accepted: 04/09/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) is an aggressive subtype with high metastatic potential, poor prognosis, and the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). The lack of these receptors limits the standard treatments, such as hormone therapies and HER2-targeted antibodies like trastuzumab. These challenges highlight the critical need for novel therapeutic strategies. CD147, a transmembrane glycoprotein overexpressed in TNBC, promotes tumor progression, metastasis, and chemoresistance, making it a promising therapeutic target. This study evaluates the antibody-dependent cellular cytotoxicity (ADCC) of HuM6-1B9, a humanized anti-CD147 antibody, against MDA-MB-231 cells, a TNBC model. METHODS CFSE-labelled MDA-MB-231 cells were co-cultured with PBMCs as effector cells (E:T ratio 80:1) in the presence of HuM6-1B9 and incubated for 4 h. Cells were then collected and stained with PI, and CFSE+/PI+ dead target cells were analyzed by flow cytometry. RESULTS Co-culturing MDA-MB-231 cells with peripheral blood mononuclear cells (PBMCs) in the presence of HuM6-1B9 demonstrated effective ADCC induction without direct cytotoxicity. HuM6-1B9 induced 54.01% cancer cell death via ADCC, significantly outperforming trastuzumab (26.14%) while sparing PBMCs. CONCLUSION These findings support HuM6-1B9 as a prospective TNBC therapeutic and warrant further investigation into its clinical potential.
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Affiliation(s)
- Kanyarat Thongheang
- Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand;
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
| | - Thanathat Pamonsupornwichit
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
| | - Kanokporn Sornsuwan
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
- Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand
| | - On-anong Juntit
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
- Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Tawan Chokepaichitkool
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Weeraya Thongkum
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
- Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Innovative Immunodiagnostic Development, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Umpa Yasamut
- Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand;
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
- Center of Innovative Immunodiagnostic Development, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chatchai Tayapiwatana
- Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand;
- Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (O.-a.J.); (W.T.)
- Center of Innovative Immunodiagnostic Development, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
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Tang Y, Liu R, Zhu J, He Q, Pan C, Zhou Z, Sun J, Li F, Zhang L, Shi Y, Yao J, Jiang D, Chen C. Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2412096. [PMID: 39888288 PMCID: PMC12021099 DOI: 10.1002/advs.202412096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 01/08/2025] [Indexed: 02/01/2025]
Abstract
Basal-like breast cancer (BLBC), overlapping with the subgroup of estrogen receptor (ER), progesterone receptor (PR), and HER2 triple-negative breast cancer, has the worst prognosis and limited therapeutics. The XPO1 gene encodes nuclear export protein 1, a promising anticancer target which mediates nucleus-cytoplasm transport of nuclear export signal containing proteins such as tumor suppressor RB1 and some RNAs. Despite drugs targeting XPO1 are used in clinical, the regulation of XPO1 expression and functional mechanism is poorly understood, especially in BLBC. This study finds that KLF5 is a transcription factor of XPO1, which increases RB1 nuclear export and cell proliferation in BLBC cells. Furthermore, XPO1 interacts with the RNA-binding protein PTBP1 to export FOXO1 mRNA to cytoplasm and thus activates the FOXO1-KLF5 axis as a feedback. This work demonstrates that XPO1 inhibitor KPT-330 in combination with CDK4/6 inhibitor additively suppressed BLBC tumor growth in vivo. These results reveal a novel positive feedback regulation loop between KLF5 and XPO1 and provide a novel treatment strategy for BLBC.
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Affiliation(s)
- Yu Tang
- Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityPeking University Cancer Hospital YunnanKunming650118China
| | - Rui Liu
- Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityPeking University Cancer Hospital YunnanKunming650118China
| | - Jing Zhu
- Yunnan Key Laboratory of Breast Cancer Precision MedicineInstitute of Biomedical EngineeringKunming Medical UniversityKunming650000China
| | - Qian He
- Yunnan Key Laboratory of Breast Cancer Precision MedicineInstitute of Biomedical EngineeringKunming Medical UniversityKunming650000China
| | - Chenglong Pan
- Department of PathologyThe First Affiliated Hospital of Kunming Medical UniversityKunming650032China
| | - Zhongmei Zhou
- School of Continuing EducationKunming Medical UniversityKunming650021China
| | - Jian Sun
- Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityPeking University Cancer Hospital YunnanKunming650118China
| | - Fubing Li
- Yunnan Key Laboratory of Breast Cancer Precision MedicineInstitute of Biomedical EngineeringKunming Medical UniversityKunming650000China
| | - Longlong Zhang
- Yunnan Key Laboratory of Breast Cancer Precision MedicineInstitute of Biomedical EngineeringKunming Medical UniversityKunming650000China
| | - Yujie Shi
- Department of PathologyHenan Provincial People's HospitalZhengzhou UniversityZhengzhou450003China
| | - Jing Yao
- Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China
- Institute of Radiation OncologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China
| | - Dewei Jiang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan ProvinceKunming Institute of ZoologyChinese Academy of SciencesKunming650201China
| | - Ceshi Chen
- Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityPeking University Cancer Hospital YunnanKunming650118China
- Yunnan Key Laboratory of Breast Cancer Precision MedicineInstitute of Biomedical EngineeringKunming Medical UniversityKunming650000China
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Pleasant VA, Merajver SD. Universal Genetic Counseling and Testing for Black Women: A Risk-Stratified Approach to Addressing Breast Cancer Disparities. Clin Breast Cancer 2025; 25:193-197. [PMID: 39721895 PMCID: PMC11911078 DOI: 10.1016/j.clbc.2024.11.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 10/26/2024] [Accepted: 11/30/2024] [Indexed: 12/28/2024]
Abstract
Black women experience disproportionate breast cancer-related mortality, with similar overall incidence to White women. Approaches to address these racial health disparities should be multifaceted. Universal genetic counseling and testing for Black women could represent one dimension of a comprehensive approach in guiding early identification of those more likely to experience higher breast cancer-related mortality. The increased risk of triple-negative breast cancer and greater likelihood of early-onset breast cancer among Black women are 2 major justifications, given that these elements are already preexisting testing criteria per the National Comprehensive Cancer Network. Increasing assessment of breast cancer-related risk in the Black community through universal genetic counseling and testing should be considered to focus enhanced screening and preventive measures in a tailored risk-appropriate context.
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Affiliation(s)
- Versha A Pleasant
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.
| | - Sofia D Merajver
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI
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Hernandez AE, Lubarsky M, Westrick AC, Cohen BL, Thompson C, Kesmodel SB, Goel N. Structural racism and breast cancer stage at presentation in a South Florida majority-minority population: a retrospective study. LANCET REGIONAL HEALTH. AMERICAS 2025; 43:100962. [PMID: 40093851 PMCID: PMC11910072 DOI: 10.1016/j.lana.2024.100962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 11/13/2024] [Accepted: 11/29/2024] [Indexed: 03/19/2025]
Abstract
Background Residential segregation, both economic, racial and ethnic, is a social determinant of health that contributes to disparities in breast cancer outcomes. The objective of this study was to examine the association of economic and racial and ethnic residential segregation, as measured by the Index of Concentration at the Extremes (ICE), with breast cancer stage at presentation. Methods In this retrospective two-institution study, we included patients with stage I-IV breast cancer from 2005 to 2017. Using five-year estimates from the American Community Survey (2009-2013), five ICE variables were computed to create five models, controlling for economic segregation, Non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models determined the association between economic and racial segregation on breast cancer stage at presentation. Findings 4898 patients were included: 56% Hispanic, 27% Non-Hispanic White, 17% NHB. Those living in the most economically marginalised neighbourhoods [by quartiles (Q)] [ORQ1 1.38 (95% CI: 1.14-1.68), p < 0.05, majority NHB neighbourhoods [ORQ11.51 (95% CI: 1.01-2.27)], majority Hispanic neighbourhoods [ORQ1 1.29 (95% CI: 1.06-1.56)], the most NHB and economically segregated neighbourhoods [NHB and economic: ORQ1 1.64 (95% CI: 1.28-2.09), and the most Hispanic and economically segregated neighbourhoods [Hispanic and economic: ORQ1 1.60 (95% CI: 1.24-1.68)] had significantly increased odds of presenting with later stage disease compared to the reference group in each category. Interpretation This study, to our knowledge, is the first to evaluate stage at presentation by ICE, which allows us to evaluate the association between racial and economic residential segregation and breast cancer disparities. Our findings suggest that structural racism influences stage at presentation. To address these disparities, effective interventions are needed to account for the social and environmental contexts in which cancer patients live and can access care. Funding Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R37CA288502. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research was also supported by a University of Miami School of Medicine DREAM Scholar Award, a NIH/NCI T32CA211034, an American Surgical Association Fellowship Award, a Breast Cancer Research Foundation, an ASCO Career Development Award, a Florida Department of Health Bankhead Cole Cancer Research Program, a NIH/NCI 5P30 240139-02 Sylvester Cancer Control Support Grant Transdisciplinary Pilot Grant, and a NIH/NCI K12CA226330.
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Affiliation(s)
- Alexandra E. Hernandez
- Division of Surgical Oncology, University of Miami Department of Surgery, Miami, FL, USA
| | - Maya Lubarsky
- Department of Internal Medicine, Case Western Reserve University Hospitals, Cleveland, OH, USA
| | | | - Brianna L. Cohen
- Division of Surgical Oncology, University of Miami Department of Surgery, Miami, FL, USA
| | - Cheyenne Thompson
- Division of Surgical Oncology, University of Miami Department of Surgery, Miami, FL, USA
| | - Susan B. Kesmodel
- Division of Surgical Oncology, University of Miami Department of Surgery, Miami, FL, USA
- University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Neha Goel
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Haque MA, Poullikkas T, Al-Amin Kaisar FM, Haque S, Khatun MH, Mamun A, Khan A. PHLPP1 depletion promotes tumorigenesis and stemness in triple-negative breast cancer cells through AKT signaling. Med Oncol 2025; 42:80. [PMID: 39979645 DOI: 10.1007/s12032-025-02630-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 02/13/2025] [Indexed: 02/22/2025]
Abstract
Breast cancer, particularly triple-negative breast cancer (TNBC), is a major cause of women's mortality, and effective treatment options are still lacking due to the absence of known mechanisms and biomarkers. Therefore, unveiling novel molecular mechanisms to identify potential biomarkers is urgently needed to ensure an effective TNBC treatment. In this study, we investigated the role of PHLPP1, a tumor suppressor gene, in the tumorigenesis and induction of cancer stem cells in TNBC using publicly available data and experimental protocols. Our study found that lower levels of PHLPP1 contributed negatively to patient overall survival. In addition, loss of PHLPP1 increased breast cancer cell proliferation, long-term colony regrowth ability, and the number of migrated and invaded cells. Consequently, we designed a stable PHLPP1 knockdown (KD) cell line to understand its impact through its stemness potential. As expected, PHLPP1 KD dramatically upregulated breast cancer stemness markers (NANOG, OCT4, and SOX2) expression and significantly increased cancer stem cell frequencies in TNBC cells. Mechanistically, PHLPP1 loss enhanced AKT phosphorylation at Ser473, thus activating AKT signaling, leading to larger tumor formation in vivo and elevated stemness expression. This study concludes that PHLPP1 has the capability to reduce the expression of cancer stemness genes by negatively regulating the AKT signaling pathway. Therefore, these findings may pave the way for discoveries in the context of cancer stemness and future strategies for developing effective treatment options for TNBC patients.
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Affiliation(s)
- Md Anwarul Haque
- Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh.
| | - Thanasis Poullikkas
- Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ET, Maastricht, The Netherlands
| | - F M Al-Amin Kaisar
- Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Shariful Haque
- Department of Pharmacy, Pabna University of Science and Technology, Pabna, 6600, Bangladesh
| | - Mst Hajera Khatun
- Department of Pharmacy, School of Science and Technology, Varendra University, Rajshahi, 6204, Bangladesh
| | - Al Mamun
- Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Alam Khan
- Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh
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Sathe AG, Diderichsen PM, Fauchet F, Phan S, Girish S, Othman AA. Exposure-Response Analyses of Sacituzumab Govitecan Efficacy and Safety in Patients With Metastatic Triple-Negative Breast Cancer. Clin Pharmacol Ther 2025; 117:570-578. [PMID: 39543869 PMCID: PMC11739744 DOI: 10.1002/cpt.3495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 10/28/2024] [Indexed: 11/17/2024]
Abstract
Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in metastatic setting). Exposure-response (E-R) relationships between SG exposure and efficacy and safety outcomes were characterized in 277 patients with mTNBC using data from the phase I/II IMMU-132-01 and phase III ASCENT (IMMU-132-05) studies. Evaluated endpoints included complete response (CR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety endpoints (individual first worst grade of select adverse events (AEs)). E-R analyses were also conducted for time to first dose reduction or delay. Patients received SG at 8 or 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle. Average SG-related serum exposure over the treatment duration (until the event) was consistently the most significant exposure metric correlated with efficacy and safety endpoints. Higher average concentration over the treatment duration for SG (CAVGSG) was the best predictor of CR and ORR. The model-predicted proportions of patients with CR and ORR at 10 mg/kg were 4.26% and 32.6%, respectively. Higher CAVG for total antibody was the best predictor of OS and PFS. The model-predicted probability of OS at 12 months at median lactate dehydrogenase (227 IU/L) was 53%. The probability of grade ≥1 evaluated AEs and the risk of dose reductions and delays significantly increased with increasing CAVGSG. The model-predicted proportions of patients with any-grade AEs were 35.9%, 67.4%, 64.7%, and 67.1% for vomiting, diarrhea, nausea, and neutropenia, respectively (10 mg/kg dose group). Neutropenia was the only evaluated AE for which CAVGSG was significantly associated with grade ≥3 events. The clinically meaningful efficacy and manageable safety achieved with SG 10 mg/kg on days 1 and 8 of every 21-day cycle dosing regimen supports the appropriateness of this clinical dosage in patients with mTNBC.
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Affiliation(s)
| | - Paul M. Diderichsen
- Integrated Drug Development ConsultingCertara USA, Inc.PrincetonNew JerseyUSA
| | - Floris Fauchet
- Integrated Drug Development ConsultingCertara USA, Inc.PrincetonNew JerseyUSA
| | - See‐Chun Phan
- Clinical ResearchGilead Sciences, Inc.Foster CityCaliforniaUSA
| | - Sandhya Girish
- Clinical PharmacologyGilead Sciences, Inc.Foster CityCaliforniaUSA
| | - Ahmed A. Othman
- Clinical PharmacologyGilead Sciences, Inc.Foster CityCaliforniaUSA
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9
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Di Rito A, Grillo A, Carbonara R. Therapeutic Management in Elderly Male Breast Cancer Patients: A Scoping Review. Curr Oncol Rep 2025; 27:120-134. [PMID: 39826033 DOI: 10.1007/s11912-024-01629-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/20/2025]
Abstract
PURPOSE OF REVIEW Male breast cancer (MBC) is a rare entity which often arises in elderly people. Aim of this review is to evaluate the principal issues related to MBC in elderly, because the therapeutic management of disease is not only related to the biological behavior of the tumor, but also to the comorbidities and frailty of older population. A scoping literature review was performed on Pubmed and Cochrane Database using the following keywords: therapeutic management/ male/ breast cancer/ elderly patients. Papers published before 2000, not edited in English or French language, or not related to the main topic, were excluded. Only articles related to therapeutic issues in MBC and including more than 10 elderly (≥ 65 years) patients were selected for the qualitative outcome analysis. RECENT FINDINGS 36 papers regarding surgery, radiotherapy, systemic therapy, racial disparities and therapeutic management in retrospective series of MBC in elderly were examined in details. MBC has a different biological behavior and a poorer prognosis than female, especially in cases with positive nodes at diagnosis. Elderly MBC patients have often larger tumors in more advanced stages at the time of diagnosis compared with younger patients. In spite of the advanced tumors at presentation, older patients present often cancers with more favorable biological characteristics, but they receive less guideline-concordant curative treatments (as adequate lymph node staging or adjuvant radiation therapy) compared to women. Moreover, racial differences in treatment of older MBC were observed. Therapeutic management of MBC in elderly patients is a subject rarely addressed in literature. Our review highlighted differences in the treatment and in guidelines-concordance for elderly MBC patients. Adequate geriatric assessment and use of therapeutic schemes adapted to age and comorbidities can avoid under/overtreatment, contributing to a better standard of care in this frail population.
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Affiliation(s)
- Alessia Di Rito
- Radiotherapy Unit, Hospital Mons. A.R. Dimiccoli, Barletta, Italy.
| | - Antonietta Grillo
- Radiotherapy Unit, Azienda Ospedaliero Universitaria Policlinico Di Bari, Bari, Italy
| | - Roberta Carbonara
- Radiation Oncology Department, General Regional Hospital "F.Miulli", Acquaviva Delle Fonti, Bari, Italy
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Garcia V, Gardecki E, Jou S, Li X, Shroyer KR, Saltz J, Acs B, Elfer K, Lennerz J, Salgado R, Gallas BD. Prioritizing cases from a multi-institutional cohort for a dataset of pathologist annotations. J Pathol Inform 2025; 16:100411. [PMID: 39720416 PMCID: PMC11667696 DOI: 10.1016/j.jpi.2024.100411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/07/2024] [Accepted: 11/12/2024] [Indexed: 12/26/2024] Open
Abstract
Objective With the increasing energy surrounding the development of artificial intelligence and machine learning (AI/ML) models, the use of the same external validation dataset by various developers allows for a direct comparison of model performance. Through our High Throughput Truthing project, we are creating a validation dataset for AI/ML models trained in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC). Materials and methods We obtained clinical metadata for hematoxylin and eosin-stained glass slides and corresponding scanned whole slide images (WSIs) of TNBC core biopsies from two US academic medical centers. We selected regions of interest (ROIs) from the WSIs to target regions with various tissue morphologies and sTILs densities. Given the selected ROIs, we implemented a hierarchical rank-sort method for case prioritization. Results We received 122 glass slides and clinical metadata on 105 unique patients with TNBC. All received cases were female, and the mean age was 63.44 years. 60% of all cases were White patients, and 38.1% were Black or African American. After case prioritization, the skewness of the sTILs density distribution improved from 0.60 to 0.46 with a corresponding increase in the entropy of the sTILs density bins from 1.20 to 1.24. We retained cases with less prevalent metadata elements. Conclusion This method allows us to prioritize underrepresented subgroups based on important clinical factors. In this manuscript, we discuss how we sourced the clinical metadata, selected ROIs, and developed our approach to prioritizing cases for inclusion in our pivotal study.
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Affiliation(s)
- Victor Garcia
- U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States of America
| | - Emma Gardecki
- U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States of America
| | - Stephanie Jou
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States of America
| | - Xiaoxian Li
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States of America
| | - Kenneth R. Shroyer
- Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States of America
| | - Joel Saltz
- Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, United States of America
| | - Balazs Acs
- Department of Oncology and Pathology, Cancer Centre Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden
| | - Katherine Elfer
- U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States of America
- Division of Cancer Prevention, National Cancer Institute, National Institute of Health, Shady Grove, MD, United States of America
| | | | - Roberto Salgado
- Division of Research, Peter Mac Callum Cancer Centre, Melbourne, Australia
- Department of Pathology, ZAS Hospitals, Antwerp, Belgium
| | - Brandon D. Gallas
- U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States of America
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11
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Eren E, Das J, Tollefsbol TO. Polyphenols as Immunomodulators and Epigenetic Modulators: An Analysis of Their Role in the Treatment and Prevention of Breast Cancer. Nutrients 2024; 16:4143. [PMID: 39683540 PMCID: PMC11644657 DOI: 10.3390/nu16234143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Breast cancer poses a substantial health challenge for women globally. Recently, there has been a notable increase in scholarly attention regarding polyphenols, primarily attributed to not only the adverse effects associated with conventional treatments but also their immune-preventive impacts. Polyphenols, nature-derived substances present in vegetation, including fruits and vegetables, have received considerable attention in various fields of science due to their probable wellness merits, particularly in the treatment and hindrance of cancer. This review focuses on the immunomodulatory effects of polyphenols in breast cancer, emphasizing their capacity to influence the reaction of adaptive and innate immune cells within the tumor-associated environment. Polyphenols are implicated in the modulation of inflammation, the enhancement of antioxidant defenses, the promotion of epigenetic modifications, and the support of immune functions. Additionally, these compounds have been shown to influence the activity of critical immune cells, including macrophages and T cells. By targeting pathways involved in immune evasion, polyphenols may augment the capacity of the defensive system to detect and eliminate tumors. The findings suggest that incorporating polyphenol-rich foods into the diet could offer a promising, collaborative (integrative) approach to classical breast cancer remedial procedures by regulating how the defense mechanism interacts with the disease.
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Affiliation(s)
- Esmanur Eren
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
| | - Jyotirmoyee Das
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
| | - Trygve O. Tollefsbol
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (E.E.); (J.D.)
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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12
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Marni R, Malla M, Chakraborty A, Voonna MK, Bhattacharyya PS, Kgk D, Malla RR. Combination of ionizing radiation and 2-thio-6-azauridine induces cell death in radioresistant triple negative breast cancer cells by downregulating CD151 expression. Cancer Chemother Pharmacol 2024; 94:685-706. [PMID: 39167147 DOI: 10.1007/s00280-024-04709-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 08/10/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer and is frequently resistant to therapy, ultimately resulting in treatment failure. Clinical trials have demonstrated the potential of sensitizing radiation therapy (RT)-resistant TNBC through the combination of chemotherapy and RT. This study sought to explore the potential of CD151 as a therapy response marker in the co-treatment strategy involving ionizing radiation (IR) and the repurposed antiviral drug 2-Thio-6-azauridine (TAU) for sensitizing RT-resistant TNBC (TNBC/RR). METHODS The investigation encompassed a variety of assessments, including viability using MTT and LDH assays, cell proliferation through BrdU incorporation and clonogenic assays, cell cycle analysis via flow cytometry, cell migration using wound scratch and Boyden chamber invasion assays, DNA damage assessment through γH2AX analysis, apoptosis evaluation through acridine-orange and ethidium bromide double staining assays, as well as caspase 3 activity measurement using a colorimetric assay. CD151 expression was examined through ELISA, flow cytometry and RT-qPCR. RESULTS The results showed a significant reduction in TNBC/RR cell viability following co-treatment. Moreover, the co-treatment reduced cell migration, induced apoptosis, downregulated CD151 expression, and increased caspase 3 activity in TNBC/RR cells. Additionally, CD151 was predicted to serve as a therapy response marker for co-treatment with TAU and IR. CONCLUSION These findings suggest the potential of combination treatment with IR and TAU as a promising strategy to overcome RT resistance in TNBC. Furthermore, CD151 emerges as a valuable therapy response marker for chemoradiotherapy.
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Affiliation(s)
- Rakshmitha Marni
- Cancer Biology Laboratory, Department of Life Sciences, GITAM (Deemed to Be University), GITAM School of Science, Visakhapatnam, 530045, A.P, India
| | - Manas Malla
- Department of Computer Science and Engineering, GITAM (Deemed to Be University), GITAM School of Technology, Visakhapatnam, 530045, A.P, India
| | | | - Murali Krishna Voonna
- Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam-, 530017, A.P, India
| | | | - Deepak Kgk
- Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam-, 530017, A.P, India
| | - Rama Rao Malla
- Cancer Biology Laboratory, Department of Life Sciences, GITAM (Deemed to Be University), GITAM School of Science, Visakhapatnam, 530045, A.P, India.
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13
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Bazzazan MA, Fattollazadeh P, Keshavarz Shahbaz S, Rezaei N. Polymeric nanoparticles as a promising platform for treating triple-negative breast cancer: Current status and future perspectives. Int J Pharm 2024; 664:124639. [PMID: 39187034 DOI: 10.1016/j.ijpharm.2024.124639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 08/04/2024] [Accepted: 08/23/2024] [Indexed: 08/28/2024]
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks expression of estrogen, progesterone, and HER2 receptor targets for therapy. Polymeric nanoparticles help address the challenges in treating TNBC by enabling tailored and targeted drug delivery. Biocompatible polymeric nanoparticles leverage enhanced tumor permeability for site-specific accumulation and ligand-mediated active targeting to boost specificity. Controlled, sustained intratumorally release of encapsulated chemotherapies, such as paclitaxel and curcumin, improves antitumor efficacy as demonstrated through preclinical TNBC models. However, the practical application of these nanomedicines still has room for improvement. Advancing personalized nanoparticle platforms that align treatments to TNBC's expanding molecular subtypes shows promise. Expanding the polymer range through novel copolymers or drug conjugates may improve tumor penetration, stability, and drug encapsulation. Incorporating gene therapies, imaging agents, or triggering stimuli responsiveness into polymeric nanoparticles can also overcome innate and acquired drug resistance in TNBC while monitoring outcomes. This article reviews the different types of nanoparticles used to treat TNBC and the different mechanisms of nanoparticles that can deliver drugs to tumor cells. Collaboration across different disciplines aimed at developing combination therapies, immuno-oncology, tumor-targeting ligands, and translating preclinical safety/efficacy via scalable manufacturing practices is essential. Well-designed polymeric nanoparticles offer immense potential for patient-centric TNBC treatment, but continued optimization across bench to bedside efforts is critical for clinical realization and transforming patient outcomes.
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Affiliation(s)
- Mohammad Amin Bazzazan
- Student Research Committee, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran; USERN Office, Qazvin University of Medical Science, Qazvin, Iran
| | - Pouriya Fattollazadeh
- Student Research Committee, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran; USERN Office, Qazvin University of Medical Science, Qazvin, Iran
| | - Sanaz Keshavarz Shahbaz
- USERN Office, Qazvin University of Medical Science, Qazvin, Iran; Cellular and Molecular Research Center, Research Institute for Prevention of Noncommunicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran.
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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14
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Goel N, Hernandez A, Cole S. Social Genomic Determinants of Health: Understanding the Molecular Pathways by Which Neighborhood Disadvantage Affects Cancer Outcomes. J Clin Oncol 2024; 42:3618-3627. [PMID: 39178356 PMCID: PMC12045328 DOI: 10.1200/jco.23.02780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 05/02/2024] [Accepted: 05/29/2024] [Indexed: 08/25/2024] Open
Abstract
PURPOSE Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival. METHODS Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics. RESULTS The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes. CONCLUSION We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.
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Affiliation(s)
- Neha Goel
- Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Alexandra Hernandez
- Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Steve Cole
- Department of Psychiatry/ Biobehavioral Sciences and Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA
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15
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Yasin R, Zafar G, Rooman Ali Syed F, Afzal S, Fatima M, Rathore Z, Chughtai A, Chughtai A. CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma. Cureus 2024; 16:e72608. [PMID: 39610583 PMCID: PMC11603255 DOI: 10.7759/cureus.72608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2024] [Indexed: 11/30/2024] Open
Abstract
Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin & eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage.
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Affiliation(s)
- Rafeya Yasin
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Ghazi Zafar
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | | | - Sameen Afzal
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Maryam Fatima
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Zonaira Rathore
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Akhtar Chughtai
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Anila Chughtai
- Histopathology, Chughtai Institute of Pathology, Lahore, PAK
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Diskul-Na-Ayudthaya P, Bae SJ, Bae YU, Van NT, Kim W, Ryu S. ANKRD1 Promotes Breast Cancer Metastasis by Activating NF- κB-MAGE-A6 Pathway. Cancers (Basel) 2024; 16:3306. [PMID: 39409926 PMCID: PMC11476229 DOI: 10.3390/cancers16193306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Early detection and surgical excision of tumors have helped improve the survival rate of patients with breast cancer. However, patients with metastatic cancer typically have a poor prognosis. In this study, we propose that ANKRD1 promotes metastasis of breast cancer. ANKRD1 was found to be highly expressed in the MDA-MB-231 and MDA-LM-2 highly metastatic breast cancer cell lines compared to the non-metastatic breast cancer cell lines (MCF-7, ZR-75-30, T47D) and normal breast cancer cells (MCF-10A). Furthermore, high-grade tumors showed increased levels of ANKRD1 compared to low-grade tumors. Both in vitro and in vivo functional studies demonstrated the essential role of ANKRD1 in cancer cell migration and invasion. The previous studies have suggested a significant role of NF-κB and MAGE-A6 in breast cancer metastasis, but the upstream regulators of this axis are not well characterized. Our study suggests that ANKRD1 promotes metastasis of breast cancer by activating NF-κB as well as MAGE-A6 signaling. Our findings show that ANKRD1 is a potential therapeutic target and a diagnostic marker for breast cancer metastasis.
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Affiliation(s)
- Penchatr Diskul-Na-Ayudthaya
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand
| | - Seon Joo Bae
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Yun-Ui Bae
- Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Konkuk University, Seoul 05030, Republic of Korea;
| | - Ngu Trinh Van
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Wootae Kim
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Seongho Ryu
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
- Department of Pathology, College of Medicine, Soonchunhyang University, Asan-si 311151, Republic of Korea
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Manna M, Brabant M, Greene R, Chamberlain MD, Kumar A, Alimohamed N, Brezden-Masley C. Canadian Expert Recommendations on Safety Overview and Toxicity Management Strategies for Sacituzumab Govitecan Based on Use in Metastatic Triple-Negative Breast Cancer. Curr Oncol 2024; 31:5694-5708. [PMID: 39330050 PMCID: PMC11431578 DOI: 10.3390/curroncol31090422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 09/13/2024] [Accepted: 09/20/2024] [Indexed: 09/28/2024] Open
Abstract
Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians' choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.
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Affiliation(s)
- Mita Manna
- Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada
- Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
- Saskatoon Cancer Centre, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada
| | - Michelle Brabant
- Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada
| | - Rowen Greene
- Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Michael Dean Chamberlain
- Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
- Saskatoon Cancer Centre, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada
| | - Aalok Kumar
- BC Cancer Surrey, University of British Columbia, Surrey, BC V3V 1Z2, Canada
| | - Nimira Alimohamed
- Department of Medicine, University of Calgary, Calgary, AB T2N 4N2, Canada
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Lai J, Deng S, Cao J, Ren Y, Xu Z, Qi X, Xu M, Liao N. Identification of biomarker associated with Trop2 in breast cancer: implication for targeted therapy. Discov Oncol 2024; 15:413. [PMID: 39240479 PMCID: PMC11379678 DOI: 10.1007/s12672-024-01261-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 08/22/2024] [Indexed: 09/07/2024] Open
Abstract
PURPOSE Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. This study aimed to explore the mutational characteristics and significance of Trop2 in breast cancer (BC). METHODS Patients diagnosed with BC (n = 77) were enrolled to investigate expression level and clinical characteristics of Trop2. Database of cBioPortal and Kaplan-Meier Plotter were used to evaluate the effects of Trop2 (TACSTD2) genomic ateration and mRNA expression levels on disease-free survival (DFS) and relapse-free survival (RFS), respectively. Based on next generation sequencing analysis, the Trop2 mutation characteristics of BC patients were deeply depicted. In addition, Trop2 expression, mutation and methylation signature associated with Trop2 mutations were analyzed. RESULTS Trop2 mutation and high expression of Trop2 were predictive biomarker for shorter DFS and RFS in BC. The positive rate of Trop2 expression in these 77 BC patients was 96.1% (74/77). Based on the Trop2 expression level, the patients were classified into Trop2 negative group, medium expression group and high expression group. The mutation frequencies of MAP3K1, NOTCH2, PTEN and MAGI2 were significantly higher in Trop2 medium expression group than high expression group. Moreover, we investigated the effect of the Trop2 mutations on other genes, including co-expressed genes, differentially mutated genes, differentially expressed genes, gene methylation and phosphorylation. We found that MED8, DPH2, KDM4A, EBNA1BP2, USP1, IPO13, CGAS, PRKAA2, NCOA7, ASCC3 and ABRACL were differentially expressed, mutated and methylated between Trop2 mutation group and wild group. CONCLUSION MAP3K1, NOTCH2, PTEN and MAGI2 mutations were significantly different between Trop2 medium expression and Trop2 high expression BC patients. The effects of Trop2 mutation on the expression, variation, methylation, and phosphorylation of other genes were comprehensively revealed. High expression level of Trop2 and Trop2 mutation were predictive biomarker for poor prognosis and targeted therapy in BC.
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Affiliation(s)
- Jianguo Lai
- Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Shuxuan Deng
- Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Jiyuan Cao
- Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Yongqi Ren
- Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Zanmei Xu
- Medical Department, Shanghai OrigiMed Co., Ltd, Shanghai, China
| | - Xiaofang Qi
- Medical Department, Shanghai OrigiMed Co., Ltd, Shanghai, China
| | - Mian Xu
- Medical Department, Shanghai OrigiMed Co., Ltd, Shanghai, China
| | - Ning Liao
- Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
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Matsubara K, Hayakawa N, Aida K, Koike J, Kikuchi E. Renal pelvic plasmacytoid subtype urothelial carcinoma accompanied with solitary mammary metastasis. Int Cancer Conf J 2024; 13:296-300. [PMID: 38962031 PMCID: PMC11217202 DOI: 10.1007/s13691-024-00681-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 04/04/2024] [Indexed: 07/05/2024] Open
Abstract
A 72-year-old female was referred to our institution for further evaluation of right renal tumor detected during work-up for macroscopic hematuria in other hospital. CT urography performed at our institution suggested renal pelvic tumor. Voiding cytology was atypical. CT also revealed a small mass in the right mammary gland. Percutaneous needle biopsies were performed on the right mammary gland and renal mass, leading to a pathological diagnosis of UC with plasmacytoid subtype, suggesting metastasis from the renal pelvic UC to the mammary gland. She had a favorable response to four cycles of dose-dense MVAC therapy; therefore, we performed nephroureterectomy. One month after nephroureterectomy, new intraperitoneal metastatic lesions were observed and pembrolizumab therapy was started. After seven doses of pembrolizumab, CT revealed a marked size reduction of intraperitoneal metastases and the mammary metastasis remained small.
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Affiliation(s)
- Keisuke Matsubara
- Department of Urology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511 Japan
| | - Nozomi Hayakawa
- Department of Urology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511 Japan
| | - Koichiro Aida
- Department of Urology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511 Japan
| | - Junki Koike
- Department of Diagnostic Pathology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki-Shi, Kanagawa 216-8511 Japan
| | - Eiji Kikuchi
- Department of Urology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511 Japan
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Kimura T, Takami T, Piao Y, Ntalla I, Saji S. Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database. Breast Cancer Res Treat 2024; 206:91-103. [PMID: 38704772 PMCID: PMC11182808 DOI: 10.1007/s10549-024-07273-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/25/2024] [Indexed: 05/07/2024]
Abstract
PURPOSE This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. METHODS The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. RESULTS In this study, 2236 patients with mTNBC (median age 66.0 years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2 months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. CONCLUSION This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.
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Affiliation(s)
| | | | - Yi Piao
- Medical Affairs, Gilead Sciences K.K., Tokyo, Japan
| | - Ioanna Ntalla
- Real-World Evidence, Gilead Sciences Europe Ltd., Stockley Park, Uxbridge, UK
| | - Shigehira Saji
- Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan
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21
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Inampudi P, Yadlapalli DC, Gullipalli M. Clinicopathological Profiles of and Patterns of Recurrence in Triple-Negative Breast Cancer Patients at a Cancer Care Center in Southern India. Cureus 2024; 16:e63886. [PMID: 39099998 PMCID: PMC11298067 DOI: 10.7759/cureus.63886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND Triple-negative breast cancer (TNBC) is characterized by the absence of expression of the estrogen receptor and the progesterone receptor by immunohistochemistry and human epidermal growth factor receptor overexpression absence either by immunohistochemistry or absence of amplification by fluorescence in-situ hybridization. TNBCs tend to have rapid growth when compared to other subtypes of breast cancer. TNBC is associated with higher histologic grade and more advanced disease at presentation. TNBC shows aggressive behavior and a high chance of recurrence. AIM The aim was to analyze the clinicopathological profiles of and recurrence patterns in TNBC patients at our institute where most patients are from rural areas. METHODS This retrospective study was done at a tertiary cancer care center in Southern India where most patients come from rural backgrounds. Institutional Ethics Committee approval was obtained before the study. Case files of all breast cancer patients registered and treated at our center from 2014 to 2019 were retrieved from the medical record department and reviewed. Data from patients diagnosed with triple-negative breast cancer were identified and analyzed. RESULTS Among the 841 breast cancer patients registered in our study, 150 (17.8%) were diagnosed with TNBC. The median age of diagnosis was 47 years. The majority of the patients, 89 (59.3%) presented with T2 tumors, and lymph node involvement was observed in 88 (58.6%) cases. Patient distribution based on cancer stage revealed that 77 (51.3%) had early-stage breast cancer (EBC), 70 (46.6%) had locally advanced breast cancer (LABC), and only three patients were categorized as having metastatic breast cancer (MBC). Modified radical mastectomy (MRM) was the preferred surgical approach in 144 (96%) cases, while only four patients underwent breast-conserving surgery (BCS). Adjuvant chemotherapy was administered to 119 (79.3%) patients, with 30 (20%) receiving both neoadjuvant and adjuvant chemotherapy (NACT/ACT). Among those who underwent NACT/ACT, a pathological complete response was observed in five (16.6%) patients out of 30 patients. The median duration of follow-up was 32.8 months. Among all patients, 36 (24%) experienced recurrence, with seven (19.4%) having local recurrence, 24 (66.6%) developing distant metastases, two patients experiencing both local and distant recurrence, and three patients developing contralateral breast cancer. Additionally, three patients experienced a second primary cancer. The most common sites of metastases were the lungs (14), followed by the bone (seven), the liver (four), and the brain (four). Recurrence rates were notably high within the first one to three years post-diagnosis. The median disease-free survival (DFS) of TNBC patients was estimated to be 65.6 months with no statistically significant difference (p=0.174) between EBC and LABC patients. CONCLUSION TNBC is known for its heterogeneity. While it is often regarded as being more responsive to chemotherapy compared to other subtypes of breast cancer, TNBCs tend to behave aggressively, basically due to the underlying aggressive tumor biology. Though there are many treatment options for different subtypes of breast cancer, therapeutic modalities are limited for TNBCs. Aggressive tumor biology with limited treatment options denotes a gap in the development of novel strategies to improve outcomes in this subset of breast cancer patients.
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Affiliation(s)
- Prudhvi Inampudi
- Medical Oncology, Ganni Subbulakshmi Garu Medical College, Rajahmundry, IND
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22
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Tolaney SM, DeMichele A, Takano T, Rugo HS, Perou C, Lynce F, Parsons HA, Santa-Maria CA, Rocque GB, Yao W, Sun SW, Mocci S, Partridge AH, Carey LA. OptimICE-RD: sacituzumab govitecan + pembrolizumab vs pembrolizumab (± capecitabine) for residual triple-negative breast cancer. Future Oncol 2024; 20:2343-2355. [PMID: 38922307 PMCID: PMC11520537 DOI: 10.1080/14796694.2024.2357534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 05/16/2024] [Indexed: 06/27/2024] Open
Abstract
Patients with early-stage triple-negative breast cancer (TNBC) with residual invasive disease after neoadjuvant therapy have a high risk of recurrence even with neoadjuvant and adjuvant treatment with pembrolizumab. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with pre-treated metastatic TNBC. Moreover, preclinical data suggest that topoisomerase I inhibitors may enhance the effects of immune checkpoint inhibitors through activation of the cGAS-STING pathway. Here we describe the international randomized phase III AFT-65/ASCENT-05/OptimICE-RD trial, which evaluates the efficacy and safety of sacituzumab govitecan plus pembrolizumab versus treatment of physician's choice (pembrolizumab ± capecitabine) among patients with early-stage TNBC with residual invasive disease after neoadjuvant therapy.Clinical Trial Registration: NCT05633654 (ClinicalTrials.gov)Other Study ID Number(s): Gilead Study ID: GS-US-595-6184Registration date: 1 December 2022Study start date: 12 December 2022Recruitment status: Recruiting.
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Affiliation(s)
- Sara M Tolaney
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215,USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Angela DeMichele
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Toshimi Takano
- The Cancer Institute Hospital of JFCR, Koto City, Tokyo, 135-8550, Japan
| | - Hope S Rugo
- University of California Comprehensive Cancer Center, San Francisco, CA 94143, USA
| | - Charles Perou
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Filipa Lynce
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215,USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Heather Anne Parsons
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215,USA
- Harvard Medical School, Boston, MA 02115, USA
| | | | | | - Wenliang Yao
- Gilead Sciences, Inc., Foster City, CA 94404, USA
| | - Shawn W Sun
- Gilead Sciences, Inc., Foster City, CA 94404, USA
| | | | - Ann H Partridge
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215,USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Lisa A Carey
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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Karthik J, Sehrawat A, Kapoor M, Sundriyal D. Navigating breast cancer brain metastasis: Risk factors, prognostic indicators, and treatment perspectives. World J Clin Oncol 2024; 15:594-598. [PMID: 38835846 PMCID: PMC11145961 DOI: 10.5306/wjco.v15.i5.594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/24/2024] [Accepted: 04/15/2024] [Indexed: 05/21/2024] Open
Abstract
In this editorial, we comment on the article by Chen et al. We specifically focus on the risk factors, prognostic factors, and management of brain metastasis (BM) in breast cancer (BC). BC is the second most common cancer to have BM after lung cancer. Independent risk factors for BM in BC are: HER-2 positive BC, triple-negative BC, and germline BRCA mutation. Other factors associated with BM are lung metastasis, age less than 40 years, and African and American ancestry. Even though risk factors associated with BM in BC are elucidated, there is a lack of data on predictive models for BM in BC. Few studies have been made to formulate predictive models or nomograms to address this issue, where age, grade of tumor, HER-2 receptor status, and number of metastatic sites (1 vs > 1) were predictive of BM in metastatic BC. However, none have been used in clinical practice. National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms; routine screening for BM in BC is not recommended in the guidelines. BM decreases the quality of life and will have a significant psychological impact. Further studies are required for designing validated nomograms or predictive models for BM in BC; these models can be used in the future to develop treatment approaches to prevent BM, which improves the quality of life and overall survival.
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Affiliation(s)
- Jayalingappa Karthik
- Department of Medical Oncology Haematology, All India Institute of Medical Sciences Rishikesh, Rishikesh 249203, Uttarakhand, India
| | - Amit Sehrawat
- Department of Medical Oncology Haematology, All India Institute of Medical Sciences Rishikesh, Rishikesh 249203, Uttarakhand, India
| | - Mayank Kapoor
- Department of Medical Oncology Haematology, All India Institute of Medical Sciences Rishikesh, Rishikesh 249203, Uttarakhand, India
| | - Deepak Sundriyal
- Department of Medical Oncology Haematology, All India Institute of Medical Sciences Rishikesh, Rishikesh 249203, Uttarakhand, India
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24
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Gnangnon FHR, Parenté A, Aboubakar M, Kiki-Migan Y, Totah T, Gbessi DG, Tonato-Bagnan JA, Laleye A, Preux PM, Denakpo JL, Blanquet V, Houinato DS. Prognostic factors and overall survival of breast cancer in Benin: a hospital-based study. BMC Womens Health 2024; 24:295. [PMID: 38762733 PMCID: PMC11102149 DOI: 10.1186/s12905-024-03114-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 04/24/2024] [Indexed: 05/20/2024] Open
Abstract
BACKGROUND In Benin, a country in West Africa, breast cancer is the leading cancer in women, both in terms of incidence and mortality. However, evidence on the mortality of breast cancer and its associated factors is lacking in this country. Our aim was to describe and analyze the clinical, histopathological, and prognostic aspects of breast cancer in Benin. METHODS A descriptive and analytical study was carried out at the CNHU-HKM and the CHU-MEL, two major tertiary referral hospitals for breast cancer management located in Cotonou, the capital city of Benin. All breast cancer medical records with histological evidence and immunohistochemistry studies were retrospectively collected between January 1, 2014, and September 30, 2020, in these two tertiary referral hospitals and analyzed in the current study. RESULTS Finally, 319 medical records were included. The mean age at diagnosis was 48.74 years. The tumors were most frequently classified as T4 (47.6%) with lymph node involvement N2 (34.5%), and metastases were clinically noted in 21.9% of cases. Stage was reported in the medical records of 284 patients. Tumors were diagnosed at very late AJCC stages: stage III (47.5%) and stage IV (24.7%). Grades SBR 2 (49.2%) and SBR 3 (32.6%) were the most frequent grades. Triple-negative breast cancer (31.3%) was the most common molecular type. The overall 5-year survival was 48.49%. In multivariable analysis, the poor prognostic factors were lymph node invasion (HR = 2.63; p = 0.026; CI: [1.12, 6.17]), the presence of metastasis (HR = 3.64; p < 0.001); CI: [2.36, 5.62] and the immunohistochemical profile (HR = 1.29; p < 0.001; CI: [1.13, 1.48]). CONCLUSIONS Breast cancer in Beninese is predominant in young adults and is often diagnosed at a late stage. The survival of breast cancer patients in Benin can be improved by enhancing early diagnosis and multidisciplinary management.
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Affiliation(s)
- Freddy Houéhanou Rodrigue Gnangnon
- Laboratory of Epidemiology of Chronic and Neurological Diseases, Lemacen, Cotonou, Benin.
- Department of Visceral Surgery, National Teaching Hospital-Hubert Koutoukou Maga, CNHU-HKM, Cotonou, Benin.
- EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, Limoges, France.
- Department of Surgical Oncology, Faculty of Health Sciences - University of Abomey-Calavi, Cotonou, Benin.
| | - Alexis Parenté
- Laboratory of Epidemiology of Chronic and Neurological Diseases, Lemacen, Cotonou, Benin
- EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, Limoges, France
| | - Moufalilou Aboubakar
- Department of Gynecological Obstetrics, National Teaching Hospital-Hubert Koutoukou Maga, CNHU-HKM, Cotonou, Benin
| | - Yannick Kiki-Migan
- Laboratory of Epidemiology of Chronic and Neurological Diseases, Lemacen, Cotonou, Benin
| | - Terence Totah
- Laboratory of Epidemiology of Chronic and Neurological Diseases, Lemacen, Cotonou, Benin
| | - Dansou Gaspard Gbessi
- Department of Visceral Surgery, National Teaching Hospital-Hubert Koutoukou Maga, CNHU-HKM, Cotonou, Benin
| | | | - Anatole Laleye
- Laboratory of Histology, Reproductive Biology, Cytogenetics and Medical Genetics, Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin
| | - Pierre-Marie Preux
- EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, Limoges, France
| | - Justin Lewis Denakpo
- Department of Gynecological Obstetrics, National Teaching Hospital-Hubert Koutoukou Maga, CNHU-HKM, Cotonou, Benin
| | - Véronique Blanquet
- EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, Limoges, France
| | - Dismand Stephan Houinato
- Laboratory of Epidemiology of Chronic and Neurological Diseases, Lemacen, Cotonou, Benin
- EpiMaCT - Epidemiology of chronic diseases in tropical zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, Inserm U1094, IRD U270, Univ. Limoges, CHU Limoges, Limoges, France
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25
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Sathe AG, Singh I, Singh P, Diderichsen PM, Wang X, Chang P, Taqui A, Phan S, Girish S, Othman AA. Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors. Clin Pharmacokinet 2024; 63:669-681. [PMID: 38578394 PMCID: PMC11106201 DOI: 10.1007/s40262-024-01366-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND AND OBJECTIVE Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. METHODS In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG. RESULTS Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes. CONCLUSIONS These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.
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Affiliation(s)
- Abhishek G Sathe
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA
| | - Indrajeet Singh
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA
| | - Pratap Singh
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA
| | - Paul M Diderichsen
- Integrated Drug Development Consulting, Certara USA, Inc., Princeton, NJ, USA
| | - Xiaohui Wang
- Integrated Drug Development Consulting, Certara USA, Inc., Princeton, NJ, USA
| | - Peter Chang
- Integrated Drug Development Consulting, Certara USA, Inc., Princeton, NJ, USA
| | - Atiya Taqui
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA
| | - See Phan
- Clinical Research, Gilead Sciences, Inc., Foster City, CA, USA
| | - Sandhya Girish
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA
| | - Ahmed A Othman
- Clinical Pharmacology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
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Hurvitz SA, Bardia A, Punie K, Kalinsky K, Carey LA, Rugo HS, Diéras V, Phan S, Delaney R, Zhu Y, Tolaney SM. Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer 2024; 10:33. [PMID: 38664404 PMCID: PMC11045722 DOI: 10.1038/s41523-024-00635-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 03/28/2024] [Indexed: 04/28/2024] Open
Abstract
In this post hoc analysis of the ASCENT study, we compared outcomes with sacituzumab govitecan (SG) vs single-agent chemotherapy in clinically important subgroups of patients with metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC refractory to/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG or treatment of physician's choice (TPC) until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review in patients without brain metastases. Patients with brain metastases were allowed if metastases were stable ≥4 weeks. In the intention-to-treat (ITT) population, 19% of patients were age ≥65 years; 12% were Black, and 12% had brain metastases. SG improved PFS and overall survival (OS), respectively, vs TPC in patients age ≥65 years (7.1 vs 2.4 months and 14.7 vs 8.9 months), or of Black race (5.4 vs 2.2 months and 13.8 vs 8.5 months), consistent with outcomes in the ITT population. Patients with brain metastases had numerically higher median PFS with SG vs TPC, but median OS was similar between treatment groups. SG was well tolerated and had a manageable safety profile consistent with the full safety population across all subgroups; neutropenia and diarrhea were the most common treatment-emergent adverse events. These findings confirm the meaningful clinical benefit of SG vs standard chemotherapy in patient subgroups with high unmet needs. SG should be considered an effective and safe treatment option for patients with mTNBC eligible for second-line or later therapy. ClinicalTrials.gov Number: NCT02574455.
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Affiliation(s)
- Sara A Hurvitz
- Clinical Research Division, Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, USA.
| | - Aditya Bardia
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
| | - Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute and University Hospitals Leuven, Leuven, Belgium
| | - Kevin Kalinsky
- Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Lisa A Carey
- University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
| | - Hope S Rugo
- University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | | | - See Phan
- Gilead Sciences Inc., Foster City, CA, USA
| | | | - Yanni Zhu
- Gilead Sciences Inc., Foster City, CA, USA
| | - Sara M Tolaney
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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Wallace G, Kundalia R, Vallebuona E, Cao B, Kim Y, Forsyth P, Soyano A, Smalley I, Pina Y. Factors associated with overall survival in breast cancer patients with leptomeningeal disease (LMD): a single institutional retrospective review. Breast Cancer Res 2024; 26:55. [PMID: 38553702 PMCID: PMC10979566 DOI: 10.1186/s13058-024-01789-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 02/15/2024] [Indexed: 04/02/2024] Open
Abstract
BACKGROUND Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD. METHODS Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. RESULTS 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD. CONCLUSIONS Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
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Affiliation(s)
- Gerald Wallace
- Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA
- Department of Neurology, Medical College of Georgia, Augusta, GA, USA
| | - Ronak Kundalia
- Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ethan Vallebuona
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Biwei Cao
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA
| | - Youngchul Kim
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA
| | - Peter Forsyth
- Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA
- Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Aixa Soyano
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Inna Smalley
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA.
| | - Yolanda Pina
- Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA.
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Bhargava S, Gjesvik J, Thy J, Larsen M, Hofvind S. Breast cancer-specific survival among immigrants and non-immigrants invited to BreastScreen Norway. J Migr Health 2024; 9:100222. [PMID: 39263378 PMCID: PMC11390177 DOI: 10.1016/j.jmh.2024.100222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 09/03/2023] [Accepted: 02/28/2024] [Indexed: 09/13/2024] Open
Abstract
Introduction We have previously shown that immigrants have lower attendance in BreastScreen Norway than non-immigrants and that non-Western immigrants have lower incidence of breast cancer, but more advanced disease. Purpose To compare breast cancer-specific survival for immigrants versus non-immigrants diagnosed with screen-detected or symptomatic breast cancer. Material and methods We analyzed data from 28,320 women aged 50-69 diagnosed with breast cancer after being invited to BreastScreen Norway. We divided women into three groups; non-immigrants, immigrants from Western countries and immigrants from non-Western countries. We stratified our analyses according to detection mode (screen-detected breast cancer, interval cancer and cancer detected outside screening), and used cox regression to model the association between immigrants/non-immigrants and time to breast cancer death. Results Among screen-detected breast cancers, 28.7% were histologic grade 3 among immigrants from non-Western countries compared to 21.3% among non-immigrants. Interval cancers and cancers detected outside screening had larger tumor diameter and a higher percentage were histologic grade 3 and lymph node positive among immigrants from non-Western countries compared to non-immigrants. Hazard ratio (95% confidence interval) adjusted for age and year of diagnosis for time to breast cancer death compared to non-immigrants was 0.70 (0.39-1.27) for immigrants from Western countries and 0.52 (0.23-1.17) for immigrants from non-Western countries. Conclusion Despite more advanced histopathological tumor characteristics among immigrants from non-Western countries compared to non-immigrants, we did not observe statistically significant differences in breast-cancer specific survival between the two groups. Keeping in mind the low number of breast cancer deaths and possible overestimation of survival among immigrants, this might imply that equity in outcome can be achieved through adequate follow-up and treatment despite inequal access.
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Affiliation(s)
- Sameer Bhargava
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway
| | - Jonas Gjesvik
- Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
| | - Jonas Thy
- Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
| | - Marthe Larsen
- Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
| | - Solveig Hofvind
- Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
- Department of Health and Care Sciences, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway
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Romo BA, Karakyriakou B, Cressey L, Brauer BL, Yang H, Warren A, Johnson AL, Kettenbach AN, Miller TW. TRIM33 Is a Co-Regulator of Estrogen Receptor Alpha. Cancers (Basel) 2024; 16:845. [PMID: 38473207 PMCID: PMC10930732 DOI: 10.3390/cancers16050845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 02/15/2024] [Accepted: 02/17/2024] [Indexed: 03/14/2024] Open
Abstract
Estrogen receptor alpha (ER)-positive breast cancer is responsible for over 60% of breast cancer cases in the U.S. Among patients diagnosed with early-stage ER+ disease, 1/3 will experience recurrence despite treatment with adjuvant endocrine therapy. ER is a nuclear hormone receptor responsible for estrogen-driven tumor growth. ER transcriptional activity is modulated by interactions with coregulators. Dysregulation of the levels of these coregulators is involved in the development of endocrine resistance. To identify ER interactors that modulate transcriptional activity in breast cancer, we utilized biotin ligase proximity profiling of ER interactomes. Mass spectrometry analysis revealed tripartite motif containing 33 (TRIM33) as an estrogen-dependent interactor of ER. shRNA knockdown showed that TRIM33 promoted ER transcriptional activity and estrogen-induced cell growth. Despite its known role as an E3 ubiquitin ligase, TRIM33 increased the stability of endogenous ER in breast cancer cells. TRIM33 offers a novel target for inhibiting estrogen-induced cancer cell growth, particularly in cases of endocrine resistance driven by ER (ESR1) gene amplification or overexpression.
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Affiliation(s)
- Bianca A. Romo
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Barbara Karakyriakou
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Lauren Cressey
- Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Brooke L. Brauer
- Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Huijuan Yang
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Alexa Warren
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Anneka L. Johnson
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Arminja N. Kettenbach
- Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
| | - Todd W. Miller
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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30
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Goel N, Lubarsky M, Hernandez AE, Benck K, Lee E, Kesmodel S, Knaul F, Kobetz E, Anderson BO. Unmet Social Needs and Breast Cancer Screening Utilization and Stage at Presentation. JAMA Netw Open 2024; 7:e2355301. [PMID: 38353954 PMCID: PMC10867685 DOI: 10.1001/jamanetworkopen.2023.55301] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 12/12/2023] [Indexed: 02/16/2024] Open
Abstract
Importance Unmet social needs in local populations may hinder the development of targeted cancer control interventions aimed at improving screening utilization and early-stage breast cancer diagnosis to ultimately improve breast cancer survival disparities. Objective To evaluate if (1) city-funded screening mammography is associated with utilization of screening mammography, (2) unmet social needs are associated with utilization of screening mammography, and (3) unmet social needs are associated with later-stage disease at diagnosis. Design, Setting, and Participants This cohort study included patients with stages I-IV invasive ductal or lobular carcinoma treated at an academic medical center (including both an underserved safety-net hospital [SNH] and a National Cancer Institute-designated academic cancer center [ACC]) from 2020 to 2023. Eligible patients were aged 18 years or older and able to consent. Data were analyzed between July 2023 and September 2023. Exposure The Health Leads Social Needs Screening Toolkit, a screening tool that gathers information on the most common social need domains affecting patient health. Main Outcomes and Measures Univariable and multivariable logistic regression was utilized to evaluate the following primary outcomes: (1) routine screening mammography and (2) American Joint Committee on Cancer 8th edition clinical stage at presentation. Results Of the 322 women who completed the Health Leads Social Needs Screening Toolkit, 201 (62%) self-identified as Hispanic, 63 (19%) as non-Hispanic Black, and 63 (19%) as non-Hispanic White. Two hundred fifty-five (76%) patients with access to city-funded screening mammography completed a screening mammogram. Patients who presented to the SNH were more likely to present with late-stage disease compared with early-stage disease (15 of 48 [31%] vs 50 of 274 [18%]; P = .04). On multivariable logistic regression, not completing a screening mammography was associated with having an increasing number of unmet social needs (OR, 0.74; 95% CI, 0.55-0.99; P = .047) and an increasing age at diagnosis (OR, 0.92; 95% CI, 0.89-0.96; P < .001). Moreover, increasing unmet social needs was significantly associated with late-stage diagnosis above and beyond screening mammography (OR, 1.38; 95% CI, 1.01-1.89; P = .04). Conclusions and Relevance In this cohort study, access to screening mammography did not translate to utilization of screening mammography, increasing unmet social needs were significantly associated with lower rates of screening mammography, and those with increasing unmet social needs were more likely to present with late-stage disease. This association transcended recruitment site (SNH vs ACC), indicating that patients in either hospital setting may benefit from unmet social needs screening to overcome access to care barriers associated with late-stage disease at diagnosis.
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Affiliation(s)
- Neha Goel
- Department of Surgery, Division of Surgical Oncology, University of Miami, Miami, Florida
- University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
- University of Miami Miller School of Medicine, Miami, Florida
- World Health Organization, Geneva, Switzerland
| | - Maya Lubarsky
- University of Miami Miller School of Medicine, Miami, Florida
| | - Alexandra E. Hernandez
- Department of Surgery, Division of Surgical Oncology, University of Miami, Miami, Florida
| | - Kelley Benck
- University of Miami Miller School of Medicine, Miami, Florida
| | - Emma Lee
- University of Miami Miller School of Medicine, Miami, Florida
| | - Susan Kesmodel
- Department of Surgery, Division of Surgical Oncology, University of Miami, Miami, Florida
- University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida
- University of Miami Miller School of Medicine, Miami, Florida
| | - Felicia Knaul
- University of Miami Institute for Advanced Study of the Americas, Coral Gables, Florida
| | - Erin Kobetz
- University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida
- University of Miami Miller School of Medicine, Miami, Florida
- Department of Public Health Sciences, University of Miami, Miami, Florida
- Department of Medicine, Division of Internal Medicine, University of Miami, Miami, Florida
| | - Benjamin O. Anderson
- Department of Surgery, University of Washington, Seattle
- World Health Organization, Geneva, Switzerland
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Hernandez AE, Westrick AC, Stoler J, Kesmodel SB, Pinheiro PS, Figueroa M, Kobetz EN, Rebbeck T, Goel N. Associations Between Neighborhood-Level Income and Triple-Negative Breast Cancer in a Majority-Minority Population. Ann Surg Oncol 2024; 31:988-996. [PMID: 37978105 DOI: 10.1245/s10434-023-14517-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/13/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Previous studies on disparities in triple-negative breast cancer (TNBC) focus on race/ethnicity, with few exploring the impact of contextual factors such as neighborhood-level income. This study evaluates the effect of neighborhood-level income on disparities in TNBC among a racially and ethnically diverse cohort, after accounting for granular individual-level risk factors of TNBC. PATIENTS AND METHODS Patients with stage I-IV breast cancer from 2005 to 2017 were identified from our local tumor registry. The primary outcome was diagnosis of TNBC. Using 5-years estimates from the American Community Survey, we obtained median household income for each census tract which was categorized into quartiles. Mixed effects logistic regression was conducted and stratified by race and ethnicity, controlling for individual-level sociodemographic, comorbidities, and tumor characteristics. RESULTS Among 5377 breast cancer registry patients, 16.5% were diagnosed with TNBC. The majority were Hispanic (50.1%) followed by non-Hispanic Black (NHB) (28.0%). After controlling for individual-level covariables including race and ethnicity, comorbidities, and tumor characteristics, women from low-income neighborhoods had increased odds of TNBC compared with other breast cancer subtypes, compared with those in high-income neighborhoods [odds ratio (OR) 1.33; 95% confidence interval (CI) 1.04, 1.70, p < 0.001]. In stratified analyses, NHB patients from low-income neighborhoods had two times the odds of TNBC diagnosis compared with those from high-income neighborhoods (OR 2.11; 95% CI 1.02, 4.37). CONCLUSION We found that living in a low-income neighborhood is associated with an increased odds of TNBC independent of granular individual-level TNBC risk factors, particularly NHB race. More striking, NHB living in low-income neighborhoods had increased odds of TNBC compared with NHB living in high-income neighborhoods. Our results suggest potential unaccounted gene-environment and/or social (api)genomic interactions between neighborhood-level income and TNBC subtype development.
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Affiliation(s)
- Alexandra E Hernandez
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Ashly C Westrick
- Center for Social Epidemiology and Population Health, University of Michigan, Ann Arbor, MI, USA
| | - Justin Stoler
- Department of Geography and Sustainable Development, University of Miami, Coral Gables, FL, USA
- Abess Center for Ecosystem Science and Policy, University of Miami, Coral Gables, FL, USA
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Susan B Kesmodel
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Paulo S Pinheiro
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Maria Figueroa
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Biochemistry and Molecular Biology Research, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Erin N Kobetz
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
- Division of Computational Medicine and Population Health, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Timothy Rebbeck
- Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, Boston, MA, USA
| | - Neha Goel
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
- Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, Boston, MA, USA.
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Lee CM, Fang S. Fat Biology in Triple-Negative Breast Cancer: Immune Regulation, Fibrosis, and Senescence. J Obes Metab Syndr 2023; 32:312-321. [PMID: 38014425 PMCID: PMC10786212 DOI: 10.7570/jomes23044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/18/2023] [Accepted: 11/21/2023] [Indexed: 11/29/2023] Open
Abstract
Obesity, now officially recognized as a disease requiring intervention, has emerged as a significant health concern due to its strong association with elevated susceptibility to diverse diseases and various types of cancer, including breast cancer. The link between obesity and cancer is intricate, with obesity exerting a significant impact on cancer recurrence and elevated mortality rates. Among the various subtypes of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive, accounting for 15% to 20% of all cases. TNBC is characterized by low expression of estrogen receptors and progesterone receptors as well as the human epidermal growth factor 2 receptor protein. This subtype poses distinct challenges in terms of treatment response and exhibits strong invasiveness. Furthermore, TNBC has garnered attention because of its association with obesity, in which excess body fat and reduced physical activity have been identified as contributing factors to the increased incidence of this aggressive form of breast cancer. In this comprehensive review, the impact of obesity on TNBC was explored. Specifically, we focused on the three key mechanisms by which obesity affects TNBC development and progression: modification of the immune profile, facilitation of fibrosis, and initiation of senescence. By comprehensively examining these mechanisms, we illuminated the complex interplay between TNBC and obesity, facilitating the development of novel approaches for prevention, early detection, and effective management of this challenging disease.
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Affiliation(s)
- Chae Min Lee
- Graduate School of Medical Science, Brain Korea 2 Project, Yonsei University College of Medicine, Seoul, Korea
- Department of Biomedical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sungsoon Fang
- Graduate School of Medical Science, Brain Korea 2 Project, Yonsei University College of Medicine, Seoul, Korea
- Department of Biomedical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Korea
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
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Kumari L, Mishra L, Patel P, Sharma N, Gupta GD, Kurmi BD. Emerging targeted therapeutic strategies for the treatment of triple-negative breast cancer. J Drug Target 2023; 31:889-907. [PMID: 37539789 DOI: 10.1080/1061186x.2023.2245579] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/30/2023] [Indexed: 08/05/2023]
Abstract
Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), has clinical features including a high degree of invasiveness, an elevated risk of metastasis, tendency to relapse, and poor prognosis. It constitutes around 10-15% of all breast cancer, and having heredity of BRCA1 mutated breast cancer could be a reason for the occurrence of TNBC in women. Overexpression of cellular and molecular targets, i.e. CD44 receptor, EGFR receptor, Folate receptor, Transferrin receptor, VEGF receptor, and Androgen receptor, have emerged as promising targets for treating TNBC. Signalling pathways such as Notch signalling and PI3K/AKT/mTOR also play a significant role in carrying out and managing crucial pro-survival and pro-growth cellular processes that can be utilised for targeted therapy against triple-negative breast cancer. This review sheds light on various targeting strategies, including cellular and molecular targets, signalling pathways, poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors PARP, immunotherapy, ADCs have all found a place in the current TNBC therapeutic paradigm. The role of photothermal therapy (PTT) and photodynamic therapy (PDT) has also been explored briefly.
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Affiliation(s)
- Lakshmi Kumari
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | - Lopamudra Mishra
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | - Preeti Patel
- Department of Pharmaceutical Chemistry, ISF College Pharmacy, Moga, Punjab, India
| | - Nitin Sharma
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
| | | | - Balak Das Kurmi
- Department of Pharmaceutics, ISF College Pharmacy, Moga, Punjab, India
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34
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Supuramanian SS, Dsa S, Harihar S. Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2023; 4:912-932. [PMID: 37970212 PMCID: PMC10645471 DOI: 10.37349/etat.2023.00173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 08/03/2023] [Indexed: 11/17/2023] Open
Abstract
Breast cancer (BC) is a leading cause of cancer-related deaths in women worldwide where the process of metastasis is a major contributor to the mortality associated with this disease. Metastasis suppressor genes are a group of genes that play a crucial role in preventing or inhibiting the spread of cancer cells. They suppress the metastasis process by inhibiting colonization and by inducing dormancy. These genes function by regulating various cellular processes in the tumor microenvironment (TME), such as cell adhesion, invasion, migration, and angiogenesis. Dysregulation of metastasis suppressor genes can lead to the acquisition of an invasive and metastatic phenotype and lead to poor prognostic outcomes. The components of the TME generally play a necessary in the metastasis progression of tumor cells. This review has identified and elaborated on the role of a few metastatic suppressors associated with the TME that have been shown to inhibit metastasis in BC by different mechanisms, such as blocking certain cell signaling molecules involved in cancer cell migration, invasion, enhancing immune surveillance of cancer cells, and promoting the formation of a protective extracellular matrix (ECM). Understanding the interaction of metastatic suppressor genes and the components of TME has important implications for the development of novel therapeutic strategies to target the metastatic cascade. Targeting these genes or their downstream signaling pathways offers a promising approach to inhibiting the spread of cancer cells and improves patient outcomes.
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Affiliation(s)
| | - Sid Dsa
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
| | - Sitaram Harihar
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
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Adrada BE, Moseley TW, Kapoor MM, Scoggins ME, Patel MM, Perez F, Nia ES, Khazai L, Arribas E, Rauch GM, Guirguis MS. Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment. Radiographics 2023; 43:e230034. [PMID: 37792593 PMCID: PMC10560981 DOI: 10.1148/rg.230034] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 05/09/2023] [Accepted: 06/01/2023] [Indexed: 10/06/2023]
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive group of tumors that are defined by the absence of estrogen and progesterone receptors and lack of ERBB2 (formerly HER2 or HER2/neu) overexpression. TNBC accounts for 8%-13% of breast cancers. In addition, it accounts for a higher proportion of breast cancers in younger women compared with those in older women, and it disproportionately affects non-Hispanic Black women. TNBC has high metastatic potential, and the risk of recurrence is highest during the 5 years after it is diagnosed. TNBC exhibits benign morphologic imaging features more frequently than do other breast cancer subtypes. Mammography can be suboptimal for early detection of TNBC owing to factors that include the fast growth of this cancer, increased mammographic density in young women, and lack of the typical features of malignancy at imaging. US is superior to mammography for TNBC detection, but benign-appearing features can lead to misdiagnosis. Breast MRI is the most sensitive modality for TNBC detection. Most cases of TNBC are treated with neoadjuvant chemotherapy, followed by surgery and radiation. MRI is the modality of choice for evaluating the response to neoadjuvant chemotherapy. Survival rates for individuals with TNBC are lower than those for persons with hormone receptor-positive and human epidermal growth factor receptor 2-positive cancers. The 5-year survival rates for patients with localized, regional, and distant disease at diagnosis are 91.3%, 65.8%, and 12.0%, respectively. The early success of immunotherapy has raised hope regarding the development of personalized strategies to treat TNBC. Imaging and tumor biomarkers are likely to play a crucial role in the prediction of TNBC treatment response and TNBC patient survival in the future. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.
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Affiliation(s)
- Beatriz E. Adrada
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Tanya W. Moseley
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Megha M. Kapoor
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Marion E. Scoggins
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Miral M. Patel
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Frances Perez
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Emily S. Nia
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Laila Khazai
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Elsa Arribas
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Gaiane M. Rauch
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
| | - Mary S. Guirguis
- From the Departments of Breast Imaging (B.E.A., T.W.M., M.M.K.,
M.E.S., M.M.P., F.P., E.S.N., E.A., G.M.R., M.S.G.), Breast Surgical Oncology
(T.W.M.), Pathology-Anatomical (L.K.), and Abdominal Imaging (G.M.R.), The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350,
Houston, TX 77030
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Goel N, Hernandez A, Merchant N, Rebbeck T. Translational Epidemiology: Genetic Ancestry in Breast Cancer: What Is the Role of Genetic Ancestry and Socioeconomic Status in Triple-Negative Breast Cancer? Adv Surg 2023; 57:1-14. [PMID: 37536846 DOI: 10.1016/j.yasu.2023.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Racial/ethnic and socioeconomic disparities seen in triple-negative breast cancer (TNBC) have prompted questions regarding the role of genetic ancestry in breast cancer (BC) subtype development, tumor biology, and ultimately prognosis. The causes of disparities in TNBC are influenced greatly by both sociopolitical factors and genetic ancestry, and now, the potential genomic underpinnings of social factors. To comprehensively understand disparities in TNBC, it is critical to take a translational epidemiologic approach that takes into account genomic and non-genomic factors. Understanding the interplay between genetic ancestry and social genomics and their proportional influence on outcomes can guide our priorities for screening, diagnosis, and interventions for this aggressive BC subtype.
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Affiliation(s)
- Neha Goel
- Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, 4th Floor, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, 4th Floor, Miami, FL 31336, USA.
| | - Alexandra Hernandez
- Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, 4th Floor, Miami, FL 31336, USA
| | - Nipun Merchant
- Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, 4th Floor, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, 4th Floor, Miami, FL 31336, USA
| | - Timothy Rebbeck
- Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, 1101 Dana. 450 Brookline Avenue, Boston, MA 02215, USA
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Molina-Aguilar C, Robles-Espinoza CD. Tackling the lack of diversity in cancer research. Dis Model Mech 2023; 16:dmm050275. [PMID: 37681401 PMCID: PMC10499025 DOI: 10.1242/dmm.050275] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/09/2023] Open
Abstract
Despite the clear benefit of studying biological samples from diverse genetic backgrounds and geographical locations, our current knowledge of disease is mostly derived from the study of European-descent individuals. In the cancer field, this is reflected in the poor representation of African and Amerindian/Latino samples in most large public data repositories. This lack of diversity is due to several reasons, but here we focus on (1) the lack of support for studies on non-European populations that are performed in low- and middle-income countries (LMICs), and (2) unequal partnerships between scientists in LMICs and those in high-income countries. We argue that expanding access to research funding, increasing the participation of underrepresented scientists in editorial boards and international conferences, facilitating the publication of studies conducted in these countries, and properly acknowledging LMIC researchers' contributions in publications and grant applications will promote equity for scientists working in LMICs. We envisage that this will translate to more impactful research in these countries, which will include more samples from diverse populations. For the cancer field, this will broaden our understanding of pathomechanisms and may help to improve the treatment of patients from all backgrounds.
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Affiliation(s)
- Christian Molina-Aguilar
- Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Santiago de Querétaro 76230, Mexico
| | - C. Daniela Robles-Espinoza
- Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Santiago de Querétaro 76230, Mexico
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK
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Obidiro O, Battogtokh G, Akala EO. Triple Negative Breast Cancer Treatment Options and Limitations: Future Outlook. Pharmaceutics 2023; 15:1796. [PMID: 37513983 PMCID: PMC10384267 DOI: 10.3390/pharmaceutics15071796] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various molecular subtypes. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off-target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment. In this review, we summarized possible treatment options for TNBC, including chemotherapy, immunotherapy, targeted therapy, combination therapy, and nanoparticle-based therapy, and some solutions for the treatment of TNBC in the future. Moreover, we gave general information about TNBC in terms of its characteristics and aggressiveness.
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Affiliation(s)
| | | | - Emmanuel O. Akala
- Center for Drug Research and Development, Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA; (O.O.); (G.B.)
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Wallace G, Kundalia R, Cao B, Kim Y, Smalley I, Forsyth P, Soyano A, Pina Y. Factors improving overall survival in breast cancer patients with leptomeningeal disease (LMD): A single institutional retrospective review. RESEARCH SQUARE 2023:rs.3.rs-2981094. [PMID: 37333166 PMCID: PMC10275046 DOI: 10.21203/rs.3.rs-2981094/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
Background Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center (MCC) from 2011-2020, to determine the changing incidence of BC-LMD, which factors impact progression of BC CNS metastasis to BC-LMD, and which factors affect OS for patients with BC-LMD. Methods Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. Results 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016-2020 when compared to 2011-2015. Patients with HR + or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC delayed BC-CNS metastasis to LMD progression. Lapatinib delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT prolonged survival for all patients. Lapatinib and trastuzumab improved OS in patients with HER2 + BC-LMD. Conclusions Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
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Affiliation(s)
| | | | - Biwei Cao
- H. Lee Moffitt Cancer Center and Research Institute
| | | | - Inna Smalley
- H. Lee Moffitt Cancer Center and Research Institute
| | | | - Aixa Soyano
- H. Lee Moffitt Cancer Center and Research Institute
| | - Yolanda Pina
- H. Lee Moffitt Cancer Center and Research Institute
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Lang Y, Chai Q, Tao W, Liao Y, Liu X, Wu B. Cost-effectiveness of sacituzumab govitecan versus chemotherapy in advanced or metastatic triple-negative breast cancer. Breast 2023; 68:173-180. [PMID: 36780838 PMCID: PMC9947096 DOI: 10.1016/j.breast.2023.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 01/16/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
PURPOSE The ASCENT trial demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of receiving sacituzumab govitecan compared with standard of care chemotherapy from the United States payer perspective. METHODS A partitioned survival approach was used to project the disease course of advanced or metastatic TNBC. Two survival modes were applied to analyze two groups of patients. The survival data were gathered from the ASCENT trial. Direct medical costs were derived from the data of Centers for Medicare & Medicaid Services. Utility data was collected from the published literature. The incremental cost-utility ratio (ICUR) was the primary outcome that measured the cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty and validate the stability of results. RESULTS In the base-case, the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9/QALY and $ 702,281/QALY for full population group and brain metastatic-negative (BMN) group with the setting of classic survival mode. And in the setting of cure survival mode, the ICUR is $ 506,504.5/QALY for the full population group and $ 274,232.0/QALY for BMN population group. One-way sensitivity analyses revealed that the unit cost of sacituzumab govitecan and body weight were key roles that lower the ICUR value. Probabilistic sensitivity analyses also showed that reducing the unit price of sacituzumab govitecan can improve the likelihood of becoming cost-effective. CONCLUSION The cost-effectiveness analysis suggested that from a US payer perspective, sacituzumab govitecan at current price is unlikely to be a preferred option for patients with advanced or metastatic TNBC at a threshold of $ 150,000/QALY.
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Affiliation(s)
- Yitian Lang
- Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.58 Puyu East Road, Huangpu District, Shanghai, 200011, China
| | - Qingqing Chai
- Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.58 Puyu East Road, Huangpu District, Shanghai, 200011, China
| | - Wenqi Tao
- Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.58 Puyu East Road, Huangpu District, Shanghai, 200011, China
| | - Yahui Liao
- Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.58 Puyu East Road, Huangpu District, Shanghai, 200011, China
| | - Xiaoyan Liu
- Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.58 Puyu East Road, Huangpu District, Shanghai, 200011, China.
| | - Bin Wu
- Medical Decision and Economic Group, Department of Pharmacy, Ren Ji Hospital, South Campus, School of Medicine, Shanghai Jiaotong University, No.2000 Jiangyue Road, Minhang District, Shanghai, 201100, China.
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Lower breast cancer survival among Black women in Brazil: a population-based retrospective study. Public Health 2023; 217:190-195. [PMID: 36907028 DOI: 10.1016/j.puhe.2023.02.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 01/29/2023] [Accepted: 02/02/2023] [Indexed: 03/12/2023]
Abstract
OBJECTIVES To analyze the rates of breast cancer survival among Black and White women according to age and stage at diagnosis. STUDY DESIGN A retrospective cohort study. METHODS The study examined women registered in the population-based cancer registry of Campinas in 2010-2014. The primary variable was the declared race (White or Black). Other races were excluded. Data were linked with the Mortality Information System, and missing information was accessed by active search. Overall survival (OS) was calculated by the Kaplan-Meier method, comparisons were done by chi-squared tests, and hazard ratios were examined by Cox regression. RESULTS The total numbers of new cases of staged breast cancer among Black and White women were 218 and 1522 cases, respectively. The rates of stages III/IV were 35.5% among White women and 43.1% among Black women (P = 0.024). The frequencies among White and Black women under 40 years old were 8.0% and 12.4% (P = 0.031), 19.6% and 26.6% (P = 0.016) for ages of 40-49 years, and 23.8% and 17.4% (P = 0.037) for ages of 60-69 years, respectively. The mean OS was 7.5 years (7.0; 8.0) among Black women and 8.4 years (8.2; 8.5) among White women. The 5-year OS was 72.3% among Black women and 80.5% among White women (P = 0.001). Black women had an age-adjusted risk of death that was 1.7 times higher (1.33; 2.20). The risk was 6.4 times higher for diagnoses in stage 0 (1.65; 24.90) and 1.5 times for diagnoses in stage IV (1.04; 2.17). CONCLUSION The 5-year OS for women with breast cancer was significantly lower among Black women than White women. Black women were more frequently diagnosed in stages III/IV, and their age-adjusted risk of death was 1.7 times higher. Differences in access to care may explain these differences.
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Manoochehri M, Borhani N, Gerhäuser C, Assenov Y, Schönung M, Hielscher T, Christensen BC, Lee MK, Gröne HJ, Lipka DB, Brüning T, Brauch H, Ko YD, Hamann U. DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy. Int J Cancer 2023; 152:1025-1035. [PMID: 36305646 DOI: 10.1002/ijc.34337] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 09/06/2022] [Accepted: 09/20/2022] [Indexed: 01/06/2023]
Abstract
Noninvasive detection of aberrant DNA methylation could provide invaluable biomarkers for earlier detection of triple-negative breast cancer (TNBC) which could help clinicians with easier and more efficient treatment options. We evaluated genome-wide DNA methylation data derived from TNBC and normal breast tissues, peripheral blood of TNBC cases and controls and reference samples of sorted blood and mammary cells. Differentially methylated regions (DMRs) between TNBC and normal breast tissues were stringently selected, verified and externally validated. A machine-learning algorithm was applied to select the top DMRs, which then were evaluated on plasma-derived circulating cell-free DNA (cfDNA) samples of TNBC patients and healthy controls. We identified 23 DMRs accounting for the methylation profile of blood cells and reference mammary cells and then selected six top DMRs for cfDNA analysis. We quantified un-/methylated copies of these DMRs by droplet digital PCR analysis in a plasma test set from TNBC patients and healthy controls and confirmed our findings obtained on tissues. Differential cfDNA methylation was confirmed in an independent validation set of plasma samples. A methylation score combining signatures of the top three DMRs overlapping with the SPAG6, LINC10606 and TBCD/ZNF750 genes had the best capability to discriminate TNBC patients from controls (AUC = 0.78 in the test set and AUC = 0.74 in validation set). Our findings demonstrate the usefulness of cfDNA-based methylation signatures as noninvasive liquid biopsy markers for the diagnosis of TNBC.
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Affiliation(s)
- Mehdi Manoochehri
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of In Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany
| | - Nasim Borhani
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Clarissa Gerhäuser
- Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Yassen Assenov
- Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Maximilian Schönung
- Section Translational Cancer Epigenomics, Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany.,Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
| | - Thomas Hielscher
- Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Brock C Christensen
- Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire, USA
| | - Min Kyung Lee
- Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire, USA
| | | | - Daniel B Lipka
- Section Translational Cancer Epigenomics, Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Thomas Brüning
- Institute for Prevention & Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany
| | - Hiltrud Brauch
- Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.,iFIT Cluster of Excellence, University of Tübingen, Tübingen, Germany.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Tübingen, Germany
| | - Yon-Dschun Ko
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany
| | - Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Chang X, Obianwuna UE, Wang J, Zhang H, Qi G, Qiu K, Wu S. Glycosylated proteins with abnormal glycosylation changes are potential biomarkers for early diagnosis of breast cancer. Int J Biol Macromol 2023; 236:123855. [PMID: 36868337 DOI: 10.1016/j.ijbiomac.2023.123855] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 03/05/2023]
Abstract
Conventional cancer management relies on tumor type and stage for diagnosis and treatment, which leads to recurrence and metastasis and death in young women. Early detection of proteins in the serum aids diagnosis, progression, and clinical outcomes, possibly improving survival rate of breast cancer patients. In this review, we provided an insight into the influence of aberrant glycosylation on breast cancer development and progression. Examined literatures revealed that mechanisms underlying glycosylation moieties alteration could enhance early detection, monitoring, and therapeutic efficacy in breast cancer patients. This would serve as a guide for the development of new serum biomarkers with higher sensitivity and specificity, providing possible serological biomarkers for breast cancer diagnosis, progression, and treatment.
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Affiliation(s)
- Xinyu Chang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Uchechukwu Edna Obianwuna
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Jing Wang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Haijun Zhang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Guanghai Qi
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Kai Qiu
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Shugeng Wu
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
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Du XL, Li Z. Incidence trends in triple-negative breast cancer among women in the United States from 2010 to 2019 by race/ethnicity, age and tumor stage. Am J Cancer Res 2023; 13:678-691. [PMID: 36895969 PMCID: PMC9989620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/03/2022] [Indexed: 03/11/2023] Open
Abstract
There were substantial ethnic disparities in the incidence rates of triple-negative breast cancer, but few studies were conducted on the incidence trend of triple-negative breast cancer by race/ethnicity. This study aimed to address the longer trends in the incidence of triple-negative breast cancer by race/ethnicity in women from 2010 to 2019, examine the incidence trends by patient age, tumor stage and time periods, and explore the changing proportions of three component receptors over time for triple-negative breast cancer. Our study identified 573,168 women with incident breast cancer at age ≥20 years between 2010 and 2019 in 18 SEER (Surveillance, Epidemiology, and End Results) registries. Of them, 62,623 (10.9%) were incident triple-negative breast cancer and 510,545 were non-triple negative breast cancer cases. The denominator of population included 320,117,009 women aged ≥20 in the same SEER areas. The study found that overall age-adjusted incidence rate of triple-negative breast cancer in women aged ≥20 years was 18.3 cases per 100,000 women. Age-adjusted incidence rate of triple-negative breast cancer was the highest in black women (33.8 cases per 100,000 women), followed by white (17.5), American Indian and Alaska Native (AIAN) (14.7), Hispanic (14.7), and Asian women (12.4). The significantly higher age-adjusted incidence of triple-negative breast cancer in black women as compared to white women appeared to be limited in younger women aged 20-44 only. Annual percentage changes in age-adjusted incidence of triple-negative breast cancer slightly decreased insignificantly in white, black and Asian women aged 20-44 and 45-54 years. There was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. In conclusion, there was a significantly higher incidence of triple-negative breast cancer in black women aged 20-44 years. From 2010 to 2019, there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer in all ethnic groups of women aged <55 years, with the exception of a significant decrease among AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years.
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Affiliation(s)
- Xianglin L Du
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston 1200 Pressler St, Houston, TX 77030, USA
| | - Zhuoyun Li
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston 1200 Pressler St, Houston, TX 77030, USA
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Nath S, Mukhopadhyay A, Roy S, Saha S, Majumder S, Dey S, Bhattacharyya S, Gupta A. A comparative analysis of features and outcome of breast cancer in younger versus older women: A single center experience from Eastern Indian subcontinent. J Cancer Res Ther 2023; 19:S59-S66. [PMID: 37147984 DOI: 10.4103/jcrt.jcrt_664_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Purpose Globally, breast cancer is the leading malignancy in females. Indeed, Asian cohorts show prevalence of breast cancer among women with ages below 40 years. Moreover, these younger cases are globally characterized by poorer prognostic features as well as survival outcomes, than older sufferers with ages above 40 years. Despite this, comparative analyses between older and younger cohorts are sparse from India, where data from the country's eastern part falls shortest. This study attempted a comprehensive analysis of breast cancer between these two cohorts representing the Eastern Indian subcontinent. Methods Documenting retrospective case-files registered between 2010 and 2015, 394 cases of younger (<40 years) and 1250 older (≥40 years) sufferers of primary breast cancer were noted. The relevant features and follow-up information were also retrieved. Kaplan-Meier analyses were performed to evaluate the survival outcome. Results The data, in general, revealed a high percentage of younger sufferers from Eastern Indian regions. Moreover, this younger cohort showed poor survival. Among the younger cohort, cases with poor pathological features (triple negative, node-positive, grade III) were proportionately higher than the older cohort. Indeed, survival among these categories scored significantly low, compared to the older cohort. Conclusion This Eastern Indian subcontinental data matched the analyses from other parts of India as well as Asian data and clearly showed the prevalence of younger sufferers of breast cancer with poor clinico-pathological features and survival outcomes. Impact Analyzing age-based features and outcomes from Eastern India, this study provides data in supplementing Indian and Asian scenarios of breast cancer.
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Panda C, Islam S, Basu M, Roy A, Alam N. Association of Augmented Immune-Staining of G-Quadruplex Tertiary DNA Structure in Chemo-Tolerant TNBC with Downregulation of WNT/Epidermal Growth Factor Receptor Pathway receptor Genes: A Pilot Clinicopathological Study. JOURNAL OF RADIATION AND CANCER RESEARCH 2023. [DOI: 10.4103/jrcr.jrcr_23_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Zhao P, Sun J, Huang X, Zhang X, Liu X, Liu R, Du G, Gan W, Yang C, Tang Y, Chen C, Jiang D. Targeting the KLF5-EphA2 axis can restrain cancer stemness and overcome chemoresistance in basal-like breast cancer. Int J Biol Sci 2023; 19:1861-1874. [PMID: 37063424 PMCID: PMC10092769 DOI: 10.7150/ijbs.82567] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/08/2023] [Indexed: 04/18/2023] Open
Abstract
Ephrin type-A receptor 2 (EphA2) is a member of the tyrosine receptor kinases, a family of membrane proteins recognized as potential anticancer targets. EphA2 highly expressed in a variety of human cancers, playing roles in proliferation, migration, and invasion. However, whether and how EphA2 regulates basal-like breast cancer (BLBC) cell stemness and chemoresistance has not been revealed. Here, KLF5 was proven to be a direct transcription factor for EphA2 in BLBC cells, and its expression was positively correlated in clinical samples from breast cancer patients. The inflammatory factor TNF-α could promote BLBC cell stemness partially by activating the KLF5-EphA2 axis. Moreover, phosphorylation of EphA2 at S897 (EphA2 pS897) induced by TNF-α and PTX/DDP contributes to chemoresistance of BLBC. Furthermore, the EphA2 inhibitor ALW-II-41-27 could effectively reduce EphA2 pS897 and tumor cell stemness in vitro and significantly enhance the sensitivity of xenografts to the chemotherapeutic drugs PTX and DDP in vivo. Clinically, tumor samples from breast patients with less response to neoadjuvant chemotherapy showed a high level of EphA2 pS897 expression. In conclusion, KLF5-EphA2 promotes stemness and drug resistance in BLBC and could be a potential target for the treatment of BLBC.
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Affiliation(s)
- Ping Zhao
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
| | - Jian Sun
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
| | - Xinwei Huang
- Key Laboratory of The Second Affiliated Hospital of Kuming Medical College, Kunming, 650101, China
| | - Xiangwu Zhang
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
| | - Xin Liu
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
| | - Rong Liu
- Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034 China
| | - Guangshi Du
- Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550025 China
| | - Wenqiang Gan
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 China
- Kunming College of Life Sciences, University of the Chinese Academy of Sciences, Kunming, 650204 China
| | - Chuanyu Yang
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 China
| | - Yiyin Tang
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
- ✉ Corresponding authors: Dewei Jiang, , orcid.org/0000-0002-7773-5449; Ceshi Chen, , orcid.org/0000-0001-6398-3516; Yiying Tang,
| | - Ceshi Chen
- The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118 China
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 China
- Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500 China
- ✉ Corresponding authors: Dewei Jiang, , orcid.org/0000-0002-7773-5449; Ceshi Chen, , orcid.org/0000-0001-6398-3516; Yiying Tang,
| | - Dewei Jiang
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 China
- Kunming College of Life Sciences, University of the Chinese Academy of Sciences, Kunming, 650204 China
- ✉ Corresponding authors: Dewei Jiang, , orcid.org/0000-0002-7773-5449; Ceshi Chen, , orcid.org/0000-0001-6398-3516; Yiying Tang,
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Shoukat I, Mueller CR. Searching for DNA methylation in patients triple-negative breast cancer: a liquid biopsy approach. Expert Rev Mol Diagn 2023; 23:41-51. [PMID: 36715539 DOI: 10.1080/14737159.2023.2173579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Liquid biopsies are proving to have diagnostic and prognostic value in many different cancers, and in breast cancer they have the potential to improve outcomes by providing valuable information throughout a patient's cancer journey. However, patients with triple negative breast cancer (TNBC) have received little benefit from such liquid biopsies due to underlying limitations in the discovery and utility of robust biomarkers. Here, we examine the development of DNA methylation-based liquid biopsy assays for breast cancer and how they pertain to TNBC. AREAS COVERED We conducted a systematic review of liquid biopsy assays for breast cancer and analyzed their relevance in TNBC. We show that the utility of DNA mutation-based assays is poor for TNBC due to the low mutational frequencies across the genome in this subtype. We offer a detailed review of mDETECT - a liquid biopsy specifically designed for assessing tumor burden in TNBC patients. EXPERT OPINION DNA methylation are foundational and robust events that occur in cancer evolution and may differentiate almost all forms of cancer, including TNBC. Longitudinal patient monitoring using DNA methylation-based liquid biopsies offers great potential for improving the detection and management of TNBC.
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Affiliation(s)
- Irsa Shoukat
- Queen's Cancer Research Institute, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
| | - Christopher R Mueller
- Queen's Cancer Research Institute, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
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Zhang W, Bai Y, Sun C, Lv Z, Wang S. Racial and regional disparities of triple negative breast cancer incidence rates in the United States: An analysis of 2011-2019 NPCR and SEER incidence data. Front Public Health 2022; 10:1058722. [PMID: 36530732 PMCID: PMC9752091 DOI: 10.3389/fpubh.2022.1058722] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 11/15/2022] [Indexed: 12/02/2022] Open
Abstract
Objective Triple negative breast cancer (TNBC) is a more aggressive subtype resistant to conventional treatments with a poorer prognosis. This study was to update the status of TNBC and the temporal changes of its incidence rate in the US. Methods Women diagnosed with breast cancer during 2011-2019 were obtained from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) Program SEER*Stat Database which covers the entire population of the US. The TNBC incidence and its temporal trends by race, age, region (state) and disease stage were determined during the period. Results A total of 238,848 (or 8.8%) TNBC women were diagnosed during the study period. TNBC occurred disproportionally higher in women of Non-Hispanic Black, younger ages, with cancer at a distant stage or poorly/undifferentiated. The age adjusted incidence rate (AAIR) for TNBC in all races decreased from 14.8 per 100,000 in 2011 to 14.0 in 2019 (annual percentage change (APC) = -0.6, P = 0.024). Incidence rates of TNBC significantly decreased with APCs of -0.8 in Non-Hispanic White women, -1.3 in West and -0.7 in Northeastern regions. Women with TNBC at the age of 35-49, 50-59, and 60-69 years, and the disease at the regional stage displayed significantly decreased trends. Among state levels, Mississippi (20.6) and Louisiana (18.9) had the highest, while Utah (9.1) and Montana (9.6) had the lowest AAIRs in 2019. New Hampshire and Indiana had significant and highest decreases, while Louisiana and Arkansas had significant and largest increases in AAIR. In individual races, TNBC displayed disparities in temporal trends among age groups, regions and disease stages. Surprisingly, Non-Hispanic White and Hispanic TNBC women (0-34 years), and Non-Hispanic Black women (≥70 years) during the entire period, as well as Asian or Pacific Islander women in the South region had increased trends between 2011 and 2017. Conclusion Our study demonstrates an overall decreased trend of TNBC incidence in the past decade. Its incidence displayed disparities among races, age groups, regions and disease stages. Special attention is needed for a heavy burden in Non-Hispanic Black and increased trends in certain groups.
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Affiliation(s)
- Wei Zhang
- Department of Basic Medicine Sciences, Cancer Institute of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University, Hangzhou, China
| | - Yuhui Bai
- Shanghai Hongqiao International School, Shanghai, China
| | - Caixing Sun
- Department of Neurosurgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China,Key Laboratory of Head & Neck Cancer, Translational Research of Zhejiang Province, Hangzhou, China
| | - Zhangchun Lv
- Department of Medical Oncology, Yongkang Traditional Chinese Medicine Hospital, Yongkang, China,*Correspondence: Zhangchun Lv
| | - Shihua Wang
- The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, United States,Shihua Wang
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Huang M, O'Shaughnessy J, Haiderali A, Pan W, Hu P, Chaudhuri M, Le Bailly De Tilleghem C, Cappoen N, Fasching PA. Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Eur J Cancer 2022; 177:45-52. [PMID: 36323052 DOI: 10.1016/j.ejca.2022.09.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/25/2022] [Accepted: 09/26/2022] [Indexed: 01/06/2023]
Abstract
OBJECTIVE In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population. METHODS The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients' survival time was partitioned into three health states - toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations. RESULTS Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time. CONCLUSIONS Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1-positive mTNBC.
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Affiliation(s)
| | - Joyce O'Shaughnessy
- Baylor University Medical Center, Texas Oncology and US Oncology, Dallas, TX, USA
| | | | | | - Peter Hu
- Merck & Co., Inc., Rahway, NJ, USA
| | | | | | | | - Peter A Fasching
- Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
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