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Park KU, Somerfield MR, Anne N, Brackstone M, Conlin AK, Couto HL, Dengel LT, Eisen A, Harvey BE, Hawley J, Kim JN, Lasebikan N, McDonald ES, Pradhan D, Shams S, Vega RM, Thompson AM, Torres MA. Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update. J Clin Oncol 2025; 43:1720-1741. [PMID: 40209128 DOI: 10.1200/jco-25-00099] [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: 01/14/2025] [Accepted: 01/22/2025] [Indexed: 04/12/2025] Open
Abstract
PURPOSE To update the ASCO evidence-based recommendations on the use of sentinel lymph node biopsy (SLNB) in patients with early-stage breast cancer treated with initial surgery. METHODS ASCO convened an Expert Panel to develop updated recommendations based on a systematic literature review (January 2016-May 2024). RESULTS Eleven randomized clinical trials (14 publications), eight meta-analyses and/or systematic reviews, and one prospective cohort study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop practice recommendations. RECOMMENDATIONS Clinicians should not recommend routine SLNB in select patients who are postmenopausal and ≥50 years of age and with negative findings on preoperative axillary ultrasound for grade 1-2, small (≤2 cm), hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer and who undergo breast-conserving therapy. Clinicians may offer postmastectomy radiation (RT) with regional nodal irradiation (RNI) and omit axillary lymph node dissection (ALND) in patients with clinically node-negative invasive breast cancer ≤5 cm who receive mastectomy and have one to two positive sentinel nodes. Clinicians may offer SLNB in patients who have cT3-T4c or multicentric tumors (clinically node-negative) or ductal carcinoma in situ treated with mastectomy, and in patients who are obese, male, or pregnant, or who have had prior breast or axillary surgery. Clinicians should not recommend ALND for patients with early-stage breast cancer who do not have nodal metastases, and clinicians should not recommend ALND for patients with early-stage breast cancer who have one or two sentinel lymph node metastases and will receive breast-conserving surgery and whole-breast RT with or without RNI.Additional information is available at www.asco.org/breast-cancer-guidelines.This guideline has been endorsed by the American Society for Radiation Oncology (ASTRO).
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Affiliation(s)
- Ko Un Park
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA
| | | | - Nirupama Anne
- Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Muriel Brackstone
- Department of Surgery, University of Western Ontario, London, ON, Canada
| | | | | | - Lynn T Dengel
- Emily Couric Clinical Cancer Center, Charlottesville, VA
| | - Andrea Eisen
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | - Jeffrey Hawley
- Stephanie Spielman Comprehensive Breast Center, The Ohio State University Medical Center, Columbus, OH
| | - Janice N Kim
- University of Washington School of Medicine, Seattle, WA
| | | | | | | | | | | | | | - Mylin A Torres
- Glenn Family Breast Center at Winship Cancer Institute, Atlanta, GA
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Sağdıç MF, Dinçer B, Özaslan C. De-escalation of axillary surgery in early breast cancer: translating ACOSOG Z0011 study into clinical practice for breast-conserving surgery patients with positive sentinel lymph node biopsy. BMC Cancer 2025; 25:706. [PMID: 40240994 PMCID: PMC12001651 DOI: 10.1186/s12885-025-14105-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] [Received: 01/14/2025] [Accepted: 04/07/2025] [Indexed: 04/18/2025] Open
Abstract
PURPOSE This retrospective study aimed to compare patients eligible for the Z0011 study with and without axillary lymph node dissection (ALND) by overall survival (OS), disease-free survival (DFS), and loco-regional recurrence. METHODS We carried out this study with the data from early-stage breast cancer patients (T1, T2, and clinical node-negative) undergoing breast-conserving surgery (BCS) and receiving adjuvant systemic therapy (chemotherapy or endocrine therapy) and adjuvant radiotherapy after sentinel lymph node biopsy (SLNB) at Ankara Oncology Hospital between January 2018-2024. We screened the data from a total of 1,218 patients and selected 126 patients with ALND and 67 patients without ALND. All selected patients satisfied the Z0011 criteria. We excluded mastectomy and metastatic patients, those without SLNB, patients with more than two positive lymph nodes, and those receiving neoadjuvant chemotherapy. Then, we compared groups by OS, DFS, and locoregional recurrence. RESULTS While the 5-year overall survival was 98.5% (95% CI, 95.8-100.0%) in the Z0011 group, it was 95.2% (95% CI, 92.1-98.3%) in the Z0011-eligible group. The 5-year DFS rate was 97.0% (95% CI, 92.0-99.0%) and 94.4% (95% CI, 91.2-97.0%) in the groups, respectively. We did not discover recurrence in the axial lymph nodes and breast at a mean follow-up of 69 months (67.46-70.43). CONCLUSION In summary, the present study demonstrated that the omission of ALND does not exert any significant influence on OS, DFS, and locoregional recurrence among patients satisfying the ACOSOG Z0011 criteria.
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Affiliation(s)
- Mehmet Furkan Sağdıç
- Department of Surgical Oncology, Ankara Etlik City Hospital, Varlik Neighborhood, Halil Sezai Erkut Avenue, Yenimahalle / ANKARA, Ankara, 06100, Turkey.
| | - Burak Dinçer
- Department of Surgical Oncology, University of Health Sciences Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Cihangir Özaslan
- Department of Surgical Oncology, University of Health Sciences Ankara Oncology Training and Research Hospital, Ankara, Turkey
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Yan X, Niu Y, Yang X, Zhao R, Cui W, Guo X, Zhang J, Ma M. FDP/FIB ratio serves as a novel biomarker for diagnosing bone marrow invasion in gastric cancer and predicting patient prognosis\. Sci Rep 2025; 15:9462. [PMID: 40108276 PMCID: PMC11923145 DOI: 10.1038/s41598-025-93056-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 03/04/2025] [Indexed: 03/22/2025] Open
Abstract
Objective This study aimed to identify laboratory indicators with significant implications for bone marrow invasion in gastric cancer patients and to evaluate their prognostic value. Methods A retrospective analysis of the clinical data of 320 gastric cancer patients who underwent either bone marrow cytological examination or bone marrow biopsy at our hospital between January 2013 and December 2023 was conducted. Among these patients, 31 patients with confirmed bone marrow invasion composed the study group, whereas 34 stage IV gastric cancer patients without bone marrow invasion composed the control group. Differences in demographic and laboratory data between the two groups were compared. Receiver operating characteristic curves were used to identify valuable indicators for predicting bone marrow invasion in patients with gastric cancer. Survival analysis was performed using the Kaplan‒Meier method and included the plotting of survival curves. Additionally, Cox proportional hazards regression analysis was performed to evaluate independent prognostic factors. Results Significantly different values (all P < 0.05) were observed for age, peripheral blood immature cells, Hb, PLT, SII, FIB, PT, FDP, D-Dimer, FDP/FIB, CEA, and CA72-4 between stage IV gastric cancer patients with and without bone marrow infiltration. The ROC analysis indicated that at a threshold value of 5.197 for FDP/FIB, the AUC was 0.958 (P < 0.01). Within the cohort of 65 stage IV gastric cancer patients, those with bone marrow invasion and high FDP/FIB ratios exhibited notably shorter median survival times than those without bone marrow invasion and with low FDP/FIB ratios (χ2 = 25.928, 20.128, P < 0.001). Multivariate analysis demonstrated that bone marrow invasion (HR = 4.148, P = 0.020) and the FDP/FIB ratio (HR = 1.026, P = 0.024) were independent risk factors influencing the prognosis and survival outcome of stage IV gastric cancer patients. Among the subset of 31 gastric cancer patients with bone marrow invasion, the median survival time for the high FDP/FIB group was 22 days, which was significantly shorter than the 60 days observed in the low FDP/FIB group (χ2 = 8.479, P = 0.004). Conclusion The FDP/FIB ratio can serve as an important indicator for the diagnosis and prognostic evaluation of bone marrow invasion in patients with gastric cancer.
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Affiliation(s)
- Xi Yan
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yinghao Niu
- Department of Clinical Biobank, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xingxiao Yang
- Department of Hospital Infection Management, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Riyang Zhao
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wenxuan Cui
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiujuan Guo
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
- , 12# Jiankang Road, Shijiazhuang, China.
| | - Jinyan Zhang
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
- , 12# Jiankang Road, Shijiazhuang, China.
| | - Ming Ma
- Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
- , 12# Jiankang Road, Shijiazhuang, China.
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Fancellu A, Giuliani G, Mulas S, Contini AM, Ariu ML, Sanna V. De-escalation of axillary treatment in early breast cancer-a narrative review of current trials. TRANSLATIONAL BREAST CANCER RESEARCH : A JOURNAL FOCUSING ON TRANSLATIONAL RESEARCH IN BREAST CANCER 2025; 6:5. [PMID: 39980812 PMCID: PMC11836741 DOI: 10.21037/tbcr-24-45] [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: 08/25/2024] [Accepted: 12/13/2024] [Indexed: 02/22/2025]
Abstract
Background and Objective In the era of de-escalation and minimally invasive locoregional treatments across many fields of surgical oncology, the treatment of the axilla in breast cancer has garnered significant interest. While the knowledge of axillary lymph node involvement is crucial for multidisciplinary management, the surgical approach to the axillary basin can have potential disadvantages that may impact the quality of life. The objective of this narrative review is to examine studies about de-escalation of axillary treatment in various clinical scenarios, namely the settings of upfront surgery and neoadjuvant systemic treatments. Moreover, trials investigating omission of axillary surgery were examined. Methods As of July 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Scopus, Web of Sciences, and ClinicalTrials.gov. Key Content and Findings In patients with clinically node-negative lymph nodes and up to two positive sentinel nodes, avoiding axillary lymph node dissection is a safe option. As for patients receiving neoadjuvant systemic treatment, axillary lymph node dissection is unnecessary if no residual tumor burden remained in the lymph nodes after surgery. Additionally, studies have shown that axillary radiotherapy can be as effective as axillary dissection in certain cases. The avoidance of any axillary surgery might be proposed to highly select sub-groups patients with small tumors and negative on clinical and ultrasound evaluation lymph nodes. Conclusions To date, determining the appropriate axillary treatment remains a complex decision that must be made by multidisciplinary teams with expertise in personalized breast cancer treatment.
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Affiliation(s)
| | | | | | | | | | - Valeria Sanna
- Unit of Medical Oncology, AOU Sassari, Sassari, Italy
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Sciallis A. Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer: A review emphasizing clinical concepts pathologists need to know. Semin Diagn Pathol 2024; 41:285-292. [PMID: 38937191 DOI: 10.1053/j.semdp.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 06/18/2024] [Indexed: 06/29/2024]
Affiliation(s)
- Andrew Sciallis
- Staff Pathologist, Pathology and Laboratory Medicine Institute (PLMI), Cleveland Clinic, Cleveland, OH 44195, United States.
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Rodriguez-Tirado C, Sosa MS. How much do we know about the metastatic process? Clin Exp Metastasis 2024; 41:275-299. [PMID: 38520475 PMCID: PMC11374507 DOI: 10.1007/s10585-023-10248-0] [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: 08/13/2023] [Accepted: 11/17/2023] [Indexed: 03/25/2024]
Abstract
Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the early and asymptomatic stages of tumor progression. In experimental models and clinical samples, DCCs can be detected in a non-proliferative state, defined as cellular dormancy. This state can persist for extended periods until DCCs reawaken, usually in response to niche-derived reactivation signals. Therefore, their clinical detection in sites like lymph nodes and bone marrow is linked to poor survival. Current cancer therapy designs are based on the biology of the primary tumor and do not target the biology of the dormant DCC population and thus fail to eradicate the initial or subsequent waves of metastasis. In this brief review, we discuss the current methods for detecting DCCs and highlight new strategies that aim to target DCCs that constitute minimal residual disease to reduce or prevent metastasis formation. Furthermore, we present current evidence on the relevance of DCCs derived from early stages of tumor progression in metastatic disease and describe the animal models available for their study. We also discuss our current understanding of the dissemination mechanisms utilized by genetically less- and more-advanced cancer cells, which include the functional analysis of intermediate or hybrid states of epithelial-mesenchymal transition (EMT). Finally, we raise some intriguing questions regarding the clinical impact of studying the crosstalk between evolutionary waves of DCCs and the initiation of metastatic disease.
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Affiliation(s)
- Carolina Rodriguez-Tirado
- Department of Microbiology and Immunology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Cancer Dormancy and Tumor Microenvironment Institute/Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
- Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
| | - Maria Soledad Sosa
- Department of Microbiology and Immunology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
- Cancer Dormancy and Tumor Microenvironment Institute/Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
- Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, 10461, USA.
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Kayraklioglu N, Katsakhyan L, Cohen PA, Singh N, Rabban JT, Matias-Guiu X. Perceptions of Controversies and Unresolved Issues in the 2014 FIGO Staging System for Endometrial Cancer: Survey Results From Members of the International Society of Gynecological Pathologists and International Gynecologic Cancer Society. Int J Gynecol Pathol 2024; 43:242-252. [PMID: 37668357 DOI: 10.1097/pgp.0000000000000977] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/06/2023]
Abstract
Long-standing controversial and unresolved issues in the current "International Federation of Gynecology and Obstetrics" staging system for endometrial cancer are well-recognized by pathologists and clinicians alike and exist primarily as a result of limitations to the existing literature. To guide the design of future outcome-based studies specifically aimed at resolving such gaps, the International Society of Gynecologic Pathologists developed a survey of the current perceptions of pathologists (n = 172) and clinicians (n= 135) from the International Society of Gynecological Pathologists and from the International Gynecologic Cancer Society on areas for potential refinement of the current International Federation of Gynecology and Obstetrics staging system. The highest priority issues for pathologists and clinicians alike were the need to determine whether stage IIIA patients (ovarian/fallopian tube involvement) can be reliably separated into favorable versus unfavorable outcome groups to avoid over-treatment of the former group and to determine whether stage IIIC patients (lymph node metastases) can be separated into favorable versus unfavorable outcome groups based on the size of lymph node metastases. The majority of pathologists and clinicians viewed lymphovascular space invasion as an independent prognostic variable and favored incorporating lymphovascular space invasion into staging, though the level of support did not meet the threshold of 75% in support that we used to define a formal consensus. While pathologists did agree on the prognostic value of reporting the extent of lymphovascular space invasion, there was no consensus on the diagnostic criteria to distinguish focal versus substantial involvement. The majority of pathologists and clinicians viewed that a universally accepted protocol for sentinel lymph node ultra-staging is lacking. Both survey groups conveyed a slight preference for incorporating tumor histotype and molecular classification into staging but the support was short of the 75% threshold for formal consensus. Collectively, this survey permits the International Society of Gynecological Pathologists to develop a pathologist and clinician-driven long-term strategy for prioritizing and designing outcome-based studies specifically targeted to resolving controversial and unresolved issues in the International Federation of Gynecology and Obstetrics staging of endometrial cancer.
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Honma N, Yoshida M, Kinowaki K, Horii R, Katsurada Y, Murata Y, Shimizu A, Tanabe Y, Yamauchi C, Yamamoto Y, Iwata H, Saji S. The Japanese breast cancer society clinical practice guidelines for pathological diagnosis of breast cancer, 2022 edition. Breast Cancer 2024; 31:8-15. [PMID: 37934318 PMCID: PMC10764572 DOI: 10.1007/s12282-023-01518-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 10/18/2023] [Indexed: 11/08/2023]
Affiliation(s)
- Naoko Honma
- Department of Pathology, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-Ku, Tokyo, 143-8540, Japan.
| | - Masayuki Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Keiichi Kinowaki
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Rie Horii
- Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina, Kita-Adachi-Gun, Saitama, 362-0806, Japan
| | - Yuka Katsurada
- Pathology and Laboratory Medicine, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Yuya Murata
- Department of Pathology, NHO Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-Ku, Tokyo, 152-0021, Japan
| | - Ai Shimizu
- Department of Surgical Pathology, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-Ku, Sapporo, 060-8648, Japan
| | - Yuko Tanabe
- Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-Ku, Tokyo, 105-8470, Japan
| | - Chikako Yamauchi
- Department of Radiation Oncology, Shiga General Hospital, 4-1-1 KyomachiShiga Prefecture, Otsu City, 520-8577, Japan
| | - Yutaka Yamamoto
- Department of Breast and Endocrine Surgery, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hiroji Iwata
- Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, 464-8681, Japan
| | - Shigehira Saji
- Department of Medical Oncology, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
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Jenkins TM, Mehr CR. Updates in the Use of Immunohistochemical Stains in Breast and Gynecologic Pathology. Arch Pathol Lab Med 2024; 148:33-47. [PMID: 37406290 DOI: 10.5858/arpa.2022-0467-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2023] [Indexed: 07/07/2023]
Abstract
CONTEXT.— The use of immunohistochemical stains in breast and gynecologic pathology has become increasingly complex, with various diagnostic, prognostic, and predictive applications. OBJECTIVE.— To provide an update and review of immunohistochemical stains used in the practice of breast and gynecologic pathology. Established and new entities are reviewed, with descriptions of histomorphology and immunohistochemical staining patterns and discussion of interpretive pitfalls. DATA SOURCES.— Data were obtained from review of the English-language literature and firsthand experience of the authors in breast and gynecologic pathology. CONCLUSIONS.— Many entities in breast and gynecologic pathology benefit from evaluation with various immunohistochemical stains. These studies not only aid in the diagnosis and staging of tumors but also can provide prognostic and predictive information. Updated guidelines for recommended ancillary studies such as mismatch repair, p53, and human epidermal growth factor receptor 2 (HER2) studies in endometrium, as well as estrogen and progesterone receptors and HER2 in breast, are discussed. Finally, the use and interpretation of established and novel immunohistochemical stains are discussed in various breast and gynecologic malignancies.
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Affiliation(s)
- Taylor M Jenkins
- From the Department of Pathology, University of Virginia Health System, Charlottesville (Jenkins)
| | - Chelsea R Mehr
- Diagnostic Medicine Institute, Geisinger Health System, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania (Mehr)
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Wang Y, Broeks A, Giardiello D, Hauptmann M, Jóźwiak K, Koop EA, Opdam M, Siesling S, Sonke GS, Stathonikos N, Ter Hoeve ND, van der Wall E, van Deurzen CHM, van Diest PJ, Voogd AC, Vreuls W, Linn SC, Dackus GMHE, Schmidt MK. External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer. Eur J Cancer 2023; 195:113401. [PMID: 37925965 DOI: 10.1016/j.ejca.2023.113401] [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: 08/24/2023] [Revised: 10/19/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND The validity of the PREDICT breast cancer prognostic model is unclear for young patients without adjuvant systemic treatment. This study aimed to validate PREDICT and assess its clinical utility in young women with node-negative breast cancer who did not receive systemic treatment. METHODS We selected all women from the Netherlands Cancer Registry who were diagnosed with node-negative breast cancer under age 40 between 1989 and 2000, a period when adjuvant systemic treatment was not standard practice for women with node-negative disease. We evaluated the calibration and discrimination of PREDICT using the observed/expected (O/E) mortality ratio, and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, we compared the potential clinical utility of PREDICT for selectively administering chemotherapy to the chemotherapy-to-all strategy using decision curve analysis at predefined thresholds. RESULTS A total of 2264 women with a median age at diagnosis of 36 years were included. Of them, 71.2% had estrogen receptor (ER)-positive tumors and 44.0% had grade 3 tumors. Median tumor size was 16 mm. PREDICT v2.2 underestimated 10-year all-cause mortality by 33% in all women (O/E ratio:1.33, 95%CI:1.22-1.43). Model discrimination was moderate overall (AUC10-year:0.65, 95%CI:0.62-0.68), and poor for women with ER-negative tumors (AUC10-year:0.56, 95%CI:0.51-0.62). Compared to the chemotherapy-to-all strategy, PREDICT only showed a slightly higher net benefit in women with ER-positive tumors, but not in women with ER-negative tumors. CONCLUSIONS PREDICT yields unreliable predictions for young women with node-negative breast cancer. Further model updates are needed before PREDICT can be routinely used in this patient subset.
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Affiliation(s)
- Yuwei Wang
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Annegien Broeks
- Core Facility Molecular Pathology and Biobanking, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Daniele Giardiello
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Eurac Research, Institute of Biomedicine, Epidemiology and Biostatistics, Bolzano, Italy
| | - Michael Hauptmann
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany
| | - Katarzyna Jóźwiak
- Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany
| | - Esther A Koop
- Department of Pathology, Gelre Ziekenhuizen, Apeldoorn, the Netherlands
| | - Mark Opdam
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Sabine Siesling
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands; Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands
| | - Gabe S Sonke
- Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Nikolas Stathonikos
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Natalie D Ter Hoeve
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Elsken van der Wall
- Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | - Paul J van Diest
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Adri C Voogd
- Department of Epidemiology, Maastricht University, Maastricht, the Netherlands
| | - Willem Vreuls
- Department of Pathology, Canisius Wilhelmina Ziekenhuis, Nijmegen, the Netherlands
| | - Sabine C Linn
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Gwen M H E Dackus
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Marjanka K Schmidt
- Department of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
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Houvenaeghel G, Cohen M, Martino M, Reyal F, Classe JM, Chauvet MP, Colombo PE, Heinemann M, Jouve E, Gimbergues P, Azuar AS, Coutant C, Gonçalves A, de Nonneville A. Negative Survival Impact of Occult Lymph Node Involvement in Small HER2-Positive Early Breast Cancer Treated by Up-Front Surgery. Cancers (Basel) 2023; 15:4567. [PMID: 37760536 PMCID: PMC10526175 DOI: 10.3390/cancers15184567] [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: 09/01/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.
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Affiliation(s)
- Gilles Houvenaeghel
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009 Marseille, France; (M.C.); (M.M.)
| | - Monique Cohen
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009 Marseille, France; (M.C.); (M.M.)
| | - Marc Martino
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009 Marseille, France; (M.C.); (M.M.)
| | - Fabien Reyal
- Institut Curie, 26 Rue d’Ulm, 75248 Paris, France;
| | - Jean-Marc Classe
- Institut René Gauducheau, Site Hospitalier Nord, Boulevard Jacques Monod, 44800 St. Herblain, France;
| | | | | | | | - Eva Jouve
- Centre Claudius Regaud, 20-24 Rue du Pont St. Pierre, 31300 Toulouse, France;
| | - Pierre Gimbergues
- Centre Jean Perrin, 58 Rue Montalembert, 63011 Clermont-Ferrand, France;
| | | | - Charles Coutant
- Centre Georges François Leclerc, 1 Rue du Professeur Marion, 21000 Dijon, France;
| | - Anthony Gonçalves
- Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009 Marseille, France;
| | - Alexandre de Nonneville
- Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, INSERM, 232 Bd de Sainte Marguerite, 13009 Marseille, France;
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12
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Wang P, Shuai J, Leng Z, Ji Y. Meta-analysis of the application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy for breast cancer. Photodiagnosis Photodyn Ther 2023; 43:103742. [PMID: 37567333 DOI: 10.1016/j.pdpdt.2023.103742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/19/2023] [Accepted: 08/08/2023] [Indexed: 08/13/2023]
Abstract
OBJECTIVE The main objective of this study was to compare the application value of indocyanine green fluorescence imaging (ICGFI) and its combined tracing method with the blue dye method in guiding sentinel lymph node biopsy for breast cancer. MATERIALS AND METHODS A computerized search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was conducted to identify all relevant literature on ICGFI compared to the sole methylene blue (MB) tracing method in guiding sentinel lymph node biopsy for breast cancer. The search was performed up until May 2023. After assessing the quality of the included studies, a meta-analysis was conducted using STATA 12.0 software. RESULTS A total of 11 relevant studies were included in this research. The analysis results showed that, in terms of the detection rate, the ICGFI group had a higher detection rate to the MB group [odds ratio (OR) = 8.64, 95% CI: 5.46-13.66, P = 0.000], and had a higher quantity compared to the MB group [weighted mean difference (WMD) = 0.72, 95% CI 0.31-1.13, P = 0.001], and it also had a lower false-negative rate [OR = 0.10, 95% CI 0.02-0.43, P = 0.002]. However, there was no statistically significant difference in the positive detection rate, and sensitivity comparison. CONCLUSION The indocyanine green fluorescence imaging and tracing method for sentinel lymph node biopsy for breast cancer are simple and effective, and they are well suited for clinical use. A multicenter randomized controlled trial with a large sample size should be conducted in the future for further validation of the method.
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Affiliation(s)
- Peng Wang
- Department of Thyroid and Breast Surgery, People's Hospital of Meishan, Meishan, Sichuan 620000, China.
| | - Jinhao Shuai
- Department of Thyroid and Breast Surgery, People's Hospital of Meishan, Meishan, Sichuan 620000, China
| | - Zhaofang Leng
- Department of Thyroid and Breast Surgery, People's Hospital of Meishan, Meishan, Sichuan 620000, China
| | - Yichi Ji
- Department of Thyroid and Breast Surgery, People's Hospital of Meishan, Meishan, Sichuan 620000, China
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13
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Tran L, Christensen P, Barroeta JE, Hunter K, Sookram J, McGregor SM, Wilkinson N, Orsi NM, Lastra RR. Prognostic Significance of Size, Location, and Number of Lymph Node Metastases in Endometrial Carcinoma. Int J Gynecol Pathol 2023; 42:376-389. [PMID: 36044323 DOI: 10.1097/pgp.0000000000000897] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Regional lymph node metastasis is a well-established negative predictive prognostic factor in endometrial carcinomas. Recently, our approach to the pathologic evaluation of lymph nodes in endometrial carcinomas has changed, mainly due to the utilization of immunohistochemical stains in the assessment of sentinel lymph nodes, which may result in the identification of previously unrecognized disease [particularly isolated tumor cells (ITCs)] on hematoxylin and eosin stained slides. However, the clinical significance of this finding is not entirely clear. Following the experience in other organs systems such as breast, the Eight Edition of the American Joint Committee on Cancer's Cancer Staging Manual has recommended utilizing the N0(i+) terminology for this finding, without impact in the final tumor stage. We performed a comparative retrospective multi-institutional survival analysis of 247 patients with endometrial carcinoma with regional lymph node metastasis of various sizes identified in nonsentinel lymphadenectomy, demonstrating that the cumulative survival of patients with isolated tumor cells in regional lymph nodes is not statistically different from patient with negative lymph nodes, and is statistically different from those with lymph nodes showing micrometastasis or larger metastatic deposits. In addition, we evaluated the prognostic implications of the number of involved regional lymph nodes, demonstrating a worsening prognosis as the number of involved lymph nodes increases from none to one, and from one to more than one. Our data suggests that regional lymph nodes with isolated tumor cells in patients with endometrial carcinoma should likely be considered, for staging purposes, as negative lymph nodes, simply indicating their presence with the (i+) terminology.
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14
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Laws A, Kantor O, King TA. Surgical Management of the Axilla for Breast Cancer. Hematol Oncol Clin North Am 2023; 37:51-77. [PMID: 36435614 DOI: 10.1016/j.hoc.2022.08.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
This review discusses the contemporary surgical management of the axilla in patients with breast cancer. Surgical paradigms are highlighted by clinical nodal status at presentation and treatment approach, including upfront surgery and neoadjuvant systemic therapy settings. This review focuses on the increasing opportunities for de-escalating the extent of axillary surgery in the era of sentinel lymph node biopsy, while also reviewing the remaining indications for axillary clearance with axillary lymph node dissection.
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Affiliation(s)
- Alison Laws
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA
| | - Olga Kantor
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA
| | - Tari A King
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA.
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15
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Abbas Y, Hamdy O. Axillary reverse mapping in breast cancer: An overview. Breast Dis 2023; 42:137-146. [PMID: 37154174 DOI: 10.3233/bd-220040] [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: 05/10/2023]
Abstract
Standard operative management for breast carcinoma has significantly shifted from extensive procedures to minor interventions.Although axillary dissection was a fundamental component of operative management, sentinel biopsy is an actual process for axillary staging. Axillary dissection may be postponed for cases that have negative SLNs or 1 or 2 infiltrated lymph nodes undergoing breast or axillary radiation. Contrarily, axillary dissection is still the conventional management for patients with clinically positive nodes.Arm lymphedema is a frequent and overwhelming complication of axillary dissection, with a worse impact on the patient's life.Axillary reverse mapping was recently introduced to map and conserve the lymph drain of the upper limb throughout axillary dissection or sentinel biopsy. A technique based on the theory that the breast's lymphatic drainage differs from those that drain the arm, so preserving lymphatic drainage of the upper limb can prevent lymphedema, thereby not raising the risk of axillary recurrence.Therefore, this technique is the reverse of sentinel biopsy, which remove the lymph nodes that drain the breast.
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Affiliation(s)
- Yara Abbas
- Mansoura Manchester Medical Program, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Omar Hamdy
- Surgical Oncology Unit, Oncology Center, Mansoura University, Mansoura, Egypt
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16
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Cserni G, Brogi E, Cody HS, Deb R, Farshid G, O'Toole S, Provenzano E, Quinn CM, Sahin AA, Schmitt F, Weaver DL, Yamaguchi R, Webster F, Tan PH. Reporting of Surgically Removed Lymph Nodes for Breast Tumors: Recommendations From the International Collaboration on Cancer Reporting. Arch Pathol Lab Med 2022; 146:1308-1318. [PMID: 36270029 DOI: 10.5858/arpa.2022-0060-ra] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/11/2022] [Indexed: 11/06/2022]
Abstract
CONTEXT.— The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. OBJECTIVE.— To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. DATA SOURCES.— Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. CONCLUSIONS.— The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.
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Affiliation(s)
- Gábor Cserni
- From the Department of Pathology, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary (Cserni).,The Department of Pathology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary (Cserni)
| | - Edi Brogi
- The Department of Pathology (Brogi), Memorial Sloan Kettering Cancer Center, New York, New York
| | - Hiram S Cody
- The Breast Service, Department of Surgery (Cody III), Memorial Sloan Kettering Cancer Center, New York, New York
| | - Rahul Deb
- The Department of Pathology, Royal Derby Hospital, University Hospitals of Derby and Burton, Derby, United Kingdom (Deb)
| | - Gelareh Farshid
- The Department of Anatomical Pathology, SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia (Farshid).,School of Medicine, Adelaide University, Adelaide, South Australia, Australia (Farshid)
| | - Sandra O'Toole
- The Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia (O'Toole).,Sydney Medical School, University New South Wales, Sydney, New South Wales, Australia (O'Toole)
| | - Elena Provenzano
- NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (Provenzano).,The Department of Histopathology, Addenbrookes Hospital, Cambridge, United Kingdom (Provenzano)
| | - Cecily M Quinn
- The Department of Histopathology, BreastCheck, Irish National Breast Screening Programme & St. Vincent's University Hospital, Dublin, Ireland (Quinn).,University College Dublin, School of Medicine, Dublin, Ireland (Quinn)
| | - Aysegul A Sahin
- Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas (Sahin)
| | - Fernando Schmitt
- The Department of Pathology, Medical Faculty of Porto University, and Molecular Unit, Institute of Pathology and Immunology of Porto University, Porto, Portugal (Schmitt).,RISE (Health Research Network) @ CINTESIS (Center for Health Technology and Services Research), Porto, Portugal (Schmitt)
| | - Donald L Weaver
- The Department of Pathology, University of Vermont Larner College of Medicine, Burlington (Weaver)
| | - Rin Yamaguchi
- The Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Fukuoka, Japan (Yamaguchi)
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, NSW, Australia, and ICCR Project Manager, Surry Hills, Australia (Webster)
| | - Puay Hoon Tan
- Cambridge Experimental Cancer Medicine Centre (ECMR), Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.,The Division of Pathology, Singapore General Hospital, Academia, Singapore (Tan)
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17
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Crystal J, Mella-Catinchi J, Xu K, Weingrad D. Current Surgical Innovations in the Treatment of Breast Cancer. Breast Cancer 2022. [DOI: 10.36255/exon-publications-breast-cancer-surgical-innovation] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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18
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Wang CW, Lee YC, Khalil MA, Lin KY, Yu CP, Lien HC. Fast cross-staining alignment of gigapixel whole slide images with application to prostate cancer and breast cancer analysis. Sci Rep 2022; 12:11623. [PMID: 35803996 PMCID: PMC9270377 DOI: 10.1038/s41598-022-15962-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 07/01/2022] [Indexed: 12/24/2022] Open
Abstract
Joint analysis of multiple protein expressions and tissue morphology patterns is important for disease diagnosis, treatment planning, and drug development, requiring cross-staining alignment of multiple immunohistochemical and histopathological slides. However, cross-staining alignment of enormous gigapixel whole slide images (WSIs) at single cell precision is difficult. Apart from gigantic data dimensions of WSIs, there are large variations on the cell appearance and tissue morphology across different staining together with morphological deformations caused by slide preparation. The goal of this study is to build an image registration framework for cross-staining alignment of gigapixel WSIs of histopathological and immunohistochemical microscopic slides and assess its clinical applicability. To the authors' best knowledge, this is the first study to perform real time fully automatic cross staining alignment of WSIs with 40× and 20× objective magnification. The proposed WSI registration framework consists of a rapid global image registration module, a real time interactive field of view (FOV) localization model and a real time propagated multi-level image registration module. In this study, the proposed method is evaluated on two kinds of cancer datasets from two hospitals using different digital scanners, including a dual staining breast cancer data set with 43 hematoxylin and eosin (H&E) WSIs and 43 immunohistochemical (IHC) CK(AE1/AE3) WSIs, and a triple staining prostate cancer data set containing 30 H&E WSIs, 30 IHC CK18 WSIs, and 30 IHC HMCK WSIs. In evaluation, the registration performance is measured by not only registration accuracy but also computational time. The results show that the proposed method achieves high accuracy of 0.833 ± 0.0674 for the triple-staining prostate cancer data set and 0.931 ± 0.0455 for the dual-staining breast cancer data set, respectively, and takes only 4.34 s per WSI registration on average. In addition, for 30.23% data, the proposed method takes less than 1 s for WSI registration. In comparison with the benchmark methods, the proposed method demonstrates superior performance in registration accuracy and computational time, which has great potentials for assisting medical doctors to identify cancerous tissues and determine the cancer stage in clinical practice.
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Affiliation(s)
- Ching-Wei Wang
- Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan. .,Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
| | - Yu-Ching Lee
- Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan
| | - Muhammad-Adil Khalil
- Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan
| | - Kuan-Yu Lin
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan
| | - Cheng-Ping Yu
- Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan.,Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, Taiwan
| | - Huang-Chun Lien
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan
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19
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Harrison B. Update on sentinel node pathology in breast cancer. Semin Diagn Pathol 2022; 39:355-366. [PMID: 35803776 DOI: 10.1053/j.semdp.2022.06.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/14/2022] [Accepted: 06/27/2022] [Indexed: 11/11/2022]
Abstract
Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.
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Affiliation(s)
- Beth Harrison
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States.
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20
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Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, Anderson B, Burstein HJ, Chew H, Dang C, Elias AD, Giordano SH, Goetz MP, Goldstein LJ, Hurvitz SA, Isakoff SJ, Jankowitz RC, Javid SH, Krishnamurthy J, Leitch M, Lyons J, Mortimer J, Patel SA, Pierce LJ, Rosenberger LH, Rugo HS, Sitapati A, Smith KL, Smith ML, Soliman H, Stringer-Reasor EM, Telli ML, Ward JH, Wisinski KB, Young JS, Burns J, Kumar R. Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022; 20:691-722. [PMID: 35714673 DOI: 10.6004/jnccn.2022.0030] [Citation(s) in RCA: 521] [Impact Index Per Article: 173.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.
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Affiliation(s)
| | | | - Jame Abraham
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - Rebecca Aft
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Doreen Agnese
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | | | | | - Chau Dang
- Memorial Sloan Kettering Cancer Center
| | | | | | | | | | | | | | | | - Sara H Javid
- Fred Hutchinson Cancer Research Center/University of Washington
| | | | | | - Janice Lyons
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | - Hope S Rugo
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | | | | | - John H Ward
- Huntsman Cancer Institute at the University of Utah
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Stafford AP, Hoskin TL, Day CN, Sanders SB, Boughey JC. Contemporary Axillary Management in cT1-2N0 Breast Cancer with One or Two Positive Sentinel Lymph Nodes: Factors Associated with Completion Axillary Lymph Node Dissection Within the National Cancer Database. Ann Surg Oncol 2022; 29:4740-4749. [PMID: 35451727 DOI: 10.1245/s10434-022-11759-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 03/23/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND Management of the axilla in patients with cT1-2N0 breast cancer with one or two positive (+) sentinel lymph nodes (SLNs) is often debated, especially in patients undergoing mastectomy. In 2018, the National Cancer Database (NCDB) began collecting the number of +SLNs, enabling identification of patients with one or two +SLNs for the first time. METHODS From the 2018 NCDB participant user file (PUF), all cT1-2N0M0 patients with one or two +SLNs were identified. The rates of completion axillary lymph node dissection (cALND) after breast-conserving surgery (BCS) and mastectomy were determined, and logistic regression was used to assess factors associated with cALND. RESULTS Of 10,531 patients with one or two +SLNs, cALND was performed in 807/6498 (12.4%) BCS patients and 1845/4033 (45.7%) mastectomy patients (p < 0.001). Factors associated with cALND in BCS were cT2 versus cT1 (16.0% versus 11.1%, p < 0.001), two versus one positive SLN (20.7% versus 10.8%, p < 0.001), and higher tumor grade (grade 3: 15.4% versus grade 1-2: 11.7%, p = 0.002). Factors associated with cALND among mastectomy were cT2 versus cT1 (48.2% versus 43.7%, p = 0.004), two versus one positive SLN (56.6% versus 42.8%, p < 0.001), younger age (age < 50 years: 49.0%, age 50+ years: 44.1%, p = 0.004), and Hispanic ethnicity (55.7% versus 45.1%, p = 0.001). After adjusting for pN category, adjuvant radiation was significantly less likely after mastectomy if cALND was performed (odds ratio (OR) 0.51, p < 0.001). CONCLUSIONS Omission of cALND with one or two +SLNs in BCS is common. Deescalation of axillary therapy in mastectomy is slower, with a cALND rate of 45.7% in 2018. With the recent updates to the National Cancer Care Network (NCCN) guidelines, we anticipate continued deescalation of axillary therapy in mastectomy patients.
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Affiliation(s)
- Arielle P Stafford
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Tanya L Hoskin
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Courtney N Day
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Stacy B Sanders
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Judy C Boughey
- Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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22
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Jebens Nordskar N, Hagen B, V Vesterfjell E, Salvesen Ø, Aune G. “Long-term outcome in endometrial cancer patients after robot-assisted laparoscopic surgery with sentinel lymph node mapping”. Eur J Obstet Gynecol Reprod Biol 2022; 271:77-82. [DOI: 10.1016/j.ejogrb.2022.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/13/2022] [Accepted: 02/03/2022] [Indexed: 11/24/2022]
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Oncogenic Alterations in Histologically Negative Lymph Nodes Are Associated with Prognosis of Patients with Stage I Lung Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14030824. [PMID: 35159091 PMCID: PMC8834139 DOI: 10.3390/cancers14030824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Lymph nodes (LNs) metastasis is one of the most important factors affecting the outcome of non-small cell lung. The aim of this study is to explore whether presence of oncogenic alterations in histologically-negative lymph nodes (LNs) can be of prognostic significance in stage I lung adenocarcinoma (LUAD). We confirmed that presence of oncogenic alterations in regional LN may be associated with higher risks of postsurgical recurrence of Stage I LUAD, particularly for certain molecular subgroups. These results warranted future studies on larger cohort of NSCLC patients using more comprehensive cancer gene panels to establish the clinical impact of molecular LN occult metastasis for localized NSCLC and identify Stage I patients at high risks for recurrence for appropriate adjuvant therapy. Abstract Background: Survival of patients with stage I non-small cell lung cancer (NSCLC) varies greatly. We sought to explore whether presence of oncogenic alterations in histologically-negative lymph nodes (LNs) can be of prognostic significance in stage I lung adenocarcinoma (LUAD). Methods: Genomic analysis of oncogenic alterations was applied to 123 stage I LUAD tumors. The same genomic variants identified in primary tumors were examined in corresponding histologically-negative LNs. Results: A total of 102 (82.9%) patients had at least one canonical oncogenic alteration detected in primary tumors, and 57 LNs from 12 patients (11.8%) were found to carry the identical oncogenic alterations detected in the corresponding primary tumor tissues, including EGFR mutations (six cases), KRAS mutations (three cases), ALK fusion (one case), BRAF mutation (one case) and HER2 & NRAS co-mutations (one case). None of these LNs was found to have occult tumor cells by routine pathological assessment or immunohistochemistry staining using antibodies against pan-cytokeratins (AE1/AE3) and the epithelial marker Ber-EP4. The detection rate of oncogenenic alterations in LN was significantly higher in RAS-mutant tumors than EGFR mutant tumors (36.36% verse 7.41%, p = 0.017). Patients with oncogenic alterations in LN showed inferior disease-free survival (DFS, p = 0.025) and overall survival (OS, p = 0.027). Furthermore, patients with RAS-mutations detected in LN had the worst DFS and OS (p = 0.001). Among the 11 patients with RAS mutation in primary tumors, DFS and OS in the four patients with mutations detected in LN were significantly shorter than the remaining seven patients without mutations LN (DFS, p = 0.001, OS, p = 0.002). Conclusions: Genomic analysis has the potential to detect oncogenic alterations in regional LNs for localized LUAD and presence of oncogenic alterations in regional LN may be associated with inferior clinical outcome of stage I LUAD, particularly for certain molecular subgroups. ClinicalTrials.gov ID NCT04266691
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Lim AR, Ghajar CM. Thorny ground, rocky soil: Tissue-specific mechanisms of tumor dormancy and relapse. Semin Cancer Biol 2022; 78:104-123. [PMID: 33979673 PMCID: PMC9595433 DOI: 10.1016/j.semcancer.2021.05.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 04/30/2021] [Accepted: 05/04/2021] [Indexed: 02/07/2023]
Abstract
Disseminated tumor cells (DTCs) spread systemically yet distinct patterns of metastasis indicate a range of tissue susceptibility to metastatic colonization. Distinctions between permissive and suppressive tissues are still being elucidated at cellular and molecular levels. Although there is a growing appreciation for the role of the microenvironment in regulating metastatic success, we have a limited understanding of how diverse tissues regulate DTC dormancy, the state of reversible quiescence and subsequent awakening thought to contribute to delayed relapse. Several themes of microenvironmental regulation of dormancy are beginning to emerge, including vascular association, co-option of pre-existing niches, metabolic adaptation, and immune evasion, with tissue-specific nuances. Conversely, DTC awakening is often associated with injury or inflammation-induced activation of the stroma, promoting a proliferative environment with DTCs following suit. We review what is known about tissue-specific regulation of tumor dormancy on a tissue-by-tissue basis, profiling major metastatic organs including the bone, lung, brain, liver, and lymph node. An aerial view of the barriers to metastatic growth may reveal common targets and dependencies to inform the therapeutic prevention of relapse.
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Affiliation(s)
- Andrea R Lim
- Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Graduate Program in Molecular and Cellular Biology, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
| | - Cyrus M Ghajar
- Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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25
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Sentinel node detection in breast cancer. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00016-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Abstract
Breast surgical oncology is a rapidly evolving field with significant advances shaped by practice-changing research. Three areas of ongoing controversy are (1) high rates of contralateral prophylactic mastectomy (CPM) in the United States despite uncertain benefit, (2) indications for and use of neoadjuvant chemotherapy (NACT) and endocrine therapy (NET), and (3) staging and treatment of the axilla, particularly after neoadjuvant systemic therapy. We discuss the patient populations for whom CPM may or may not be beneficial, indications for NACT and NET, and the trend toward de-escalation of locoregional axillary treatment.
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Affiliation(s)
- Lily Gutnik
- Duke University School of Medicine, DUMC 3513, Durham, NC 27707, USA. https://twitter.com/LGutnik
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Herrero M, Ciérvide R, Calle-Purón ME, Valero J, Buelga P, Rodriguez-Bertos I, Benassi L, Montero A. Macrometastasis at selective lymph node biopsy: A practical going-for-the-one clinical scoring system to personalize decision making. World J Clin Oncol 2021; 12:675-687. [PMID: 34513601 PMCID: PMC8394159 DOI: 10.5306/wjco.v12.i8.675] [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: 12/29/2020] [Revised: 05/05/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Axillary sentinel lymph node biopsy (SLNB) is standard treatment for patients with clinically and pathological negative lymph nodes. However, the role of completion axillary lymph node dissection (cALND) following positive sentinel lymph node biopsy (SLNB) is debated.
AIM To identify a subgroup of women with high axillary tumor burden undergoing SLNB in whom cALND can be safely omitted in order to reduce the risk of long-term complications and create a Preoperative Clinical Risk Index (PCRI) that helps us in our clinical practice to optimize the selection of these patients.
METHODS Patients with positive SLNB who underwent a cALND were included in this study. Univariate and multivariate analysis of prognostic and predictive factors were used to create a PCRI for safely omitting cALND.
RESULTS From May 2007 to April 2014, we performed 1140 SLN biopsies, of which 125 were positive for tumor and justified to practice a posterior cALND. Pathologic findings at SLNB were micrometastases (mic) in 29 cases (23.4%) and macrometastasis (MAC) in 95 cases (76.6%). On univariate analysis of the 95 patients with MAC, statistically significant factors included: age, grade, phenotype, histology, lymphovascular invasion, lymph-node tumor size, and number of positive SLN. On multivariate analysis, only lymph-node tumor size (≤ 20 mm) and number of positive SLN (> 1) retained significance. A numerical tool was created giving each of the parameters a value to predict preoperatively which patients would not benefit from cALND. Patients with a PCRI ≤ 15 has low probability (< 10%) of having additional lymph node involvement, a PRCI between 15-17.6 has a probability of 43%, and the probability increases to 69% in patients with a PCRI > 17.6.
CONCLUSION The PCRI seems to be a useful tool to prospectively estimate the risk of nodal involvement after positive SLN and to identify those patients who could omit cALND. Further prospective studies are necessary to validate PCRI clinical generalization.
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Affiliation(s)
- Mercedes Herrero
- Department of Gynecology and Obstetrics, HM Hospitales, Madrid 28050, Spain
| | - Raquel Ciérvide
- Department of Radiation Oncology, HM Hospitales, Madrid 28050, Spain
| | - Maria Elisa Calle-Purón
- Department of Preventive Medicine and Public Health, Complutense University of Madrid, Madrid 28050, Spain
| | - Javier Valero
- Department of Gynecology and Obstetrics, HM Hospitales, Madrid 28050, Spain
| | - Paula Buelga
- Department of Gynecology and Obstetrics, HM Hospitales, Madrid 28050, Spain
| | | | - Leticia Benassi
- Department of Gynecology and Obstetrics, HM Hospitales, Madrid 28050, Spain
| | - Angel Montero
- Department of Radiation Oncology, HM Hospitales, Madrid 28050, Spain
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Wang G, Zhang S, Wang M, Liu L, Liu Y, Tang L, Bai H, Zhao H. Prognostic significance of occult lymph node metastases in breast cancer: a meta-analysis. BMC Cancer 2021; 21:875. [PMID: 34330233 PMCID: PMC8325175 DOI: 10.1186/s12885-021-08582-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 07/10/2021] [Indexed: 12/01/2022] Open
Abstract
Background Occult metastases in axillary lymph nodes have been reported to be associated with poor prognosis in patients with breast cancer. However, studies on the prognostic value of occult metastases have shown controversial results. This meta-analysis aimed to evaluate the prognostic significance of occult lymph node metastases in breast cancer. Methods Studies published until May, 2020, which retrospectively examined negative lymph nodes by stepsectioning and/or immunohistochemistry, were retrieved from MEDLINE, EMBASE, CNKI, and Cochrane Library databases. The pooled Relative Risk (RR) with 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS) were calculated to examine the associations between occult metastases and prognosis. Results Patients with occult metastases in axillary lymph nodes had poorer five-year DFS (RR = 0.930; 95% CI = 0.907–0.954) and OS (RR = 0.972; 95% CI = 0.954–0.990). Furthermore, the DFS (RR = 0.887; 95% CI = 0.810–0.972) and OS (RR = 0.896; 95% CI = 0.856–0.939) of patients with occult metastases were significantly lower after a ten-year follow-up. Conclusions Occult metastases in the axillary lymph nodes are associated with poorer DFS andOS of patients with breast cancer. Occult metastases might serve as a predictive factor of survival outcomes in patients with breast cancer.
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Affiliation(s)
- Guixin Wang
- General Surgery Department, Dalian University Affiliated Xinhua Hospital, Dalian, 116000, China.,Breast Surgery Department, The Second Hospital of Dalian Medical University, Dalian, 116000, China
| | - Shuhao Zhang
- Cardiology Department, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, China
| | - Meiling Wang
- Breast Surgery Department, The Second Hospital of Dalian Medical University, Dalian, 116000, China
| | - Lin Liu
- General Surgery Department, Dalian University Affiliated Xinhua Hospital, Dalian, 116000, China
| | - Yaqian Liu
- Breast Surgery Department, The Second Hospital of Dalian Medical University, Dalian, 116000, China
| | - Lianjun Tang
- General Surgery Department, Dalian Jinzhou First People's Hospital, Dalian, 116000, China
| | - He Bai
- General Surgery Department, Dalian University Affiliated Xinhua Hospital, Dalian, 116000, China
| | - Haidong Zhao
- Breast Surgery Department, The Second Hospital of Dalian Medical University, Dalian, 116000, China.
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Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis. Eur J Cancer 2021; 154:128-137. [PMID: 34265505 DOI: 10.1016/j.ejca.2021.06.028] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 06/08/2021] [Accepted: 06/17/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. EXPERIMENTAL DESIGN Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. RESULTS In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512). CONCLUSIONS DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
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30
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Sentinel lymph node assessment in breast cancer-an update on current recommendations. Virchows Arch 2021; 480:95-107. [PMID: 34164706 DOI: 10.1007/s00428-021-03128-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/16/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023]
Abstract
Sentinel lymph node biopsy (SLNB) has become the preferred method of surgical pathological nodal staging of early breast cancer by the end of the nineties. As the most likely sites of metastasis, the SLNs allow a more precise staging, and indeed gross sectioning, step sectioning, immunohistochemistry, and molecular staging methods have been used to disclose metastatic involvement of these lymph nodes. This review summarizes the backgrounds of SLNB, trends in related surgery and pathology. It also gives an insight into European National recommendations related to SLN and divergent daily practices in European pathology departments, on the basis of replies to questionnaires from 84 pathologists from 38 European countries. The questionnaires revealed the post-neoadjuvant setting as an area where a significant minority of pathologists report less confidence in classifying residual nodal involvement into TNM categories. The review also summarizes the neoadjuvant therapy-related aspects of SLNB.
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31
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Ruth JR, Pant DK, Pan TC, Seidel HE, Baksh SC, Keister BA, Singh R, Sterner CJ, Bakewell SJ, Moody SE, Belka GK, Chodosh LA. Cellular dormancy in minimal residual disease following targeted therapy. Breast Cancer Res 2021; 23:63. [PMID: 34088357 PMCID: PMC8178846 DOI: 10.1186/s13058-021-01416-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 03/09/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Breast cancer mortality is principally due to tumor recurrence, which can occur following extended periods of clinical remission that may last decades. While clinical latency has been postulated to reflect the ability of residual tumor cells to persist in a dormant state, this hypothesis remains unproven since little is known about the biology of these cells. Consequently, defining the properties of residual tumor cells is an essential goal with important clinical implications for preventing recurrence and improving cancer outcomes. METHODS To identify conserved features of residual tumor cells, we modeled minimal residual disease using inducible transgenic mouse models for HER2/neu and Wnt1-driven tumorigenesis that recapitulate cardinal features of human breast cancer progression, as well as human breast cancer cell xenografts subjected to targeted therapy. Fluorescence-activated cell sorting was used to isolate tumor cells from primary tumors, residual lesions following oncogene blockade, and recurrent tumors to analyze gene expression signatures and evaluate tumor-initiating cell properties. RESULTS We demonstrate that residual tumor cells surviving oncogenic pathway inhibition at both local and distant sites exist in a state of cellular dormancy, despite adequate vascularization and the absence of adaptive immunity, and retain the ability to re-enter the cell cycle and give rise to recurrent tumors after extended latency periods. Compared to primary or recurrent tumor cells, dormant residual tumor cells possess unique features that are conserved across mouse models for human breast cancer driven by different oncogenes, and express a gene signature that is strongly associated with recurrence-free survival in breast cancer patients and similar to that of tumor cells in which dormancy is induced by the microenvironment. Although residual tumor cells in both the HER2/neu and Wnt1 models are enriched for phenotypic features associated with tumor-initiating cells, limiting dilution experiments revealed that residual tumor cells are not enriched for cells capable of giving rise to primary tumors, but are enriched for cells capable of giving rise to recurrent tumors, suggesting that tumor-initiating populations underlying primary tumorigenesis may be distinct from those that give rise to recurrence following therapy. CONCLUSIONS Residual cancer cells surviving targeted therapy reside in a well-vascularized, desmoplastic microenvironment at both local and distant sites. These cells exist in a state of cellular dormancy that bears little resemblance to primary or recurrent tumor cells, but shares similarities with cells in which dormancy is induced by microenvironmental cues. Our observations suggest that dormancy may be a conserved response to targeted therapy independent of the oncogenic pathway inhibited or properties of the primary tumor, that the mechanisms underlying dormancy at local and distant sites may be related, and that the dormant state represents a potential therapeutic target for preventing cancer recurrence.
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Affiliation(s)
- Jason R Ruth
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Dhruv K Pant
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- the Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Tien-Chi Pan
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- the Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Hans E Seidel
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Sanjeethan C Baksh
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Blaine A Keister
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Rita Singh
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Christopher J Sterner
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- the Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Suzanne J Bakewell
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Susan E Moody
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - George K Belka
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
- the Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Lewis A Chodosh
- Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
- 2-PREVENT Translational Center of Excellence at the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
- the Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
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Houvenaeghel G, de Nonneville A, Cohen M, Chopin N, Coutant C, Reyal F, Mazouni C, Gimbergues P, Azuar AS, Chauvet MP, Classe JM, Daraï E, Martinez A, Rouzier R, de Lara CT, Lambaudie E, Barrou J, Goncalves A. Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort ☆. ESMO Open 2021; 6:100151. [PMID: 33984674 PMCID: PMC8314870 DOI: 10.1016/j.esmoop.2021.100151] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/07/2021] [Accepted: 04/15/2021] [Indexed: 01/15/2023] Open
Abstract
Background Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. Patients and methods We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i−), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. Results As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. Conclusion LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.
LN micro-metastases have no detectable prognostic impact. pN1 status, but not pN1mi, significantly impacted overall survival, disease-free survival, metastasis-free survival. In the subgroup of patients with known tumor subtype, pN1=1, as pN1>1, but not pN1mi, had a significant prognostic impact on OS. LN micro-metastases should not be considered as a determining factor in indicating adjuvant chemotherapy.
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Affiliation(s)
- G Houvenaeghel
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France.
| | - A de Nonneville
- Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - M Cohen
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - N Chopin
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - C Coutant
- Department of Surgical Oncology, Centre Georges François Leclerc, Dijon, France
| | - F Reyal
- Department of Surgical Oncology, Institut Curie, Paris Cedex 05, Paris, France
| | - C Mazouni
- Department of Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - P Gimbergues
- Department of Surgical Oncology, Centre Jean Perrin, Clermont Ferrand, France
| | - A-S Azuar
- Department of Surgical Oncology, Hôpital de Grasse, Grasse, France
| | - M-P Chauvet
- Department of Surgical Oncology, Centre Oscar Lambret, Lille, France
| | - J-M Classe
- Department of Surgical Oncology, Institut René Gauducheau, St Herblain, France
| | - E Daraï
- Department of Surgical Oncology, Hôpital Tenon, Paris, France
| | - A Martinez
- Department of Surgical Oncology, Centre Claudius Regaud, Toulouse, France
| | - R Rouzier
- Department of Surgical Oncology, Hôpital René Huguenin, Saint Cloud, France
| | - C T de Lara
- Department of Surgical Oncology, Institut Bergonié, Bordeaux, France
| | - E Lambaudie
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - J Barrou
- Department of Surgical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
| | - A Goncalves
- Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, Marseille, France
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Sims TT, Boruta DM. Sentinel lymph node isolated tumor cells in early staged endometrioid endometrial cancer: Utility or futility? Gynecol Oncol 2021; 161:331-332. [PMID: 33902864 DOI: 10.1016/j.ygyno.2021.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Travis T Sims
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - David M Boruta
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
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Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat? Gynecol Oncol 2021; 161:347-352. [PMID: 33678480 DOI: 10.1016/j.ygyno.2021.02.017] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 02/08/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS. RESULTS 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS. CONCLUSIONS Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made.
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Kato S, Yoshiba S, Mori S, Kodama T. Optimization of the delivery of molecules into lymph nodes using a lymphatic drug delivery system with ultrasound. Int J Pharm 2021; 597:120324. [PMID: 33540016 DOI: 10.1016/j.ijpharm.2021.120324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/28/2020] [Accepted: 01/22/2021] [Indexed: 02/01/2023]
Abstract
Conventional treatment for lymph node (LN) metastasis such as systemic chemotherapy have notable disadvantages that lead to the development of unwanted effects. Previously, we have reported the lymphatic administration of drugs into metastatic LNs using a lymphatic drug delivery system (LDDS). However, prior studies of the LDDS have not attempted to optimize the conditions for efficient drug delivery. Here, we investigated the influence of several factors on the efficiency of drug delivery by a LDDS in conjunction with ultrasound (US). First, the effect of the injection rate on delivery efficiency was evaluated. Fluorescent molecules injected into an upstream LN were delivered more effectively into a downstream LN when a lower injection rate was used. Second, the influence of molecular weight on drug delivery efficiency was determined. We found that molecules with a molecular weight >10,000 were poorly delivered into the LN. Finally, we assessed whether the administration route affected the delivery efficiency. We found that the delivery efficiency was higher when molecules were administered into an upstream LN that was close to the target LN. These findings revealed the importance of a drug's physical properties if it is to be administered by LDDS to treat LN metastasis.
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Affiliation(s)
- Shigeki Kato
- Laboratory of Biomedical Engineering for Cancer, Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
| | - Shota Yoshiba
- Laboratory of Biomedical Engineering for Cancer, Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Shiro Mori
- Laboratory of Biomedical Engineering for Cancer, Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan
| | - Tetsuya Kodama
- Laboratory of Biomedical Engineering for Cancer, Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan; Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi 980-8579, Japan.
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Alkushi A, Omair A, Arabi H, Masuadi E, Abualkhair O. Predictability of 21-Gene Recurrence Score Assay by Using Pathological and Immunohistochemical Parameters in Breast Cancer. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2020; 14:1178223420977848. [PMID: 33343196 PMCID: PMC7727040 DOI: 10.1177/1178223420977848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/06/2020] [Indexed: 11/25/2022]
Abstract
Background: Oncotype Dx is used to predict the long-term recurrence risk in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer (BC). This study aimed at establishing a correlation between clinicopathological parameters and recurrence score (RS), subsequently improving predictability and ultimately justifying the use of the multigene assay. Materials and methods: A retrospective analysis of the pathology and clinical data of 114 female patients with BC who had Oncotype Dx testing between 2012 and 2019. The pathological parameters included are tumor cell type, tumor grade, pathological stage, and mitotic index (MI). The expression of ER, progesterone receptor (PR), HER2, and Ki67 was assessed by immunohistochemistry. A univariate and multivariate linear regression analysis was performed to assess the correlation between these parameters and the RS. Results: In univariate analysis, age (˂40 years), higher tumor grade, and low PR expression were significantly associated with higher RS (P = .02; ˂.001; and ˂.001, respectively). Both MI and Ki67 were also strongly correlated with an increase in the RS with a P value of .01 (Spearman correlation 0.34 and 0.33). In multivariate linear regression analysis, age, MI, and Ki67 lost their significance, but both higher grade and PR remained significantly associated with a higher RS along with the tumor stage (P ˂ .001; ˂.001; and .04, respectively). Conclusions: Tumor grade and PR immunohistochemical expression are the main predictors of RS in our study population. Other clinicopathological features were not significant predictors of change in RS in multivariate analysis.
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Affiliation(s)
- Abdulmohsen Alkushi
- Department of Pathology, King Abdulaziz Medical City of National Guard, Riyadh, Saudi Arabia.,College of Medicine, King Saud bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Center Riyadh, Saudi Arabia
| | - Ahmad Omair
- College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Haitham Arabi
- Department of Pathology, King Abdulaziz Medical City of National Guard, Riyadh, Saudi Arabia
| | - Emad Masuadi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Center Riyadh, Saudi Arabia
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Falco M, Masojć B, Kram A. Locoregional relapse is a strong prognostic indicator of distant metastatic progression in breast cancer patients after negative sentinel lymph node biopsy. Breast J 2020; 26:2364-2370. [PMID: 33289332 DOI: 10.1111/tbj.14118] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 10/19/2020] [Accepted: 10/22/2020] [Indexed: 12/30/2022]
Abstract
PURPOSE Sentinel lymph node biopsy is routinely used in breast cancer patients with clinically negative axillary lymph nodes. Locoregional relapses after negative sentinel lymph node biopsy are infrequent, occurring in up to 3% of patients. METHODS Six thousand and eight patients underwent breast cancer surgery in our center between 2006 and 2015. We analyzed 1466 patients with negative sentinel lymph node biopsy and no prior systemic treatment. Mastectomy without irradiation was used in 25.4% of these patients and breast-conserving surgery with adjuvant radiotherapy in 74.6%. Forty-seven (3.21%) locoregional relapses were identified within a median of 51 months (10-138 months). The molecular type was analyzed as a risk factor for locoregional relapses and distant metastases. The locoregional relapse location was then analyzed as a risk factor for distant metastases. RESULTS Triple-negative breast cancer (P = .003), age <40 year (P = .007), multifocality (P = .011), and mastectomy (P < .0001) were risk factors for locoregional relapses. Patients who developed locoregional relapses more frequently developed distant metastases (P < .0001). The distribution of molecular types did not differ significantly in patients with locoregional relapses and distant metastases, concentrating in triple-negative and Luminal B tumor cases with distant metastases in almost 58% of cases, while not occurring in Luminal A patients. The locoregional-to-distant metastasis interval was shorter in cases of chest wall and lymph nodes relapse compared with breast-only relapse locations(P = .028). CONCLUSION Molecular type, especially triple-negative, young age, mastectomy without adjuvant irradiation, and multifocality are risk factors for locoregional relapse in sentinel lymph node biopsy negative breast cancer patients. Locoregional relapse is an important risk factor for developing distant metastasis, except in Luminal A breast cancer patients and those who suffer from breast-only relapse.
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Affiliation(s)
- Michał Falco
- Radiation Oncology Department, West Pomeranian Oncology Center, Szczecin, Poland
| | - Bartłomiej Masojć
- Radiation Oncology Department, West Pomeranian Oncology Center, Szczecin, Poland
| | - Andrzej Kram
- Pathology Department, West Pomeranian Oncology Center, Szczecin, Poland
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Li Y, Zhang H, Zhang W, Ren Y, Qiao Y, Li K, Chen H, Pu S, He J, Zhou C. A Competing Risk Analysis Model to Determine the Prognostic Value of Isolated Tumor Cells in Axillary Lymph Nodes for T1N0M0 Breast Cancer Patients Based on the Surveillance, Epidemiology, and End Results Database. Front Oncol 2020; 10:572316. [PMID: 33072606 PMCID: PMC7531361 DOI: 10.3389/fonc.2020.572316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 08/25/2020] [Indexed: 11/16/2022] Open
Abstract
Introduction Knowledge of the association between isolated tumor cells (ITCs) in breast cancer patients and the outcome is very limited. We aimed to determine the prognostic value of axillary lymph node ITCs for T1N0M0 female breast cancer (FBC) patients. Methods Data for T1N0M0 FBC patients staged ITCs negative [pN0(i−)] and positive [pN0(i+)] were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Prognostic predictors were identified by Kaplan–Meier analysis, competing risk model, and Fine–Gray multivariable regression model. Results A total of 94,599 subjects were included, 88,632 of whom were staged at pN0(i−) and 5,967 were pN0(i+). Patients staged pN0(i+) had worse breast cancer-specific survival (BCSS) [hazard ratio (HR): 1.298, 95% CI = 1.069–1.576, P = 0.003] and higher breast cancer-specific death (BCSD) rate (Gray’s test, P = 0.002) than pN0(i−) group. In the Fine–Gray multivariable regression analysis, the pN0(i+) group had higher BCSD rate (HR: 1.321, 95% CI = 1.109–1.575, P = 0.002) than pN0(i−) group. In subgroup analyses, no significant difference in BCSD was shown between the chemotherapy and non-chemotherapy subgroup (Gray’s test, P = 0.069) or radiotherapy and non-radiotherapy subgroup (Gray’s test, P = 0.096). Conclusion ITC was independently related to the increase of the BCSD rate and could be identified as a reliable survival predictor for T1N0M0 FBC patients.
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Affiliation(s)
- Yijun Li
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,School of Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Huimin Zhang
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wei Zhang
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yu Ren
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yan Qiao
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kunlong Li
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,School of Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Heyan Chen
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,School of Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Shengyu Pu
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,School of Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Jianjun He
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Can Zhou
- Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Imai K, Nanjo H, Takashima S, Hiroshima Y, Atari M, Matsuo T, Kuriyama S, Ishii Y, Wakamatsu Y, Sato Y, Motoyama S, Saito H, Nomura K, Minamiya Y. Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing. Thorac Cancer 2020; 11:3547-3554. [PMID: 33075198 PMCID: PMC7705915 DOI: 10.1111/1759-7714.13699] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/25/2020] [Accepted: 09/25/2020] [Indexed: 12/25/2022] Open
Abstract
Background Although lobectomy is considered the standard surgery for any non‐small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid‐IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. Methods This retrospective study analyzed the pathological reports from NSCLC resections over a six‐year period between 2014 and 2020. Using a new device for rapid‐IHC, we applied a high‐voltage, low‐frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid‐IHC can provide a nodal diagnosis within 20 minutes. Results Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid‐IHC. In addition, rapid‐IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid‐IHC received complete lobectomies. Five‐year relapse‐free survival and overall survival among patients receiving segmentectomy with rapid‐IHC were 88.77% and 88.79%, respectively. Conclusions Rapid‐IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating‐current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer. Key points Significant findings of the study Rapid immunohistochemistry driven by alternating‐current field mixing (completed within 20 minutes intraoperatively) is simple, highly accurate, and preserves lymph node tissue for subsequent pathological examination, including molecular assessments. What this study adds Segmentectomy for lung cancer is oncologically safe, but only when there is adequate intraoperative node staging. Rapid immunohistochemistry will assist clinicians when making intraoperative nodal diagnoses.
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Affiliation(s)
- Kazuhiro Imai
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Hiroshi Nanjo
- Department of Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Shinogu Takashima
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Yuko Hiroshima
- Department of Pathology, Akita University Graduate School of Medicine, Akita, Japan
| | - Maiko Atari
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Tsubasa Matsuo
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Shoji Kuriyama
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Yoshiaki Ishii
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Yuki Wakamatsu
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Yusuke Sato
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Satoru Motoyama
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
| | - Hajime Saito
- Department of Chest Surgery, Iwate Medical University, Morioka, Japan
| | - Kyoko Nomura
- Department of Health Environmental Science and Public Health, Akita University Graduate School of Medicine, Akita, Japan
| | - Yoshihiro Minamiya
- Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan
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Kantor O, Wong S, Weiss A, Metzger O, Mittendorf EA, King TA. Prognostic significance of residual nodal disease after neoadjuvant endocrine therapy for hormone receptor-positive breast cancer. NPJ Breast Cancer 2020; 6:35. [PMID: 32821803 PMCID: PMC7426953 DOI: 10.1038/s41523-020-00177-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 07/22/2020] [Indexed: 12/30/2022] Open
Abstract
Axillary management after NET has not been well studied and the significance of residual axillary node disease after NET remains uncertain. We used the National Cancer Data Base to examine the prognostic significance of residual nodal disease after NET. From 2010-2016, 4,496 patients received NET for cT1-3N0-1M0 hormone receptor-positive, HER2-negative breast cancer. Among cN0 patients treated with NET, final node status was ypN0 in 65%, isolated tumor cells (ITCs) in 3%, ypN1mi in 6%, and ypN1 in 26%. In cN1 patients, nodal pathologic complete response was uncommon (10%), and residual nodal disease included ITCs in 1%, ypN1mi in 3%, and ypN1 in 86%. There were no differences in 5-year overall survival (OS) between patients with pathologic node-negative disease, ITCs, or micrometastases after NET. When compared to a matched cohort of upfront surgery patients, there were also no differences in 5-year OS between NET and upfront surgery patients for any residual nodal disease category. These findings suggest NET patient outcomes mirror those of upfront surgery patients and present an opportunity to consider de-escalation of axillary management strategies in NET patients.
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Affiliation(s)
- Olga Kantor
- Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA USA
- Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA USA
| | | | - Anna Weiss
- Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA USA
- Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA USA
| | - Otto Metzger
- Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA USA
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA USA
| | - Elizabeth A. Mittendorf
- Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA USA
- Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA USA
| | - Tari A. King
- Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA USA
- Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA USA
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Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, Zackrisson S, Senkus E. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2020; 30:1194-1220. [PMID: 31161190 DOI: 10.1093/annonc/mdz173] [Citation(s) in RCA: 1315] [Impact Index Per Article: 263.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- F Cardoso
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
| | | | - S Ohno
- Breast Oncology Center, Cancer Institute Hospital, Tokyo, Japan
| | - F Penault-Llorca
- Department of Pathology, Centre Jean Perrin, Clermont-Ferrand; .,UMR INSERM 1240, IMoST Université d'Auvergne, Clermont-Ferrand
| | - P Poortmans
- Department of Radiation Oncology, Institut Curie, Paris;,Paris Sciences & Lettres – PSL University, Paris, France
| | - I T Rubio
- Breast Surgical Oncology Unit, Clinica Universidad de Navarra, Madrid, Spain
| | - S Zackrisson
- Department of Translational Medicine, Diagnostic Radiology, Lund University and Skåne University Hospital Malmö, Malmö, Sweden
| | - E Senkus
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
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Nicolini A, Rossi G, Ferrari P, Carpi A. Minimal residual disease in advanced or metastatic solid cancers: The G0-G1 state and immunotherapy are key to unwinding cancer complexity. Semin Cancer Biol 2020; 79:68-82. [PMID: 32201368 DOI: 10.1016/j.semcancer.2020.03.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 02/20/2020] [Accepted: 03/13/2020] [Indexed: 02/07/2023]
Abstract
In the last decade, a large amount of research has focused on elucidating the mechanisms that account for homing disseminated cancer cells (DCCs) from solid tumours to distant organs, which successively progress to overt metastatic disease; this is currently incurable. A better understanding of DCC behaviour is expected to allow detectable metastasis prevention by more effectively targeting 'metastatic seeds before they sprout'. As DCC biology co-evolved with that of the primary tumour, and due to the many similarities between them, the term 'niche' has been borrowed from normal adult stem cells (ASCs) to define the site of DCC metastatic colonisation. Moreover, heterogeneity, survival, protection, stemness and plasticity as well as the prolonged G0-G1 dormant state in the metastatic niche have been the main aspects of intense investigation. Consistent with these findings, in solid cancers with minimal residual disease (MRD), it has been proposed to prolong adjuvant therapy by targeting specific molecular pathway(s) involving DCC dormancy. However, so far, few disappointing clinical data have been reported. As an alternative strategy, because immune-surveillance contributes to the steady state of the DCC population and likely to the G0-G1 state of cancer cells, we have used prolonged immune-modulatory cytostatic chemotherapy, active immune stimulation with an INF-β/IL-2 sequence or drugs inhibiting myeloid-derived suppressor cell (MDSC)/Treg-mediated immune suppression. This strategy, mainly aimed at boosting the immune response, is based on recent findings suggesting the downregulation of immune escape mechanisms as well as other principal hallmarks during the G0-G1 state and/or in MRD. Preliminary clinical and/or laboratory data suggest the efficacy of this strategy in gastrointestinal and some endocrine-dependent cancers. Following this, we propose therapeutic schedules to prevent DCC activation and proliferation in solid cancers at a high risk of relapse or as maintenance therapy in metastatic patients after complete response (CR) to conventional treatment.
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Affiliation(s)
- Andrea Nicolini
- Department of Oncology, Transplantations and New Technologies in Medicine, University of Pisa, Italy.
| | - Giuseppe Rossi
- National Research Council (CNR), Epidemiology and Biostatistics Unit, Institute of Clinical Physiology and G. Monasterio Foundation, Pisa, Italy
| | - Paola Ferrari
- Unit of Oncology 1, University Hospital of Pisa, Pisa, Italy
| | - Angelo Carpi
- Department of Clinical and Experimental Medicine, University of Pisa, Italy
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Montero A, Ciérvide R, García-Aranda M, Rubio C. Postmastectomy radiation therapy in early breast cancer: Utility or futility? Crit Rev Oncol Hematol 2020; 147:102887. [PMID: 32018127 DOI: 10.1016/j.critrevonc.2020.102887] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 01/08/2020] [Accepted: 01/27/2020] [Indexed: 01/31/2023] Open
Abstract
Postmastectomy radiation therapy (PMRT) has been shown to reduce the risk of locoregional recurrence (LRR), in patients with locally advanced breast cancer who are considered of high-risk because of large tumors (>5 cm) or presence of axillary lymph-node involvement, as well as to reduce breast cancer mortality. However, controversy still remains with respect to indication of PMRT in case of early-stages invasive tumors. This review aims to analyze the impact that PMRT has on final results in women with breast tumors in different scenarios that would otherwise be considered as early breast cancer, such as extensive DCIS, tumors without axillary lymph-node involvement or with minimal microscopic nodal-involvement. The existence of risk factors including young age, premenopausal status, and presence of lymphovascular invasion (LVI), high grade or tumor size >2 cm has been associated with an increased risk of LRR in these patients at early-stages and advises to consider PMRT in selected cases.
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Affiliation(s)
- Angel Montero
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain; Breast Cancer Unit, Hospital Universitario HM Sanchinarro, Madrid, Spain.
| | - Raquel Ciérvide
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain; Breast Cancer Unit, Hospital Universitario HM Sanchinarro, Madrid, Spain
| | - Mariola García-Aranda
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain; Breast Cancer Unit, Hospital Universitario HM Sanchinarro, Madrid, Spain
| | - Carmen Rubio
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain; Breast Cancer Unit, Hospital Universitario HM Sanchinarro, Madrid, Spain
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Abstract
With active screening for early detection and advancements in treatment, there has been a significant decrease in mortality from breast cancer. However, a significant proportion of patients with non-metastatic breast cancer at time of diagnosis will relapse. Therefore, it is suggested that the dissemination of bloodstream tumor cells (circulating tumor cells, CTCs) undetectable by currently available diagnostic tools occurs during the early stages of breast cancer progression, and may be the potential source of micrometastases responsible for treatment failures. Here, we review the clinical significance of CTCs, as detected by the FDA-approved CellSearch® System, in both metastatic and non-metastatic breast cancer patients. Studies so far suggest that CTCs are prognostic of poorer outcomes in breast cancer patients; however, there is currently insufficient data to support use of CTC data to guide treatment. Therefore, there are ongoing studies to evaluate the utility of assessing CTC phenotypes to develop personalized breast cancer treatment, which will be reviewed in this chapter.
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Giuliano AE. The evolution of sentinel node biopsy for breast cancer: Personal experience. Breast J 2019; 26:17-21. [PMID: 31876042 DOI: 10.1111/tbj.13729] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 11/18/2019] [Indexed: 12/17/2022]
Abstract
Sentinel node biopsy has dramatically altered the treatment of breast cancer worldwide. The author's investigation into its use in breast cancer began nearly 30 years ago and evolved from simply identifying a node predictive of the axillary status to being a therapeutic procedure eliminating axillary dissection for selected node-negative and some node-positive women. This paper summarizes a personal experience with the evolution of this technique.
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Affiliation(s)
- Armando E Giuliano
- Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California
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47
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Torres VC, Li C, He Y, Sinha L, Papavasiliou G, Sattar HA, Brankov JG, Tichauer KM. Angular restriction fluorescence optical projection tomography to localize micrometastases in lymph nodes. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-4. [PMID: 31705637 PMCID: PMC6839382 DOI: 10.1117/1.jbo.24.11.110501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/14/2019] [Indexed: 06/10/2023]
Abstract
Lymph node biopsy is a primary means of staging breast cancer, yet standard pathological techniques are time-consuming and typically sample less than 1% of the total node volume. A low-cost fluorescence optical projection tomography (OPT) protocol is demonstrated for rapid imaging of whole lymph nodes in three dimensions. The relatively low scattering properties of lymph node tissue can be leveraged to significantly improve spatial resolution of lymph node OPT by employing angular restriction of photon detection. It is demonstrated through porcine lymph node metastases models that simple filtered-backprojection reconstruction is sufficient to detect and localize 200-μm-diameter metastases (the smallest clinically significant) in 1-cm-diameter lymph nodes.
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Affiliation(s)
- Veronica C. Torres
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Chengyue Li
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Yusheng He
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Lagnojita Sinha
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Georgia Papavasiliou
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Husain A. Sattar
- University of Chicago, Department of Pathology, Chicago, Illinois, United States
| | - Jovan G. Brankov
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
- Illinois Institute of Technology, Department of Electrical and Computer Engineering, Chicago, Illinois, United States
| | - Kenneth M. Tichauer
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
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Khoury T, Fang Y, Karabakhtsian R, Mokhtar Desouki M, Nayak A, Hanna M, Sanati S, Peng X, Yan L, Li X, Fadare O, Ambrosone C, Jabbour N, Gaudioso C. The clinical significance of metastatic breast carcinoma to intramammary lymph node. Breast J 2019; 26:197-205. [PMID: 31588665 DOI: 10.1111/tbj.13636] [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: 03/13/2019] [Revised: 08/20/2019] [Accepted: 09/06/2019] [Indexed: 11/28/2022]
Abstract
The incidence of involved intramammary lymph node (intra-MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra-MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T-stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow-up. Stage 4 cases and/or neo-adjuvant treated patients were excluded. AJCC TN-stage was calculated twice, with and without intra-MLN. Five-year overall survival (OS) and relapse (local and/or distant)-free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra-MLN, TN-stage correlated with OS (P = .016) but not with RFS (P = .19). However, when intra-MLN was included, TN-stage correlated with both OS (P < .001) and RFS (P = .016). In the multivariate analysis, when intra-MLN was excluded, only radiation therapy (RT) correlated with RFS (HR = 0.19, 95% CI: 0.054-0.66, P = .009). However, when intra-MLN was included in the TN-stage both RT (HR = 0.13, 95% CI: 0.04-0.45, P = .001) and TN-stage 3 (HR = 8.92, 95% CI: 1.47-54, P = .017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra-MLN involvement was excluded. When intra-MLN was included, multifocality became insignificant but TN-stage 3 correlated with OS (HR = 8.59, 95% CI: 1.06-69.71, P = .044). Positive intra-MLN is an independent factor in predicting both RFS and OS.
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Affiliation(s)
- Thaer Khoury
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York
| | - Yisheng Fang
- Department of Pathology, University of Texas Southwest at Dallas, Dallas, Texas
| | | | | | - Anupma Nayak
- Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mathew Hanna
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Souzan Sanati
- Department of Pathology, Washington University, St. Louis, Missouri
| | - Xuan Peng
- Department of Biostatics, Roswell Park Cancer Institute, Buffalo, New York
| | - Li Yan
- Department of Biostatics, Roswell Park Cancer Institute, Buffalo, New York
| | - Xiaoxian Li
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Oluwole Fadare
- Department of Pathology, University of California San Diego Health, La Jolla, California
| | - Christine Ambrosone
- Department of Population Science, Roswell Park Cancer Institute, Buffalo, New York
| | - Nashwan Jabbour
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York
| | - Carmelo Gaudioso
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York
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49
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Liu H, Ren F, Zhou X, Ma C, Wang T, Zhang H, Sun Q, Li Z. Ultra-Sensitive Detection and Inhibition of the Metastasis of Breast Cancer Cells to Adjacent Lymph Nodes and Distant Organs by Using Long-Persistent Luminescence Nanoparticles. Anal Chem 2019; 91:15064-15072. [DOI: 10.1021/acs.analchem.9b03739] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Hanghang Liu
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Feng Ren
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Xingguo Zhou
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Changqiu Ma
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Tingting Wang
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Hao Zhang
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Qiao Sun
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
| | - Zhen Li
- Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu 215123, P. R. China
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[Decision making factors of the management of ductal carcinoma in situ of the breast with microinvasion]. Bull Cancer 2019; 106:1000-1007. [PMID: 31351573 DOI: 10.1016/j.bulcan.2019.05.005] [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: 12/07/2018] [Revised: 05/02/2019] [Accepted: 05/11/2019] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Microinvasive in situ ductal carcinomas of the breast are rare and of good prognosis. They are grouped with early stage invasive carcinomas in the TNM 2017 classification. This study assessed practitioners' treatment decisions and their justifications in comparison to the literature. MATERIALS AND METHODS Three clinical cases were evaluated by anonymous forms regarding sentinel node decisions, tumour bed boost irradiation and hormone therapy. RESULTS Sentinel lymph node was performed by 93.1%, 100% and 44.4% of the practitioners respectively. Radiation boost was a treatment option chosen by 62.1% and 61.1% of practitioners in both clinical cases. Hormone therapy was advocated for 65.5%, 94.7% and 50.0% patients depending on the clinical case. CONCLUSION The therapeutic attitude proposed in microinvasive breast carcinomas was heterogeneous in this study, reflecting the absence of specific recommendations. In view of the existing literature, it is not currently possible to propose recommendations for these three therapeutic options. Prospective cohorts and meta-analyses of the microinvasive subgroup could provide answers.
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