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Yan M, Dong Z, Zhu Z, Qiao C, Wang M, Teng Z, Xing Y, Liu G, Liu G, Cai L, Meng H. Cancer type and survival prediction based on transcriptomic feature map. Comput Biol Med 2025; 192:110267. [PMID: 40311464 DOI: 10.1016/j.compbiomed.2025.110267] [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: 06/11/2024] [Revised: 04/05/2025] [Accepted: 04/22/2025] [Indexed: 05/03/2025]
Abstract
This study achieved cancer type and survival time prediction by transforming transcriptomic features into feature maps and employing deep learning models. Using transcriptomic data from 27 cancer types and survival data from 10 types in the TCGA database, a pan-cancer transcriptomic feature map was constructed through data cleaning, feature extraction, and visualization. Using Inception network and gated convolutional modules yielded a pan-cancer classification accuracy of 91.8 %. Additionally, by extracting 31 differential genes from different cancer feature maps, an interaction network diagram was drawn, identifying two key genes, ANXA5 and ACTB. These genes are potential biomarkers related to cancer progression, angiogenesis, metastasis, and treatment resistance. Survival prediction analysis on 10 cancer types, combined with feature maps and data amplification, cancer survival prediction accuracy reached from 0.75 to 0.91. This transcriptomic feature map provides a novel approach for cancer omics analysis, to facilitate personalized treatments and reflecting individual differences.
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Affiliation(s)
- Ming Yan
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Zirou Dong
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Zhaopo Zhu
- Center for Medical Genetics & Hunan Key Laboratory, School of Life Sciences, Central South University, Changsha, Huna, 410008, China
| | - Chengliang Qiao
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Meizhi Wang
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Zhixia Teng
- College of Information and Computer Engineering, Northeast Forestry University, Harbin, China
| | - Yongqiang Xing
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Guojun Liu
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Guoqing Liu
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China
| | - Lu Cai
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China.
| | - Hu Meng
- Inner Mongolia Key Laboratory of Life Health and Bioinformatics, College of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China.
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Zhang W, Jing X, Li B, Wu X. Clearance of Cell-Free DNA: A Novel Target for Therapeutic Utilization in Multiple Systemic Disorders. ACS Biomater Sci Eng 2025; 11:2069-2079. [PMID: 40178087 DOI: 10.1021/acsbiomaterials.5c00049] [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] [Indexed: 04/05/2025]
Abstract
Cell-free DNA (cfDNA) holds significant promise for diagnostic and therapeutic advancements in medicine. This review delineates the utility of cfDNA in diagnostics and its therapeutic potential through clearance mechanisms for an array of diseases. Damage-associated molecular patterns (DAMPs) are endogenous molecules released by host cells during stress, or injury. As a trigger for inflammatory responses via damage-associated molecular patterns (DAMPs), cfDNA's removal via nanotechnological approaches can attenuate inflammation and promote tissue repair. While the application of cfDNA clearance is particularly auspicious in cancer, sepsis, and inflammatory conditions, it is confronted with challenges including toxicity, specificity, and the rigors of clinical trial validation. Collectively, this review delineates novel therapeutic targets to inform the development of innovative treatment strategies.
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Affiliation(s)
- Wenjun Zhang
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi030001, China
| | - Xuan Jing
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi030001, China
| | - Bing Li
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi030001, China
| | - Xiuping Wu
- Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China
- Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi030001, China
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Bianco V, Valentino M, Pirone D, Miccio L, Memmolo P, Brancato V, Coppola L, Smaldone G, D’Aiuto M, Mossetti G, Salvatore M, Ferraro P. Classifying breast cancer and fibroadenoma tissue biopsies from paraffined stain-free slides by fractal biomarkers in Fourier Ptychographic Microscopy. Comput Struct Biotechnol J 2024; 24:225-236. [PMID: 38572166 PMCID: PMC10990711 DOI: 10.1016/j.csbj.2024.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/21/2024] [Accepted: 03/21/2024] [Indexed: 04/05/2024] Open
Abstract
Breast cancer is one of the most spread and monitored pathologies in high-income countries. After breast biopsy, histological tissue is stored in paraffin, sectioned and mounted. Conventional inspection of tissue slides under benchtop light microscopes involves paraffin removal and staining, typically with H&E. Then, expert pathologists are called to judge the stained slides. However, paraffin removal and staining are operator-dependent, time and resources consuming processes that can generate ambiguities due to non-uniform staining. Here we propose a novel method that can work directly on paraffined stain-free slides. We use Fourier Ptychography as a quantitative phase-contrast microscopy method, which allows accessing a very wide field of view (i.e., mm2) in one single image while guaranteeing high lateral resolution (i.e., 0.5 µm). This imaging method is multi-scale, since it enables looking at the big picture, i.e. the complex tissue structure and connections, with the possibility to zoom-in up to the single-cell level. To handle this informative image content, we introduce elements of fractal geometry as multi-scale analysis method. We show the effectiveness of fractal features in describing and classifying fibroadenoma and breast cancer tissue slides from ten patients with very high accuracy. We reach 94.0 ± 4.2% test accuracy in classifying single images. Above all, we show that combining the decisions of the single images, each patient's slide can be classified with no error. Besides, fractal geometry returns a guide map to help pathologist to judge the different tissue portions based on the likelihood these can be associated to a breast cancer or fibroadenoma biomarker. The proposed automatic method could significantly simplify the steps of tissue analysis and make it independent from the sample preparation, the skills of the lab operator and the pathologist.
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Affiliation(s)
- Vittorio Bianco
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | - Marika Valentino
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
- DIETI, Department of Electrical Engineering and Information Technologies, University of Naples “Federico II”, via Claudio 21, 80125 Napoli, Italy
| | - Daniele Pirone
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | - Lisa Miccio
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | - Pasquale Memmolo
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | | | - Luigi Coppola
- IRCCS SYNLAB SDN, Via E. Gianturco 113, Napoli 80143, Italy
| | | | | | - Gennaro Mossetti
- Pathological Anatomy Service, Casa di Cura Maria Rosaria, Via Colle San Bartolomeo 50, 80045 Pompei, Napoli, Italy
| | | | - Pietro Ferraro
- CNR-ISASI, Institute of Applied Sciences and Intelligent Systems “E. Caianiello”, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
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Arif T, Shteinfer-Kuzmine A, Shoshan-Barmatz V. Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1. Biomolecules 2024; 14:1304. [PMID: 39456237 PMCID: PMC11506819 DOI: 10.3390/biom14101304] [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: 08/26/2024] [Revised: 10/13/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024] Open
Abstract
Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca2+, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca2+ homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health. Most cancer cells undergo metabolic reprogramming, often referred to as the "Warburg effect", supplying tumors with energy and precursors for the biosynthesis of nucleic acids, phospholipids, fatty acids, cholesterol, and porphyrins. Given its multifunctional nature and overexpression in many cancers, VDAC1 presents an attractive target for therapeutic intervention. Our research has demonstrated that silencing VDAC1 expression using specific siRNA in various tumor types leads to a metabolic rewiring of the malignant cancer phenotype. This results in a reversal of oncogenic properties that include reduced tumor growth, invasiveness, stemness, epithelial-mesenchymal transition. Additionally, VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and modifying the expression of extracellular matrix- and structure-related genes, such as collagens and glycoproteins. Furthermore, VDAC1 depletion affects several epigenetic-related enzymes and substrates, including the acetylation-related enzymes SIRT1, SIRT6, and HDAC2, which in turn modify the acetylation and methylation profiles of histone 3 and histone 4. These epigenetic changes can explain the altered expression levels of approximately 4000 genes that are associated with reversing cancer cells oncogenic properties. Given VDAC1's critical role in regulating metabolic and energy processes, targeting it offers a promising strategy for anti-cancer therapy. We also highlight the role of VDAC1 expression in various disease pathologies, including cardiovascular, neurodegenerative, and viral and bacterial infections, as explored through siRNA targeting VDAC1. Thus, this review underscores the potential of targeting VDAC1 as a strategy for addressing high-energy-demand cancers. By thoroughly understanding VDAC1's diverse roles in metabolism, energy regulation, mitochondrial functions, and other cellular processes, silencing VDAC1 emerges as a novel and strategic approach to combat cancer.
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Affiliation(s)
- Tasleem Arif
- Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Anna Shteinfer-Kuzmine
- National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
| | - Varda Shoshan-Barmatz
- National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel;
- Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
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Dandena FG, Teklewold BT, Darebo TD, Suga YD. Epidemiology and clinical characteristics of breast cancer in Ethiopia: a systematic review. BMC Cancer 2024; 24:1102. [PMID: 39232684 PMCID: PMC11375980 DOI: 10.1186/s12885-024-12822-5] [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: 04/22/2024] [Accepted: 08/19/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND According to GLOBOCAN 2020 Breast cancer is the most common cancer among women and the prevalence is increasing worldwide and in Ethiopia. This review assessed studies conducted in Ethiopia on the clinical features and epidemiology of breast cancer. METHODS Data base search conducted PubMed, Google Scholar African Journals Online (AJOL), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Hinari without time restrictions. The search keywords included; prevalence and pattern, clinical presentation, histological and molecular subtypes, and management. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline to identify, search, extract articles, and report this systematic review. The protocol was registered in PROSPERO, ID: CRD42023403320. RESULTS Twenty studies were included in the review with 33,369 participants and 3 were community-based and 17 were hospital-based. In all except two reviewed studies, breast cancer is the most common cancer among women of Ethiopia. The most frequent presenting symptom was a breast lump/mass and commonly affected side was right breast. Most patients presented at a late stage and they were premenopausal age group. The commonest histology type is ductal carcinoma, that the most prevalent receptor was estrogen receptor positive, and the most common molecular subtype was Luminal A in pathology samples. Surgery is main stay of treatment and the most common surgical technique practiced in Ethiopia is modified radical mastectomy. CONCLUSION Breast cancer incidence is rising, and it accounts for the major cancer burden in the country. There is a need for additional awareness-raising and health education because delayed presentation are critical problems throughout Ethiopia. For planning and monitoring cancer patterns, comprehensive demographic and clinical data from a population or facility-based registry are needed in the regions. The available treatment options are still limited in Ethiopia it needs infrastructural development.
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Affiliation(s)
- Firaol Guyassa Dandena
- Departement of Research, Quality and patient safety, CURE International, Addis Ababa, Ethiopia.
- Department of Surgery, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
| | | | - Tadele Dana Darebo
- School of Public Health, Wolaita Sodo University, Wolaita Sodo, Ethiopia
| | - Yisihak Debodina Suga
- Department of Surgery, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
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Sajjanar AB, Naseri S, Dawande P, Vagha S. Mucinous Carcinoma of the Breast With Neuroendocrine Differentiation: A Case Report of Cyto-Histopathology Findings. Cureus 2024; 16:e68015. [PMID: 39347193 PMCID: PMC11429729 DOI: 10.7759/cureus.68015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 08/28/2024] [Indexed: 10/01/2024] Open
Abstract
Mucinous breast carcinoma is a rare neoplasm. A minority of breast neoplasms exhibit a mucinous component, with purely mucinous cases being less frequent. It is more typically found in postmenopausal women. The etiology is multifactorial and involves dietary factors, reproductive factors, and hormonal factors. Mucinous carcinoma can grow to a large size at the time of diagnosis, although it typically grows slowly and palpable. Transcriptomic genetic studies have explained that mucinous tumors are of luminal A molecular subtype. Mucinous A tumors have different transcriptome characteristics than mucinous B tumors, which have a gene expression pattern resembling neuroendocrine (NE) carcinomas. Diagnosis of mucinous carcinoma with NE differentiation by fine needle aspiration cytology (FNAC) is reported infrequently. Histopathology is mandatory in the evaluation of mucinous breast carcinoma. NE carcinoma of the breast is an underestimated subtype of BC which has characteristics of heterogenicity, rarity, and poor differentiation. In this instance, we present a case of breast carcinoma exhibiting NE differentiation. A postmenopausal woman aged 63, with no family history of breast cancer, presented with a firm mass in the upper lateral quadrant of her right breast. This lump, causing discomfort for the past two years, was accompanied by nipple retraction and the discharge of bloody fluid. The clinical examination revealed the palpable presence of the lump. Ultrasonography-guided FNAC suggested Mucinous breast carcinoma with NE differentiation. The patient underwent a modified radical mastectomy, and the tissue was evaluated by immunohistochemistry which confirmed the diagnosis.
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Affiliation(s)
- Anita B Sajjanar
- Department of Pathology, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research, Nagpur, IND
| | - Suhit Naseri
- Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Pratibha Dawande
- Department of Pathology, Datta Meghe Medical College, Datta Meghe Institute of Higher Education and Research, Nagpur, IND
| | - Sunita Vagha
- Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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7
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Li T, Chen YC, Ao P. Heterogeneous Evolution of Breast Cancer Cells-An Endogenous Molecular-Cellular Network Study. BIOLOGY 2024; 13:564. [PMID: 39194502 DOI: 10.3390/biology13080564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/29/2024]
Abstract
Breast cancer heterogeneity presents a significant challenge in clinical therapy, such as over-treatment and drug resistance. These challenges are largely due to its obscure normal epithelial origins, evolutionary stability, and transitions on the cancer subtypes. This study aims to elucidate the cellular emergence and maintenance of heterogeneous breast cancer via quantitative bio-process modeling, with potential benefit to therapeutic strategies for the disease. An endogenous molecular-cellular hypothesis posits that both pathological and physiological states are phenotypes evolved from and shaped by interactions among a number of conserved modules and cellular factors within a biological network. We hereby developed a model of core endogenous network for breast cancer in accordance with the theory, quantifying its intrinsic dynamic properties with dynamic modeling. The model spontaneously generates cell states that align with molecular classifications at both the molecular and modular level, replicating four widely recognized molecular subtypes of the cancer and validating against data extracted from the TCGA database. Further analysis shows that topologically, a singular progression gateway from normal breast cells to cancerous states is identified as the Luminal A-type breast cancer. Activated positive feedback loops are found to stabilize cellular states, while negative feedback loops facilitate state transitions. Overall, more routes are revealed on the cellular transition between stable states, and a traceable count explains the origin of breast cancer heterogeneity. Ultimately, the research intended to strength the search for therapeutic targets.
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Affiliation(s)
- Tianqi Li
- Center for Quantitative Life Sciences & Physics Department, Shanghai University, Shanghai 200444, China
| | - Yong-Cong Chen
- Center for Quantitative Life Sciences & Physics Department, Shanghai University, Shanghai 200444, China
| | - Ping Ao
- School of Biomedical Engineering, Sichuan University, Chengdu 610065, China
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Dnyanmote AS, M P H, Kumar S, Vasava K. Double Trouble: A Rare Case of Synchronous Breast and Thyroid Carcinomas. Cureus 2024; 16:e65256. [PMID: 39184812 PMCID: PMC11342579 DOI: 10.7759/cureus.65256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 07/24/2024] [Indexed: 08/27/2024] Open
Abstract
Breast carcinoma and thyroid carcinoma are among the most common cancers affecting women. Although it is rare to encounter synchronous primary tumors of the thyroid and breast in clinical practice, the incidence of both differentiated thyroid and breast cancers has significantly risen over the last 20 years. Despite having a lower mortality risk compared to other types of cancer, managing a dual diagnosis of these malignancies poses unique challenges and requires a thorough evaluation and strategic treatment plan. Here, we report a rare case of double primary malignancy of the breast and thyroid in a 59-year-old female who presented with complaints of a lump in the left breast, along with an incidental finding of thyroid swelling, which had conflicting findings in various preliminary evaluations. In this reported case, the patient underwent a total thyroidectomy based on a frozen section report suggestive of papillary carcinoma along with a modified radical mastectomy because of mucinous carcinoma of the left breast, which by itself is a rarity. This constituted a great challenge in managing both malignancies simultaneously. In conclusion, synchronous breast and thyroid carcinomas constitute an atypical clinical scenario that requires detailed evaluation and a multidisciplinary management approach. Further research is needed to understand this condition's underlying pathophysiology and genetic background to improve therapeutic outcomes for affected individuals.
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Affiliation(s)
- Anuradha S Dnyanmote
- Department of General Surgery, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Himashree M P
- Department of General Surgery, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Sandeep Kumar
- Department of General Surgery, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Kinjal Vasava
- Department of General Surgery, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pune, IND
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Vellan CJ, Islam T, De Silva S, Mohd Taib NA, Prasanna G, Jayapalan JJ. Exploring novel protein-based biomarkers for advancing breast cancer diagnosis: A review. Clin Biochem 2024; 129:110776. [PMID: 38823558 DOI: 10.1016/j.clinbiochem.2024.110776] [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: 02/16/2024] [Revised: 04/26/2024] [Accepted: 05/29/2024] [Indexed: 06/03/2024]
Abstract
This review provides a contemporary examination of the evolving landscape of breast cancer (BC) diagnosis, focusing on the pivotal role of novel protein-based biomarkers. The overview begins by elucidating the multifaceted nature of BC, exploring its prevalence, subtypes, and clinical complexities. A critical emphasis is placed on the transformative impact of proteomics, dissecting the proteome to unravel the molecular intricacies of BC. Navigating through various sources of samples crucial for biomarker investigations, the review underscores the significance of robust sample processing methods and their validation in ensuring reliable outcomes. The central theme of the review revolves around the identification and evaluation of novel protein-based biomarkers. Cutting-edge discoveries are summarised, shedding light on emerging biomarkers poised for clinical application. Nevertheless, the review candidly addresses the challenges inherent in biomarker discovery, including issues of standardisation, reproducibility, and the complex heterogeneity of BC. The future direction section envisions innovative strategies and technologies to overcome existing challenges. In conclusion, the review summarises the current state of BC biomarker research, offering insights into the intricacies of proteomic investigations. As precision medicine gains momentum, the integration of novel protein-based biomarkers emerges as a promising avenue for enhancing the accuracy and efficacy of BC diagnosis. This review serves as a compass for researchers and clinicians navigating the evolving landscape of BC biomarker discovery, guiding them toward transformative advancements in diagnostic precision and personalised patient care.
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Affiliation(s)
- Christina Jane Vellan
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Tania Islam
- Department of Surgery, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Sumadee De Silva
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, Sri Lanka
| | - Nur Aishah Mohd Taib
- Department of Surgery, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Galhena Prasanna
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, Sri Lanka
| | - Jaime Jacqueline Jayapalan
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia; Universiti Malaya Centre for Proteomics Research (UMCPR), Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
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10
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Kos Z, Nielsen TO, Laenkholm AV. Breast Cancer Histopathology in the Age of Molecular Oncology. Cold Spring Harb Perspect Med 2024; 14:a041647. [PMID: 38151327 PMCID: PMC11146312 DOI: 10.1101/cshperspect.a041647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023]
Abstract
For more than a century, microscopic histology has been the cornerstone for cancer diagnosis, and breast carcinoma is no exception. In recent years, clinical biomarkers, gene expression profiles, and other molecular tests have shown increasing utility for identifying the key biological features that guide prognosis and treatment of breast cancer. Indeed, the most common histologic pattern-invasive ductal carcinoma of no special type-provides relatively little guidance to management beyond triggering grading, biomarker testing, and clinical staging. However, many less common histologic patterns can be recognized by trained pathologists, which in many cases can be linked to characteristic biomarker and gene expression patterns, underlying mutations, prognosis, and therapy. Herein we describe more than a dozen such histomorphologic subtypes (including lobular, metaplastic, salivary analog, and several good prognosis special types of breast cancer) in the context of their molecular and clinical features.
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Affiliation(s)
- Zuzana Kos
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
- BC Cancer Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada
| | - Torsten O Nielsen
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
- Molecular and Advanced Pathology Core, Vancouver, British Columbia V6H 3Z6, Canada
| | - Anne-Vibeke Laenkholm
- Department of Surgical Pathology, Zealand University Hospital, 4000 Roskilde, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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11
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Warm HL, Kandt LD, Schaumann N, Werlein C, Gronewold M, Christgen H, Hellmann M, Lafos M, Auber B, Hillemanns P, Kreipe H, Christgen M. Immunohistochemical marker profiles for the differentiation of collagenous spherulosis from adenoid cystic carcinoma of the breast. Hum Pathol 2024; 148:7-13. [PMID: 38677556 DOI: 10.1016/j.humpath.2024.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/19/2024] [Accepted: 04/22/2024] [Indexed: 04/29/2024]
Abstract
Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC. We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). MYB rearrangement, a common alteration in ACC, was assessed by fluorescence in situ hybridization. Patient age ranged between 40-60 years for CS lesions and 30-90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma in situ (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in CDH1/E-cadherin. MYB rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] versus 5/18 [27%], P < 0.001). In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.
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Affiliation(s)
- Henriette L Warm
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Leonie D Kandt
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Nora Schaumann
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Christopher Werlein
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Malte Gronewold
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Henriette Christgen
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Malin Hellmann
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Marcel Lafos
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Bernd Auber
- Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Peter Hillemanns
- Clinic for Obstetrics, Gynecology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Hans Kreipe
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Matthias Christgen
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
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12
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Chiang YF, Huang KC, Chen HY, Hamdy NM, Huang TC, Chang HY, Shieh TM, Huang YJ, Hsia SM. Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway. Int J Mol Sci 2024; 25:3904. [PMID: 38612715 PMCID: PMC11011552 DOI: 10.3390/ijms25073904] [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: 02/04/2024] [Revised: 03/11/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
Breast cancer (BC) represents one of the most prevalent malignant threats to women globally. Tumor relapse or metastasis is facilitated by BC stemness progression, contributing to tumorigenicity. Therefore, comprehending the characteristics of stemness progression and the underlying molecular mechanisms is pivotal for BC advancement. Hinokitiol (β-thujaplicin), a tropolone-related compound abundant in the heartwood of cupressaceous plants, exhibits antimicrobial activity. In our study, we employed three BC cell lines (MDA-MB-231, MCF-7, and T47D) to assess the expression of stemness-, apoptosis-, and autophagy-related proteins. Hinokitiol significantly reduced the viability of cancer cells in a dose-dependent manner. Furthermore, we observed that hinokitiol enhances apoptosis by increasing the levels of cleaved poly-ADP-ribose polymerase (PARP) and phospho-p53. It also induces dysfunction in autophagy through the upregulation of LC3B and p62 protein expression. Additionally, hinokitiol significantly suppressed the number and diameter of cancer cell line spheres by reducing the expression of cluster of differentiation44 (CD44) and key transcription factors. These findings underscore hinokitiol's potential as a therapeutic agent for breast cancer, particularly as a stemness-progression inhibitor. Further research and clinical studies are warranted to explore the full therapeutic potential of hinokitiol in the treatment of breast cancer.
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Affiliation(s)
- Yi-Fen Chiang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan; (Y.-F.C.); (K.-C.H.); (H.-Y.C.)
| | - Ko-Chieh Huang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan; (Y.-F.C.); (K.-C.H.); (H.-Y.C.)
| | - Hsin-Yuan Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan; (Y.-F.C.); (K.-C.H.); (H.-Y.C.)
| | - Nadia M. Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt;
| | - Tsui-Chin Huang
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan;
| | - Hsin-Yi Chang
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan;
| | - Tzong-Ming Shieh
- School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan
| | - Yun-Ju Huang
- Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan City 710301, Taiwan;
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan; (Y.-F.C.); (K.-C.H.); (H.-Y.C.)
- School of Food and Safety, Taipei Medical University, Taipei 110301, Taiwan
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 110301, Taiwan
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13
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Flaherty RL, Sflomos G, Brisken C. Is There a Special Role for Ovarian Hormones in the Pathogenesis of Lobular Carcinoma? Endocrinology 2024; 165:bqae031. [PMID: 38551031 PMCID: PMC10988861 DOI: 10.1210/endocr/bqae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Indexed: 04/04/2024]
Abstract
Lobular carcinoma represent the most common special histological subtype of breast cancer, with the majority classed as hormone receptor positive. Rates of invasive lobular carcinoma in postmenopausal women have been seen to increase globally, while other hormone receptor-positive breast cancers proportionally have not followed the same trend. This has been linked to exposure to exogenous ovarian hormones such as hormone replacement therapy. Reproductive factors resulting in increased lifetime exposure to endogenous ovarian hormones have also been linked to an increased risk of lobular breast cancer, and taken together, these data make a case for the role of ovarian hormones in the genesis and progression of the disease. In this review, we summarize current understanding of the epidemiological associations between ovarian hormones and lobular breast cancer and highlight mechanistic links that may underpin the etiology and biology.
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Affiliation(s)
- Renée L Flaherty
- Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK
| | - George Sflomos
- Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Cathrin Brisken
- Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK
- Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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14
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Vijayalakshmi P, Indu S, Ireen C, Manjunathan R, Rajalakshmi M. Octyl Gallate and Gallic Acid Isolated from Terminalia bellirica Circumvent Breast Cancer Progression by Enhancing the Intrinsic Apoptotic Signaling Pathway and Elevating the Levels of Anti-oxidant Enzymes. Appl Biochem Biotechnol 2023; 195:7214-7235. [PMID: 36988844 DOI: 10.1007/s12010-023-04450-9] [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] [Accepted: 03/15/2023] [Indexed: 03/30/2023]
Abstract
Exploration of new strategies and identification of less expensive novel chemoprevention agents against breast cancer progression have become the need of the hour. Thus, the present study aimed at evaluating the anti-cancer efficacies of octyl gallate (OG) and gallic acid (GA) isolated from Terminalia bellirica (T. bellirica) in breast cancer cell lines and DMBA-induced Sprague-Dawley animal model. The results of western blot analysis show significant (p < 0.05) downregulation of anti-apoptotic protein (Bcl-2 and Bcl-xL) expression and up-regulation of pro-apoptotic protein (Bak and Bax) expression in both MCF-7 and MDA-MB-231 cell lines. Our findings also show that DMBA-induced Sprague-Dawley rats (50-55 days old) orally administered with OG (20 mg/kg body wt.) and GA (20 mg/kg body wt.) for a treatment period of 14 weeks were observed for normalized body weight changes and hematological indices and significant reduction of tumor markers carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15.3), and oxidative stress (TBARS) in serum, while the activity of anti-oxidant enzyme (SOD, CAT, and GPx) levels estimated in the mammary tissue was found restored back to normal. Computational molecular interaction study was also performed to substantiate the in vitro obtained results. The tissue histology reveals the therapeutic role of OG and GA. The study conducted brings to limelight of the molecular mechanisms of intrinsic apoptotic signaling pathway through which OG and GA exert their chemopreventive action. Both OG and GA can be explored further as chemotherapeutic natural drugs for their ability to prevent breast cancer progression.
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Affiliation(s)
- Periyasamy Vijayalakshmi
- DBT-BIF Centre, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
- Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Sabapathy Indu
- DBT-BIF Centre, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
- Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Christopher Ireen
- DBT-BIF Centre, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
- Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Reji Manjunathan
- Multi-Disciplinary Research Unit, Chengalpattu Government Medical College, Chengalpattu, 603001, Tamil Nadu, India
| | - Manikkam Rajalakshmi
- DBT-BIF Centre, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India.
- Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India.
- Department of Zoology, Holy Cross College (Autonomous), Tiruchirappalli, Tamil Nadu, India.
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15
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Bhise K, Gavande NS, Iyer AK. Leveraging hypoxia in triple-negative breast cancer as a promising treatment strategy. Drug Discov Today 2023; 28:103761. [PMID: 37660983 DOI: 10.1016/j.drudis.2023.103761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/08/2023] [Accepted: 08/29/2023] [Indexed: 09/05/2023]
Abstract
Current treatment strategies for triple-negative breast cancer (TNBC) are based upon conventional chemotherapy, immunotherapy, or a combination of both. The treatment regimen for chemotherapy is often a combination of two or more drugs, either dose dense or low dose for synergy. Anthracyclines, alkylating agents, antimicrotubule agents, and antimetabolites for early-stage TNBC; and antimetabolites, non-taxane microtubule inhibitors, and cross-linker platinums for late-stage TNBC are usually administered in the clinical setting. Newer options for patients with advanced TNBC, such as poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, have recently emerged for cases where surgery is not a viable option and the disease has metastasized. This review outlines the current trends in hypoxia-inspired treatment strategies for TNBC with a focus on clinical trials.
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Affiliation(s)
- Ketki Bhise
- Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA
| | - Navnath S Gavande
- Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA; Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA
| | - Arun K Iyer
- Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA; Molecular Imaging Program, Karmanos Cancer Institute, Detroit, MI, USA.
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16
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Abstract
Breast carcinomas classified based on traditional morphologic assessment provide useful prognostic information. Although morphology is still the gold standard of classification, recent advances in molecular technologies have enabled the classification of these tumors into four distinct subtypes based on its intrinsic molecular profile that provide both predictive and prognostic information. This article describes the association between the different molecular subtypes with the histologic subtypes of breast cancer and illustrates how these subtypes may affect the appearance of tumors on imaging studies.
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Affiliation(s)
- Madhuchhanda Roy
- Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, B1761 WIMR, 1111 Highland Avenue, Madison, WI 53705, USA.
| | - Amy M Fowler
- Department of Radiology, Section of Breast Imaging and Intervention, University of Wisconsin - Madison, 600 Highland Avenue, Madison, WI 53792-3252, USA; Department of Medical Physics, University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792-3252, USA
| | - Gary A Ulaner
- Hoag Family Cancer Institute, 16105 Sand Canyon Avenue, Ste 215, Irvine, CA 92618, USA; Department of Radiology, Department of Translational Genomics, University of Southern California, Los Angeles, CA 90007, USA
| | - Aparna Mahajan
- Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, B1781 WIMR, 1111 Highland Avenue, Madison, WI 53705, USA
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17
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Doloi R, Gupta SM. MicroRNAs: The key players regulating the crosstalk between Hippo and Wnt/β-catenin pathways in breast cancer. Life Sci 2023; 329:121980. [PMID: 37516428 DOI: 10.1016/j.lfs.2023.121980] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/21/2023] [Accepted: 07/21/2023] [Indexed: 07/31/2023]
Abstract
Breast Cancer has the highest burden in females worldwide and is predicted to increase by many folds with increasing lifestyle related risk factors, genetic mutations, and an aging population. The Hippo signalling and Wnt signalling pathways were identified as important signal transducers involved in maintaining organ development, tissue homeostasis, cell proliferation and apoptosis. microRNAs are short nucleotide sequences which act as regulatory components driving signal transductions in most cancers and can serve as both diagnostic and prognostic markers. Several reports have implicated that deregulated Hippo as well as Wnt signalling mediated by miRNAs together drive tumorigenesis, metastases and chemoresistance in breast cancer. Recent evidences on a crosstalk between Hippo and Wnt components elucidated how these pathways might be synchronized to have overlapping functions to promote tumorigenesis. Since miRNAs are demonstrated to target most of the components in both the pathways, in this review, we talk about the crosstalk between Hippo and Wnt signalling pathways and the potential microRNAs that might regulate the interplay between the two pathways in breast cancer, which has not been explored earlier.
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Affiliation(s)
- Rinki Doloi
- Indian Council of Medical Research - National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH), Mumbai 400012, India
| | - Sadhana M Gupta
- Indian Council of Medical Research - National Institute for Research in Reproductive and Child Health (ICMR-NIRRCH), Mumbai 400012, India.
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18
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Önder CE, Ziegler TJ, Becker R, Brucker SY, Hartkopf AD, Engler T, Koch A. Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer. Cancers (Basel) 2023; 15:3602. [PMID: 37509265 PMCID: PMC10377262 DOI: 10.3390/cancers15143602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/03/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
The poor outcome of metastasized breast cancer (BC) stresses the need for reliable personalized oncology and the significance of models recapitulating the heterogeneous nature of BC. Here, we cultured metastatic tumor cells derived from advanced BC patients with malignant ascites (MA) or malignant pleural effusion (MPE) using organoid technology. We identified the characteristics of tumor organoids by applying immunohistochemistry and mutation analysis. Tumor organoids preserved their expression patterns and hotspot mutations when compared to their original metastatic counterpart and are consequently a well-suited in vitro model for metastasized BC. We treated the tumor organoids to implement a reliable application for drug screenings of metastasized cells. Drug assays revealed that responses are not always in accord with expression patterns, pathway activation, and hotspot mutations. The discrepancy between characterization and functional testing underlines the relevance of linking IHC stainings and mutational analysis of metastasized BC with in vitro drug assays. Our metastatic BC organoids recapitulate the characteristics of their original sample derived from MA and MPE and serve as an invaluable tool that can be utilized in a preclinical setting for guiding therapy decisions.
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Affiliation(s)
- Cansu E Önder
- Research Institute for Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - Teresa J Ziegler
- Research Institute for Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - Ronja Becker
- Research Institute for Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - Sara Y Brucker
- Research Institute for Women's Health, University of Tübingen, 72076 Tübingen, Germany
- Department of Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - Andreas D Hartkopf
- Department of Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - Tobias Engler
- Department of Women's Health, University of Tübingen, 72076 Tübingen, Germany
| | - André Koch
- Research Institute for Women's Health, University of Tübingen, 72076 Tübingen, Germany
- Department of Women's Health, University of Tübingen, 72076 Tübingen, Germany
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19
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Ait Oumghar I, Barkaoui A, Ghazi AE, Chabrand P. Modeling and simulation of bone cells dynamic behavior under the late effect of breast cancer treatments. Med Eng Phys 2023; 115:103982. [PMID: 37120177 DOI: 10.1016/j.medengphy.2023.103982] [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: 07/26/2022] [Revised: 04/14/2023] [Accepted: 04/19/2023] [Indexed: 05/01/2023]
Abstract
Breast Cancer (BC) treatments have been proven to interfere with the health of bones. Chemotherapy and endocrinal treatment regimens such as tamoxifen and aromatase inhibitors are frequently prescribed for women with BC. However, these drugs increase bone resorption and reduce the Bone Mineral Density (BMD), thus increasing the risk of bone fracture. In the current study, a mechanobiological bone remodeling model has been developed by coupling cellular activities, mechanical stimuli, and the effect of breast cancer treatments (chemotherapy, tamoxifen, and aromatase inhibitors). This model algorithm has been programmed and implemented on MATLAB software to simulate different treatment scenarios and their effects on bone remodeling and also predict the evolution of Bone Volume fraction (BV/TV) and the associated Bone Density Loss (BDL) over a period of time. The simulation results, achieved from different combinations of Breast Cancer treatments, allow the researchers to predict the intensity of each combination treatment on BV/TV and BMD. The combination of chemotherapy, tamoxifen, and aromatase inhibitors, followed by the combination of chemotherapy and tamoxifen remain the most harmful regimen. This is because they have a strong ability to induce the bone degradation which is represented by a decrease of 13.55% and 11.55% of the BV/TV value, respectively. These results were compared with the experimental studies and clinical observations which showed good agreement. The proposed model can be used by clinicians and physicians to choose the most appropriate combination of treatments, according to the patient's case.
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Affiliation(s)
- Imane Ait Oumghar
- Université Internationale de Rabat, LERMA Lab, Rocade Rabat Salé 11100, Rabat-Sala El Jadida, Morocco; Université Aix-Marseille, ISM, 163 av. de Luminy F-13288, Marseille cedex 09, France
| | - Abdelwahed Barkaoui
- Université Internationale de Rabat, LERMA Lab, Rocade Rabat Salé 11100, Rabat-Sala El Jadida, Morocco.
| | - Abdellatif El Ghazi
- Université Internationale de Rabat, TIC Lab, Rocade Rabat Salé 11100, Rabat-Sala El Jadida, Morocco
| | - Patrick Chabrand
- Université Aix-Marseille, ISM, 163 av. de Luminy F-13288, Marseille cedex 09, France
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20
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Stebbing J, Takis PG, Sands CJ, Maslen L, Lewis MR, Gleason K, Page K, Guttery D, Fernandez-Garcia D, Primrose L, Shaw JA. Comparison of phenomics and cfDNA in a large breast screening population: the Breast Screening and Monitoring Study (BSMS). Oncogene 2023; 42:825-832. [PMID: 36693953 PMCID: PMC10005936 DOI: 10.1038/s41388-023-02591-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/26/2023]
Abstract
To assess their roles in breast cancer diagnostics, we aimed to compare plasma cell-free DNA (cfDNA) levels with the circulating metabolome in a large breast screening cohort of women recalled for mammography, including healthy women and women with mammographically detected breast diseases, ductal carcinoma in situ and invasive breast cancer: the Breast Screening and Monitoring Study (BSMS). In 999 women, plasma was analyzed by nuclear magnetic resonance (NMR) and Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and then processed to isolate and quantify total cfDNA. NMR and UPLC-MS results were compared with data for 186 healthy women derived from the AIRWAVE cohort. Results showed no significant differences between groups for all metabolites, whereas invasive cancers had significantly higher plasma cfDNA levels than all other groups. When stratified the supervised OPLS-DA analysis and total cfDNA concentration showed high discrimination accuracy between invasive cancers and the disease/medication-free subjects. Furthermore, comparison of OPLS-DA data for invasive breast cancers with the AIRWAVE cohort showed similar discrimination between breast cancers and healthy controls. This is the first report of agreement between metabolomics and plasma cfDNA levels for discriminating breast cancer from healthy subjects in a true screening population. It also emphasizes the importance of sample standardization. Follow on studies will involve analysis of candidate features in a larger validation series as well as comparing results with serial plasma samples taken at the next routine screening mammography appointment. The findings here help establish the role of plasma analysis in the diagnosis of breast cancer in a large real-world cohort.
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Affiliation(s)
- Justin Stebbing
- Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK
- School of Life Sciences, Faculty of Science and Engineering, ARU, East Road, Cambridge, CB1 1PT, UK
| | - Panteleimon G Takis
- National Phenome Centre and Imperial Clinical Phenotyping Centre & Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, IRDB Building, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
| | - Caroline J Sands
- National Phenome Centre and Imperial Clinical Phenotyping Centre & Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, IRDB Building, Imperial College London, Hammersmith Campus, London, W12 0NN, UK
| | - Lynn Maslen
- National Phenome Centre and Imperial Clinical Phenotyping Centre & Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, IRDB Building, Imperial College London, Hammersmith Campus, London, W12 0NN, UK
| | - Matthew R Lewis
- National Phenome Centre and Imperial Clinical Phenotyping Centre & Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, IRDB Building, Imperial College London, Hammersmith Campus, London, W12 0NN, UK
| | - Kelly Gleason
- Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK
| | - Karen Page
- Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK
| | - David Guttery
- Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK
| | - Daniel Fernandez-Garcia
- Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK
| | - Lindsay Primrose
- Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK
| | - Jacqueline A Shaw
- Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK
- Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK
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21
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Triple-Negative Apocrine Carcinomas: Toward a Unified Group With Shared Molecular Features and Clinical Behavior. Mod Pathol 2023; 36:100125. [PMID: 36870308 DOI: 10.1016/j.modpat.2023.100125] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/27/2023] [Indexed: 02/09/2023]
Abstract
Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.
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22
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Kimura K, Kawabata S, Oku H, Ikari A, Tominaga T, Takai S, Sakane J, Tanaka M, Aoki C, Ota M, Minami E, Hirose Y, Lee SW, Iwamoto M. Breast neuroendocrine tumor arising in the axilla of a man: a case report. J Med Case Rep 2022; 16:467. [PMID: 36528621 PMCID: PMC9759905 DOI: 10.1186/s13256-022-03683-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/18/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Accessory breast carcinomas of the axilla of males are rare, and primary breast neuroendocrine tumors (BNETs) are rare as well. We present a case of a BNET arising in the axilla of a man. CASE PRESENTATION A 64-year-old Japanese man presented with a hard 15-mm mass in the axilla and axillary lymph node swelling. Histopathological examination of the incisional biopsy specimen revealed a neuroendocrine carcinoma. Therefore, wide radical excision of the axillary tumor and axillary lymph node dissection were performed. Hematoxylin and eosin staining showed that the solid tumor was mainly located in the subcutaneous adipose tissues and appeared to invade the skin. The tumor phenotypes were positive for CAM 5.2, synaptophysin, estrogen receptor, progesterone receptor, and GATA-binding protein 3; they were negative for human epidermal growth receptor 2. The neuroendocrine component comprised more than 90% of the tumor, and the Ki-67 index was 21%. These results indicated that the tumor was a BNET. This patient underwent adjuvant chemotherapy, endocrine therapy, and radiotherapy. CONCLUSIONS BNET cases in males are rare. The clinical and histological criteria as well as treatment for these rare cases are discussed.
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Affiliation(s)
- Kosei Kimura
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Shigeru Kawabata
- Department of Pathology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Hiroyo Oku
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Ayana Ikari
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Tomo Tominaga
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Saki Takai
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Junna Sakane
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Michiaki Tanaka
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Chinatsu Aoki
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Monika Ota
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Erika Minami
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yoshinobu Hirose
- Department of Pathology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Sang-Woong Lee
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Mitsuhiko Iwamoto
- Department of Breast and Endocrine Surgery, Osaka Medical and Pharmaceutical University, Osaka, Japan
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Distinct Uroplakin II Staining Pattern in Apocrine Breast Carcinoma. Appl Immunohistochem Mol Morphol 2022; 30:681-686. [PMID: 36227121 DOI: 10.1097/pai.0000000000001072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 09/12/2022] [Indexed: 11/26/2022]
Abstract
Uroplakin II (UPII) has been shown as a highly specific marker of urothelial carcinoma; however, it can also stain subtypes of apocrine-differentiated breast carcinoma. Given that urothelium and breast epithelium share other common immunohistochemical markers, such as CK7 and GATA3, this can lead to a potential diagnostic pitfall. We stained a cohort of triple-negative breast cancer with UPII. Compared with the diffuse, cytoplasmic staining in urothelial carcinoma, UPII was positive in 38.9% of apocrine carcinoma (7/18) with a course, granular cytoplasmic staining pattern and negative in all nonapocrine triple-negative breast cancer cases. Furthermore, the same staining pattern was present in all apocrine metaplasia of the breast (4/4) and apocrine sweat glands in normal skin (6/6). This distinct subcellular localization of UPII staining in breast carcinoma can offer a potential solution to the above diagnostic pitfall.
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24
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Balouchi-Anaraki S, Mohammadsadeghi S, Norouzian M, Rasolmali R, Talei AR, Mehdipour F, Ghaderi A. Expression of Interleukin-21 and Interleukin-21 receptor in lymphocytes derived from tumor-draining lymph nodes of breast cancer. Breast Dis 2022; 41:373-382. [PMID: 36189580 DOI: 10.3233/bd-220013] [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: 11/15/2022]
Abstract
BACKGROUND Interleukin-21 (IL-21) is produced by various cell types inducing positive and negative effects in immunity against tumors. OBJECTIVE To investigate the expression of IL-21 by CD4+T and IL-21 receptor (IL-21R) by B lymphocytes isolated from breast-tumor draining lymph nodes (TDLNs). METHODS Fresh lymph node samples were obtained from 45 patients with breast cancer. To assess IL-21 expression, mononuclear cells were briefly stimulated whereas IL-21R expression was assessed in unstimulated B cells. Cells were stained with antibodies for CD4, IL-21, CD19 and IL-21R and acquired by flow cytometry. RESULTS The frequency of IL-21+CD4+T cells did not show significant association with disease parameters. However, the geometric mean fluorescence intensity (gMFI) of IL-21 in CD4+T cells was significantly lower in patients with grade III tumor than grade I + II (P = 0.042). In non-involved LNs, the intensity of IL-21 was significantly higher in patients with stage II compared with stage III (P = 0.038) and correlated negatively with the number of involved LNs. The frequency of IL-21R+CD19+B cells was significantly higher in grade III than grade I + II (P = 0.037). CONCLUSION The higher intensity of IL-21 in CD4+T cells showed association with good prognosticators in breast cancer and warrants further investigation of the role played by IL-21 in immunity against breast cancer.
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Affiliation(s)
- Sima Balouchi-Anaraki
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Mohammadsadeghi
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzieh Norouzian
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Laboratory Sciences, School of Allied Medical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Reza Rasolmali
- Department of Pathology, Shiraz Central Hospital, Shiraz, Iran
| | - Abdol-Rasoul Talei
- Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fereshteh Mehdipour
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abbas Ghaderi
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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25
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El Arab KF, Bourhafour M, Elqasseh R, Khoaja A, Bouchbika Z, Benchakroun N, Jouhadi H, Tawfiq N, Ennachit M, Elkarroumi M, Benider A, Sahraoui S. Primary neuroendocrine tumors of the breast: About a case and of the review of the literature. Int J Surg Case Rep 2022; 99:107642. [PMID: 36122420 PMCID: PMC9568780 DOI: 10.1016/j.ijscr.2022.107642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/30/2022] Open
Abstract
primary neuroendocrine carcinomas of the breast represent a minority and are currently included in the latest WHO classification of breast tumors. Their morphological and immunohistochemical features (chromogranin and synaptophysin expression) allow the retain the diagnosis. we report a case of primary neuroendocrine carcinoma of the breast in 50 years old Moroccan women who presented nodule 4,2 cm palpable and mobile of the left breast. Lumpectomy axillary lymph node resection was performed. a histopathological examination disclosed the diagnosis of primary breast neuroendocrine tumors with negative surgical margins and positive lymph nodes (13 N+/19 N). The tumor cells were positive for neuroendocrine markers, a highKi67 proliferation index and the membrane expression of the invasive tumor cells to the anti-HER2 antibody was 2, a FISH done which was equivocal. Our patient received 6 courses of chemotherapythen radiotherapy; currently she received adjuvant hormonal treatment with Tamoxifene.
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Affiliation(s)
- K Fares El Arab
- Department of Medical Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco.
| | - M Bourhafour
- Department of Medical Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - R Elqasseh
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - A Khoaja
- Department of Anathomopathology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, university Hassan II, Casablanca, Morocco
| | - Z Bouchbika
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - N Benchakroun
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - H Jouhadi
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - N Tawfiq
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - M Ennachit
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - M Elkarroumi
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - Abdellatif Benider
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - S Sahraoui
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
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Jiang X, Xu C. Deep Learning and Machine Learning with Grid Search to Predict Later Occurrence of Breast Cancer Metastasis Using Clinical Data. J Clin Med 2022; 11:jcm11195772. [PMID: 36233640 PMCID: PMC9570670 DOI: 10.3390/jcm11195772] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/30/2022] [Accepted: 09/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background: It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under-treatment or over-treatment. Deep neural network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tuning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15 years after the initial treatment. We developed prediction models using the deep feedforward neural network (DFNN) methods, as well as models using nine other machine learning methods, including naïve Bayes (NB), logistic regression (LR), support vector machine (SVM), LASSO, decision tree (DT), k-nearest neighbor (KNN), random forest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared our feedforward deep learning models to the models trained using the nine other machine learning methods. Results: Based on the mean test AUC (Area under the ROC Curve) results, DFNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM, respectively, out of 10 methods. The top performing methods in predicting 5-year BCM are XGB (1st), RF (2nd), and KNN (3rd). For predicting 10-year BCM, the top performers are XGB (1st), RF (2nd), and NB (3rd). Finally, for 15-year BCM, the top performers are SVM (1st), LR and LASSO (tied for 2nd), and DFNN (3rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DFNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05, DFNN overall performs comparably to other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions: Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods, such as XGB, RF, and SVM, are very strong competitors of DFNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DFNN is much more than that required to do grid search with the other nine machine learning methods.
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Affiliation(s)
- Xia Jiang
- Correspondence: ; Tel.: +412-648-9310
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27
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Zhang D, Li L, Ma F. Prognosis stratification and postoperative radiation therapy utilization in adenoid cystic carcinoma of the breast. Breast 2022; 66:40-48. [PMID: 36113374 PMCID: PMC9483639 DOI: 10.1016/j.breast.2022.09.003] [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: 06/26/2022] [Revised: 08/26/2022] [Accepted: 09/05/2022] [Indexed: 12/27/2022] Open
Abstract
PURPOSE Adenoid cystic carcinoma of the breast (ACCB) is a rare malignancy with a favorable prognosis. Little information exists regarding the impact of postoperative radiation therapy (RT) on survival outcome in patients with ACCB. This study aimed to evaluate the clinical significance of postoperative RT in ACCB. METHODS Data of patients with ACCB were extracted from the Surveillance, Epidemiology, and End Results database (2000-2019). Univariate and multivariable Cox regression analyses were performed to identify prognostic factors. In addition, a nomogram model was constructed and internally validated for discrimination and calibration. The value of postoperative RT was respectively accessed in each risk subgroup according to nomogram-deduced individualized score. RESULTS A total of 689 eligible patients were included in the analysis. Partial mastectomy was associated with an increased risk of death compared with partial mastectomy plus postoperative RT (P = 0.020), but total mastectomy with or without postoperative RT was comparable (P = 0.624). Then, in-depth analysis was performed for patients receiving breast-conserving therapy (n = 485, the training set vs. the testing set = 340 vs. 145). Age at diagnosis, histological grade, and T stage were identified as prognostic factors for overall survival (OS) (All P < 0.05). A nomogram was constructed to provide predictive accuracy toward individual OS rates of ACCB and to divide patients into different risk subgroups. Notably, compared with non-RT, postoperative RT significantly improved OS in the high-risk subgroup (P = 0.006 for the training set, and P = 0.013 for the overall population) but not in the low-risk subgroup (P = 0.807 for the training set, and P = 0.293 for the overall population), suggesting that these patients may be able to exempt from postoperative RT. CONCLUSION A robust and effective nomogram was developed to predict prognosis and assist in treatment decisions in patients with ACCB undergoing partial mastectomy.
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Schneider N, Reed E, Kamel F, Ferrari E, Soloviev M. Rational Approach to Finding Genes Encoding Molecular Biomarkers: Focus on Breast Cancer. Genes (Basel) 2022; 13:genes13091538. [PMID: 36140706 PMCID: PMC9498645 DOI: 10.3390/genes13091538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/18/2022] [Accepted: 08/23/2022] [Indexed: 12/04/2022] Open
Abstract
Early detection of cancer facilitates treatment and improves patient survival. We hypothesized that molecular biomarkers of cancer could be rationally predicted based on even partial knowledge of transcriptional regulation, functional pathways and gene co-expression networks. To test our data mining approach, we focused on breast cancer, as one of the best-studied models of this disease. We were particularly interested to check whether such a ‘guilt by association’ approach would lead to pan-cancer markers generally known in the field or whether molecular subtype-specific ‘seed’ markers will yield subtype-specific extended sets of breast cancer markers. The key challenge of this investigation was to utilize a small number of well-characterized, largely intracellular, breast cancer-related proteins to uncover similarly regulated and functionally related genes and proteins with the view to predicting a much-expanded range of disease markers, especially that of extracellular molecular markers, potentially suitable for the early non-invasive detection of the disease. We selected 23 previously characterized proteins specific to three major molecular subtypes of breast cancer and analyzed their established transcription factor networks, their known metabolic and functional pathways and the existing experimentally derived protein co-expression data. Having started with largely intracellular and transmembrane marker ‘seeds’ we predicted the existence of as many as 150 novel biomarker genes to be associated with the selected three major molecular sub-types of breast cancer all coding for extracellularly targeted or secreted proteins and therefore being potentially most suitable for molecular diagnosis of the disease. Of the 150 such predicted protein markers, 114 were predicted to be linked through the combination of regulatory networks to basal breast cancer, 48 to luminal and 7 to Her2-positive breast cancer. The reported approach to mining molecular markers is not limited to breast cancer and therefore offers a widely applicable strategy of biomarker mining.
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Affiliation(s)
- Nathalie Schneider
- Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK
| | - Ellen Reed
- Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK
| | - Faddy Kamel
- Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK
| | - Enrico Ferrari
- School of Life Sciences, University of Lincoln, Lincoln LN6 7TS, UK
| | - Mikhail Soloviev
- Department of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK
- Correspondence:
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Yao Q, Hou W, Chen J, Bai Y, Long M, Huang X, Zhao C, Zhou L, Niu D. Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer. Front Med (Lausanne) 2022; 9:943887. [PMID: 35966872 PMCID: PMC9366086 DOI: 10.3389/fmed.2022.943887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/24/2022] [Indexed: 11/15/2022] Open
Abstract
Background Adenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC. Methods We applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information. Results A total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity. Conclusion This study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.
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Affiliation(s)
- Qian Yao
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Wei Hou
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Junbing Chen
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yanhua Bai
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Mengping Long
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiaozheng Huang
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Chen Zhao
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Lixin Zhou
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Dongfeng Niu
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
- *Correspondence: Dongfeng Niu
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30
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Butcher MR, White MJ, Rooper LM, Argani P, Cimino-Mathews A. MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas. Am J Surg Pathol 2022; 46:878-888. [PMID: 35522890 DOI: 10.1097/pas.0000000000001913] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.
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Affiliation(s)
| | | | | | - Pedram Argani
- Departments of Pathology
- Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ashley Cimino-Mathews
- Departments of Pathology
- Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
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Chen K, Zhang J, Beeraka NM, Tang C, Babayeva YV, Sinelnikov MY, Zhang X, Zhang J, Liu J, Reshetov IV, Sukocheva OA, Lu P, Fan R. Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers. Front Oncol 2022; 12:820968. [PMID: 35814391 PMCID: PMC9258420 DOI: 10.3389/fonc.2022.820968] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 05/16/2022] [Indexed: 12/11/2022] Open
Abstract
Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including "obesity," "oncogenic signaling pathways," "inflammation," "surgery," "radiotherapy," "conventional therapies," and "diet." Multiple studies indicated that effective BC treatment requires the involvement of diet- and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients' overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.
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Affiliation(s)
- Kuo Chen
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jin Zhang
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Narasimha M. Beeraka
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), JSS Medical College, Mysuru, India
| | - Chengyun Tang
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Yulia V. Babayeva
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Mikhail Y. Sinelnikov
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Xinliang Zhang
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Jiacheng Zhang
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Junqi Liu
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Igor V. Reshetov
- Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Olga A. Sukocheva
- Discipline of Health Sciences, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia
| | - Pengwei Lu
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ruitai Fan
- Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Ortega MA, Fraile-Martinez O, García-Montero C, Borja-Vergel S, Torres-Carranza D, Pekarek L, Arribas CB, De León-Luis JA, Sánchez-Rojo C, Alvarez-Mon MA, García-Honduvilla N, Buján J, Coca S, Alvarez-Mon M, Saez MA, Guijarro LG. Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma—A Histopathological Study. Medicina (B Aires) 2022; 58:medicina58060722. [PMID: 35743985 PMCID: PMC9229273 DOI: 10.3390/medicina58060722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/25/2022] Open
Abstract
Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.
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Affiliation(s)
- Miguel A. Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
- Cancer Registry and Pathology Department, Principe de Asturias University Hospital, 28806 Alcala de Henares, Spain
- Correspondence: (M.A.O.); (M.A.S.)
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Sandra Borja-Vergel
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
| | - Diego Torres-Carranza
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
| | - Leonel Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain
| | - Coral Bravo Arribas
- Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain; (C.B.A.); (J.A.D.L.-L.)
- Health Research Institute Gregorio Marañón, 28009 Madrid, Spain
| | - Juan A. De León-Luis
- Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain; (C.B.A.); (J.A.D.L.-L.)
- Health Research Institute Gregorio Marañón, 28009 Madrid, Spain
| | - Cristina Sánchez-Rojo
- Department of Obstetrics and Gynecology, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain;
| | - Miguel Angel Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Natalio García-Honduvilla
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Julia Buján
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Santiago Coca
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias, 28806 Alcala de Henares, Spain
| | - Miguel A. Saez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (O.F.-M.); (C.G.-M.); (S.B.-V.); (D.T.-C.); (L.P.); (M.A.A.-M.); (N.G.-H.); (J.B.); (S.C.); (M.A.-M.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
- Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain
- Correspondence: (M.A.O.); (M.A.S.)
| | - Luis G. Guijarro
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain;
- Health Research Institute Gregorio Marañón, 28009 Madrid, Spain
- Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcalá, 28801 Alcala de Henares, Spain
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Thirumal Kumar D, Udhaya Kumar S, Jain N, Sowmya B, Balsekar K, Siva R, Kamaraj B, Sidenna M, George Priya Doss C, Zayed H. Computational structural assessment of BReast CAncer type 1 susceptibility protein (BRCA1) and BRCA1-Associated Ring Domain protein 1 (BARD1) mutations on the protein-protein interface. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2022; 130:375-397. [PMID: 35534113 DOI: 10.1016/bs.apcsb.2022.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Breast cancer type 1 susceptibility protein (BRCA1) is closely related to the BRCA2 (breast cancer type 2 susceptibility protein) and BARD1 (BRCA1-associated RING domain-1) proteins. The homodimers were formed through their RING fingers; however they form more compact heterodimers preferentially, influencing BRCA1 residues 1-109 and BARD1 residues 26-119. We implemented an integrative computational pipeline to screen all the mutations in BRCA1 and identify the most significant mutations influencing the Protein-Protein Interactions (PPI) in the BRCA1-BARD1 protein complex. The amino acids involved in the PPI regions were identified from the PDBsum database with the PDB ID: 1JM7. We screened 2118 missense mutations in BRCA1 and none in BARD1 for pathogenicity and stability and analyzed the amino acid sequences for conserved residues. We identified the most significant mutations from these screenings as V11G, M18K, L22S, and T97R positioned in the PPI regions of the BRCA1-BARD1 protein complex. We further performed protein-protein docking using the ZDOCK server. The native protein-protein complex showed the highest binding score of 2118.613, and the V11G mutant protein complex showed the least binding score of 1992.949. The other three mutation protein complexes had binding scores between the native and V11G protein complexes. Finally, a molecular dynamics simulation study using GROMACS was performed to comprehend changes in the BRCA1-BARD1 complex's binding pattern due to the mutation. From the analysis, we observed the highest deviation with lowest compactness and a decrease in the intramolecular h-bonds in the BRCA1-BARD1 protein complex with the V11G mutation compared to the native complex or the complexes with other mutations.
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Affiliation(s)
- D Thirumal Kumar
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India; Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
| | - S Udhaya Kumar
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Nikita Jain
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Baviri Sowmya
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Kamakshi Balsekar
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - R Siva
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Balu Kamaraj
- Department of Neuroscience Technology, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Jubail, Saudi Arabia
| | - Mariem Sidenna
- Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha, Qatar
| | - C George Priya Doss
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Hatem Zayed
- Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha, Qatar.
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Garutti M, Griguolo G, Botticelli A, Buzzatti G, De Angelis C, Gerratana L, Molinelli C, Adamo V, Bianchini G, Biganzoli L, Curigliano G, De Laurentiis M, Fabi A, Frassoldati A, Gennari A, Marchiò C, Perrone F, Viale G, Zamagni C, Zambelli A, Del Mastro L, De Placido S, Guarneri V, Marchetti P, Puglisi F. Definition of High-Risk Early Hormone-Positive HER2−Negative Breast Cancer: A Consensus Review. Cancers (Basel) 2022; 14:cancers14081898. [PMID: 35454806 PMCID: PMC9029479 DOI: 10.3390/cancers14081898] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/06/2022] [Accepted: 04/06/2022] [Indexed: 11/16/2022] Open
Abstract
Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. During the past three decades, several improvements in the adjuvant treatment of hormone receptor-positive/HER2−negative breast cancer have been achieved with the introduction of optimized adjuvant chemotherapy and endocrine treatment. However, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (hIGh Risk DEfinition in breast cancer) working group was established with the aim of reviewing evidence from the literature to synthesize the current relevant features that predict hormone-positive/HER2−negative early breast cancer relapse. A panel of experts in breast cancer was involved in identifying clinical, pathological, morphological, and genetic factors. A RAND consensus method was used to define the relevance of each risk factor. Among the 21 features included, 12 were considered relevant risk factors for relapse. For each of these, we provided a consensus statement and relevant comments on the supporting scientific evidence. This work may guide clinicians in the practical management of hormone-positive/HER2−negative early breast cancers.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
- Correspondence: ; Tel.: +39-04-3465-9092
| | - Gaia Griguolo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (G.G.); (V.G.)
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, 35100 Padova, Italy
| | - Andrea Botticelli
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, 00100 Rome, Italy;
| | - Giulia Buzzatti
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
| | - Carmine De Angelis
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80100 Naples, Italy; (C.D.A.); (S.D.P.)
| | - Lorenzo Gerratana
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
| | - Chiara Molinelli
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
| | - Vincenzo Adamo
- Department of Human Pathology, Papardo Hospital, University of Messina, 89121 Messina, Italy;
| | - Giampaolo Bianchini
- Department of Medical Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy;
- School of Medicine and Surgery, Università Vita-Salute San Raffaele, 20020 Milan, Italy
| | - Laura Biganzoli
- Ospedale Santo Stefano, Prato Sandro Pitigliani Medical Oncology Division, Hospital of Prato, 59100 Prato, Italy;
| | - Giuseppe Curigliano
- Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20100 Milan, Italy;
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
| | - Michelino De Laurentiis
- Department of Breast and Thoracic Oncology, IRCCS INT Fondazione G. Pascale, 80144 Napoli, Italy;
| | - Alessandra Fabi
- Precision Medicine in Breast Cancer Unit, Department of Woman and Child Health and Public Health, IRCCS, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy;
| | - Antonio Frassoldati
- Department of Traslational Medicine and for Romagna, Clinical Oncology, S Anna University Hospital, Università degli Studi di Ferrara, 44121 Ferrara, Italy;
| | - Alessandra Gennari
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy;
- Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy
| | - Caterina Marchiò
- Candiolo Cancer Institute, FPO IRCCS, 10060 Candiolo, Italy;
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Francesco Perrone
- Clinical Trials Unit, Istituto Nazionale Tumori di Napoli, IRCCS Fondazione Pascale, 80144 Naples, Italy;
| | - Giuseppe Viale
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
- Department of Pathology, European Institute of Oncology IRCCS, 20122 Milan, Italy
| | - Claudio Zamagni
- Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, 40100 Bologna, Italy;
| | - Alberto Zambelli
- Breast Cancer Section Department of Biomedical Sciences, IRCCS Humanitas Research Hospital, Humanitas University, Rozzano, 20089 Milan, Italy;
| | - Lucia Del Mastro
- Department of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy; (G.B.); (C.M.); (L.D.M.)
- Dipartimento di Medicina Interna e Specialità Mediche, University of Genova, 16159 Genova, Italy
| | - Sabino De Placido
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80100 Naples, Italy; (C.D.A.); (S.D.P.)
| | - Valentina Guarneri
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35100 Padova, Italy; (G.G.); (V.G.)
- Division of Oncology 2, Istituto Oncologico Veneto IRCCS, 35100 Padova, Italy
| | - Paolo Marchetti
- IRCCS Istituto Dermopatico dell’Immacolata (IDI-IRCCS), 00167 Rome, Italy;
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; (L.G.); (F.P.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
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35
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Bhatia S, Kramer M, Russo S, Naik P, Arun G, Brophy K, Andrews P, Fan C, Perou CM, Preall J, Ha T, Plenker D, Tuveson DA, Rishi A, Wilkinson JE, McCombie WR, Kostroff K, Spector DL. Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor Intrinsic Characteristics. Cancer Res 2022; 82:1174-1192. [PMID: 35180770 PMCID: PMC9135475 DOI: 10.1158/0008-5472.can-21-2807] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 01/13/2022] [Accepted: 02/16/2022] [Indexed: 11/16/2022]
Abstract
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, highlighting the unmet clinical need for targeted therapies and better model systems. Here, we developed and comprehensively characterized a diverse biobank of normal and breast cancer patient-derived organoids (PDO) with a focus on TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBC). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibit signatures of aggressive MYC-driven, basal-like breast cancers and are largely comprised of luminal progenitor (LP)-like cells. The TNBC LP-like cells are distinct from normal LPs and exhibit hyperactivation of NOTCH and MYC signaling. Overall, this study validates TNBC PDOs as robust models for understanding breast cancer biology and progression, paving the way for personalized medicine and tailored treatment options. SIGNIFICANCE A comprehensive analysis of patient-derived organoids of TNBC provides insights into cellular heterogeneity and mechanisms of tumorigenesis at the single-cell level.
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Affiliation(s)
- Sonam Bhatia
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Melissa Kramer
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Suzanne Russo
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Payal Naik
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Gayatri Arun
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Kyle Brophy
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Peter Andrews
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Cheng Fan
- University of North Carolina, Lineberger Comprehensive Cancer Center, Department of Genetics, Chapel Hill, North Carolina
| | - Charles M Perou
- University of North Carolina, Lineberger Comprehensive Cancer Center, Department of Genetics, Chapel Hill, North Carolina
| | - Jonathan Preall
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Taehoon Ha
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Dennis Plenker
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - David A Tuveson
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
| | - Arvind Rishi
- Northwell Health, Department of Pathology, Lake Success, New York
| | - John E Wilkinson
- University of Michigan, Department of Pathology, Ann Arbor, Michigan
| | | | - Karen Kostroff
- Northwell Health, Department of Surgical Oncology, Lake Success, New York
| | - David L Spector
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York
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Petroušková P, Hudáková N, Maloveská M, Humeník F, Cizkova D. Non-Exosomal and Exosome-Derived miRNAs as Promising Biomarkers in Canine Mammary Cancer. Life (Basel) 2022; 12:life12040524. [PMID: 35455015 PMCID: PMC9032658 DOI: 10.3390/life12040524] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023] Open
Abstract
Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. Since the discovery of microRNAs (miRNAs or miRs) as post-transcriptional gene regulators, they have become attractive biomarkers in oncological research. Except for intracellular miRNAs and cell-free miRNAs, exosome-derived miRNAs (exomiRs) have drawn much attention in recent years as biomarkers for cancer detection. Analysis of exosomes represents a non-invasive, pain-free, time- and money-saving alternative to conventional tissue biopsy. The purpose of this review is to provide a summary of miRNAs that come from non-exosomal sources (canine mammary tumor, mammary tumor cell lines or canine blood serum) and from exosomes as promising biomarkers of CMC based on the current literature. As is discussed, some of the miRNAs postulated as diagnostic or prognostic biomarkers in CMC were also altered in HBC (such as miR-21, miR-29b, miR-141, miR-429, miR-200c, miR-497, miR-210, miR-96, miR-18a, miR19b, miR-20b, miR-93, miR-101, miR-105a, miR-130a, miR-200c, miR-340, miR-486), which may be considered as potential disease-specific biomarkers in both CMC and HBC.
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Affiliation(s)
- Patrícia Petroušková
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Nikola Hudáková
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Marcela Maloveská
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Filip Humeník
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Dasa Cizkova
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 10 Bratislava, Slovakia
- Correspondence: ; Tel.: +421-918-752-157
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37
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Williams R, Jobling S, Sims AH, Mou C, Wilkinson L, Collu GM, Streuli CH, Gilmore AP, Headon DJ, Brennan K. Elevated EDAR signalling promotes mammary gland tumourigenesis with squamous metaplasia. Oncogene 2022; 41:1040-1049. [PMID: 34916592 PMCID: PMC8837535 DOI: 10.1038/s41388-021-01902-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/05/2021] [Accepted: 06/09/2021] [Indexed: 01/10/2023]
Abstract
Ectodysplasin A receptor (EDAR) is a death receptor in the Tumour Necrosis Factor Receptor (TNFR) superfamily with roles in the development of hair follicles, teeth and cutaneous glands. Here we report that human Oestrogen Receptor (ER) negative breast carcinomas which display squamous differentiation express EDAR strongly. Using a mouse model with a high Edar copy number, we show that elevated EDAR signalling results in a high incidence of mammary tumours in breeding female mice. These tumours resemble the EDAR-high human tumours in that they are characterised by a lack of oestrogen receptor expression, contain extensive squamous metaplasia, and display strong β-catenin transcriptional activity. In the mouse model, all of the tumours carry somatic deletions of the third exon of the CTNNB1 gene that encodes β-catenin. Deletion of this exon yields unconstrained β-catenin signalling activity. We also demonstrate that β-catenin activity is required for transformed cell growth, showing that increased EDAR signalling creates an environment in which β-catenin activity can readily promote tumourigenesis. Together, this work identifies a novel death receptor oncogene in breast cancer, whose mechanism of transformation is based on the interaction between the WNT and Ectodysplasin A (EDA) pathways.
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Affiliation(s)
- Rebecca Williams
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Stephanie Jobling
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Andrew H Sims
- Applied Bioinformatics of Cancer, Edinburgh Breakthrough Unit, Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research Centre, Edinburgh, Midlothian, UK
| | - Chunyan Mou
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK
| | - Lorna Wilkinson
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Giovanna M Collu
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Charles H Streuli
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Andrew P Gilmore
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Denis J Headon
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
| | - Keith Brennan
- Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
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Ruiz J, Recuero M, Cárdenas JD, Cifuentes I, Álvarez J, Romero C, Chacón JI. Low-grade triple-negative breast carcinomas. A report of 2 cases and an update of current concepts. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2022; 55:26-35. [PMID: 34980437 DOI: 10.1016/j.patol.2021.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 11/27/2020] [Accepted: 01/05/2021] [Indexed: 06/14/2023]
Abstract
Triple negative breast cancer is defined by the lack of expression of estrogen, progesterone and HER2 receptors. Significant molecular, morphological and clinical heterogeneity is present in this group of neoplasms. Although the majority are high-grade tumors, low-grade triple negative breast cancers can occur and their evolution, molecular characteristics and therapeutic management vary from the former. In the current review, we focus on the histological and immunohistochemical phenotypes of two new low-grade cases: an acinic cell carcinoma and an adenoid cystic carcinoma. Data originated from the pathology department of a third-level hospital over an 18-month period, within a breast cancer screening program. Low-grade triple negative cancers should be suspected in triple negative breast cancers with low proliferative rates as, unlike high-grade tumors, they require a multidisciplinary approach. They can be diagnosed at an early stage by immunohistochemistry using core needle biopsy.
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Fawzy A, Alqelaiti YA, Almatrafi MM, Almatrafi OM, Alqelaiti EA. Common Sensitive Prognostic Marker in Breast Cancer and their Clinical Significance: A Review Article. ARCHIVES OF PHARMACY PRACTICE 2022. [DOI: 10.51847/t8d3bp2l19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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40
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Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression. Mod Pathol 2022; 35:1624-1635. [PMID: 35697931 PMCID: PMC9596373 DOI: 10.1038/s41379-022-01112-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/08/2022] [Accepted: 05/12/2022] [Indexed: 11/28/2022]
Abstract
Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. Here, we report comprehensive clinico-pathological and molecular findings for 27 patients diagnosed with BC-OGC at Institut Curie between 2000 and 2021. Seventeen (63%) cases were invasive carcinomas of no special type (IC NST) with OGC (OGC-IC NST), four (15%) were mixed or multifocal cases with and without OGC (OGC-Mixed), and six (22%) were metaplastic carcinomas with OGC (OGC-MC). All OGC-IC NST and OGC-Mixed cases were ER+ HER2- tumors (most being luminal A based on transcriptomic subtyping, when available), while all OGC-MC were triple-negative. The median age at diagnosis was 46, 45 and 62 years for OGC-IC NST, OGC-Mixed and OGC-MC, respectively. Three patients developed distant metastases (one OGC-IC NST, two OGC-Mixed), one of whom died of metastatic disease (OGC-Mixed), and one other patient died of locally advanced disease (OGC-MC). Histopathological evaluation comparing 13 OGC-IC NST and 19 control IC NST without OGC confirmed that OGC-IC NST showed significantly higher density of vessels (by CD34 immunohistochemistry (IHC)), iron deposits (Perls stain), and CD68 and CD163-positive cell infiltrates. Genomic findings for nine OGC-IC NST and four OGC-MC were consistent with the underlying histologic subtype, including activating alterations of the PI3K/AKT/mTOR pathway in 7/13 cases. Using RNA-seq data, differential gene expression analysis between OGC-IC NST (n = 7) and control IC NST without OGC (n = 7) revealed significant overexpression of TNFSF11 (RANK-L), TNFRSF11A (RANK), CSF1 (M-CSF), CSF1R, and genes encoding osteoclastic enzymes (MMP9, ACP5, CTSK, CTSB) in OGC-IC NST, while OPG (osteoprotegerin) was underexpressed. We also confirmed for the first time RANK-L expression in BC with OGC by IHC (seen in 15 out of 16 cases, and only in 2 of 16 controls without OGC). These findings could offer a rationale for further investigating RANK-L as a therapeutic target in BC with OGC.
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41
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Vohra P, Chen YY, Krings G. Less Common Triple-Negative Breast Cancers. A COMPREHENSIVE GUIDE TO CORE NEEDLE BIOPSIES OF THE BREAST 2022:463-573. [DOI: 10.1007/978-3-031-05532-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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42
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Jeong J, Park CS, Lee JW, Kim K, Kim HS, Jun SY, Oh SJ. Computer-Aided Diagnosis Parameters of Invasive Carcinoma of No Special Type on 3T MRI: Correlation with Pathologic Immunohistochemical Markers. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2022; 83:149-161. [PMID: 36237358 PMCID: PMC9238214 DOI: 10.3348/jksr.2021.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/25/2021] [Accepted: 06/15/2021] [Indexed: 11/16/2022]
Abstract
Purpose To investigate the correlation between computer-aided diagnosis (CAD) parameters in 3-tesla (T) MRI and pathologic immunohistochemical (IHC) markers in invasive carcinoma of no special type (NST). Materials and Methods A total of 94 female who were diagnosed with NST carcinoma and underwent 3T MRI using CAD, from January 2018 to April 2019, were included. The relationship between angiovolume, curve peak, and early and late profiles of dynamic enhancement from CAD with pathologic IHC markers and molecular subtypes were retrospectively investigated using Dwass, Steel, Critchlow-Fligner multiple comparison analysis, and univariate binary logistic regression analysis. Results In NST carcinoma, a higher angiovolume was observed in tumors of higher nuclear and histologic grades and in lymph node (LN) (+), estrogen receptor (ER) (−), progesterone receptor (PR) (−), human epidermal growth factor 2 (HER2) (+), and Ki−67 (+) tumors. A high rate of delayed washout and a low rate of delayed persistence were observed in Ki−67 (+) tumors. In the binary logistic regression analysis of NST carcinoma, a high angiovolume was significantly associated with a high nuclear and histologic grade, LN (+), ER (−), PR (−), HER2 (+) status, and non-luminal subtypes. A high rate of washout and a low rate of persistence were also significantly correlated with the Ki-67 (+) status. Conclusion Angiovolume and delayed washout/persistent rate from CAD parameters in contrast enhanced breast MRI correlated with predictive IHC markers. These results suggest that CAD parameters could be used as clinical prognostic, predictive factors.
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Affiliation(s)
- Jinho Jeong
- Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Suk Park
- Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Jung Whee Lee
- Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Kijun Kim
- Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Hyeon Sook Kim
- Department of Radiology, Eunpyeong St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sun-Young Jun
- Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Se-Jeong Oh
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
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43
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44
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Accardo G, Capobianco AM, Torre GL, Thodas A, Marino G, Sisti LG, Vita G. Adenoid cystic carcinoma of the breast and intraoperative electron radiotherapy: single case report and review of literature. Future Oncol 2021; 18:871-881. [PMID: 34904444 DOI: 10.2217/fon-2021-0860] [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: 11/21/2022] Open
Abstract
Adenoid cystic carcinoma (ACC) of the breast is a very rare neoplasm. It presents a triple-negative phenotype in most cases, but its prognosis is generally considered to be better than other breast cancers with the same immunohistochemical pattern. Due to its controversial features, no data are available in the literature regarding a consensus approach for ACC treatment, especially for subtypes with worse prognosis like solid basaloid ACC. We present for the first time a rare case of ACC with multifocal presentation treated with breast-conservative surgery and intraoperative electron radiotherapy, thus supporting this treatment of ACC in selected patients like young women affected by the solid basaloid variant who commonly present a worse prognosis. In this case, no local or systemic recurrence was detected after 30 months of follow-up.
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Affiliation(s)
- Giuseppe Accardo
- Department of Breast Surgery, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
| | - Alba Ml Capobianco
- Head of Multidisciplinary Oncology Unit, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
| | - Giuseppe La Torre
- Department of Breast Surgery, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
| | - Alexios Thodas
- Department of Breast Surgery, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
| | - Graziella Marino
- Department of Breast Surgery, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
| | - Leuconoe Grazia Sisti
- Center for Global Health Research and studies and Department of Public Health, Section of Hygiene, Catholic University of Sacred Heart, 00168, Rome, Italy
| | - Giulia Vita
- Department of Pathology, Centro di riferimento oncologico della Basilicata (IRCCS-CROB), 85028, Rionero in Vulture (PZ), Italy
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45
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Thennavan A, Beca F, Xia Y, Recio SG, Allison K, Collins LC, Tse GM, Chen YY, Schnitt SJ, Hoadley KA, Beck A, Perou CM. Molecular analysis of TCGA breast cancer histologic types. CELL GENOMICS 2021; 1. [PMID: 35465400 DOI: 10.1016/j.xgen.2021.100067] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Breast cancer is classified into multiple distinct histologic types, and many of the rarer types have limited characterization. Here, we extend The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset with additional histologic type annotations, in a total of 1063 breast cancers. We analyze this extended dataset to define transcriptomic and genomic profiles of six rare special histologic types: cribriform, micropapillary, mucinous, papillary, metaplastic, and invasive carcinoma with medullary pattern. We show the broader applicability of our constructed special histologic type gene signatures in the TCGA Pan-Cancer Atlas dataset with a predictive model that detects mucinous histologic type across cancers of other organ systems. Using a normal mammary cell differentiation score analysis, we order histologic types into a continuum from stem cell-like to luminal progenitor-like to mature luminal-like. Finally, we classify TCGA-BRCA into 12 consensus groups based on integrated genomic and histological features. We present a rich openly accessible resource of histologic and genomic characterization of TCGA-BRCA to enable studies of the range of breast cancers.
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Affiliation(s)
- Aatish Thennavan
- Oral and Craniofacial Biomedicine Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Francisco Beca
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Youli Xia
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.,Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Susana Garcia Recio
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.,Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Kimberly Allison
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Laura C Collins
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Gary M Tse
- Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong
| | - Yunn-Yi Chen
- Department of Pathology and Laboratory Medicine, University of California, San Francisco, CA, 94143, USA
| | - Stuart J Schnitt
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA
| | - Katherine A Hoadley
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.,Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | | | - Charles M Perou
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.,Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.,Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Kobayashi H, Nakai T, Nakanishi Y, Esumi M, Masuda S. Phylogenetic analysis of combined lobular and ductal carcinoma of the breast. Mol Med Rep 2021; 24:718. [PMID: 34396426 PMCID: PMC8383046 DOI: 10.3892/mmr.2021.12357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 07/12/2021] [Indexed: 11/18/2022] Open
Abstract
Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.
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MESH Headings
- Adult
- Breast
- Breast Neoplasms/classification
- Breast Neoplasms/genetics
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/classification
- Carcinoma, Ductal, Breast/genetics
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Intraductal, Noninfiltrating/genetics
- Carcinoma, Intraductal, Noninfiltrating/pathology
- Carcinoma, Lobular/classification
- Carcinoma, Lobular/genetics
- Carcinoma, Lobular/pathology
- Female
- Genotype
- High-Throughput Nucleotide Sequencing
- Humans
- Middle Aged
- Mutation
- Phylogeny
- Polymorphism, Single Nucleotide
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Affiliation(s)
- Hiroko Kobayashi
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Tokiko Nakai
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan
| | - Yoko Nakanishi
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Mariko Esumi
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Shinobu Masuda
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan
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Niţă I, Niţipir C, Toma ŞA, Limbău AM, Pîrvu E, Bădărău IA. The importance of androgen receptors in breast cancer. Med Pharm Rep 2021; 94:273-281. [PMID: 34430848 DOI: 10.15386/mpr-1842] [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: 08/05/2020] [Revised: 11/05/2020] [Accepted: 02/03/2021] [Indexed: 11/23/2022] Open
Abstract
Background and aim Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells. Till now, it is known that androgen receptor (AR) is present in about 60-80% of BC cells but, unfortunately, there is no targeted therapy available yet. Methods We revised the recent literature that included the AR mechanism of action in patients diagnosed with breast cancer, the preclinical, retrospective and clinical studies and the aspects related to the prognosis of these patients, depending on the molecular subtype. Results A total of 12 articles were eligible for this review. AR positivity was assessed using immunohistochemistry. Herein, neither 1 nor 10% cut-points were robustly prognostic. AR was an independent prognostic marker of BC outcome, especially in triple negative BC group. Conclusion AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.
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Affiliation(s)
- Irina Niţă
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,Medical Oncology Department, Elias University Emergency Hospital, Bucharest, Romania
| | - Cornelia Niţipir
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,Medical Oncology Department, Elias University Emergency Hospital, Bucharest, Romania
| | | | | | - Edvina Pîrvu
- Medical Oncology Department, "Colţea" Clinical Hospital, Bucharest, Romania
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Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers (Basel) 2021; 13:4287. [PMID: 34503097 PMCID: PMC8428369 DOI: 10.3390/cancers13174287] [Citation(s) in RCA: 740] [Impact Index Per Article: 185.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023] Open
Abstract
Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50. Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like). The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences.
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Affiliation(s)
- Sergiusz Łukasiewicz
- Department of Surgical Oncology, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-091 Lublin, Poland; (S.Ł.); (A.S.)
| | - Marcin Czeczelewski
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; (M.C.); (A.F.)
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland; (M.C.); (A.F.)
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Robert Sitarz
- Department of Surgical Oncology, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-091 Lublin, Poland; (S.Ł.); (A.S.)
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Andrzej Stanisławek
- Department of Surgical Oncology, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-091 Lublin, Poland; (S.Ł.); (A.S.)
- Department of Oncology, Chair of Oncology and Environmental Health, Medical University of Lublin, 20-081 Lublin, Poland
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Nardi RPD, Uchoa D, Remonatto G, Biazus JV, Damin AP. Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas. ACTA ACUST UNITED AC 2021; 67:265-270. [PMID: 34406251 DOI: 10.1590/1806-9282.67.02.20200683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.
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Affiliation(s)
- Rosana Pellin De Nardi
- Universidade Federal do Rio Grande do Sul, Postgraduate Program in Gynecology and Obstetrics - Porto Alegre (RS), Brazil
| | - Diego Uchoa
- Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Division of Pathology - Porto Alegre (RS), Brazil
| | - Gabriela Remonatto
- Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre, Division of Pathology - Porto Alegre (RS), Brazil
| | - Jorge Villanova Biazus
- Universidade Federal do Rio Grande do Sul, Postgraduate Program in Gynecology and Obstetrics - Porto Alegre (RS), Brazil.,Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre Breast Surgery Division - Porto Alegre (RS), Brazil
| | - Andrea Pires Damin
- Universidade Federal do Rio Grande do Sul, Postgraduate Program in Gynecology and Obstetrics - Porto Alegre (RS), Brazil.,Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre Breast Surgery Division - Porto Alegre (RS), Brazil
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50
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Gulbahce HE, Downs-Kelly E, Herget KA, Stoddard GJ. The 21-Gene Recurrence Score in Special Histologic Subtypes of Breast Cancer: A Population-Based Study. Arch Pathol Lab Med 2021; 146:478-484. [PMID: 34343231 DOI: 10.5858/arpa.2020-0837-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2021] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers. OBJECTIVE.— To determine association of histologic type (HT) and RS, specifically high-risk RS. DESIGN.— We used RSs linked to Surveillance, Epidemiology, and End Results program registries of invasive breast cancers diagnosed in 2004 through 2015. Multivariable logistic regression was used to evaluate association between HT and high-risk RS. Relationships between HT and low-, intermediate-, and high-risk RS were compared with χ2 test. Kaplan-Meier curves were compared using log-rank test. RESULTS.— A total of 110 318 patients had RS testing. Of these, 23 220 (21%) had low, 70 822 (64.2%) intermediate, and 16 276 (14.8%) high RS. Histologic types were 80 476 (73%) ductal, 12 713 (11.5%) lobular, 12 449 (11.3%) mixed, 2151 (2%) mucinous, 610 (0.6%) tubular 382 (0.4%) micropapillary, 365 (0.3%) salivary, 208 (0.2%) papillary, 49 (0.04%) medullary, 26 (0.02%) metaplastic, 26 (0.02%) neuroendocrine, and 863 (0.8%) unknown. The distribution of low-, intermediate-, and high-risk RS was significantly different among HTs. Higher percentages of high-risk RS were identified in patients with ductal, medullary, and metaplastic types (P < .001). The odds of having high-risk RS were lower for some HTs, including micropapillary, after multivariable adjustment (P < .05). The low number of estrogen receptor-positive medullary and metaplastic carcinomas tested had higher odds of having high-risk RS. In T1 and T2 tumors, when ductal, lobular, mixed, and other types combined were compared, the mortality was different. CONCLUSIONS.— This population-based study of RS in HTs showed high-risk RSs are identified in traditionally good prognostic subtypes. Micropapillary carcinoma has lower odds of high-risk RS even after multivariable adjustment.
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Affiliation(s)
- H Evin Gulbahce
- From the Department of Pathology, Huntsman Cancer Institute (Gulbahce), University of Utah Health, Salt Lake City
| | - Erinn Downs-Kelly
- the Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio (Downs-Kelly)
| | | | - Gregory J Stoddard
- the Department of Internal Medicine, Division of Epidemiology (Stoddard), University of Utah Health, Salt Lake City
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