Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
View Publication
Export 
BiBTeXBACKGROUND Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. METHODS We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. RESULTS There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 \times 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 \times 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 \times 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 \times 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 \times 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). CONCLUSIONS/IMPACT: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis.
DOI: 10.1158/1055-9965.EPI-11-0775
Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer
Publication type: Journal article
Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Human Diseases: Hereditary breast ovarian cancer syndrome
Citation: Cancer Epidemiology Biomarkers & Prevention 21(1):134-147
Date Published: 5th Jan 2012
Registered Mode: imported from a bibtex file
Export PNG
Download
Submitter
Views: 979
Created: 15th Jul 2020 at 13:29
Last updated: 7th Dec 2021 at 17:58
TagsThis item has not yet been tagged.
AttributionsNone
Related items
The German Consortium for Hereditary Breast and Ovarian Cancer HBOC has been founded in 1996 by the German Cancer Aid and has been funded by the German Cancer Aid until recently. GC-HBOC currently comprises 17 university centers providing genetic counseling, histopathological and molecular tissue analysis, genetic testing, and specific structured surveillance programs for early cancer detection at each clinical unit, all based on defined standard operating procedures.
Programme: LIFE Management Cluster
Public web page: http://www.konsortium-familiaerer-brustkrebs.de/
Start date: 1st Jan 1996
Projects: LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0002-7247-282X
Projects: LHA - Leipzig Health Atlas, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, LIFE Heart, MMML - Molecular mechanisms in malignant lymphoma, GLA - German Lymphoma Alliance, MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, e:Med, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, NLP4CR - Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, SepNet - German Competence Network Sepsis, LIFE Child, HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, GGN - German Glioma Network, CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, CapSys - Systems Medicine of Community Acquired Pneumonia, ProstataCA, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, SMITH - Smart Medical Information Technology for Healthcare, Task Force COVID-19 Leipzig, NFDI4Health, POLAR - Polypharmacy, Drug Interactions, Risks, Management of health information systems, LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application, Project Test Demonstrator, Fundus photography as tool for analysis of eyes of subjects with diabetes, Clinical Trials Leipzig, NFDI4Health - TA3 Services, STOP-NUC, SCALE-TORT
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0001-8344-0658
Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, SepNet - German Competence Network Sepsis, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, LIFE Child, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, LIFE Adult
Web page: https://www.uniklinikum-leipzig.de/einrichtungen/life
Taxonomy URI: http://purl.obolibrary.org/obo/DOID_5683
Synonyms: BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC)
Definitions: Xref MGI., An autosomal dominant disease characterized by the higher than normal tendency associated with BRCA1 and BRCA2 to develop breast and ovarian cancers in genetically related families.
