Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA) Journal Article
| Authors: | Mavaddat, N.; Barrowdale, D.; Andrulis, I. L.; Domchek, S. M.; Eccles, D.; Nevanlinna, H.; Ramus, S. J.; Spurdle, A.; Robson, M.; Sherman, M.; Mulligan, A. M.; Couch, F. J.; Engel, C.; McGuffog, L.; Healey, S.; Sinilnikova, O. M.; Southey, M. C.; Terry, M. B.; Goldgar, D.; O'Malley, F.; John, E. M.; Janavicius, R.; Tihomirova, L.; Hansen, T. V. O.; Nielsen, F. C.; Osorio, A.; Stavropoulou, A.; Benítez, J.; Manoukian, S.; Peissel, B.; Barile, M.; Volorio, S.; Pasini, B.; Dolcetti, R.; Putignano, A. L.; Ottini, L.; Radice, P.; Hamann, U.; Rashid, M. U.; Hogervorst, F. B.; Kriege, M.; van der Luijt, R. B.; Peock, S.; Frost, D.; Evans, D. G.; Brewer, C.; Walker, L.; Rogers, M. T.; Side, L. E.; Houghton, C.; Weaver, J.; Godwin, A. K.; Schmutzler, R. K.; Wappenschmidt, B.; Meindl, A.; Kast, K.; Arnold, N.; Niederacher, D.; Sutter, C.; Deissler, H.; Gadzicki, D.; Preisler-Adams, S.; Varon-Mateeva, R.; Schönbuchner, I.; Gevensleben, H.; Stoppa-Lyonnet, D.; Belotti, M.; Barjhoux, L.; Isaacs, C.; Peshkin, B. N.; Caldés, T.; De Al Hoya, M.; Cañadas, C.; Heikkinen, T.; Heikkilä, P.; Aittomäki, K.; Blanco, I.; Lazaro, C.; Brunet, J.; Agnarsson, B. A.; Arason, A.; Barkardottir, R. B.; Dumont, M.; Simard, J.; Montagna, M.; Agata, S.; D'Andrea, E.; Yan, M.; Fox, S.; Rebbeck, T. R.; Rubinstein, W.; Tung, N.; Garber, J. E.; Wang, X.; Fredericksen, Z.; Pankratz, V. S.; Lindor, N. M.; Szabo, C.; Offit, K.; Sakr, R. |
| Article Title: | Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA) |
| Abstract: | Background: 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 × 10 -5), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 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 × 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 × 10 -14), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 × 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. ©2011 AACR. |
| Keywords: | adult; protein expression; aged; middle aged; carrier protein; gene mutation; cancer grading; ovarian neoplasms; disease association; genetic predisposition to disease; cancer prevention; ovary cancer; breast cancer; cancer screening; breast neoplasms; brca1 protein; brca2 protein; prediction; cancer invasion; genes, brca1; genes, brca2; nucleotide sequence; breast tumor; estrogen receptor; progesterone receptor; tumor classification; germ-line mutation; cancer morphology; neoplasm grading |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 21 |
| Issue: | 1 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-01-01 |
| Start Page: | 134 |
| End Page: | 147 |
| Language: | English |
| DOI: | 10.1158/1055-9965.epi-11-0775 |
| PROVIDER: | scopus |
| PMCID: | PMC3272407 |
| PUBMED: | 22144499 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: CEBPE" - "Molecular Sequence Numbers: GENBANK: NG_012772;" - "Source: Scopus" |
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