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 x 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend 6.8 x 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 x 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 x 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 x 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. Cancer Epidemiol Biomarkers Prev; 21(1); 134-47. (C) 2011 AACR.
Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) / N., Mavaddat; D., Barrowdale; I. L., Andrulis; S. M., Domchek; D., Eccles; H., Nevanlinna; S. J., Ramus; A., Spurdle; M., Robson; M., Sherman; A. M., Mulligan; F. J., Couch; C., Engel; L., Mcguffog; S., Healey; O. M., Sinilnikova; M. C., Southey; Terry, Mb; D., Goldgar; F., O'Malley; John, Em; R., Janavicius; L., Tihomirova; T. V. O., Hansen; F. C., Nielsen; A., Osorio; A., Stavropoulou; J., Benitez; S., Manoukian; B., Peissel; M., Barile; S., Volorio; B., Pasini; R., Dolcetti; A. L., Putignano; Ottini, Laura; P., Radice; U., Hamann; M. U., Rashid; F. B., Hogervorst; M., Kriege; R. B., Hebon Van Der Luijt; S., Peock; D., Frost; D. G., Evans; C., Brewer; L., Walker; M. T., Rogers; L. E., Side; C., Embrace Houghton; J., Weaver; A. K., Godwin; R. K., Schmutzler; B., Wappenschmidt; A., Meindl; K., Kast; N., Arnold; D., Niederacher; C., Sutter; H., Deissler; D., Gadzicki; S., Preisler Adams; R., Varon Mateeva; I., Schonbuchner; H., Gevensleben; D., Stoppa Lyonnet; M., Belotti; L., Gemo Study Collaborators Barjhoux; C., Isaacs; B. N., Peshkin; T., Caldes; M., De La Hoya; C., Canadas; T., Heikkinen; P., Heikkila; K., Aittomaki; I., Blanco; C., Lazaro; J., Brunet; B. A., Agnarsson; A., Arason; R. B., Barkardottir; M., Dumont; J., Simard; M., Montagna; S., Agata; E., D'Andrea; M., Yan; Fox S., Kconfab Investigators; T. R., Rebbeck; W., Rubinstein; N., Tung; J. E., Garber; X. S., Wang; Z., Fredericksen; V. S., Pankratz; N. M., Lindor; C., Szabo; K., Offit; R., Sakr; M. M., Gaudet; C. F., Singer; M. K., Tea; C., Rappaport; P. L., Mai; M. H., Greene; A., Sokolenko; E., Imyanitov; A. E., Toland; L., Senter; K., Sweet; M., Thomassen; A. M., Gerdes; T., Kruse; M., Caligo; P., Aretini; J., Rantala; A., Von Wachenfeld; K., Swe Brca Collaborators Henriksson; L., Steele; S. L., Neuhausen; R., Nussbaum; M., Beattie; K., Odunsi; L., Sucheston; S. A., Gayther; K., Nathanson; J., Gross; C., Walsh; B., Karlan; G., Chenevix Trench; D. F., Easton; Antoniou A. C., Consortium Of Investigators Of Modifiers Of Brca1/2. - In: CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION. - ISSN 1055-9965. - 21:1(2012), pp. 134-147. [10.1158/1055-9965.epi-11-0775]
Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
OTTINI, LAURA;
2012
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 x 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend 6.8 x 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 x 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 x 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 x 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. Cancer Epidemiol Biomarkers Prev; 21(1); 134-47. (C) 2011 AACR.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
