Pathological characteristics of BRCA-associated breast cancers in Hispanics

Abstract

The immunophenotype of BRCA-associated breast cancer has been studied in predominantly non-Hispanic whites (NHW). We evaluated the pathological characteristics of BRCA-associated invasive breast cancer in Hispanics. A case-control study was conducted on breast cancers from Hispanic and NHW women who enrolled in an IRB-approved registry and underwent BRCA gene analysis. BRCA negative controls (41 Hispanic, 39 NHW) were matched on age and ethnicity to BRCA positive cases (39 Hispanic, 35 NHW). A tissue array was constructed to characterize the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and p53 by immunohistochemistry. Mean age at diagnosis was 37.1 years (range 24-59) for Hispanics (80% with Mexican ancestry) and 40.1 years (range 21-63) for NHW (P = 0.03). Hispanic BRCA1 cases were more likely than BRCA negative controls to have tumors that were ER-negative (P < 0.001) and PR-negative (P = 0.001), had higher levels of Ki-67 (P = 0.001) and p53 expression, and lower levels of HER2 overexpression. When stratified by genes, there were no significant differences in expression of ER, Ki-67, HER2, and p53 by ethnicity among mutation carriers. However, a significantly higher proportion of BRCA-positive Hispanics had PR-negative tumors compared to BRCA-positive NHW (80 vs. 57%, OR = 2.9, 95% CI 1.0-8.1, P = 0.04). Hispanic BRCA-associated breast cancers were found to have the unique immunophenotype associated with BRCA mutations; however, there was a trend toward a difference in PR expression among Hispanic BRCA1 and BRCA2 cases. Additional research on the molecular mechanisms involved in the loss of PR in this population is warranted as it could have important implications for the treatment and prevention of breast cancer in Hispanics.