Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis

Purpose: Breast tumors of BRCA1 mutation carriers and those of early onset breast cancer cases share similar histological features, being generally hi gh-grade, highly proliferative, aneuploid tumors that are predominantly est rogen- and progesterone-receptor negative. Because histological features of tumors of premenopausal women differ from those of tumors of older women, we sought to determine whether the immunophenotype of breast tumors of BRCA 1 mutation carriers was influenced by age at diagnosis. Experimental Design: We examined 31 breast tumors from BRCA1 mutation carri ers and compared them with 81 tumors of age-matched (plus or minus 5 years) breast cancer patients unselected for family history. Tumors were further matched for histology, grade, and size. Paraffin-embedded tumor tissues wer e examined for protein expression of estrogen receptor (ER), PR, Ki-67, cyc lin D1, TP53, HER2, beta -catenin, and cyclin E using immunohistochemical a pproaches. Results: ER (P = 0.01), PR (P = 0.06), and cyclin D1 (P = 0.002) were less frequently expressed and Ki-67 (P = 0.01) and beta -catenin (P = 0.04) were more frequently expressed in tumors of BRCA1 mutation carriers than contro ls. After age stratification, we found a significant difference in the freq uency of tumors of BRCA1 mutation carriers diagnosed before 50 years of age compared with age-matched controls that stained positive for ER (P = 0.01) , PR (P = 0.03), Ki-67 (P = 0.008), cyclin D1 (P < 0.001), HER2 (P = 0.04), and beta -catenin (P = 0.05). However, no significant differences were obs erved in tumors of BRCA1 mutation carriers diagnosed at age 50 or older com pared with age-matched controls. Conclusions: These data suggest that age at diagnosis, possibly related to menopausal status, may be an important factor in the expression of specific proteins in breast tumors of BRCA1 mutation carriers.