THE HISTOLOGIC PHENOTYPES OF BREAST-CARCINOMA OCCURRING BEFORE AGE 40YEARS IN WOMEN WITH AND WITHOUT BRCA1 OR BRCA2 GERMLINE MUTATIONS - APOPULATION-BASED STUDY

BACKGROUND. Women with breast carcinoma diagnosed before age 40 years have a greater prevalence of germline BRCA1 and BRCA2 mutations than w omen with breast carcinoma diagnosed at older ages. Several recognizab le histologic characteristics have been identified in breast carcinoma from studies of BRCA1/2 mutation carriers who belong to multiple-case families. The authors attempted to determine whether breast carcinoma occurring before age 40 years in BRCA1 or BRCA2 mutation carriers who were not selected for family history could be distinguished histologi cally from one another and from breast carcinoma in women of a similar age without a germline BRCA1 or BRCA2 mutation. METHODS. The study un dertook a histologic assessment of breast carcinomas diagnosed before age 40 years identified from a population-based study. RESULTS. Breast carcinoma in BRCA1 mutation carriers was associated with a distinct h istologic appearance; these tumors were high grade, and had exceptiona lly high mean mitotic counts, a syncytial growth pattern, pushing marg ins, and confluent necrosis. Atypical medullary carcinoma was overrepr esented in BRCA1 mutation carriers. All low grade tumors and tumors wi th low mitotic rates belonged to the group without BRCA1 or BRCA2 muta tions. Pleomorphic lobular carcinomas and extensive intraduct carcinom as were more common in BRCA2 mutation carriers. CONCLUSIONS. Breast ca rcinoma occurring in women with a germline BRCA1 or BRCA2 mutation hav e recognizable histologic phenotypes, which may be useful in identifyi ng individuals more likely to carry germline mutations. Histologic exa mination of breast carcinoma should become an important part of the ev aluation of women seeking genetic testing for germline mutations in th ese breast carcinoma susceptibility genes. (C) 1998 American Cancer So ciety.