Pathological features and BRCA1 mutation screening in premenopausal breast cancer patients

Risk calculations for carrying BRCA1/BRCA2 mutations are based on family history and the age of onset of cancers. However, women may carry these deleterious mutations without a strong family history. Additional criteria for risk estimation would be of value. It has been recently established that BRCA1-associated breast cancers are associated with poor tumor differentiation (TD3) and estrogen receptor (ER) negativity. The aim of this study is to determine whether morphological features of breast cancers in premenopausal patients (age < 45 years) could determine additional women who may benefit from BRCA1 screening.

In a prospective, systematic study of 76 consecutive breast cancer patients (age < 45 years), genomic DNA was obtained from peripheral blood, and eight mutations in BRCA1 (10.5%) were found. Archival paraffin-embedded breast cancer specimens were then analyzed for tumor differentiation and ER status.

In patients < 45 years of age, 25% (6 of 24) of ER-negative and TD3 breast cancers were found to harbor mutations in BRCA1. Only 5.6% (2 of 36) of BRCA1-associated breast cancers did not have this morphological profile, compared with 94.4% (34 of 36) patients without BRCA1 mutations, giving an odds ratio of 5.67 (95% confidence interval, 1.04-32; P = 0.05). Finally, only one patient with BRCA1 mutations had a significant family history.

In patients with early-onset breast cancer, the use of morphological criteria provides an additional strategy to determine those patients who might benefit from genetic testing.