Abstract P5-05-05: Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Abstract

Abstract Background Bilateral salpingo-oophorectomy reduces breast cancer (BC) risk by about 50% in BRCA1/2 mutation carriers when performed premenopausally. It has been hypothesized that growth activity of BCs originating after risk-reducing salpingo-oophorectomy (RRSO) is lower. We compared tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO with those of tumors originating without RRSO. Methods From a cohort of 271 female BRCA1/2-associated patients with screen detected BC, 20 BRCA1/2 mutation carriers with PBC detected ≥12 months after RRSO were selected (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at PBC diagnosis (± 2.5 years) and for BRCA1 or BRCA2 mutation (intended matching ratio 1:2). Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated. Pathology samples were revised for histological subtype, tumor differentiation grade, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Imaging examinations (magnetic resonance imaging (MRI), mammography) before and at BC diagnosis were revised. Results Median age at PBC diagnosis was 52 years (range 35-67). MRI detected more BC than mammography in the RRSO-group as compared to the non-RRSO group (83% vs. 39%, P = 0.02). Tumor size at diagnosis was smaller in the RRSO group (11.0 mm vs. 17.0 mm, P = 0.01). Mitotic activity indexes (MAI) in the RRSO and non-RRSO group were 12 vs. 22 mitotic counts/2 mm2 (P = 0.02). No significant differences in differentiation grade, ER and HER2 status were found. PR-status was more often positive in the RRSO group without reaching statistical significance (38% vs. 13%, P = 0.07). Median DT in the RRSO group was 124 days (range 89-193) and 93 days (range 54-253) in the non-RRSO group (P = 0.47). Conclusion BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological behavior. When confirmed in larger series, this may have consequences for BC screening protocols for BRCA1/2 mutation carriers after RRSO. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-05.