Long-term results of the Toronto magnetic resonance imaging (MRI) breast surveillance study of women with BRCA1 or BRCA2 mutations.

Abstract

542 Background: Although the addition of MRI to mammography for breast cancer screening in women with BRCA mutations has been shown to significantly increase sensitivity, some groups have reported high interval cancer and node-positive rates for BRCA1 mutation carriers, and the impact on survival is unknown. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality for women with BRCA mutations enrolled in our MRI screening program. Methods: From 1997 to 2009, 496 women ages 25 to 65 (median 44) with a BRCA1(54%) or BRCA2 (46%) mutation, 380 with no previous cancer, were enrolled in a prospective screening trial that included annual breast MRI and mammography. Women underwent a total of 1847 screening rounds (median 3, range 1-9). Results: 57 cancers were identified (53 detected at screening, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs. mammography was 86% vs. 19% overall (p<0.0001), 74% vs. 35% from 1997 to 2002 (p=0.02), and 94% vs. 9% from 2003 to 2009 (p<0.0001). The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs. noninvasive disease. Overall specificity of MRI vs. mammography was 90% vs. 97%. Of the 37 invasive cancers, 36 were ≤ 2 cm and 33 were node-negative. 97% of incident cancers were stage 0 or 1. Compared to BRCA2 mutation carriers, cancers in BRCA1 carriers were significantly more likely to be ER-negative (p=0.01) and treated with chemotherapy (p=0.04), and trended towards being larger, higher grade and more likely to be invasive. At a mean follow-up of 68 months from cancer diagnosis, only 1 of 28 previously unaffected women with invasive cancer had died of breast cancer, her tumor detected on her first screen at age 48, with no other distant recurrences (annual breast cancer mortality rate=0.6%). Conclusions: Despite a relatively short median follow-up of 5.5 years, given the early relapse pattern of BRCA-related cancers, these results are very encouraging. MRI surveillance appears to be a viable alternative to prophylactic mastectomy for women with BRCA1 or BRCA2 mutations.