Multifocal breast cancers are more prevalent in BRCA2 versus BRCA1 mutation carriers

Abstract

AbstractMultifocal/multicentric breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ∼10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort of BRCA1/2 mutation carriers with breast cancer from Northern Ireland via cross-sectional analysis. Data from 211 women with BRCA1/2 mutations (BRCA1 - 91), (BRCA2 - 120), with breast cancer were collected including age, tumour focality, size, type, grade, and receptor profile. The prevalence of multifocality/multicentricity within this group was 25%, but within subgroups, prevalence amongst BRCA2 carriers was more than double that of BRCA1 carriers (p=0.001). Women affected by multifocal/multicentric tumours had proportionately higher oestrogen receptor positivity (p=0.001) and lower triple negativity (p=0.004). These observations are likely to be driven by the higher BRCA2 mutation prevalence observed within this cohort. Odds of a BRCA2 carrier developing multifocal/multicentric cancer were almost four-fold higher than a BRCA1 carrier (OR: 3.71, CI: 1.77-7.78, p=0.001). These findings were subsequently validated in a second, large independent cohort of patients with BRCA-associated breast cancers from a UK-wide multicentre study. This confirmed a significantly higher prevalence of multifocal/multicentric tumours amongst BRCA2 mutation carriers compared with BRCA1 mutation carriers. This has important implications for clinicians involved in the treatment of BRCA2-associated breast cancer, both in the diagnostic process, in ensuring that tumour focality is adequately assessed to facilitate treatment decision-making, and for breast surgeons, particularly if breast conserving surgery is being considered as a treatment option for these patients.