Contributing factors of contralateral breast cancer in patients with BRCA mutation (ON-BRCA II study, KoREa-BSG 11)

Background: The cumulative risk of contralateral breast cancer (CBC) in BRCA1/2 carriers is remarkably higher than in non-carriers. This study aimed to investigate the clinicopathological predictors associated with the risk of metachronous CBC among breast cancer patients with BRCA1/2 mutations using correspondence analysis. Methods: This retrospective study included patients who underwent BRCA testing between January 2008 and December 2018. The inclusion criterion was patients being between 20 and 80-years-old with invasive breast cancer (pT1-3, N0-3). We performed univariate and multivariate survival analyses to assess the risks associated with BRCA mutations, and conducted correspondence analysis to identify contributing factors for CBC among subgroup by age and BRCA mutations. Results: Total of 4009 patients were included in this analysis. After median follow-up of 93 months, 278 cases of CBC were documented. Among 576 patients with BRCA mutations, there was no difference in the incidence of CBC between BRCA1 and BRCA2 carriers (P = 0.07). Correspondence analysis revealed that, in younger patients (< 50 years) with BRCA1 mutations, the triple-negative subtype (r = 0.93) and high grade (r = 0.74) showed the closest geometric proximity associated with CBC. In BRCA2 carriers, high Ki-67 labeling index (≥ 20%) demonstrated prominent geometric association in the biplot related to CBC, regardless of age (r = 0.93). Conclusion: Although no difference was found in the risk of CBC between BRCA 1/2 mutations, correspondence analysis revealed different contributing factors. For young BRCA carriers with a triple-negative subtype and poor pathologic parameters such as high grade and Ki-67 index, risk-reducing contralateral prophylactic mastectomy could be considered as a treatment strategy.