A Clinicopathological Study of Early-Stage Synchronous Bilateral Breast Cancer: A Retrospective Evaluation and Prospective Validation of Potential Risk Factors

BACKGROUND The aim of the present study was to investigate potential risk factors for synchronous bilateral breast cancer sBBC). METHODS A retrospective analysis was performed of patients diagnosed and treated with operable bilateral breast cancer (BBC) between June 2007 and December 2011. Risk factors for sBBC were evaluated in this cohort and further validated in a prospective observational validation analysis of patients between January 2012 and December 2012. Patients treated with operable unilateral breast cancer during the same period were used as a control group. RESULTS A total of 11,247 patients with primary breast cancer underwent operations at the Fudan University Shanghai Cancer Center between June 2007 and December 2012. The incidence of sBBC was 1.6%. The age at diagnosis (HR = 2.4, 95% C.I.: 1.4-4.0, p = 0.001), presence of sclerosing adenosis (HR = 11.8, 95% C.I.: 5.3-26.3, p<0.001), lobular carcinoma component involvement (HR = 5.6, 95% C.I.: 2.6-12.1, p<0.001), and family history of first-degree relatives with breast cancer (HR = 2.0, 95% C.I.: 1.1-3.4, p<0.001) were independent risk factors for sBBC. A subsequent validation study failed to confirm the significance of family history. No significant difference on survival was found between patients with early-stage sBBC and control cases. CONCLUSIONS Patients with the presence of sclerosing in the affected breast, and lobular carcinoma component involvement may be at high risk for developing sBBC. This study supports the hypothesis that the host-carcinoma biological relationship, especially for the tumor microenvironment, played a critical role in the carcinogenesis of sBBC.