Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

BACKGROUND: This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment. METHODS: Risk was assessed, among 8752 Dutch women diagnosed with BBC between 1989 and 2008, using standardised incidence ratios (SIR) and Cox regression analyses to estimate the hazard ratio (HR) of TNBC for different treatment modalities. RESULTS: Significant increased SIRs were observed for all TNBCs combined, haematological malignancies, stomach, colorectal, non-melanoma skin, lung, head and neck, endometrial, and ovarian cancer. A 10-fold increased risk was found for ovarian cancer among women younger than 50 years (SIR=10.0, 95% confidence interval (CI)=5.3–17.4). Radiotherapy was associated with increased risks of all TNBCs combined (HR=1.3; 95%CI=1.1–1.6, respectively). Endocrine therapy was associated with increased risks of all TNBCs combined (HR=1.2; 95%CI=1.0–1.5), haematological malignancies (HR=2.0; 95%CI=1.1–3.9), and head and neck cancer (HR=3.3; 95%CI=1.1–10.4). After chemotherapy decreased risks were found for all TNBCs combined (HR=0.63; 95%CI=0.5–0.87). CONCLUSION: Increased risk of TNBC could be influenced by genetic factors (ovarian cancer) or an effect of treatment (radiotherapy and endocrine therapy). More insight in the TNBC risk should further optimise and individualise treatment and surveillance protocols in (young) women with BBC.