Several observational studies have investigated the role of body mass index (BMI) in second primary cancer incidence in women with breast cancer. We conducted a systematic review and meta-analysis of the evidence to assess the strength of this association. PubMed and Embase were searched for observational studies up to May 2012, and the reference lists of studies included in the analysis were examined. Random effects models were used to estimate summary relative risks (RRs) and 95 % confidence intervals (CIs). Thirteen prospective studies, five cohort and eight nested case-control studies, were included. In categorical meta-analyses of BMI, obesity was associated to significantly increased risks of contralateral breast (RR = 1.37, 95 % CI: 1.20-1.57), breast (RR = 1.40, 95 % CI: 1.24-1.58), endometrial (RR = 1.96, 95 % CI: 1.43-2.70), and colorectal (RR = 1.89, 95 % CI: 1.28-2.79) second primary cancers. For a BMI increase of 5 kg/m(2), dose-response meta-analyses resulted in significantly increased RRs of 1.12 (95 % CI: 1.06-1.20) and 1.14 (95 % CI: 1.07-1.21) for contralateral breast and breast second primary cancers, respectively. The summary RR for endometrial second primary cancers was 1.46 (95 % CI: 1.17-1.83) for a 5-unit increment. This result emphasizes the importance of prevention policies aiming to reduce overweight and obesity prevalence. Clinical trials in breast cancer patients with excess body weight evaluating the effect of normal weight restoration on second primary cancer incidence are needed.
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