Risk factors for metachronous contralateral breast cancer: A systematic review and meta-analysis

Background: The risk of developing metachronous contralateral breast cancer (CBC) is a recurrent topic at the outpatient clinic. We aimed to provide CBC risk estimates of published patient, pathological, and primary breast cancer (PBC) treatment-related factors. Methods: PubMed was searched for publications on factors associated with CBC risk. Meta-analyses were performed with grouping of studies by mutation status (i.e., BRCA1, BRCA2, CHEK2 c.1100delC), familial cohorts, and general population-based cohorts. Results: Sixty-eight papers satisfied our inclusion criteria. Strong associations with CBC were found for carrying a BRCA1 (RR = 3.7; 95%CI:2.8–4.9), BRCA2 (RR = 2.8; 95%CI:1.8–4.3) or CHEK2 c.1100delC (RR = 2.7; 95%CI:2.0–3.7) mutation. In population-based cohorts, PBC family history (RR = 1.8; 95%CI:1.2–2.6), body mass index (BMI) ≥30 kg/m2 (RR = 1.5; 95%CI:1.3–1.9), lobular PBC (RR = 1.4; 95%CI:1.1–1.8), estrogen receptor-negative PBC (RR = 1.5; 95%CI:1.0–2.3) and treatment with radiotherapy <40 years (RR = 1.4; 95%CI:1.1–1.7) was associated with increased CBC risk. Older age at PBC diagnosis (RR per decade = 0.93; 95%CI:0.88–0.98), and treatment with chemotherapy (RR = 0.7; 95%CI:0.6–0.8) or endocrine therapy (RR = 0.6; 95%CI:0.5–0.7) were associated with decreased CBC risk. Conclusions: Mutation status, family history, and PBC treatment are key factors for CBC risk. Age at PBC diagnosis, BMI, lobular histology and hormone receptor status have weaker associations and should be considered in combination with key factors to accurately predict CBC risk.