Risk factors for metachronous contralateral breast cancer suggest two aetiological pathways

Although many studies show an increased risk of metachronous contralateral breast cancer (CBC) in women with a positive family history and young age at diagnosis of the initial breast cancer, the aetiological pathways are still enigmatic. In a cohort of 8478 primary breast cancer patients diagnosed between 1975 and 2006, 558 cases of metachronous CBC were identified. Using multivariate Cox proportional hazards models, we analysed risk factors assessed at the time of the first primary tumour, including patient demographics, tumour characteristics and treatment among 4681 breast cancer patients for whom data on key variables were available. The analysis was performed separately in patients who developed CBC without and with prior recurrence(s). Risk of CBC without prior recurrent disease was increased by a positive family history [adjusted relative risk (RR) 2.8 (95% confidence interval (CI) 1.4-5.5)]; and decreased by endocrine treatment [RR 0.6 (95% CI 0.4-1.0)]. We found an increased risk of CBC with prior recurrent disease with younger age [RR 1.2 (95% CI 1.4-3.0)]; positive family history [RR 2.1 (95%CI 0.8-5.0)]; and extensive lymph node involvement [RR 2.0 (95% CI 1.2-3.6)]. Our results suggest that nodal status of the primary tumour may be as important a risk factor as family history or age, which indicates a high susceptibility to breast cancer or an impaired host defence mechanism. It may also imply that some CBCs are metastases from the first primary tumour, particularly in patients who present with recurrent disease before CBC.