Second primary cancers after adjuvant radiotherapy in early breast cancer patients: a national population based study under the Danish Breast Cancer Cooperative Group (DBCG)

Background and purpose: To analyze the long-term risk of second primary solid non-breast cancer in a national population-based cohort of 46,176 patients treated for early breast cancer between 1982 and 2007.

Patients and methods: All patients studied were treated according to the national guidelines of the Danish Breast Cancer Cooperative Group. The risk of second primary cancers was estimated by Standardised incidence ratios (SIRs) and multivariate Cox regression models were used to estimate adjusted hazard ratios (HR) among irradiated women compared to non-irradiated. All irradiated patients were treated on linear accelerators. Second cancers were a priori categorized into two groups; radiotherapy-associated- (oesophagus, lung, heart/mediastinum, pleura, bones, and connective tissue) and non-radiotherapy-associated sites (all other cancers).

Results: 2358 second cancers had occurred during the follow-up. For the radiotherapy-associated sites the HR among irradiated women was 1.34 (95% CI 1.11-1.61) with significantly increased HRs for the time periods of 10-14 years (HR 1.55; 95% CI 1.08-2.24) and ≥ 15 years after treatment (HR 1.79; 95% CI 1.14-2.81). There was no increased risk for the non-radiotherapy-associated sites (HR 1.04; 95% CI 0.94-1.1). The estimated attributable risk related to radiotherapy for the radiotherapy-associated sites translates into one radiation-induced second cancer in every 200 women treated with radiotherapy.

Conclusions: Radiotherapy treated breast cancer patients have a small but significantly excess risk of second cancers.