Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients

Abstract

<b><i>Introduction:</i></b> The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa. <b><i>Methods:</i></b> Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (<i>n</i> = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. <b><i>Results:</i></b> Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47–0.90%) and among SPCs, 7.21% (4.99–9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61–5.07). <b><i>Discussion/Conclusion:</i></b> The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.