An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC.
This population-based cohort study included female patients diagnosed with first invasive BC between 2003-2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry, and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC, and CBC-subtypes.
Of 83,144 BC patients, 2,816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI]=3.7-4.0%). Overall, adjuvant chemotherapy: HR = 0.70; 95%CI=0.62-0.80, endocrine therapy: HR = 0.46; 95%CI=0.41-0.52, and trastuzumab with chemotherapy: HR = 0.57; 95%CI=0.45-0.73 were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48; 95%CI=0.36-0.62) and aromatase inhibitors (HR = 0.32; 95%CI=0.23-0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of ER-positive CBC (HR = 0.41; 95%CI=0.36-0.47), but not ER-negative CBC (HR = 1.32, 95%CI=0.90-1.93), compared to no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84; 95%CI=1.62-4.99), compared to patients not receiving chemotherapy for ER-negative first BC.
Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduces CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC-subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction.