Kramer I, et al. - In this population-based cohort study including 83,144 female patients diagnosed with first invasive breast cancer (BC), researchers determined the impact of several adjuvant systemic regimens on subtype-specific risk of contralateral breast cancer (CBC). Participants were followed-up until 2016. They analyzed clinico-pathological data from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA, the Dutch Pathology Registry. For all invasive metachronous CBC, and CBC-subtypes, they calculated cumulative incidences (death and distant metastases as competing risk) and hazard ratios. Development of a CBC was reported in 2,816 cases; the 10-year cumulative incidence was 3.8%. Compared to no endocrine therapy, endocrine therapy statistically significantly reduced the risk of ER-positive CBC, but not ER-negative CBC. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up vs patients not receiving chemotherapy for ER-negative first BC. Findings revealed attenuation in CBC risk with endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy. However, each adjuvant therapy regimen influenced the CBC-subtype distribution differentially. The largest CBC risk reduction was observed in association with taxane-containing chemotherapy and aromatase inhibitors.