Tailored to fit: balancing over- and undertreatment in early-stage triple-negative breast cancer patients

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that accounts for about 10–20% of cases. Because TNBC lacks targets for hormone or HER2 therapies, chemotherapy remains the main systemic treatment. Yet many people with early-stage TNBC may be overtreated, experiencing side effects without clear benefit. This thesis improved risk classification in early-stage TNBC by analysing a unique Dutch cohort of chemotherapy-naïve breast cancer patients who, according to the guidelines at the time of diagnosis, did not receive chemotherapy. We found that tumors surrounded by more immune cells—measured as tumor-infiltrating lymphocytes (TILs) —were associated with better long-term survival even without chemotherapy. We also found that, in the absence of chemotherapy, women with a germline BRCA1 mutation had poorer outcomes and a higher risk of second primary cancers, including cancer in the other breast. To translate these insights into practice, we integrated TILs into PREDICT, a widely used prognostic tool, using a large cohort of early-stage TNBC patients with TIL scores. The updated model, PREDICTₛTILs, better distinguishes lower-risk from higher-risk TNBC patients and supports more personalised chemotherapy decisions. These findings may reduce unnecessary treatment while ensuring intensive therapy is targeted to those who need it most.