Completion versus early discontinuation of chemotherapy and the impact on five-year all-cause mortality in women treated for early-stage breast cancer from 2015-2020: a cohort study using a target trial emulation approach

AIM: Chemotherapy is given for early-stage breast cancer; however, some patients discontinue before completing all planned cycles. This study investigated the impact of early chemotherapy discontinuation on treatment outcomes. METHODS: This retrospective cohort study used a target trial emulation framework to conduct a causal analysis of the all-cause mortality impact of completing a standard course of chemotherapy. Early-stage breast cancer patients treated with chemotherapy in England between 01/01/2014-31/12/2015 were identified from National Disease Registration Service and Systemic Anti-Cancer Therapy datasets. Five-year OS was estimated for patients completing >=six chemotherapy cycles relative to discontinuing chemotherapy early (<six cycles), representing standard treatment during the study period. A clone-censor-weight approach was used to account for time-related bias and baseline confounding. Absolute risk and hazard ratios were calculated. RESULTS: 10,253 patients were included. 68% (n=7,014) received >=six chemotherapy cycles and 32% (n=3,239) <six cycles. Individuals completing >=six cycles showed superior five-year OS compared to discontinuation <six cycles (absolute risk difference - 1.6, 95% confidence interval (CI), -3.2, -0.1); hazard ratio 0.85, 95% CI 0.74, 0.98). Subgroup analyses showed OS benefit in patients diagnosed at stage 2 relative to stage 3 (HR 0.82, 95% CI 0.69, 0.98), ER+/HER2+ histology (HR 0.46, 95% CI 0.24, 0.96) and non-white ethnicity (HR 0.56, 95% CI 0.34, 0.91) when receiving six cycles. CONCLUSION: Patients who completed >=six cycles showed improved OS compared to those who discontinued before receiving six cycles. These findings support identification and pre-emptive management of patients at high risk of discontinuing chemotherapy prematurely, to maximise treatment benefit.