Omission of anthracyclines from neoadjuvant chemotherapy for breast cancer: a population-based analysis

Background — Most individuals diagnosed with high-risk breast cancer are treated with anthracycline-containing neoadjuvant chemotherapy (NAC). There is interest to identify individuals for whom anthracyclines can be avoided. A paucity of data exists on the extent to which anthracyclines are omitted in the neoadjuvant setting and its associated effectiveness.

Objective — To investigate the extent to which anthracycline-free NAC is used in the treatment of breast cancer and the impact of its omission on risks of mortality.

Methods — Population-based analysis of individuals diagnosed with stage I–III invasive breast cancer between 2012 and 2021 treated with NAC and surgery in Ontario, Canada. Baseline characteristics of patients who did and did not receive an anthracycline were compared. Five-year cumulative risks of breast cancer and all-cause mortality were calculated. Cause-specific hazard ratios (HRs) and 95% CIs were calculated using adjusted multivariable proportional hazards models for the whole cohort and subsets stratified by stage and receptor subtype.

Results — The cohort includes 6672 patients; 6126 received an anthracycline, 546 received an anthracycline-free regimen. Median follow-up was 3.9 years. The 5-year cumulative incidence of breast cancer mortality was 12.3% for individuals treated with an anthracycline-free regimen and 14.5% for those who received an anthracycline (p = 0.10). On multivariable analysis, individuals treated with non-anthracycline NAC did not experience an increased risk of breast cancer mortality (HR = 0.88; 95% CI: 0.65,1.18, p = 0.38) or all-cause mortality (HR 0.86; 95% CI 0.67, 1.10, p = 0.23). For patients with stage I or II HER2+ disease, treatment with non-anthracycline NAC was associated with excellent survival.

Conclusions — Most individuals treated with NAC received an anthracycline but its omission for selected patients with early HER2+ breast cancer was associated with excellent outcomes.