Pathologic complete response and survival in early-stage HER2-positive breast cancer patients treated with or without anthracyclines

The development of novel human epidermal growth factor receptor type-2 (HER2)-targeted therapies for HER2-positive breast cancer (HER2+ breast cancer (BC)) in recent decades has called for a reassessment of the benefit of including anthracyclines in neoadjuvant regimens, given their association with cardiotoxicity and secondary malignancies. Our study assessed the value of adding anthracyclines in a real-world cohort of early-stage HER2+ BC patients treated with trastuzumab with or without pertuzumab. We retrospectively evaluated 446 patients with early-stage HER2+ BC treated with neoadjuvant chemotherapy at two Chilean centers between 2010 and 2023. Patients received trastuzumab alone or trastuzumab plus pertuzumab, with anthracycline-containing or anthracycline-free regimens. Our primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints included invasive disease-free survival (iDFS) and overall survival (OS). Multivariate models assessed the predictive role of anthracyclines and pathological biomarkers (ER status, Ki67, HER2 amplification). Elevated Ki67, low ER expression and increased HER2 amplification were independent predictors of pCR. The addition of anthracyclines did not significantly improve pCR rates, even among patients treated with single HER2 targeted therapy (trastuzumab alone). With a median follow-up of 47 months, anthracyclines had no impact on iDFS (log-rank p = 0.19) or OS (p = 0.96). Subgroup and interaction analyses confirmed no benefit in other biomarker-defined populations. Overall, anthracyclines did not improve response to treatment or survival in HER2+ BC, even without dual HER2 blockade. These findings support anthracycline-free regimens, even in health systems with limited access to dual HER2-blockade with pertuzumab.