Taxane-Induced Peripheral Neuropathy–Driven Treatment Modification and Pathologic Complete Response After Neoadjuvant TCHP in HER2-Positive Breast Cancer: A Retrospective Cohort Study

BackgroundNeoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) is a widely used regimen for HER2-positive breast cancer, achieving high rates of pathologic complete response (pCR).Taxane-induced peripheral neuropathy (CIPN) represents a clinically relevant doselimiting toxicity that may lead to premature taxane discontinuation.Evidence guiding the optimal neoadjuvant strategy after CIPN onset remains limited in real-world, toxicity-driven treatment modification scenarios. Patients and MethodsWe conducted a retrospective cohort study including patients with HER2-positive breast cancer treated with neoadjuvant TCHP at a single institution.Peripheral neuropathy was assessed during routine clinical care and graded according to CTCAE v6.0.Among patients who developed clinically significant CIPN prompting modification of the planned neoadjuvant regimen, the analysis focused on this subset (nested cohort), in whom post-neuropathy management consisted of either taxane discontinuation without anthracycline switch (taxanediscontinuation strategy) or switching to an anthracycline-based regimen (TCHPAC).The primary endpoint was pCR, defined as absence of invasive disease in breast and axillary lymph nodes (ypT0/is ypN0).Multivariable logistic regression was used to evaluate the association between post-neuropathy strategy and pCR, adjusting for prespecified clinicopathologic covariates.Prespecified stratified analyses were performed according to hormone receptor (HR) status, Ki-67 category, and clinical nodal status. ResultsAmong 843 patients treated with neoadjuvant TCHP, 180 (21.4%) developed CIPN that prompted treatment modification.Of these, 96 patients were managed with the taxanediscontinuation (non-anthracycline) strategy and 84 with the TCHPAC strategy.pCR was achieved in 25.0% of patients in the taxane-discontinuation (non-anthracycline) strategy group compared with 64.3% in the TCHPAC group (P = 0.001).In multivariable analysis, switching to an anthracycline-based regimen after CIPN was independently associated with a higher likelihood of achieving pCR compared with taxane discontinuation alone (adjusted OR 5.21, 95% CI 2.11-14.82;P = 0.001).The direction and magnitude of this association were consistent across prespecified subgroups, with no significant interaction observed according to HR status, Ki-67, or clinical nodal status. ConclusionIn this large real-world cohort of HER2-positive breast cancer treated with neoadjuvant TCHP, switching to an anthracycline-based regimen after taxane-induced peripheral neuropathy was associated with a markedly higher probability of achieving pCR compared with taxane discontinuation alone.These findings support a pragmatic, efficacy-preserving strategy for patients unable to complete taxane therapy due to CIPN and address a clinically relevant gap not directly covered by current treatment guidelines.