Anthracycline-Free Neoadjuvant Pertuzumab-Trastuzumab-Taxane in Patients with HER2-Positive Early Breast Cancer: Hormone Receptor Status as a Key Determinant of Pathological Complete Response

Background: Neoadjuvant chemotherapy plus dual HER2 blockade is standard for HER2-positive early breast cancer (EBC), but the impact of hormone receptor (HR) status and PIK3CA mutations with anthracycline-free regimens remains unclear. Methods: We retrospectively analyzed 56 patients with stage II–III HER2-positive EBC treated with neoadjuvant pertuzumab–trastuzumab–taxane (THP) at a single institution. Pathological complete response (pCR, ypT0/is ypN0) was the primary endpoint; secondary endpoints were safety and early disease-free/overall survival (DFS/OS), while associations of HR status and PIK3CA mutations with pCR were explored. Results: The overall pCR rate was 60.7%, in line with major dual-HER2 neoadjuvant trials. HR-negative patients achieved higher pCR rates than HR-positive patients (85.7% vs. 45.7%; p = 0.007; odds ratio 7.125), identifying HR status as the main clinical factor associated with response. Among 36 patients with PIK3CA testing, pCR rates appeared similar in mutated and wild-type tumors (62.5% vs. 60.7%), but the small number of mutated cases precludes firm conclusions. At a median follow-up of 42 months, only five DFS and one OS event had occurred, so survival analyses are exploratory and should be interpreted cautiously. THP demonstrated an excellent safety profile, with minimal grade 3–4 toxicity, and no clinically relevant hematological, cardiac, or pulmonary events. Conclusions: Anthracycline-free THP is a highly active, well-tolerated neoadjuvant option for HER2-positive EBC, with particularly high pCR rates in HR-negative disease. HR status emerged as a key determinant of pCR, whereas the role of PIK3CA mutations remains inconclusive and requires confirmation in larger prospective studies.