Immediate efficacy and safety profile of a de-escalated neoadjuvant THP regimen in early HER2-positive breast cancer: preliminary results of a prospective study

De-escalation of neoadjuvant therapy for HER2‑positive breast cancer remains one of the key trends in modern oncology. The search for treatment regimens that reduce toxicity without compromising antitumor efficacy remains a clinically relevant challenge. Purpose of the study . To evaluate the immediate efficacy (pathological complete response rate) and safety profile of a de-escalated 12‑week neoadjuvant THP regimen (paclitaxel, trastuzumab, pertuzumab) in patients with early HER2‑positive breast cancer. Patients and methods. A prospective single-center study conducted at the P. A. Hertsen Moscow Oncology Research Institute included 55 patients with verified stage IIA–IIB HER2‑positive breast cancer. All patients received THP neoadjuvant therapy consisting of 12 weekly infusions of paclitaxel (80 mg/m²) combined with dual HER2 blockade (trastuzumab + pertuzumab, 4 cycles). The primary endpoint was the pathological complete response (pCR) rate (ypT0/is ypN0). Secondary endpoints included the toxicity profile and the rate of breast-conserving surgery. Results . A pathological complete response was achieved in 34 (61.8 %; 95 % CI 48.6–73.5) of 55 patients in the overall cohort. Subgroup analysis revealed a statistically significant association between efficacy and biological subtype: the pCR rate was 76.2 % in non-luminal HER2‑positive cancer compared to 52.9 % in the luminal subtype (p = 0.04). High tumor grade (G3, 87.5 %) and high Ki‑67 index (>30 %, 73.2 %) were also significant factors associated with a high probability of pCR. The rate of lymph node metastasis eradication in patients with initial cN1 status was 85.0 %. The safety profile was favorable: no cases of febrile neutropenia or grade 3–4 toxicity were recorded, and no dose reductions were required. Conclusion . The de-escalated 12‑week THP regimen demonstrates high immediate efficacy, comparable to standard platinum-containing regimens, with an exceptionally favorable safety profile. The results support the use of this regimen as a de-escalation option, particularly for patients with non-luminal tumor subtypes and those at high risk of toxicity from standard treatment regimens.