Pathologic Complete Response Rates in Early-Stage Human Epidermal Growth Factor 2 (HER2)-Positive Breast Cancer...

Background Achieving a pathological complete response (pCR) is a major goal of neoadjuvant therapy for early-stage human epidermal growth factor 2 (HER2)-positive breast cancer. The introduction of anti-HER2 agents into chemotherapy has significantly increased pCR rates. Trastuzumab, the first humanized monoclonal antibody targeting the extracellular domain of HER2, improves both pCR and event-free survival when added to standard regimens. Pertuzumab, which binds to domain II of HER2 and inhibits HER2-HER3 dimerization, provides complementary activity. Despite these advances, additional biomarkers predicting pCR are still being explored. This study aimed to assess pCR rates and identify clinicopathological factors associated with improved response and survival.  Methodology Our retrospective study included 140 patients with early HER2-positive breast cancer who received neoadjuvant chemotherapy (NAC) at the Regional Oncology Center in Agadir between January 2018 and December 2022. Logistic regression was applied to evaluate the impact of clinico-pathological variables on pCR, and a p-value below 0.05 was considered statistically significant. Kaplan-Meier curves were used to assess progression-free survival (PFS) and overall survival (OS). Survival comparisons were performed using the log-rank test. Multivariate Cox regression models were constructed to evaluate the impact of different covariates on pCR.  Results The median age of the cohort was 49.5 ± 10.2 years. Among the 140 patients, 58 (41.4%) were diagnosed at stage II and 82 (58.6%) at stage III. Lymph node involvement was found in 74 cases (52.9%), and hormone receptor (HR) positivity was noted in 77 patients (55%). Following curative surgery, pCR was achieved in 72 patients (51.4%). Multivariate analysis identified age <50 years (p = 0.043), lymph node involvement (p < 0.001), nuclear grade 3 (p < 0.001), and Ki67 ≥35% (p < 0.001) as independent predictors of pCR. Overall, the three-year PFS and the three-year OS rates were 95.5% (95% CI: 92.0-99.1%) and 98.4% (95% CI: 96.2-100%), respectively. Patients who achieved pCR demonstrated significantly longer PFS compared with those who did not (three-year PFS: 98.6% vs. 92.3%, p = 0.027). The most frequently reported adverse events (AEs) were fatigue in 92 cases (65.7%), anemia in 92 cases (65.7%), and nausea/vomiting in 77 patients (55%). The most common grade 3-4 AEs were fatigue in 22 patients (15.7%), nausea/vomiting in 13 patients (9.3%), and anemia in 11 patients (7.8%). Cardiac toxicity occurred in 10 patients (7.1%). Conclusions Anti-HER2 therapies combined with NAC improved pCR rates while maintaining a manageable safety profile. Clinicopathological factors such as tumor grade, nodal status, HR status, and Ki67 also influenced pCR. However, emerging predictive biomarkers are currently under investigation to further optimize escalation and de-escalation treatment strategies. Future studies on larger cohorts incorporating these additional biomarkers are needed to enhance predictive models and guide personalized therapy.