NEOADJUVANT TRASTUZUMAB, WITH OR WITHOUT PERTUZUMAB, COMBINED WITH CHEMOTHERAPY FOR EARLY HER2-POSITIVE BREAST CANCER: A REAL-WORLD EXPERIENCE FROM A TERTIARY CANCER CENTRE

Abstract

Background: Neoadjuvant chemotherapy combined with trastuzumab, with or without pertuzumab, is standard of care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with clinical trial pathological complete response (pCR) rates of 45–61%. Real-world evidence from low- and middle-income settings, where dual anti HER2 therapy access remains limited, is sparse. This study evaluated the efficacy and safety of neoadjuvant HER2 directed therapy plus chemotherapy in routine practice at a tertiary cancer centre in India. Methods: Consecutive patients with HER2-positive early breast cancer who received neoadjuvant chemotherapy plus trastuzumab, with or without pertuzumab, between January 2023 and August 2025 were retrospectively identified. Clinicopathological characteristics, regimens, treatment-related toxicity, and pathological response were analysed. pCR was defined as absence of invasive residual disease in the breast and axillary lymph nodes (ypT0/is ypN0). Categorical variables were compared using Chi-square or Fisher exact tests; a two-sided p value <0.05 was considered significant. Results: Eighty-one female patients were analysed; 70 (86.4%) had clinically node-positive disease and 48 (59.3%) were hormone receptor (HR)-positive. Overall pCR was 48.1% (39/81). pCR rates were 41.7% (20/48) in HR-positive and 57.6% (19/33) in HR-negative tumours (p=0.159). Sixty-nine patients (85.2%) received single-agent anti-HER2 therapy (trastuzumab) and 12 (14.8%) received dual anti-HER2 therapy (trastuzumab plus pertuzumab). pCR was achieved in 40.6% (28/69) of single-agent recipients versus 91.7% (11/12) of dual-therapy recipients (p=0.001). Diarrhoea (24.7%), fatigue (16.0%), nausea (14.8%), and mucositis (12.4%) were the most common adverse events. Asymptomatic left ventricular ejection fraction decline occurred in one patient (1.2%); no symptomatic heart failure or grade 3–4 cardiac events were observed. Conclusion: In this real-world Indian cohort, neoadjuvant HER2-directed therapy plus chemotherapy demonstrated efficacy comparable to pivotal clinical trials, with markedly higher pCR observed with dual anti-HER2 blockade. Cardiac and overall tolerability was favourable. Wider access to dual anti-HER2 therapy in the neoadjuvant setting should be prioritised.