Efficacy and Safety of Neoadjuvant Dual HER2-Targeted Therapy in Older and Younger Patients With HER2-Positive Early Breast Cancer: A Real-World Retrospective Analysis

BACKGROUND: Neoadjuvant chemotherapy combined with dual HER2-targeted therapy improves pathological complete response (pCR) rates in early-stage HER2-positive breast cancer. However, data on its efficacy and tolerability in older adults remain limited. OBJECTIVE: To evaluate the efficacy, toxicity, and survival outcomes of neoadjuvant dual anti-HER2 therapy in older adults with HER2-positive early breast cancer. METHODS: This retrospective cohort included patients with HER2-positive early breast cancer treated with neoadjuvant dual anti-HER2 therapy at Queen Mary Hospital, Hong Kong, between January 2017 and December 2023. Patients were stratified by age (< 65 vs. ≥ 65 years). The primary outcome was pCR. Multivariable logistic regression identified predictors of pCR. Progression-free survival (PFS) was assessed using the Kaplan-Meier method with log-rank testing. Treatment-related toxicities (TRT) were graded according to CTCAE v5.0. RESULTS: A total of 227 patients were included, 43 (18.9%) were aged ≥ 65 years. The pCR rate was 51.2% in older patients and 62.0% in younger patients (P = .194). Higher clinical T-stage was significantly associated with lower pCR (OR = 0.25, 95% CI, 0.06-0.67, P = .02). Older patients experienced more grade ≥ 3 TRT (55.8% vs. 28.3%, P < .001), with neutropenia (32.6% vs. 12.0%) and diarrhoea (16.3% vs. 7.1%) being most common. Unplanned hospitalisations were more frequent (14.0% vs. 4.9%, P = .001). No significant difference in PFS was observed (P = .21). Five-year PFS rates were 87.4% (95% CI, 76.3%-100%) in older patients and 95.2% (95% CI, 92.0-98.6%) in younger patients. CONCLUSION: Older patients achieved pCR and PFS comparable to younger counterparts but experienced higher toxicity and hospitalisation rates. Age-specific and de-escalation strategies warrant further study.