Interaction between hormone receptor status and the route of administration of dual HER2 blockade in HER2-positive breast cancer: a real-world exploratory study

Abstract Purpose To compare pathological complete response (pCR) rates between all-intravenous (IV) dual HER2 blockade and a mixed regimen of subcutaneous (SC) trastuzumab plus IV pertuzumab in HER2-positive breast cancer, and to explore the interaction between route of administration and hormone receptor (HR) status. Methods This single-center retrospective study stratified patients treated between January 2019 and December 2024 by route of administration. The primary endpoint was pCR (ypT0/is ypN0). The HR status × route interaction was assessed with an interaction term and the likelihood ratio test; sensitivity analyses used a clinical-stage proxy and a stricter HR-positivity threshold. Results Of 562 eligible patients, 332 were analyzed. The overall pCR rate was 55.4% (184/332): 58.5% (110/188) with all-IV versus 51.4% (74/144) with SC + IV (P = 0.237). HR-negative status (adjusted OR = 2.13, 95% CI 1.34–3.38, P = 0.001) and high Ki67 expression (adjusted OR = 2.06, 95% CI 1.09–3.89, P = 0.025) predicted pCR independently, whereas route of administration did not (OR = 0.78, P = 0.284). In HR+/HER2 + patients, pCR was 52.0% (53/102) with all-IV versus 40.0% (32/80) with SC + IV; in HR−/HER2 + patients, 65.5% (55/84) versus 66.1% (39/59). The adjusted interaction OR was 0.57 (95% CI 0.22–1.46; P = 0.240); sensitivity analyses were non-significant. Conclusion HR-negative status and high Ki67 independently predicted pCR. No significant interaction was found between HR status and route of administration, and the two regimens did not differ significantly overall; the difference favoring all-IV in HR+/HER2 + patients (Δ = 12.0%) is exploratory and requires prospective verification.