Simultaneous anthracycline-based chemotherapy and dual HER2 blockade in early-stage HER2-positive breast cancer: A retrospective analysis.

Abstract

e12741 Background: Early-stage HER2-positive breast cancer represents a biologically aggressive subtype; however, outcomes have substantially improved with the introduction of HER2-targeted therapies. Anthracyclines have been considered a cornerstone of chemotherapy, but their role is increasingly being questioned. Recently, antibody–drug conjugates are being evaluated in clinical trials with the aim of redefining treatment standards in the early setting. However, some comparative concepts remain methodologically limited, particularly when anthracycline-based regimens are administered without concurrent HER2-targeted therapy and compared with modern regimens that include simultaneous HER2 blockade. From both a biological and clinical perspective, the concomitant administration of chemotherapy and HER2-directed treatment appears critical to maximize antitumor efficacy. Non-pegylated liposomal doxorubicin (Myocet) has been developed to reduce cardiotoxicity while preserving antitumor activity, offering a potential strategy for anthracycline-based approaches with an improved safety profile. Methods: We performed a retrospective analysis of 164 consecutive patients with early-stage HER2-positive breast cancer treated at the Department of Obstetrics and Gynecology, Medical University of Innsbruck between April 2013 and February 2022. Patients were routinely assigned to receive six cycles of a neoadjuvant regimen consisting of Myocet, docetaxel and dual HER2 blockade administered concurrently. Primary endpoint was pathological complete response (pCR) rates. Secondary endpoints included overall survival, disease free survival and cardiotoxicity. Results: A total of 164 patients were analyzed. Median follow-up was 8,38 years (Q1,Q3; 6,5, 10,08). The median age at diagnosis was 50,8 years (Q1, Q3; 42,7, 58,7). In our cohort, 56% of patients were pre- and 43% postmenopausal. Regarding hormone receptor (HR) status, 42% (69/164) were HR negative and 58% (95/164) HR positive. PCR rate was achieved in 81,1% (133/164) of patients. Patients exhibiting HR negative cancers showed pCR more often, 92,8% (64/69), compared to HR positive patients, 72,6% (69/95). Overall survival in our cohort was on median 90,4 months (Q1, Q3; 65,4, 110,2) and disease-free survival 83,2 months (Q1, Q3; 60, 106,5). Data regarding cardiotoxicity was available for 89% (146/164) of patients at the time of their operation and 90% (147/164) of patients at the end of their treatment. At both time points, two patients (1%; 2/146, 2/147) had a left ventricular dysfunction grade CTCAE 2 (LVEF 40-49% and LVEF reduction of > 10%). Conclusions: In our cohort providing real world data, simultaneous anthracycline-based chemotherapy and dual HER2 blockade in early-stage HER2-positive breast cancer was an effective treatment with a pCR rate of 81,1% and excellent cardiac safety.