Abstract PO2-01-07: Real-world efficacy of dual HER2-blockade in combination with anthracycline-containing and anthracycline-free neoadjuvant treatment in early breast cancer (BC)
Authors: de Castro Beatriz Alonso , Reboredo Cristina , Calvo Lourdes , Perez-Lopez Maria-Eva , Rodriguez Martin Igor Gomez Randulfe , diaz Sofia silva , Vazquez Iria Parajo , Novoa Silvia Antolin 
Published: May 2024

Abstract
BACKGROUND: Neoadjuvant therapy with antiHER-2 blockade is the standard of care for HER-2 positive early BC. The objective of this treatment is tumor downstaging to increase resectability and pathological complete response (pCR), a reliable surrogate endpoint for survival. Adding Trastuzumab (T) to chemotherapy resulted in an improvement in pCR, however, resistance to this agent is common and the incorporation of Pertuzumab (P) to the neoadjuvant scene demonstrated an increase in pCR in the Peony (39.3% vs 21.8%) and Neosphere trials (45.8% vs 29%). Across all studies, pCR is even higher in patients (pts) with negative hormonal receptor (HR) status (50%-63%) (3, 4). Tryphaena and Berenice found low rates of cardiotoxicity with T-P combination. Recently, TRAIN-2 data showed that anthracyclines and platinum have a similar pCR (67% vs 68%), but febrile neutropenia and cardiotoxicity is higher in the anthracycline group, concluding that omitting this therapy might be a preferred approach in the presence of dual HER2 blockade. Our study investigated the pCR benefit of dual HER2 blockade with anthracyclines and platinum in HER2 positive early BC. METHODS: We conducted a retrospective, unicenter, observational study of pts, treated with neoadjuvant T-P plus chemotherapy, in HER-2 positive early BC, between April 2015 and December 2022 at University Hospital A Coruña (Spain). The primary endpoint was total pCR in breast and axila (tpCR: ypT0/is ypN0). Secondary endpoints were: association between clinicopatological characteristics and pCR; and between cardiotoxicity and treatment pattern. Statistical analyses were conducted with Statistical Package for the Social Science (SPSS). RESULTS: During the study period, from April 2015 to May 2022, 154 pts were enrrolled. The median age was 51,3 years [range 26 – 799 years], all patients were female. Infiltrating ductal carcinoma was present in 92.2% pts, and 5.8% were inflammatory BC. At diagnosis, 11.7%, 61.7% and 26.6% had stages I, II and III, respectively, and 51.3% revealed axillary node involvement. Among observed cases, 94 (61%) were positive HR; 68 (45%) had histological grade 2 and 83 (53.9%) histological grade 3 tumors; and 151 pts (99.3%) presented a ki-67 level &gt;20%. HER2 by immunohistochemistry (IHC) resulted in 3+ for 133 pts (86.9%) and in 2+ for 20 pts (13.1%), all of them with positive result by in situ hybridation (ISH). P-T were mostly combined with anthracyclines (64.9%). tpCR rate was 50.6%, and it was not significantly different according chemotherapy approach. tpCR was significantly higher among HR negative tumours (73.3%) compared with HR positive (36.2%) (p= 0.001), and in HER2 positive 3+ (55.6%) compared with HER2 positive 2+ (15%) tumours (p= 0.001). Achievement of tpCR was not significantly associated with tumor size, stage, histological grade and ki-67 level. Breast pCR was higher than tpCR (54.2%). 13 pts (8.4%) presented recurrence disease, in 76.9% of cases was a metastatic relapse. Cardiotoxicity was low during all stages of treatment and was not significantly associated with chemotherapy pattern. CONCLUSIONS: Neoadjuvant T-P plus chemotherapy with either anthracyclines or platinum therapy, demonstrated same efficacy and cardiac safety in our real-world study. pCR rates are lower in positive HR and HER2 positive 2+, needing more investigation with combination strategies including hormonotherapy, Our results are similar to data from randomized trials and other real-world efficacy studies, but we need more follow-up to identify late cardiotoxicity by anthracyclines and recurrences in positive HR tumors.
Citation Format: Beatriz Alonso de Castro, Cristina Reboredo, Lourdes Calvo, Maria-Eva Perez-Lopez, Martin Igor Gomez Randulfe Rodriguez, Sofia silva diaz, Iria Parajo Vazquez, Silvia Antolin Novoa. Real-world efficacy of dual HER2-blockade in combination with anthracycline-containing and anthracycline-free neoadjuvant treatment in early breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-07.