Abstract PO2-02-09: Pathological complete response to neoadjuvant systemic therapy and its predictive factors among early breast cancer subtypes: the emerging role of HER2

Abstract

Abstract Purpose Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer (BC) is a prognostic factor for relapse-free and overall survival (OS). Despite recent therapeutic developments for early BC, there are still a significant proportion of patients who do not achieve pCR. In this study we established pCR rates in routine care and investigated possible predictive factors of pCR, including HER2 status. Methods We evaluated 980 stage I-III BC patients receiving NACT between 2013 and 2022. Patient characteristics, rates of pCR (ypT0-is ypN0), toxicities, treatment modifications and survival outcomes were recorded. Standard histopathological variables were recorded [with HER2-low status, defined as HER2 1+ on immunohistochemistry (IHC) or 2+ on IHC without in situ hybridization (ISH) gene amplification]. Overall survival (OS) and relapse-free survival (RFS) were calculated. Median follow-up time was 60.3 months (interquartile range 19.7-78.7). Results The mean age of the study population was 49.6 ± 11.2 years. 64% had stage II disease, 70.5% had grade 3 disease, and 90.5% had ductal histopathology. 34.6% had estrogen receptor (ER)-positive/HER2-negative, 27.1% had triple-negative (TN), and 38.3% had HER2-positive BC. 233 patients (23.8%) had HER2-low disease. pCR rate was 35.8% in the overall population, 16.8% in ER-positive/HER2 negative BC, 32.7% in TNBC and 55.2% in HER2-positive BC. pCR rate differed according to grade, histology, HER2 status, radiological and clinical response of disease (p < 0.001) and early discontinuation of NACT (p = 0.001), but not according to age, menopausal status, BRCA status, platinum use, NACT dose reduction or delays, neutrophils-to-lymphocytes, platelets-to-lymphocytes, or lymphocytes-to-monocytes ratios. OS and RFS were better following pCR [HR 0.23 (95% CI, 0.14-0.38, p < 0.001) and HR 0.27 (95% CI, 0.18-0.40, p < 0.001), respectively]. Among HER2-negative BC patients (605, 61.7% of the entire cohort), there was a trend to lower pCR rate in HER2-low compared to HER2-negative (IHC 0) BC (19.7% vs 26.3% respectively, p = 0.06). pCR rate was significantly lower in ER-positive/HER2-low compared to ER-positive/HER2-negative (IHC 0) BC (12.1% vs 20.9% respectively, p = 0.031), while no difference in pCR rates was observed in TNBC patients by HER2 status. Despite a lower rate of pCR, Kaplan-Meyer curve showed that OS was significantly better in the HER2-low BC compared to HER2-negative (IHC 0) population at 100-months follow up. Multivariable Cox-regression model in the HER2-negative BC cohort demonstrated that HER2-low status was an independent predictor of OS (HR 0.59, 95% CI, 0.39-0.89 p = 0.012). Conclusions In our real-world analysis, pCR rates are consistent with the published data. Many patients still have residual disease following NACT, predicting worse outcomes, and may benefit from further adjuvant systemic therapies. Consistent with other studies, our findings suggest a possible prognostic and predictive role of HER2-low status especially among patients with ER-positive BC. This could lay the foundations for novel therapies targeting HER2 among HER2-low cancer subtypes. Citation Format: Matilde Corianò, Nicolo M.L. Battisti, Hala Aziz, Nalinie Joharatnam Hogan, Antonino Musolino, Alistair Ring. Pathological complete response to neoadjuvant systemic therapy and its predictive factors among early breast cancer subtypes: the emerging role of HER2 [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 PO2-02-09.