Abstract PO4-02-09: Clinical outcomes of neoadjuvant chemotherapy in HER2-low early breast cancer

Abstract BACKGROUND: According to immunohistochemistry (IHC) expression of HER2 receptor, breast cancer (BC) can be classified as either IHC score 0, 1+, 2+ or 3+. Until recently, two distinct BC subtypes were recognized depending on the HER2 IHC expression and in situ hybridization (ISH) score: HER2 positive (IHC 3+ or IHC 2+ ISH-amplified) and HER2 negative (IHC 0, 1+ or 2+ ISH negative). More recently a new BC entity termed HER2-low was acknowledged, defined as either HER2 IHC 1+ or 2+ ISH-negative. Given that no treatment benefit was observed in HER2-low group of patients in the pivotal trastuzumab studies, many years had to pass before the discovery of antibody-drug conjugates such as trastuzumab deruxtecan, that led to a significant improvement in the clinical outcome of HER2-low BC, compared to standard therapy options. It is still debated whether HER2-low BC represents a distinct biological subtype. The aim of this study was to determine whether there is an impact of HER2-low status on the effect of neoadjuvant chemotherapy (NACT) and its primary indicator - the rate of the pathologic complete response (pCR). METHODS: A retrospective study of 363 BC cases who received NACT between January 2020 and December 2022 at University Hospital Centre Zagreb, Croatia, was conducted with prior Ethics Committee approval. Histopathological characteristics of tumours available from the hospital information system (BIS), including hormone receptor status (ER, PR), HER2 status and Ki-67 at the time of diagnosis and after neoadjuvant treatment, as well as pCR rates, were analysed. pCR rates were calculated for HER2-low and HER2 0 cases. Chi square test was used to analyse association between pCR rate and HER2 status. RESULTS: After exclusion of HER2 positive BC cases, as well as cases with missing data, a total of 215 patients were included in the analysis. Of those, 101 (47%) were HER2-low, and 114 (53%) were HER2 negative. The majority of patients (N=151, 70.2%) had luminal BC, while 64 (29.8%) patients had triple negative BC (TNBC). In the luminal group, 86 cases (57%) were HER2-low, and 65 (43%) were HER2 0. In the TNBC group, 15 cases (23.4%) were HER2-low and 49 (76.6%) were HER2 0. The rate of pCR among luminal subtypes was 6.2% for HER2-low tumours, and 15.4% for HER2 0 tumours (p=.051559), approaching statistical significance. In the TNBC group, the pCR rate for HER2-low group was 60%, compared to 40% in the HER2 0 group, trending towards, but not reaching statistical significance (p=.191564). CONCLUSION: A trend toward higher pCR rates after neoadjuvant chemotherapy was observed in the luminal HER2 0 group compared to HER2-low luminal BC, almost reaching statistical significance. Interestingly, in TNBC there was a trend towards higher pCR rates among the HER2-low group, although a small number of patients precludes any definitive conclusions. Further trials that include novel targeted therapies are needed, as that might lead to significant changes in therapeutic approach, as well as clinical outcome of HER2-low BC patients. Citation Format: Dora Gudelj, Katarina Čular, Lea Toula, Marija Križić, Marina Popović, Natalija Dedić Plavetić, Ana Kelečić, Gordana Ivanac, Majana Soče, Iva Kukal Gjergjaj, Tajana Silovski. Clinical outcomes of neoadjuvant chemotherapy in HER2-low early breast cancer 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 PO4-02-09.