Clinicopathologic features of early stage HER2-low breast cancer.

Abstract

e12545 Background: Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Traditionally, BC is divided into 3 categories: hormone receptor positive (HR+) if tumors overexpress either estrogen or progesterone receptors, HER2-positive (Pos) if tumors overexpress the human epidermal growth factor receptor protein (HER2), and triple negative if tumors lack overexpression of HER2, ER, or PR. 15% of all BC are HER2-Pos, which has poorer outcomes when compared to HER2-Neg. Early HER2 targeted therapies only showed benefit for treating tumors with high enough HER2 overexpression. Thus, HER2-Pos refers to tumors which stained 3+ for HER2 on immunohistochemistry (IHC) or 2+ with a positive result on amplification of the HER2 gene by fluorescence in-situ hybridization (FISH). In the recent DESTINY-Breast04 study, the drug trastuzumab deruxtecan showed benefit in treating metastatic BC patients with low levels of HER2 overexpression. HER2-Low, now a clinically relevant group, is defined as 1+ by IHC or 2+ and FISH negative. However, early stage HER2-Low BC is treated the same as HER2-Neg by the current standard of care. Large registry trials have described the HER2-Low patient population, mostly in the metastatic setting. Our study aims to describe the prevalence, pathological and clinical aspects of HER2-Low when compared to HER2-Neg BC in early stage BC patients within a community practice setting in the United States. Methods: This retrospective study analyzed 1,106 patients of which 120 were excluded due to being HER2-Pos. 986 HER2-Neg and HER2-Low patients of stages I-III were included. Patients had diagnosis dates between January 1st, 2015 and December 31st, 2022. Categorical and continuous analyses (two-proportion Z test) were performed to describe differences between HER2-Low and HER2-Neg patients at the time of diagnosis in age, tumor histology and grade, and need for chemotherapy. Results: 49% of patients (n = 1,106) were found to be HER2-Low. 91% of HER2-low patients were HR+, compared to 87% of HER2-Neg who were HR+ (p = 0.04). HER2-Low patients were more likely than HER2-Neg to have ductal carcinoma (82% vs. 75%, p = 0.01) and to be classified as grade 2 (58% vs. 48%, p = 0.001). The median age of patients with HER2-Low was 69 compared to 70 in patients with HER2-Neg disease. 36% of HER2-Low patients needed chemotherapy (neoadjuvant or adjuvant) compared to 35% who were HER2-Neg (p = 0.74). Conclusions: Our study revealed that HER2-Low patients were more likely than HER2-Neg patients to be HR+, grade 2, and to have ductal histology. In this early stage BC population, there was no difference in need for chemotherapy between HER2-Low and HER2-Neg patients. Future studies with a more racially diverse patient population looking at parameters of progression-free survival and overall survival in HER2-Low early stage BC population should be pursued.