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Background: - Low levels of HER2 expression among women with HER2-negative breast cancer is an emerging target. In addition, prior studies have suggested that low levels of HER2 expression might confer resistance to chemotherapy among women with triple-negative breast cancer (TNBC). In this study, we assess the response to neoadjuvant chemotherapy among women with TNBC with varying degrees of HER2 expression. Methodology: - Utilizing the National Cancer Database, we identified adult women treated with neoadjuvant chemotherapy for a diagnosis of clinical TNM stage I to III triple-negative invasive ductal carcinoma of the breast between the years 2010 and 2018. Baseline characteristics were compared between HER2 immunohistochemistry (IHC) scores of 0, 1 +, and 2+ (Women with HER2 2+ expression had to be negative for amplification in the HER2 gene by FISH) using Chi-square for categorical variables. The odds of achieving a complete pathological response were compared among women with different HER2 expression statuses in a multivariate logistic regression model adjusting for age, race, ethnicity, grade of the tumor, and clinical TNM stage at diagnosis. A multivariate cox proportional hazards regression model was used to identify the prognostic effect of HER2 expression on overall survival (OS) adjusting for age at diagnosis, race, ethnicity, grade of tumor, and clinical TNM stage at diagnosis. Results: - A total of 11,038 women with HER2 IHC score of 0, 8,718 women with a score of 1+ and 2,700 women with a score of 2+ were included in the final analysis. The median age at diagnosis was 52 for women with a HER2 IHC score of 0, 53 for women with a HER2 IHC score of 1+ and 54 for women with an IHC score of 2+/FISH negative. The rates of complete pathological response among women with HER2 IHC scores of 0, 1+, and 2+ were 39.5%, 38.1%, and 36.1% respectively. In multivariate analysis, a significant difference in the odds of achieving complete pathological response was not observed for women with HER2 1+ (OR: 1.1, 95% CI: 0.95-1.20, p = 0.3) or HER2 2+ (OR: 0.9, 95% CI: 0.7-1.0, p = 0.1) tumors compared to women with HER2 IHC score of 0. In multivariate Cox regression analysis, women with TNBC with HER2 IHC score 2+ were found to have a better OS (Hazard Ratio [HR]: 0.88, 95% CI: 0.80-0.97, p = 0.01) compared to women with HER2 IHC score of 0 whereas a significant difference in OS was not observed between women with HER2 IHC scores of 0 and 1+ (HR: 0.95, 95% CI: 0.89–1.01, p = 0.1). Conclusion: - This study demonstrates that HER2 expression status does not influence the rates of complete pathological response to neoadjuvant chemotherapy in women with TNBC. However, women with HER2 IHC score of 2+ were found to have a favorable prognosis, which needs to be evaluated further in future studies. Citation Format: Pravash Budhathoki, Anish Shah, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-05. |
