Abstract HER2-11: HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB)
Authors: Peiffer Daniel , Howard Frederick M. , Chen Nan , Hahn Olwen M. , Nanda Rita , Olopade Olufunmilayo I. , Huo Dezheng 
Published: March 2023

Abstract
Title: Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) Background: Characterization of HER2 status has focused on HER2 overexpressing BC, which are uniquely sensitive to HER2-directed therapy. However, approximately 60% of BC traditionally characterized as HER2-negative express low levels of HER2 on immunohistochemistry (IHC). Although these ‘HER2-low’ cancers are insensitive to traditional HER2 blockade, a recent randomized clinical trial showed that antibody drug conjugates such as trastuzumab deruxtecan (T-DXd) are effective in this population. Given the heterogenity of low level HER2 expression and the impact of T-DXd on outcomes in this population, further data on the epidemiology and prognosis of HER2-low BC is needed. Methods: We conducted a retrospective cohort study of patients (pts) in the NCDB diagnosed from 2010 to 2019 with invasive BC classified as HER2-negative, and with HER2 IHC results available. We compared demographics and other clinical characteristics of HER2 0 vs HER2-low (defined as IHC score of 1+ or 2+) cases in this cohort. A logistic regression was used to quantify the independent association of demographic and clinical factors with HER2-low status, and odds ratios (OR) and 95% confidence intervals (CI) were reported. Overall survival (OS) was compared for HER2 0 vs HER2-low by receptor subtype and stage, and a multivariable Cox model was fit to also control for age, race/ethnicity, comorbidity score, treatment facility type, grade, and histologic type. In pts who received neoadjuvant chemotherapy (NAC), a logistic regression was used to determine if pathological complete response (pCR) rate was different between HER2-low and HER2 0 pts. Results: We identified 1,191,389 pts, including 394,937 HER2 0 and 796,452 HER2-low; median follow-up was 54 months with 84.1% of pts surviving. Hispanic and Black pts and pts with higher grade, non-ductal, triple-negative breast cancer (TNBC) and affect minority Hispanic and Black women (table 1). On multivariable analysis, TNBC (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.47 – 0.49), lobular (OR 0.74, 95% CI 0.73 – 0.75) and other non-ductal histology (OR 0.66, 95% CI 0.64 – 0.67) had lower likelihood of HER2-low status. Hispanic ethnicity remained associated with lower likelihood of HER2-low (OR 0.89, 95% CI 0.87 – 0.91), whereas Black race was associated with a slight increased likelihood of HER2-low status (OR 1.06, 95% CI 1.04 – 1.08). In multivariable survival analysis of TNBC patients, HER2-low BC was associated with improved OS for stage 2 (hazard ratio [HR] 0.93, 95% CI 0.90 – 0.96), stage 3 (HR 0.92, 95% CI 0.88 – 0.96) and stage 4 (HR 0.92, 95% CI 0.87 – 0.97) cancer. By contrast, survival analysis of hormone receptor positive cancer showed that HER2-low BC was associated with improved OS only for stage 4 disease (HR 0.96, 95% CI 0.92 – 0.99). In 62,667 pts receiving NAC, HER2-low status was associated with a lower likelihood of pCR (OR 0.88, 95% CI 0.84 – 0.92). Conclusions: HER2-low BC is most frequently HR+ with a ductal histology, and is associated with a lower likelihood of response to chemotherapy but an improved OS, especially for metastatic cases. This lower pCR in the HER2-low population could be explained by a higher proportion of these tumors being HR+. There are racial/ethnic differences in the incidence of HER2-low BC, largely mediated by differences in rates of TNBC, and fewer Black and Hispanic pts will be candidates for therapies targeting low level HER2 expression.
Citation Format: Daniel Peiffer, Frederick M. Howard, Nan Chen, Olwen M. Hahn, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo. HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) [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 HER2-11.