Abstract HER2-04: HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0
Authors: Raghavendra Akshara Singareeka , Liu Diane , Mouabbi Jason , Tripathy Debu 
Published: March 2023

Abstract
Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 Background: Amplification and/or overexpression of the HER2 gene is detected in approximately 15% to 20% of breast cancer (BC) patients. HER2-targeted therapies improve survival in HER2+ BC. Current HER2 diagnostic tests and thresholds were designed and optimized to predict benefit from HER2-directed therapies. The DESTINY-Breast04 trial demonstrated notable efficacy of HER2 antibody-drug conjugate trastuzumab deruxtecan, in patients whose tumors are not conventionally HER2+, but defined as HER2-low (IHC 1 or 2+ without HER2 amplification). A better understanding of the HER2-low phenotype is therefore of critical importance. Methods: Eligible pts were adults with metastatic HER2 IHC (0,1+,2+/FISH negative) BC seen at MD Anderson between 2006 and 2019. Primary biopsy of the breast was used to test biomarkers. HER2 low was defined as IHC 1+ or 2+ and FISH-negative. HER2-negative was defined as HER2 IHC 0. Multi-covariate logistic regression models were used to evaluate effect of clinical factors on HER2 low status and pCR. Overall survival (OS) was defined as time from diagnosis date until death. Disease free survival (DFS) was defined as time from definitive surgery date until the first local/distant recurrence or death from any cause. Patients alive without events (death for OS, recurrence/death for DFS) were censored at last follow-up date. OS and DFS times were estimated by Kaplan-Meier method. Multivariate Cox proportional hazards regression models were applied to assess effect of covariates of interest on OS and DFS. Results: A total of 3053 early stage and 1203 de novo female BC patients were included in the analysis. The prevalence of HER2 low for early stage patients was 59.3% (1811/3053) and for de novo metastatic disease 59.3% (713/1203). In early stage patients, white race, higher nuclear grade and positive ER status were significantly associated with HER2 low status in multicovariate logistic regression. Univariately, pCR rate was significantly associated with negative ER (10.2% in negative vs 2.7% in positive), negative PR (8.6% vs 2%) and negative lymphatic vascular invasion (9.2% vs 2%). Multicovariate logistic regression showed ER (p=0.0124), PR (p=0.0439) status and lymphatic vascular invasion (p&lt; 0.0001) were significantly associated with pCR status. With median follow-up of 8.5 years, median OS time was 5.3 years (95% CI: [4.9, 5.4]), 5.4 years and 4.8 years in HER2 low and HER2 0 groups, respectively. In multicovariate Cox regression, HER2 low was significantly associated with longer OS (HR=0.87, p=0.008), adjusted for age, race, stage, nuclear grade, lymphatic-vascular invasion and ER/PR status. In patients who received neoadjuvant chemotherapy, adjusted for stage, nuclear grade, ER and PR status and pCR, HER2 low was significantly associated with a longer OS time (HR=0.87, p=0.04). Median DFS time was 1.9 years (95% CI: (1.8, 2.0)). Age, stage, histology, nuclear grade, and ER and PR status were significantly associated with DFS by multicovariate Cox regression. Among de novo cases, higher nuclear grade (HR [II vs I]=1.838, p =0.008; HR [III vs I]=1.856, p=0.007) and positive ER status (OR=1.933, p &lt;.0001) were associated with high percentage of HER2 low by multicovariate logistic regression. Median OS time was 3.2 years (95% CI: (3.0, 3.5)). By multicovariate Cox regression, race, histology, nuclear grade, ER and PR status, and HER2 low status (HR=0.834, p=0.0260) were significantly associated with OS time. Conclusions: In metastatic BC pts, HER2 low status was significantly associated with a longer OS and DFS when compared to HER2 0. Nuclear grade and ER positivity was significantly associated with HER2 low status. Biomarkers on recurrence tumor will be presented. This real world data helps to establish the prevalence of HER2 low and their outcomes for this selective cohort.
Citation Format: Akshara Singareeka Raghavendra, Diane Liu, Jason Mouabbi, Debu Tripathy. HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 [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 HER2-04.