BMRK-06 Brain Metastasis Free Survival of Her2 Low and Her2 Zero Triple Negative Metastatic Breast Cancer: A Wilmot Cancer Institute Experience (The Herzelo-TNBC Study)

BACKGROUND It is unclear if level of HER2 expression in metastasis triple negative breast cancer (mTNBC) affects risk of CNS metastasis (CNS-failure). Objective: to compare risk of CNS-failure between HER2-Low [immunohistochemistry 2+ (with ISH-negative) or 1+) and HER2-Zero (immunohistochemistry 0) mTNBC. METHOD This is a single-institution retrospective study of mTNBC diagnosed January 2010-January 2022. CNS metastasis at the time of mTNBC diagnosis were excluded. Overall survival (OS) and cause-specific risk of CNS-failure was described using Kaplan-Meier method stratified by HER2 status and compared using log-rank test. A multivariate Cox model was used to estimate hazard ratio (HR) for OS and cause-specific CNS-failure. Because death prior to CNS-failure is a competing-risk, cumulative incidence of CNS failure by HER2 status was estimated and compared using Gray’s test. To adjust for other covariates, Fine-Gray model was used to estimate sub-distribution hazard. Significance level for this study was 10%. HRs were reported with 90% confidence intervals (CI). RESULTS As of August 2023, 31 CNS-failures and 68 deaths were observed among 86 patients (57 HER2-Low, 29 HER2-Zero) enrolled. Baseline variables were similar in 2 groups except a higher proportion of bone metastasis in HER2-Low group (62% vs 42%, p=0.08). OS was not different between 2 groups in an unadjusted analysis [median(mo): HER2-Low=15.9 vs HER2-Zero =17.8, p=0.51], and in Cox model (HR=1.12, 90%CI=0.72-1.73, p=0.68). Cause-Specific analysis: HER2-Low group had shorter time to CNS-failure in unadjusted [median(mo): HER2-Low=22.0 vs HER2-Zero =33.4, p=0.082] and in Cox model (HR=2.29, 90%CI=1.20-4.37, p=0.035). Competing-Risk analysis: HER2-Low group had higher cumulative risk of CNS-failure in unadjusted analysis [median(mo): HER2-Low=34.5 vs HER2-Zero =not reached, p=0.049] and in Fine-Gray model (HR=2.69, 90%CI=1.42-5.12, p=0.011). CONCLUSION This single-institution study shows a higher risk of CNS-failure in HER2-Low compared to HER2-Zero mTNBC, even after accounting for death as competing risk.