Stereotactic Radiosurgery Outcomes on Brain Metastases in HER-2 Low Versus HER-2 High Breast Cancer
Abstract/Description/Artist Statement
Purpose/Objectives: HER2 low breast cancer is a newly defined and common subtype with limited data regarding central nervous system (CNS) outcomes following stereotactic radiosurgery (SRS). We evaluated whether HER2 status is prognostic for overall survival (OS) and CNS disease control among patients with breast cancer brain metastases treated with SRS.
Materials/Methods: We performed a retrospective cohort study of patients with metastatic breast cancer treated with SRS for brain metastases from February 1, 2014, to January 31, 2025. HER2 high disease was defined as immunohistochemistry (IHC) 3+ or IHC 2+ with in situ hybridization (ISH) positivity, and HER2 low as IHC 1+ or 2+ with ISH negativity. The primary endpoint was OS from SRS. Secondary endpoints included any CNS progression, local progression, distant progression, and leptomeningeal disease (LMD). OS was analyzed using Kaplan–Meier estimates and multivariable Cox regression. CNS outcomes were evaluated using cumulative incidence with death as a competing risk, Gray’s test, and multivariable Fine–Gray regression.
Results: Among 180 patients (HER2 low, 85 [47.2%]; HER2 high, 95 [52.8%]), median follow up was 15.7 months (range, 0.5–132.3), and 133 deaths (73.9%) had occurred at analysis. Survival was significantly longer in HER2 high compared with HER2 low disease (median OS 29.6 vs 11.3 months; log rank p < .0001), with corresponding 12 month OS rates of 76.7% and 48.8%. On multivariable Cox regression, HER2 high status remained independently associated with improved OS (HR 0.37; 95% CI, 0.20–0.69; p = .0017), whereas prior whole brain radiotherapy and greater intracranial disease burden were associated with worse survival. With death treated as a competing risk, 12 and 24 month cumulative incidence was 54.9% and 65.9% for any CNS progression, 12.9% and 17.8% for local progression, 49.8% and 60.0% for distant progression, and 16.2% and 23.7% for leptomeningeal disease, without significant differences by HER2 status. Salvage SRS was more frequently utilized among HER2 high versus HER2 low patients (50.5% vs 34.1%; p = .0183). Among patients not receiving HER2 directed therapy at SRS, HER2 high disease was associated with lower cumulative incidence of any CNS and distant CNS progression (Gray p = .0349 and p = .0034); however, HER2 status was not independently associated with CNS outcomes in multivariable Fine–Gray models.
Conclusions: HER2 high status was independently associated with improved OS following SRS for breast cancer brain metastases, whereas CNS progression and LMD risks were similar across HER2 subtypes after accounting for competing risks. Increased utilization of salvage SRS among HER2 high patients likely reflects longer survival and greater opportunity for iterative CNS directed management.
Faculty Advisor/Mentor
Emily Lebow
Faculty Advisor/Mentor Email
emily.lebow@pennmedicine.upenn.edu
Faculty Advisor/Mentor Department
Radiation Oncology
College/School Affiliation
Eastern Virginia School of Medicine
Student Level Group
Medical
Presentation Type
Poster
Stereotactic Radiosurgery Outcomes on Brain Metastases in HER-2 Low Versus HER-2 High Breast Cancer
Purpose/Objectives: HER2 low breast cancer is a newly defined and common subtype with limited data regarding central nervous system (CNS) outcomes following stereotactic radiosurgery (SRS). We evaluated whether HER2 status is prognostic for overall survival (OS) and CNS disease control among patients with breast cancer brain metastases treated with SRS.
Materials/Methods: We performed a retrospective cohort study of patients with metastatic breast cancer treated with SRS for brain metastases from February 1, 2014, to January 31, 2025. HER2 high disease was defined as immunohistochemistry (IHC) 3+ or IHC 2+ with in situ hybridization (ISH) positivity, and HER2 low as IHC 1+ or 2+ with ISH negativity. The primary endpoint was OS from SRS. Secondary endpoints included any CNS progression, local progression, distant progression, and leptomeningeal disease (LMD). OS was analyzed using Kaplan–Meier estimates and multivariable Cox regression. CNS outcomes were evaluated using cumulative incidence with death as a competing risk, Gray’s test, and multivariable Fine–Gray regression.
Results: Among 180 patients (HER2 low, 85 [47.2%]; HER2 high, 95 [52.8%]), median follow up was 15.7 months (range, 0.5–132.3), and 133 deaths (73.9%) had occurred at analysis. Survival was significantly longer in HER2 high compared with HER2 low disease (median OS 29.6 vs 11.3 months; log rank p < .0001), with corresponding 12 month OS rates of 76.7% and 48.8%. On multivariable Cox regression, HER2 high status remained independently associated with improved OS (HR 0.37; 95% CI, 0.20–0.69; p = .0017), whereas prior whole brain radiotherapy and greater intracranial disease burden were associated with worse survival. With death treated as a competing risk, 12 and 24 month cumulative incidence was 54.9% and 65.9% for any CNS progression, 12.9% and 17.8% for local progression, 49.8% and 60.0% for distant progression, and 16.2% and 23.7% for leptomeningeal disease, without significant differences by HER2 status. Salvage SRS was more frequently utilized among HER2 high versus HER2 low patients (50.5% vs 34.1%; p = .0183). Among patients not receiving HER2 directed therapy at SRS, HER2 high disease was associated with lower cumulative incidence of any CNS and distant CNS progression (Gray p = .0349 and p = .0034); however, HER2 status was not independently associated with CNS outcomes in multivariable Fine–Gray models.
Conclusions: HER2 high status was independently associated with improved OS following SRS for breast cancer brain metastases, whereas CNS progression and LMD risks were similar across HER2 subtypes after accounting for competing risks. Increased utilization of salvage SRS among HER2 high patients likely reflects longer survival and greater opportunity for iterative CNS directed management.