2635 - Survival and CNS Disease Control among Patients with HER2 Low vs. HER2 High Metastatic Breast Cancer with Brain Metastases Treated with SRS
Presenter(s)
I. Messing1, M. D. Riina1, L. C. Linkowski1, X. Wang2, M. J. Kallan2, H. G. Hubbeling3, R. A. Lustig1, J. F. Dorsey1, S. Nagda1, J. D. Kolker1, G. Kurtz3, D. O'Rourke4, N. Amankulor4, C. Jackson4, I. Cajigas4, J. Y. K. Lee4, A. DeMichele5, A. Clark5, P. Shah5, M. Alonso-Basanta1, and E. S. Lebow1; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, 3Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 4Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, 5Department of Medicine, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Personalized management according to molecularly defined subgroups is critical to improving outcomes among patients with metastatic breast cancer. HER2 status has been recently expanded to include the HER2 low categorization. We hypothesized that HER2 status (HER2 low versus HER2 high) is prognostic for survival and CNS disease control after stereotactic radiosurgery (SRS) for brain metastases among patients with metastatic breast cancer.
Materials/Methods: We identified consecutive patients with HER2 low (IHC 1+ or IHC 2+ and ISH-negative) or HER2 high (IHC 3+ or ISH-positive) metastatic breast cancer with brain metastases treated with SRS at our institution. Overall survival (OS) and the cumulative incidence function from time of SRS for any CNS progression, distant progression, and leptomeningeal disease (LMD) were estimated using a non-parametric method with death as the competing event and Cox proportional hazards models were used to test clinically relevant factors.
Results: We evaluated 407 treated brain metastases among 71 patients with metastatic breast cancer, including 35 patients (49%) with HER2 low and 36 (51%) patients with HER2 high disease. Median follow up time was 16.9 months. Median age was 54 years, and 31 (44%) of patients underwent surgical resection prior to SRS. HER2 low patients were more likely to have extracranial disease at the time of SRS (94% vs 69%, p = .012) and HER2 high patients were more likely to receive HER2 directed therapy at the time of SRS (81% vs 14%, p < .001). Median OS after SRS was greater for HER2 high patients (25.7 vs 9.4 months, p < .001) with 12- and 24-month OS for HER2 low and HER2 high patients being 43%/26% and 72%/53%, respectively. The median time to LMD was shorter for patients with HER2 low versus HER2 high patients (6.3 vs 20.3 months, p = .037), and the 24-month rate of LMD was greater among patients with HER2 low disease compared to HER2 high (26% vs 11%). Risk of LMD was not significantly associated with prior surgical resection, receipt of HER2 directed therapy at SRS, or extracranial disease status. There was no difference in median time to distant (6.7 vs 7.5 months, p = .370) or CNS (6.1 vs 7.7 months, p = .286) progression for HER2 low and HER2 high patients. On univariable analysis, KPS of 60 or lower (HR 6.57, 95% CI 2.23 - 19.3, p < .001) and Graded Prognostic Assessment (GPA) (HR 0.63, 95% CI 0.47 - 0.85, p = .003) were associated with OS. Lower GPA was also associated with decreased risk of distant (HR 0.51, 95% CI 0.36 - 0.72, p < .001) and any type of CNS (HR 0.54, 95% CI 0.38 - 0.75, p < .001) progression. Two patients (2.8%) developed symptomatic radiation necrosis.
Conclusion: HER2 status was prognostic among patients with metastatic breast cancer brain metastases treated with SRS. Patients with HER2 low disease had worse survival and increased risk of LMD compared to patients with HER2 high disease. Rates of symptomatic toxicity were low among all patients.