Stereotactic Radiation Therapy Demonstrates Improved Tumor Control Versus Whole Brain Radiation Therapy in Breast Cancer Brain Metastasis for All Receptor Subtypes

Abstract

Breast cancer receptor status (RS) has implications for patient overall survival (OS), regional recurrence (RR), and distant metastasis. However, little is known about whether RS of breast cancer brain metastasis (BM) impacts clinical outcomes, particularly related to radiation therapy response (RTR). Our study aims to evaluate whether RS affects RTR, brain RR following radiation therapy (RT), and OS in patients with BM. Forty-two patients completed 106 breast cancer BM treatments with any RT modality, including stereotactic radiosurgery (SRS) 12-20 Gy, stereotactic radiation therapy (SRT) majority 5 Gy x 5 or 3 Gy x 10 (range 15 - 50.4 Gy, 5 - 28 fractions), post-resection SRS/SRT, or whole brain radiation therapy (WBRT) majority 2.5-3 Gy x 10-15 fractions (range 20 - 40 Gy, 5 - 20 fractions). RTR was evaluated as length of progression-free survival for treated lesion(s). Lesions were considered progression-free if they partially or completely responded, or remained stable following RT. OS was analyzed for all patients and by RS type. RTR and RR were analyzed for each treatment course, based on RS and treatment modality. SRS and SRT were treated as one modality (SRS/SRT). Analysis was conducted using Kaplan-Meier curves and COX proportional model analysis. Median OS from date of BM diagnosis was 31.33 months. Survival at 1, 2, 3, and 5 years was 84.1%, 75.2%, 37.9%, and 10.8%, respectively. ER-negative BM patients had significantly decreased OS (p = 0.024); however ER status did not significantly impact RTR (p = 0.306) or RR (p = 0.318). PR status did not affect OS, RTR, or RR (p = 0.173, p = 0.852, p = 0.207, respectively). Similarly, HER 2 status alone did not affect OS, RTR, or RR (p = 0.561, p = 0.988, p = 0.211, respectively). Compared to all other RS combinations, triple negative (TN) patients had a strong trend for poorer OS (p = 0.063). However, there were no significant differences in RTR (p = 0.157) or RR (p = 0.655). Among RT modalities, lesions treated with SRS/SRT exhibited significantly better RTR (p = 0.0082) and significantly less likelihood of RR (p = 0.032) compared to WBRT. ER-negative and TN breast cancers classically have poorer response to therapies, yet for BM, these patients exhibited comparable local and regional control after RT compared to other receptor combinations. While studies have posited that these tumors are less radiosensitive at the breast, our results suggest that RS does not affect BM radiosensitivity in these patients. This result suggests that the poorer OS of ER-negative and TN patients may be due to extracranial disease. Furthermore, breast cancer BM treated with SRS/SRT demonstrated significantly improved radiation response and lower probability of RR compared to WBRT. These findings suggest that for breast cancer patients, including ER-negative and TN subtypes, SRS/SRT may be an effective therapy for brain metastases.