Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases

• Published in: Breast cancer research and treatment Vol. 176; no. 1; pp. 171 - 179
• Main Authors: Cagney, Daniel N., Lamba, Nayan, Montoya, Sofia, Li, Puyao, Besse, Luke, Martin, Allison M., Brigell, Rachel H., Catalano, Paul J., Brown, Paul D., Leone, Jose P., Tanguturi, Shyam K., Haas-Kogan, Daphne A., Alexander, Brian M., Lin, Nancy U., Aizer, Ayal A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2019; Springer; Springer Nature B.V
• Subjects: Brain cancer; Breast cancer; Cancer research; Cancer therapies; Care and treatment; Clinical Trial; Diseases; Epidermal growth factor; ErbB-2 protein; Medicine; Medicine & Public Health; Metastases; Metastasis; Oncology; Patients; Radiation; Relapse; Toxicity; Recurrence; Breast cancer; Brain metastases; HER2; Subtype; Radiation
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-019-05236-6

Purpose Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms. Methods We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression. Results Of the 349 patients, 116 had HR+/HER2− subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2− subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78–5.75, p  < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99–5.02, p  < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36–10.56, p  = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11–3.10, p  = 0.02). Conclusions We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.