Daniel N Cagney1, Nayan Lamba2, Sofia Montoya3, Puyao Li3, Luke Besse3, Allison M Martin3, Rachel H Brigell3, Paul J Catalano4,5, Paul D Brown6, Jose P Leone7, Shyam K Tanguturi3, Daphne A Haas-Kogan3, Brian M Alexander3, Nancy U Lin7, Ayal A Aizer3. 1. Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. dcagney@bwh.harvard.edu. 2. Harvard Medical School, Boston, MA, USA. 3. Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. 4. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 5. Department of Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 6. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Abstract
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.
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.
Entities:
Keywords:
Brain metastases; Breast cancer; HER2; Radiation; Recurrence; Subtype
Authors: Aki Morikawa; Milan Grkovski; Sujata Patil; Komal L Jhaveri; Kendrick Tang; John L Humm; Andrei Holodny; Kathryn Beal; Heiko Schöder; Andrew D Seidman Journal: Breast Cancer Res Treat Date: 2021-06-10 Impact factor: 4.872
Authors: Matthew N Mills; Chetna Thawani; Nicholas B Figura; Daniel E Oliver; Aixa E Soyano; Arnold Etame; Timothy J Robinson; James K Liu; Michael A Vogelbaum; Peter A Forsyth; Brian J Czerniecki; Hatem H Soliman; Hyo S Han; Hsiang-Hsuan Michael Yu; Kamran A Ahmed Journal: J Neurooncol Date: 2021-03-19 Impact factor: 4.130