Vol 26, No 3 (2021)
Research paper
Published online: 2021-03-26

open access

Page views 823
Article views/downloads 490
Get Citation

Connect on Social Media

Connect on Social Media

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer

Waqar Haque1, Vivek Verma2, Sebastian Adeberg3, Robert Rustomily4, Simon Lo5, E. Brian Butler1, Bin S. Teh1
Rep Pract Oncol Radiother 2021;26(3):341-351.


BACKGROUND: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.

MATERIALS AND METHODS: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.

RESULTS: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER–/HER2+, and ER–/HER2–, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER–/HER2– disease had worse OS than patients with ER+/HER2– disease, for both patients treated with SRS and for patients treated with WBRT.

CONCLUSIONS: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.

Article available in PDF format

View PDF Download PDF file


  1. Lee YT. Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol. 1983; 23(3): 175–180.
  2. Tsukada Y, Fouad A, Pickren JW, et al. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer. 1983; 52(12): 2349–2354, doi: 10.1002/1097-0142(19831215)52:12<2349::aid-cncr2820521231>3.0.co;2-b.
  3. Cummings MC, Simpson PT, Reid LE, et al. Metastatic progression of breast cancer: insights from 50 years of autopsies. J Pathol. 2014; 232(1): 23–31.
  4. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010; 28(20): 3271–3277.
  5. Martin AM, Cagney DN, Catalano PJ, et al. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study. JAMA Oncol. 2017; 3(8): 1069–1077.
  6. Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017; 18(8): 1049–1060.
  7. Pestalozzi B, Holmes E, Azambuja Ede, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol. 2013; 14(3): 244–248.
  8. Bilimoria KY, Stewart AK, Winchester DP, et al. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008; 15(3): 683–690.
  9. Kann BH, Park HS, Johnson SB, et al. Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in the United States. J Natl Compr Canc Netw. 2017; 15(12): 1494–1502.
  10. Haque W, Verma V, Butler EB, et al. Utilization of Stereotactic Radiosurgery for Renal Cell Carcinoma Brain Metastases. Clin Genitourin Cancer. 2018; 16(4): e935–e943.
  11. Jiang W, Haque W, Verma V, et al. Stereotactic radiosurgery for brain metastases from newly diagnosed small cell lung cancer: practice patterns and outcomes. Acta Oncol. 2019; 58(4): 491–498.
  12. Nam BH, Kim SY, Han HS, et al. Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res. 2008; 10(1): R20.
  13. Sperduto P, Kased N, Roberge D, et al. Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases. J Clin Oncol. 2012; 30(4): 419–425.
  14. Sperduto PW, Mesko S, Li J, et al. Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases From 1985 to Today. Int J Radiat Oncol Biol Phys. 2020; 107(2): 334–343.
  15. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10(11): 1037–1044.
  16. Soffietti R, Kocher M, Abacioglu UM, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011; 29(2): 134–141.
  17. Brown PD, Jaeckle K, Ballman KV, et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016; 316(4): 401–409.
  18. Yamamoto M, Serizawa T, Higuchi Y, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014; 15(4): 387–395.
  19. Thomas A, Khan SA, Chrischilles EA, et al. Initial Surgery and Survival in Stage IV Breast Cancer in the United States, 1988-2011. JAMA Surg. 2016; 151(5): 424–431.
  20. Wu SG, Zhang WW, Sun JY, et al. The survival benefits of local surgery in stage IV breast cancer are not affected by breast cancer subtypes: a population-based analysis. Oncotarget. 2017; 8(40): 67851–67860.
  21. Khan S, Zhao F, Solin L, et al. A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). J Clin Oncol. 2020; 38(18 Suppl): LBA2–LBA2.
  22. Tawbi HA, Forsyth PA, Algazi A, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012; 13(5): 459–465.
  23. Long G, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018; 19(5): 672–681.
  24. Verma V, Sprave T, Haque W, et al. A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors. J Immunother Cancer. 2018; 6(1): 128.
  25. Verma V. Economic sustainability of immune-checkpoint inhibitors: the looming threat. Nat Rev Clin Oncol. 2018; 15(12): 721–722.
  26. Magnuson WJ, Lester-Coll NH, Wu AJ, et al. Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naïve Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. J Clin Oncol. 2017; 35(10): 1070–1077.
  27. Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020; 382(7): 597–609.
  28. Haque W, Verma V, Butler EB, et al. Addition of chemotherapy to hypofractionated radiotherapy for glioblastoma: practice patterns, outcomes, and predictors of survival. J Neurooncol. 2018; 136(2): 307–315.
  29. Haque W, Verma V, Butler EB, et al. Racial and Socioeconomic Disparities in the Delivery of Immunotherapy for Metastatic Melanoma in the United States. J Immunother. 2019; 42(6): 228–235.
  30. Haque W, Verma V, Butler EB, et al. Patterns of Care and Outcomes of Hypofractionated Chemoradiation Versus Conventionally Fractionated Chemoradiation for Glioblastoma in the Elderly Population. Am J Clin Oncol. 2018; 41(2): 167–172.
  31. Haque W, Verma V, Hatch S, et al. Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat. 2018; 170(3): 559–567.
  32. Haque W, Verma V, Farach A, et al. Postmastectomy radiation therapy for triple negative, node-negative breast cancer. Radiother Oncol. 2019; 132: 48–54.

Reports of Practical Oncology and Radiotherapy