Radiation Therapy for Triple-Negative Breast Cancer

  • Suzanne B. EvansEmail author
  • Bruce G. Haffty


The distinct natural history of triple-negative breast cancer and predilection for recurrence make this disease challenging to manage from a multimodality standpoint. Radiation therapy remains an integral part of the management of TNBC that results in improved outcomes. The available data regarding radiation therapy in the setting of TNBC is reviewed. There is insufficient data to allow for tailoring of the locoregional management decisions based on subtype alone. These authors advocate for the use of radiation along traditional pathways, with caution to be employed before considering treatment strategies that are more novel.


Radiation therapy Triple-negative breast cancer Breast conservation therapy 


  1. 1.
    Fisher B, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41.CrossRefPubMedGoogle Scholar
  2. 2.
    Early Breast Cancer Trialists’ Collaborative Group. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16.CrossRefGoogle Scholar
  3. 3.
    McGale P, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935):2127–35.CrossRefPubMedGoogle Scholar
  4. 4.
    Zaky SS, et al. The negative effect of triple-negative breast cancer on outcome after breast-conserving therapy. Ann Surg Oncol. 2011;18(10):2858–65.CrossRefPubMedGoogle Scholar
  5. 5.
    Gonzalez-Angulo AM, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. 2011;17(5):1082–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kwan ML, et al. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res. 2009;11(3):R31.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Carey LA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492–502.CrossRefPubMedGoogle Scholar
  8. 8.
    Lakhani SR, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol. 2002;20(9):2310–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Moran MS, et al. Long-term outcomes and clinicopathologic differences of African-American versus white patients treated with breast conservation therapy for early-stage breast cancer. Cancer. 2008;113(9):2565–74.CrossRefPubMedGoogle Scholar
  10. 10.
    Ray M, Polite BN. Triple-negative breast cancers: a view from 10,000 feet. Cancer J. 2010;16(1):17–22.CrossRefPubMedGoogle Scholar
  11. 11.
    Widschwendter P, et al. The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial. Breast Cancer Res. 2015;17:129.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Heitz F, et al. Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases. Eur J Cancer. 2009;45(16):2792–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Dent R, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.CrossRefPubMedGoogle Scholar
  14. 14.
    Elias AD. Triple-negative breast cancer: a short review. Am J Clin Oncol. 2010;33(6):637–45.CrossRefPubMedGoogle Scholar
  15. 15.
    Punglia, R.S, et al. Local therapy and survival in breast cancer. N Engl J Med. 2007;356(23):2399–405.CrossRefGoogle Scholar
  16. 16.
    Haffty BG, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006;24(36):5652–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Nguyen PL, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Millar EK, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol. 2009;27(28):4701–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Lowery AJ, et al. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133(3):831–41.CrossRefPubMedGoogle Scholar
  20. 20.
    Abdulkarim BS, et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol. 2011;29(21):2852–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kindts I, et al. Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival. The Breast. 32:18–25.Google Scholar
  22. 22.
    Moran MS, et al. Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer. Ann Surg Oncol. 2014;21(3):704–16.CrossRefPubMedGoogle Scholar
  23. 23.
    Pilewskie M, et al. Effect of margin width on local recurrence in triple-negative breast cancer patients treated with breast-conserving therapy. Ann Surg Oncol. 2014;21(4):1209–14.CrossRefPubMedGoogle Scholar
  24. 24.
    Punglia RS, et al. Impact of interval from breast conserving surgery to radiotherapy on local recurrence in older women with breast cancer: retrospective cohort analysis. BMJ. 2010;340Google Scholar
  25. 25.
    Huang J, et al. Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol. 2003;21(3):555–63.CrossRefPubMedGoogle Scholar
  26. 26.
    Gupta S, et al. The effect of waiting times for postoperative radiotherapy on outcomes for women receiving partial mastectomy for breast cancer: a systematic review and meta-analysis. Clinical Oncology. 28(12):739–49.Google Scholar
  27. 27.
    Vrieling C, et al. Prognostic factors for local control in breast cancer after long-term follow-up in the EORTC boost vs no boost trial: a randomized clinical trial. JAMA Oncol. 2017;3(1):42–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Bartelink H, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 2015;16(1):47–56.CrossRefPubMedGoogle Scholar
  29. 29.
    Offersen BV, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol. 2015;114(1):3–10.CrossRefPubMedGoogle Scholar
  30. 30.
    The S.T.G, et al. The UK Standardisation of Breast Radiotherapy (START) TTrial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 371(9618):1098–107.Google Scholar
  31. 31.
    Whelan TJ, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–20.CrossRefPubMedGoogle Scholar
  32. 32.
    Hypofractionated radiotherapy for breast cancer. N Engl J Med. 2010;362(19):1843–4.Google Scholar
  33. 33.
    Bane AL, et al. Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy. Ann Oncol. 2014;25(5):992–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Smith BD, et al. Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;81(1):59–68.CrossRefPubMedGoogle Scholar
  35. 35.
    Anderson BM, et al. Locoregional recurrence by molecular subtype after multicatheter interstitial accelerated partial breast irradiation: results from the Pooled Registry of Multicatheter Interstitial Sites research group. Brachytherapy. 2016;15(6):788–95.CrossRefPubMedGoogle Scholar
  36. 36.
    Wilkinson JB, et al. Outcomes according to breast cancer subtype in patients treated with accelerated partial breast irradiation. Clin Breast Cancer. 2017;17(1):55–60.CrossRefPubMedGoogle Scholar
  37. 37.
    Strnad V, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 387(10015):229–38.Google Scholar
  38. 38.
    Ferlay J, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.CrossRefPubMedGoogle Scholar
  39. 39.
    Konigsberg R, et al. Breast cancer subtypes in patients aged 70 years and older. Cancer Invest. 2016;34(5):197–204.CrossRefPubMedGoogle Scholar
  40. 40.
    Wildiers H, et al. Relationship between age and axillary lymph node involvement in women with breast cancer. J Clin Oncol. 2009;27(18):2931–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Bastiaannet E, et al. Lack of survival gain for elderly women with breast cancer. Oncologist. 2011;16(4):415–23.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Barthelemy P, et al. Adjuvant chemotherapy in elderly patients with early breast cancer. Impact of age and comprehensive geriatric assessment on tumor board proposals. Crit Rev Oncol Hematol. 2011;79(2):196–204.CrossRefPubMedGoogle Scholar
  43. 43.
    Lin NU, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012;118(22):5463–72.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Gangi A, et al. Triple-negative breast cancer is not associated with increased likelihood of nodal metastases. Ann Surg Oncol. 2014;21(13):4098–103.CrossRefPubMedGoogle Scholar
  45. 45.
    Giuliano AE, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann Surg. 2016;264(3):413–20.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hennequin C, et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys. 2013;86(5):860–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Whelan TJ, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–16.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Poortmans PM, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373(4):317–27.CrossRefPubMedGoogle Scholar
  50. 50.
    Liedtke C, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.CrossRefPubMedGoogle Scholar
  51. 51.
    Jwa E, et al. Locoregional recurrence by tumor biology in breast cancer patients after preoperative chemotherapy and breast conservation treatment. Cancer Res Treat. 2016;48(4):1363–72.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Mamounas EP, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30(32):3960–6.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kyndi M, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26(9):1419–26.CrossRefPubMedGoogle Scholar
  54. 54.
    Kyndi M, et al. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol. 2009;90(1):74–9.CrossRefPubMedGoogle Scholar
  55. 55.
    O’Rorke MA, et al. The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: a systematic review and meta-analysis of 5507 patients. Cancer Treat Rev. 47:12–21.Google Scholar
  56. 56.
    Truong PT, et al. Is biological subtype prognostic of locoregional recurrence risk in women with pT1-2N0 breast cancer treated with mastectomy? Int J Radiat Oncol Biol Phys. 2014;88(1):57–64.CrossRefPubMedGoogle Scholar
  57. 57.
    Chen X, et al. Radiotherapy can improve the disease-free survival rate in triple-negative breast cancer patients with T1-T2 disease and one to three positive lymph nodes after mastectomy. Oncologist. 2013;18(2):141–7.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Wang J, et al. Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial. Radiother Oncol. 2011;100(2):200–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Therapeutic RadiologyYale University School of MedicineNew HavenUSA
  2. 2.Department of Radiation OncologyRutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical SchoolNew BrunswickUSA

Personalised recommendations