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Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer

Jennifer F De Los Santos, MD
Section Editors
Daniel F Hayes, MD
David E Wazer, MD
Deputy Editor
Sadhna R Vora, MD


Globally, breast cancer is the most frequently diagnosed and the leading cause of cancer death in women. For women with newly diagnosed, non-metastatic breast cancer, treatment consists of a multidisciplinary approach that involves input from surgery, radiation oncology, and medical oncology.

The objective of adjuvant radiation therapy (RT) is to eradicate any tumor deposits remaining following surgery for patients treated by either breast-conserving surgery or mastectomy [1]. Doing so reduces risk of locoregional recurrence (LRR) and improves breast cancer-specific and overall survivals.

This topic will review the role of adjuvant RT. Other aspects of the management of women with newly diagnosed, non-metastatic breast cancer are covered separately. (See "Overview of the treatment of newly diagnosed, non-metastatic breast cancer".)


Approach — For most women treated with breast-conserving surgery, we administer whole breast radiation therapy (WBRT). This includes women treated with neoadjuvant therapy, even if they experienced a complete response to treatment.

As discussed below, adjuvant WBRT reduces the risks of recurrence and breast cancer death. (See 'Whole breast radiation therapy' below.)


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Literature review current through: Dec 2016. | This topic last updated: Thu Jan 05 00:00:00 GMT+00:00 2017.
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  1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, et al. 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; 378:1707.
  2. Kunkler IH, Williams LJ, Jack WJ, et al. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol 2015; 16:266.
  3. Meric F, Buchholz TA, Mirza NQ, et al. Long-term complications associated with breast-conservation surgery and radiotherapy. Ann Surg Oncol 2002; 9:543.
  4. Jacobson G, Bhatia S, Smith BJ, et al. Randomized trial of pentoxifylline and vitamin E vs standard follow-up after breast irradiation to prevent breast fibrosis, evaluated by tissue compliance meter. Int J Radiat Oncol Biol Phys 2013; 85:604.
  5. Smith BD, Bentzen SM, Correa CR, et al. Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys 2011; 81:59.
  6. James ML, Lehman M, Hider PN, et al. Fraction size in radiation treatment for breast conservation in early breast cancer. Cochrane Database Syst Rev 2010; :CD003860.
  7. Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013; 14:1086.
  8. Shaitelman SF, Schlembach PJ, Arzu I, et al. Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial. JAMA Oncol 2015; 1:931.
  9. Jagsi R, Griffith KA, Boike TP, et al. Differences in the Acute Toxic Effects of Breast Radiotherapy by Fractionation Schedule: Comparative Analysis of Physician-Assessed and Patient-Reported Outcomes in a Large Multicenter Cohort. JAMA Oncol 2015; 1:918.
  10. Romestaing P, Lehingue Y, Carrie C, et al. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol 1997; 15:963.
  11. Bartelink H, Horiot JC, Poortmans P, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 2001; 345:1378.
  12. Vrieling C, Collette L, Fourquet A, et al. The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC 'boost vs. no boost' trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. Radiother Oncol 2000; 55:219.
  13. Bartelink H, Horiot JC, Poortmans PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 2007; 25:3259.
  14. Bartelink H, Maingon P, Poortmans P, 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; 16:47.
  15. Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys 2009; 74:987.
  16. American Society of Breast Surgeons, Consensus statement for Accelerated Partial Breast Irradiation www.breastsurgeons.org (Accessed on July 27, 2010).
  17. Arthur DW, Vicini FA, Kuske RR, et al. Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy 2003; 2:124.
  18. Wilder RB, Curcio LD, Khanijou RK, et al. Results with accelerated partial breast irradiation in terms of estrogen receptor, progesterone receptor, and human growth factor receptor 2 status. Int J Radiat Oncol Biol Phys 2010; 78:799.
  19. Valachis A, Mauri D, Polyzos NP, et al. Partial breast irradiation or whole breast radiotherapy for early breast cancer: a meta-analysis of randomized controlled trials. Breast J 2010; 16:245.
  20. Strnad V, Ott OJ, Hildebrandt G, 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 2016; 387:229.
  21. Polgár C, Fodor J, Major T, et al. Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial. Int J Radiat Oncol Biol Phys 2007; 69:694.
  22. Ribeiro GG, Magee B, Swindell R, et al. The Christie Hospital breast conservation trial: an update at 8 years from inception. Clin Oncol (R Coll Radiol) 1993; 5:278.
  23. Dodwell DJ, Dyker K, Brown J, et al. A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer. Clin Oncol (R Coll Radiol) 2005; 17:618.
  24. Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer 2015; 51:451.
  25. Strnad V, Polgar C, Ott O, et al. Accelerated Partial Breast Irradiation Using Sole Interstitial Multicatheter Brachytherapy vs Whole Breast Irradiation for Early Breast Cancer: 5-year Results of a Randomized Phase III Trial – Part I: Local Control and Survival Results. American Society of Radiation Oncology (ASTRO) 2015; LBA 7.
  26. Presley CJ, Soulos PR, Herrin J, et al. Patterns of use and short-term complications of breast brachytherapy in the national medicare population from 2008-2009. J Clin Oncol 2012; 30:4302.
  27. Chao KK, Vicini FA, Wallace M, et al. Analysis of treatment efficacy, cosmesis, and toxicity using the MammoSite breast brachytherapy catheter to deliver accelerated partial-breast irradiation: the william beaumont hospital experience. Int J Radiat Oncol Biol Phys 2007; 69:32.
  28. Hepel JT, Tokita M, MacAusland SG, et al. Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 2009; 75:1290.
  29. Chen PY, Vicini FA, Benitez P, et al. Long-term cosmetic results and toxicity after accelerated partial-breast irradiation: a method of radiation delivery by interstitial brachytherapy for the treatment of early-stage breast carcinoma. Cancer 2006; 106:991.
  30. Smith GL, Xu Y, Buchholz TA, et al. Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer. JAMA 2012; 307:1827.
  31. Olivotto IA, Whelan TJ, Parpia S, et al. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 2013; 31:4038.
  32. Julian TB, Costantino JP, Vicini FA, et al. Early Toxicity Results with 3-D Conformal External Beam Therapy (CEBT) from the NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial. Int J Radiat Oncol Biol Phys 2011; 81:S7.
  33. Norris D, Julian T. Update on the NSABP B39/ RTOG 0413 Clinical Trial. Comparing Partial to Whole Breast Irradiation Therapy. http://accc-cancer.org/oncology_issues/articles/janfeb08/norris.pdf (Accessed on June 10, 2011).
  34. Trial details available at www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=409590&version=patient&protocolsearchid=2096975 (Accessed on February 08, 2006).
  35. Poortmans PM, Collette S, Kirkove C, et al. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med 2015; 373:317.
  36. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med 2015; 373:307.
  37. Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986; 73:580.
  38. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010; 252:426.
  39. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011; 305:569.
  40. Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 2013; 14:297.
  41. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol 2014; 32:3600.
  42. Swisher SK, Vila J, Tucker SL, et al. Locoregional Control According to Breast Cancer Subtype and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Undergoing Breast-conserving Therapy. Ann Surg Oncol 2016; 23:749.
  43. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet 2014; 383:603.
  44. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol 2013; 14:1269.
  45. Fisher B, Bryant J, Dignam JJ, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 2002; 20:4141.
  46. Pötter R, Gnant M, Kwasny W, et al. Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer. Int J Radiat Oncol Biol Phys 2007; 68:334.
  47. Fyles AW, Manchul L, McCready D, et al. Long-term results of a randomized trial of tamoxifen with or without radiation in women over 50 years of age with T1/2 breast cancer (abstract). Int J Radiat Oncol Biol Phys 2006; 66:S4.
  48. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 2013; 31:2382.
  49. Tinterri C, Gatzemeier W, Zanini V, et al. Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial. Breast 2009; 18:373.
  50. Ford HT, Coombes RC, Gazet JC, et al. Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer. Ann Oncol 2006; 17:401.
  51. van de Water W, Bastiaannet E, Scholten AN, et al. Breast-conserving surgery with or without radiotherapy in older breast patients with early stage breast cancer: a systematic review and meta-analysis. Ann Surg Oncol 2014; 21:786.
  52. Albert JM, Pan IW, Shih YC, et al. Effectiveness of radiation for prevention of mastectomy in older breast cancer patients treated with conservative surgery. Cancer 2012; 118:4642.
  53. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087.
  54. Danish Breast Cancer Cooperative Group, Nielsen HM, Overgaard M, et al. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol 2006; 24:2268.
  55. Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005; 97:116.
  56. Pierce LJ, Oberman HA, Strawderman MH, Lichter AS. Microscopic extracapsular extension in the axilla: is this an indication for axillary radiotherapy? Int J Radiat Oncol Biol Phys 1995; 33:253.
  57. Recht A, Comen EA, Fine RE, et al. Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. Pract Radiat Oncol 2016; 6:e219.
  58. EBCTCG (Early Breast Cancer Trialists' Collaborative Group), McGale P, Taylor C, 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; 383:2127.
  59. Huo D, Hou N, Jaskowiak N, et al. Use of Postmastectomy Radiotherapy and Survival Rates for Breast Cancer Patients with T1-T2 and One to Three Positive Lymph Nodes. Ann Surg Oncol 2015; 22:4295.
  60. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997; 337:949.
  61. Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999; 353:1641.
  62. Wang J, Shi M, Ling R, et al. Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial. Radiother Oncol 2011; 100:200.
  63. Liu J, Mao K, Jiang S, et al. The role of postmastectomy radiotherapy in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB. Oncotarget 2016; 7:24848.
  64. Huang EH, Tucker SL, Strom EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol 2004; 22:4691.
  65. Abdel-Wahab M, Wolfson A, Raub W, et al. The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation. Int J Radiat Oncol Biol Phys 1998; 40:875.
  66. Buchholz TA, Tucker SL, Masullo L, et al. Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. J Clin Oncol 2002; 20:17.
  67. Ring A, Webb A, Ashley S, et al. Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer? J Clin Oncol 2003; 21:4540.
  68. Panades M, Olivotto IA, Speers CH, et al. Evolving treatment strategies for inflammatory breast cancer: a population-based survival analysis. J Clin Oncol 2005; 23:1941.
  69. McGuire SE, Gonzalez-Angulo AM, Huang EH, et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys 2007; 68:1004.
  70. Pierce LJ, Lippman M, Ben-Baruch N, et al. The effect of systemic therapy on local-regional control in locally advanced breast cancer. Int J Radiat Oncol Biol Phys 1992; 23:949.
  71. Huang EH, Tucker SL, Strom EA, et al. Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys 2005; 62:351.
  72. Mamounas EP, Anderson SJ, Dignam JJ, 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; 30:3960.
  73. Thorsen LB, Offersen BV, Danø H, et al. DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer. J Clin Oncol 2016; 34:314.
  74. Chang JS, Park W, Kim YB, et al. Long-term survival outcomes following internal mammary node irradiation in stage II-III breast cancer: results of a large retrospective study with 12-year follow-up. Int J Radiat Oncol Biol Phys 2013; 86:867.
  75. Hennequin C, Bossard N, Servagi-Vernat S, 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; 86:860.
  76. Fisher B, Dignam J, Mamounas EP, et al. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 1996; 14:1982.
  77. Fisher B, Dignam J, Bryant J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529.
  78. Dalberg K, Johansson H, Johansson U, Rutqvist LE. A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group. Cancer 1998; 82:2204.
  79. Bellon JR, Come SE, Gelman RS, et al. Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial. J Clin Oncol 2005; 23:1934.
  80. Valakh V, Trombetta MG, Werts ED, et al. Influence of concurrent anastrozole on acute and late side effects of whole breast radiotherapy. Am J Clin Oncol 2011; 34:245.
  81. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 2005; 23:7811.
  82. Halyard, MY, Pisansky, TM, Solin, LJ, et al. Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831. J Clin Oncol 2006; 24s:abstr 523.
  83. Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 1997; 386:804.
  84. Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002; 108:171.
  85. Pellegrini L, Yu DS, Lo T, et al. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 2002; 420:287.
  86. Pierce LJ, Strawderman M, Narod SA, et al. Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 2000; 18:3360.
  87. Shanley S, McReynolds K, Ardern-Jones A, et al. Late toxicity is not increased in BRCA1/BRCA2 mutation carriers undergoing breast radiotherapy in the United Kingdom. Clin Cancer Res 2006; 12:7025.
  88. Morris MM, Powell SN. Irradiation in the setting of collagen vascular disease: acute and late complications. J Clin Oncol 1997; 15:2728.
  89. Lin A, Abu-Isa E, Griffith KA, Ben-Josef E. Toxicity of radiotherapy in patients with collagen vascular disease. Cancer 2008; 113:648.
  90. Chen AM, Obedian E, Haffty BG. Breast-conserving therapy in the setting of collagen vascular disease. Cancer J 2001; 7:480.
  91. De Naeyer B, De Meerleer G, Braems S, et al. Collagen vascular diseases and radiation therapy: a critical review. Int J Radiat Oncol Biol Phys 1999; 44:975.