Annals of Surgical Oncology

, Volume 22, Issue 5, pp 1434–1440 | Cite as

Influence of Neoadjuvant Chemotherapy on Radiotherapy for Breast Cancer

  • Amit K. GargEmail author
  • Thomas A. Buchholz
Breast Oncology


Neoadjuvant chemotherapy is a standard treatment option for patients with locally advanced operable breast cancer and is increasingly used in early breast cancer. Initial randomized trials of neoadjuvant chemotherapy established equivalency to adjuvant chemotherapy in terms of survival, but they also demonstrated improved rates of breast conservation and the ability to modify the risk of locoregional recurrence after a favorable response to chemotherapy. High-quality nonrandomized data have helped to tailor radiotherapy treatment recommendations after neoadjuvant chemotherapy and breast-conserving surgery or mastectomy. Results from an ongoing phase 3 randomized trial (NSABP B-51/RTOG 1304) will help to clarify the value of locoregional radiotherapy for patients with clinical N1 disease that becomes node negative after neoadjuvant chemotherapy.



The authors declare no conflict of interest.


  1. 1.
    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;30:3960–6.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.PubMedGoogle Scholar
  3. 3.
    Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001:96–102.Google Scholar
  4. 4.
    Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672–85.PubMedGoogle Scholar
  5. 5.
    Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMedGoogle Scholar
  6. 6.
    Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. N Engl J Med. 1995;333:1444–55.Google Scholar
  7. 7.
    Early Breast Cancer Trialists’ Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355(9217):1757–70.Google Scholar
  8. 8.
    Darby S, McGale P, Correca C, et al; 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.CrossRefPubMedGoogle Scholar
  9. 9.
    Overgaard M, Hansen PS, Overgaard J, et al; Danish Breast Cancer Cooperative Group 82b Trial. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med. 1997;337:949–55.CrossRefPubMedGoogle Scholar
  10. 10.
    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(9165):1641–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337:956–62.CrossRefPubMedGoogle Scholar
  12. 12.
    Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483–93.PubMedGoogle Scholar
  13. 13.
    Akay CL, Meric-Bernstam F, Hunt KK, et al. Evaluation of the MD Anderson Prognostic Index for local-regional recurrence after breast conserving therapy in patients receiving neoadjuvant chemotherapy. Ann Surg Oncol. 2012;19:901–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Buchholz TA, Katz A, Strom EA, et al. Pathologic tumor size and lymph node status predict for different rates of locoregional recurrence after mastectomy for breast cancer patients treated with neoadjuvant versus adjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2002;53:880–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Buchholz TA, Tucker SL, Masullo L, et al. Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation. J Clin Oncol. 2002;20:17–23.CrossRefPubMedGoogle Scholar
  16. 16.
    Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience. J Clin Oncol. 2004;22:2303–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Garg AK, Oh JL, Oswald MJ, et al. Effect of postmastectomy radiotherapy in patients <35 years old with stage II–III breast cancer treated with doxorubicin-based neoadjuvant chemotherapy and mastectomy. Int J Radiat Oncol Biol Phys. 2007;69:1478–83.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Garg AK, Strom EA, McNeese MD, et al. T3 disease at presentation or pathologic involvement of four or more lymph nodes predict for locoregional recurrence in stage II breast cancer treated with neoadjuvant chemotherapy and mastectomy without radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59:138–45.CrossRefPubMedGoogle Scholar
  19. 19.
    Huang EH, Strom EA, Perkins GH, et al. Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score. Int J Radiat Oncol Biol Phys. 2006;66:352–7.CrossRefPubMedGoogle Scholar
  20. 20.
    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;22:4691–9.CrossRefPubMedGoogle Scholar
  21. 21.
    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;68:1004–9.CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Nagar H, Mittendorf EA, Strom EA, et al. Local-regional recurrence with and without radiation therapy after neoadjuvant chemotherapy and mastectomy for clinically staged T3N0 breast cancer. Int J Radiat Oncol Biol Phys. 2011;81:782–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Boughey JC, Peintinger F, Meric-Bernstam F, et al. Impact of preoperative versus postoperative chemotherapy on the extent and number of surgical procedures in patients treated in randomized clinical trials for breast cancer. Ann Surg. 2006;244:464–70.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Mieog JS, van der Hage JA, van de Velde CJ. Neoadjuvant chemotherapy for operable breast cancer. Br J Surg. 2007;94:1189–200.CrossRefPubMedGoogle Scholar
  25. 25.
    Mittendorf EA, Buchholz TA, Tucker SL, et al. Impact of chemotherapy sequencing on local-regional failure risk in breast cancer patients undergoing breast-conserving therapy. Ann Surg. 2013;257:173–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Buzdar AU, Valero V, Ibrahim NK, et al. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2–positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007;13:228–33.CrossRefPubMedGoogle Scholar
  27. 27.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377–84.CrossRefPubMedGoogle Scholar
  28. 28.
    Kuerer HM, Sahin AA, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230:72–8.CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Mamounas EP, Brown A, Anderson S, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005;23:2694–702.CrossRefPubMedGoogle Scholar
  30. 30.
    Marks LB, Prosnitz LR. Reducing local therapy in patients responding to preoperative systemic therapy: are we outsmarting ourselves?. J Clin Oncol. 2014;32:491–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Whelan TJ, Olivotto I, Ackerman I, et al. NCIC-CTG MA.20: an intergroup trial of regional nodal irradiation in early breast cancer. J Clin Oncol. 2011;29(Suppl):LBA1003.Google Scholar
  32. 32.
    Le Scodan R, Selz J, Stevens D, et al. Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. Int J Radiat Oncol Biol Phys. 2012;82:e1–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Shim SJ, Park W, Huh SJ, et al. The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). Int J Radiat Oncol Biol Phys. 2014;88:65–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455–61.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–18.CrossRefPubMedGoogle Scholar
  36. 36.
    Wang X, Pan T, Pinnix C, et al. Cardiac motion during deep-inspiration breath-hold: implications for breast cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82:708–14.CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Buchholz TA, Lehman CD, Harris JR, et al. Statement of the science concerning locoregional treatments after preoperative chemotherapy for breast cancer: a National Cancer Institute conference. J Clin Oncol. 2008;26:791–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Cutter DJ, Darby SC, Yusuf SW. Risks of heart disease after radiotherapy. Tex Heart Inst J. 2011;38:257–8.PubMedCentralPubMedGoogle Scholar
  39. 39.
    Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer. Cancer. 2007;109:650–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Kong FM, Pan C, Eisbruch A, Ten Haken RK. Physical models and simpler dosimetric descriptors of radiation late toxicity. Semin Radiat Oncol. 2007;17:108–20.CrossRefPubMedGoogle Scholar
  41. 41.
    McGale P, Darby SC, Hall P, et al. Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol. 2011;100:167–75.CrossRefPubMedGoogle Scholar
  42. 42.
    Parkin DM, Darby SC. Cancers in 2010 attributable to ionising radiation exposure in the UK. Br J Cancer. 2011;105:S57–65.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Kronowitz SJ, Robb GL. Radiation therapy and breast reconstruction: a critical review of the literature. Plast Reconstr Surg. 2009;124:395–408.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  1. 1.Department of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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