Vol 27, No 2 (2022)
Review paper
Published online: 2022-03-17

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The role of radiotherapy in the management of nodal disease in breast cancer

John Lenihan1, Guhan Rangaswamy1, Clare Faul1
Rep Pract Oncol Radiother 2022;27(2):331-343.

Abstract

The management of nodal disease in breast cancer has evolved over the last two decades. With minimalist surgical approaches for early breast cancers becoming commonplace, the question of whether radiation can replace surgery to reduce morbidity is an important question in this population, as decision making has become more complex. In more advanced disease, and in patients with significant high-risk clinical and/or pathological features, the dilemma of who should receive regional nodal irradiation has been addressed in large studies but remains controversial. In this article, we summarise and discuss the recent trials which guide modern clinical practice, as well as some of the ongoing studies which aim to address outstanding questions within the field.

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References

  1. Winters S, Martin C, Murphy D, et al. Breast Cancer Epidemiology, Prevention, and Screening. Prog Mol Biol Transl Sci. 2017; 151: 1–32.
  2. Zardavas D, Irrthum A, Swanton C, et al. Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol. 2015; 12(7): 381–394.
  3. Tonellotto F, Bergmann A, de Souza Abrahão K, et al. Impact of Number of Positive Lymph Nodes and Lymph Node Ratio on Survival of Women with Node-Positive Breast Cancer. Eur J Breast Health. 2019; 15(2): 76–84.
  4. Voordeckers M, Vinh-Hung V, Van de Steene J, et al. The lymph node ratio as prognostic factor in node-positive breast cancer. Radiother Oncol. 2004; 70(3): 225–230.
  5. Beenken SW, Urist MM, Zhang Y, et al. Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg. 2003; 237(5): 732–8; discussion 738.
  6. Schmitt M, Eber J, Antoni D, et al. Should the management of radiation therapy for breast cancer be standardized? Results of a survey on current French practices in breast radiotherapy. Rep Pract Oncol Radiother. 2021; 26(5): 814–826.
  7. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002; 347(16): 1227–1232.
  8. Onitilo AA, Engel JM, Stankowski RV, et al. Survival Comparisons for Breast Conserving Surgery and Mastectomy Revisited: Community Experience and the Role of Radiation Therapy. Clin Med Res. 2015; 13(2): 65–73.
  9. van Maaren MC, de Munck L, de Bock GH, et al. 10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study. Lancet Oncol. 2016; 17(8): 1158–1170.
  10. Veronesi U, Viale G, Paganelli G, et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010; 251(4): 595–600.
  11. O'Hea BJ, Hill AD, El-Shirbiny AM, et al. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center. J Am Coll Surg. 1998; 186(4): 423–427.
  12. Darby S, McGale P, Correa C, et al. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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): 1707–1716.
  13. Moore M, Kinne D. Axillary lymphadenectomy: A diagnostic and therapeutic procedure. J Surg Oncol. 1997; 66(1): 2–6, doi: 10.1002/(sici)1096-9098(199709)66:1<2::aid-jso2>3.0.co;2-8.
  14. Graversen HP, Blichert-Toft M, Andersen JA, et al. Breast cancer: risk of axillary recurrence in node-negative patients following partial dissection of the axilla. Eur J Surg Oncol. 1988; 14(5): 407–412.
  15. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002; 347(8): 567–575.
  16. Chargari C, Castadot P, Macdermed D, et al. Internal mammary lymph node irradiation contributes to heart dose in breast cancer. Med Dosim. 2010; 35(3): 163–168.
  17. Choi J, Kim YB, Shin KH, et al. Radiation Pneumonitis in Association with Internal Mammary Node Irradiation in Breast Cancer Patients: An Ancillary Result from the KROG 08-06 Study. J Breast Cancer. 2016; 19(3): 275–282.
  18. Courdi A, Chamorey E, Ferrero JM, et al. Influence of internal mammary node irradiation on long-term outcome and contralateral breast cancer incidence in node-negative breast cancer patients. Radiother Oncol. 2013; 108(2): 259–265.
  19. Haviland JS, Owen JR, Dewar JA, et al. START Trialists' Group. 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(11): 1086–1094.
  20. Najas GF, Stuart SR, Marta GN, et al. Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. Rep Pract Oncol Radiother. 2021; 26(6): 920–927.
  21. Solis Campos JA, Veillon Contreras GA, Tudela BT. Hypofractionated radiation therapy for early breast cancer: Follow up of a new treatment standard. Rep Pract Oncol Radiother. 2020; 25(6): 886–889.
  22. Vinh-Hung V, Nguyen NP, Verschraegen C. Hypofractionated Nodal Irradiation for Breast Cancer: A Case for Caution. JAMA Oncol. 2019; 5(1): 13–14.
  23. McGale P, Taylor C, Correa C, et al. EBCTCG (Early Breast Cancer Trialists' Collaborative Group). 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): 2127–2135.
  24. Budach W, Bölke E, Kammers K, et al. Adjuvant radiation therapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials- an update. Radiat Oncol. 2015; 10: 258.
  25. 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(6): 569–575.
  26. Giuliano AE, Ballman KV, McCall L, et al. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017; 318(10): 918–926.
  27. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol. 2014; 32(32): 3600–3606.
  28. Galimberti V, Cole BF, Zurrida S, et al. International Breast Cancer Study Group Trial 23-01 investigators. 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(4): 297–305.
  29. Galimberti V, Cole BF, Viale G, et al. International Breast Cancer Study Group Trial 23-01. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol. 2018; 19(10): 1385–1393.
  30. Sakorafas GH, Peros G, Cataliotti L, et al. Sequelae following axillary lymph node dissection for breast cancer. Expert Rev Anticancer Ther. 2006; 6(11): 1629–1638.
  31. Donker M, van Tienhoven G, Straver ME, 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): 1303–1310.
  32. Rutgers EJ, Donker M, Poncet C, et al. Abstract GS4-01: Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023). Cancer Res. 2019; 79(4_Suppl): GS4-01.
  33. Sávolt Á, Péley G, Polgár C, et al. Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol. 2017; 43(4): 672–679.
  34. Curigliano G, Burstein HJ, P Winer E, et al. Panel Members of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017, St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017; 28(8): 1700–1712.
  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(7): 609–618.
  36. Boughey JC, Suman VJ, Mittendorf EA, et al. Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013; 310(14): 1455–1461.
  37. Caudle AS, Yang WT, Krishnamurthy S, et al. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. 2016; 34(10): 1072–1078.
  38. Oncology AfCTi. Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With Node-Positive Breast Cancer Treated With Chemotherapy.
  39. Henke G, Knauer M, Ribi K, et al. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial. Trials. 2018; 19(1): 667.
  40. NCI, Group RTO. Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery.
  41. Poortmans PM, Weltens C, Fortpied C, et al. European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups. Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial. Lancet Oncol. 2020; 21(12): 1602–1610.
  42. Poortmans PM, Collette S, Kirkove C, et al. EORTC Radiation Oncology and Breast Cancer Groups. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med. 2015; 373(4): 317–327.
  43. Whelan TJ, Olivotto IA, Levine MN, et al. MA.20 Study Investigators. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015; 373(4): 307–316.
  44. 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(4): 314–320.
  45. McGale P, Taylor C, Correa C. Early Breast Cancer Trialists' Collaborative Group C , C. 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): 2127–2135.
  46. 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(5): 860–866.
  47. Reznik J, Cicchetti MG, Degaspe B, et al. Analysis of axillary coverage during tangential radiation therapy to the breast. Int J Radiat Oncol Biol Phys. 2005; 61(1): 163–168.



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