Radiation therapy and early breast cancer: current controversies

Boyages, John

doi:10.5694/mja16.01020

ARTICLE
AUTHORS
REFERENCES

Topics

Neoplasms

Surgical procedures, operative

Summary

Radiation therapy (RT) is an important component of breast cancer treatment.
RT reduces local recurrence and breast cancer mortality after breast conservation for all patients and for node-positive patients after a mastectomy.
Short courses of RT over 3–4 weeks are generally as effective as longer courses.
A patient subgroup where RT can be avoided after conservative surgery has not been consistently identified.
A radiation boost reduces the risk of a recurrence in the breast but may be omitted for older patients with good prognosis tumours with clear margins.
Axillary recurrences can take a long time to appear, with 35% occurring after 5 years.
Leaving disease untreated in regional nodes is associated with reduced survival.
Not all patients require radiation after neoadjuvant chemotherapy and a subsequent mastectomy.
Modern RT equipment and techniques will further improve survival rates.

Macquarie University, Sydney, NSW

Correspondence: john.boyages@mq.edu.au

Acknowledgements:

I thank Ellen Tailby for research assistance, Philippa Sutton for editing and managing earlier versions of the manuscript, and Sergio Duque and Lesley Baker for the volumetric modulated arc therapy plan of the patient shown in Box 5.

Competing interests:

No relevant disclosures.

1. Grubbé EH. Priority in the therapeutic use of X-rays. Radiology 1933; 21: 156-162.
2. Keynes G. The Radium Treatment of Primary Carcinoma of the Breast. Can Med Assoc J 1934; 30: 24-30.
3. Halsted WS. I. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907; 46: 1-19.
4. Ginzton EL, Nunan CS. History of microwave electron linear accelerators for radiotherapy. Int J Radiat Oncol Biol Phys 1985; 11: 205-216.
5. Darby S, McGale P, Correa C, 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: 1707-1716.
6. McGale P, Taylor C, Correa 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: 2127-2135.
7. Esposito E, Anninga B, Harris S, et al. Intraoperative radiotherapy in early breast cancer. Br J Surg 2015; 102: 599-610.
8. Fisher B, Anderson S, Bryant J, 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: 1233-1241.
9. Winzer KJ, Sauer R, Sauerbrei W, et al. Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence. Eur J Cancer 2004; 40: 998-1005.
10. Fyles AW, McCready DR, Manchul LA, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 2004; 351: 963-970.
11. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 2004; 351: 971-977.
12. Potter 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: 334-340.
13. Blamey RW, Bates T, Chetty U, et al. Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur J Cancer 2013; 49: 2294-2302.
14. 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: 266-273.
15. Australian Government Actuary. Australian life tables 2010–12: females. http://www.aga.gov.au/publications/life_table_2010-12/05-ALT-Females.asp (accessed July 2017).
16. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687-1717.
17. Boyages J, Taylor R, Chua B, et al. A risk index for early node-negative breast cancer. Br J Surg 2006; 93: 564-571.
18. Mannino M, Yarnold JR. Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever be safely withheld? Radiother Oncol 2009; 90: 14-22.
19. Hernandez RK, Sorensen HT, Pedersen L, et al. Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer 2009; 115: 4442-4449.
20. Chakrabarti J, Kenny FS, Syed BM, et al. A randomised trial of mastectomy only versus tamoxifen for treating elderly patients with operable primary breast cancer-final results at 20-year follow-up. Crit Rev Oncol Hematol 2011; 78: 260-264.
21. 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: 1086-1094.
22. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010; 362: 513-520.
23. Bane AL, Whelan TJ, Pond GR, et al. Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy. Ann Oncol 2014; 25: 992-998.
24. Australian Government Cancer Australia. Clinical practice recommendations and practice points. https://canceraustralia.gov.au/publications-and-resources/clinical-practice-guidelines/hypofractionated-radiotherapy-early-operable-breast-cancer/clinical-practice-recommendations-and-practice-points (accessed July 2017).
25. 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: 59-68.
26. Harnett A, Smallwood J, Titshall V, et al. Diagnosis and treatment of early breast cancer, including locally advanced disease–summary of NICE guidance. BMJ 2009; 338: 598-600.
27. Shah C, Parsai S, Kotecha R, et al. Overview of outcomes with accelerated partial breast irradiation. In: Arthur DW, Vicini FA, Wazer DE, et al., editors. Short course breast radiotherapy. Cham: Springer, 2016; pp 229-244.
28. Coles CE, Yarnold JR. Accelerated partial breast irradiation: the new standard? Lancet 2016; 387: 201-202.
29. 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: 229-238.
30. Holland R, Connolly JL, Gelman R, et al. The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. J Clin Oncol 1990; 8: 113-118.
31. Boyages J, Bosch C, Langlands AO, et al. Breast conservation: long-term Australian data. Int J Radiat Oncol Biol Phys 1992; 24: 253-260.
32. Boyages J, Recht A, Connolly JL, et al. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 1990; 19: 29-41.
33. Connolly JL, Boyages J, Nixon AJ, et al. Predictors of breast recurrence after conservative surgery and radiation therapy for invasive breast cancer. Mod Pathol 1998; 11: 134-139.
34. Leong C, Boyages J, Jayasinghe UW, et al. Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma. Cancer 2004; 100: 1823-1832.
35. 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: 47-56.
36. Vrieling C, van Werkhoven E, Maingon P, 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: 42-48.
37. Houssami N, Macaskill P, Marinovich ML, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer 2010; 46: 3219-3232.
38. Hunt KK, Ballman KV, McCall LM, et al. Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial. Ann Surg 2012; 256: 428-436.
39. Houssami N, Marinovich ML. Margins in breast-conserving surgery for early breast cancer: how much is good enough? Curr Breast Cancer Rep 2016; 8: 127-134.
40. Moran MS, Schnitt SJ, Giuliano AE, 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. Int J Radiat Oncol Biol Phys 2014; 88: 553-564.
41. Bodilsen A, Bjerre K, Offersen BV, et al. Importance of margin width in breast-conserving treatment of early breast cancer. J Surg Oncol 2016; 113: 609-615.
42. Wang W, French J, Boyages J. Put the felt pen away: time to move on from a clinical mark-up for a breast boost. J Med Imaging Radiat Oncol 2012; 56: 375-378.
43. 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-e234.
44. 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: 3960-3966.
45. 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: 2483-2493.
46. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2006; 24: 2019-2027.
47. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg 2014; 260: 608-614; discussion 614-606.
48. Fowble BL, Einck JP, Kim DN, et al. Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer. Int J Radiat Oncol Biol Phys 2012; 83: 494-503.
49. Truin W, Vugts G, Roumen RM, et al. Differences in response and surgical management with neoadjuvant chemotherapy in invasive lobular versus ductal breast cancer. Ann Surg Oncol 2016; 23: 51-57.
50. Abdulkarim BS, Cuartero J, Hanson J, 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: 2852-2858.
51. Lowery AJ, Kell MR, Glynn RW, et al. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 2012; 133: 831-841.
52. Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 2010; 28: 1684-1691.
53. Taghian AG, Jeong JH, Mamounas EP, et al. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol 2006; 24: 3927-3932.
54. Bazan JG, White JR. The role of postmastectomy radiation therapy in patients with breast cancer responding to neoadjuvant chemotherapy. Semin Radiat Oncol 2016; 26: 51-58.
55. de Boer M, van Dijck JA, Bult P, et al. Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. J Natl Cancer Inst 2010; 102: 410-425.
56. Chua B, Ung O, Taylor R, et al. Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma. Cancer 2001; 92: 1769-1774.
57. 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: 426-432; discussion 432-423.
58. Giuliano AE, Ballman K, McCall L, 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: 413-420.
59. Boyages J, Winch C. Axillary versus sentinel-lymph-node dissection for micrometastatic breast cancer. Lancet Oncol 2013; 14: e250-e251.
60. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies–improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015; 26: 1533-1546.
61. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol 2014; 32: 3600-3606.
62. 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: 567-575.
63. 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: 1303-1310.
64. Haffty BG, Hunt KK, Harris JR, et al. Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. J Clin Oncol 2011; 29: 4479-4481.
65. Stibbe EP. The Internal Mammary Lymphatic Glands. J Anat 1918; 52: 257-264.
66. Putti F. Ricerche anatomiche sui linfonodi mammari interni. Chir Ital 1953; 7: 161-172.
67. Coombs NJ, Boyages J, French JR, et al. Internal mammary sentinel nodes: ignore, irradiate or operate? Eur J Cancer 2009; 45: 789-794.
68. Thorsen LB, Offersen BV, Dano 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: 314-320.
69. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015; 373: 307-316.
70. 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: 860-866.
71. 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: 867-872.
72. 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: 259-265.
73. Verma V, Vicini F, Tendulkar RD, et al. Role of internal mammary node radiation as a part of modern breast cancer radiation therapy: a systematic review. Int J Radiat Oncol Biol Phys 2016; 95: 617-631.

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Radiation therapy and early breast cancer: current controversies

Topics

Summary

Author

Comment

Do you have any competing interests to declare? *