Radiotherapy in Geriatric Breast Cancer Patients

radyasyon_onkolojisi_102

Nesrin AKTÜRKa , İlknur ALSAN ÇETİNb
aİzmir Atatürk Training and Research Hospital, Department of Radiation Oncology, İzmir,Türkiye
bMarmara University Faculty of Medicine, Department of Radiation Oncology, İstanbul, Türkiye

Aktürk N, Alsan Çetin İ. Radiotherapy in geriatric breast cancer patients. In: Metcalfe E, ed. Radiotherapy and Current Developments in Geriatric Cancers. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.15-24.

ABSTRACT
Nearly one third of breast cancer (BC) cases are diagnosed after age of 70, however, there is insufficient data for specified treatments due to lesser representation in clinical trials. Adjuvant radiotherapy (RT) has an important role in local control and overall survival of BC. Safely omitting RT in elderly women with early-stage cancer is still controversial. Hypofractionated schemes or partial breast irradiation techniques are reasonable options with shorter treatment time for patients who receive minimized treatments due to their comorbidities and functional limitations. Postmastectomy RT (PMRT) is an unreplaceable treatment modality for high-risk locally advanced BC, but for medium-risk BC its role is under investigation. Results of ongoing trials will determine the patients that PMRT can be omitted. Treatment of older women with BC should be customized due to the heterogeneity of the population, benefits and toxicities of RT, moreover risk group analyses, and geriatric assessment should be considered individually.

Keywords: Breast cancer; radiotherapy; women; geriatric

Referanslar

  1. Cancer statistics review, 1975-2018 - SEER statistics; 2022. [cited: April 29, 2024]. Available from: [Link]
  2. SEER Explorer: An interactive website for SEER cancer statistics. Surveillance Research Program, National Cancer Institute. [cited: April 29, 2023]. Available from: [Link]
  3. Biganzoli L, Battisti NML, Wildiers H, McCartney A, Colloca G, Kunkler IH, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol. 2021;22(7):e327-e40. [Crossref]  [PubMed]
  4. Akkila S, Mahal S, Dawdy K, Cao X, Szumacher E. Functional decline and resilience in older adults over the age of 70 receiving radiotherapy for breast cancer: A pilot study. J Geriatr Oncol. 2023;14(3):101476. [Crossref]  [PubMed]
  5. Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285(7):885-92. [Crossref]  [PubMed]
  6. Punglia RS, Hughes KS, Muss HB. Management of older women with early-stage breast cancer. Am Soc Clin Oncol Educ Book. 2015:48-55. [Crossref]  [PubMed]
  7. George M, Smith A, Sabesan S, Ranmuthugala G. Physical Comor-bidities and Their Relationship with Cancer Treatment and Its Outcomes in Older Adult Populations: Systematic Review. JMIR Cancer. 2021;7(4):e26425. [Crossref]  [PubMed]  [PMC]
  8. National Institute for Health and Care Excellence. Breast cancer quality standard: NICE quality standards (QS12). 2011. Available from: [Link]
  9. Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, 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;12:378(9804):1707-16. [Crossref]  [PubMed]
  10. Huang XZ, Chen Y, Chen WJ, Zhang X, Wu CC, Zhang CY, et al. Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis. Oncotarget. 2017;8(17):28215-25. [Crossref]  [PubMed]  [PMC]
  11. Donato V, Valeriani M, Zurlo A. Short course radiation therapy for elderly cancer patients. Evidence from the literature review. Crit Rev Oncol Hematol. 2003;45(3):305-11. [Crossref]  [PubMed]
  12. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018;8(3):145-52. [Crossref]  [PubMed]
  13. Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 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;16:387(10015):229-38.
  14. Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, 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(4):451-63. [Crossref]  [PubMed]
  15. Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;14:394(10215):2155-64. [Crossref]  [PubMed]
  16. Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, et al; RAPID Trial Investigators. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165-72. [Crossref]  [PubMed]
  17. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al; IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017;390(10099):1048-60. [Crossref]  [PubMed]
  18. Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14(13):1269-77. [Crossref]  [PubMed]
  19. Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C, et al. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technol Assess. 2016;20(73):1-188. [Crossref]  [PubMed]  [PMC]
  20. Sasieni PD, Sawyer EJ. Intraoperative radiotherapy for early breast cancer - insufficient evidence to change practice. Nat Rev Clin Oncol. 2020; 17(12):723-4. [Crossref]  [PubMed]  [PMC]
  21. Piroth MD, Strnad V, Krug D, Fastner G, Baumann R, Combs SE, et al. Long-Term Results of the TARGIT-A Trial: More Questions than Answers. Breast Care (Basel). 2022;17(1):81-4. [Crossref]  [PubMed]  [PMC]
  22. Vaidya JS, Bulsara M, Wenz F, Sperk E, Massarut S, Alvarado M, et al; TARGIT-A authors. The TARGIT-A Randomized Trial: TARGIT-IORT Versus Whole Breast Radiation Therapy: Long-Term Local Control and Survival. Int J Radiat Oncol Biol Phys. 2023;115(1):77-82. [Crossref]  [PubMed]
  23. Shaitelman SF, Anderson BM, Arthur DW, Bazan JG, Bellon JR, Bradfield L, et al. Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2024;14(2):112-32. [Crossref]  [PubMed]
  24. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, 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):1086-94. [Crossref]  [PubMed]
  25. Offersen BV, Alsner J, Nielsen HM, Jakobsen EH, Nielsen MH, Krause M, et al; Danish Breast Cancer Group Radiation Therapy Committee. Hypofractionated Versus Standard Fractionated Radiotherapy in Patients With Early Breast Cancer or Ductal Carcinoma In Situ in a Randomized Phase III Trial: The DBCG HYPO Trial. J Clin Oncol. 2020;38(31):3615-25. [Crossref]  [PubMed]
  26. Cante D, Franco P, Sciacero P, Girelli G, Pasquino M, Casanova Borca V, et al. Hypofractionated whole-breast radiotherapy and concomitant boost after breast conservation in elderly patients. Tumori. 2016;102(2):196-202. [Crossref]  [PubMed]
  27. Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020;395(10237):1613-26. [Crossref]  [PubMed]
  28. Brunt AM, Haviland JS, Sydenham M, Agrawal RK, Algurafi H, Alhasso A, et al. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin Oncol. 2020;38(28):3261-72. [Crossref]  [PubMed]  [PMC]
  29. Krug D, Baumann R, Combs SE, Duma MN, Dunst J, Feyer P, et al; Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO). Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward. Strahlenther Onkol. 2021;197(4):269-80. [Crossref]  [PubMed]  [PMC]
  30. Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, 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(22):3259-65. [Crossref]  [PubMed]
  31. Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J, et al; European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups. 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. [Crossref]  [PubMed]
  32. Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, 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(19):2382-7. [Crossref]  [PubMed]  [PMC]
  33. Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM; PRIME II investigators. 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(3):266-73. [Crossref]  [PubMed]
  34. Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N Engl J Med. 2023;388(7):585-94. [Crossref]  [PubMed]
  35. Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, 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(10):963-70. [Crossref]  [PubMed]
  36. Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, et al; National Surgical Adjuvant Breast and Bowel Project. 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(20):4141-9. [Crossref]  [PubMed]
  37. Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120-8. [Crossref]  [PubMed]  [PMC]
  38. Recht A, Edge SB, Solin LJ, Robinson DS, Estabrook A, Fine RE, et al; American Society of Clinical Oncology. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19(5):1539-69. [Crossref]  [PubMed]
  39. Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, 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. [Crossref]  [PubMed]
  40. Smith BD, Haffty BG, Hurria A, Galusha DH, Gross CP. Postmastectomy radiation and survival in older women with breast cancer. J Clin Oncol. 2006;24(30):4901-7. [Crossref]  [PubMed]
  41. Killander F, Anderson H, Rydén S, Möller T, Aspegren K, Ceberg J, et al. Radiotherapy and tamoxifen after mastectomy in postmenopausal women -- 20 year follow-up of the South Sweden Breast Cancer Group randomised trial SSBCG II:I. Eur J Cancer. 2007;43(14):2100-8. [Crossref]  [PubMed]
  42. Recht A, Comen EA, Fine RE, Fleming GF, Hardenbergh PH, Ho AY, et al. Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. Ann Surg Oncol. 2017;24(1):38-51. [Crossref]  [PubMed]  [PMC]
  43. Verma R, Chandarana M, Barrett J, Anandadas C, Sundara Rajan S. Post-mastectomy radiotherapy for women with early breast cancer and one to three positive lymph nodes. Cochrane Database Syst Rev. 2023;6(6):CD014463. [Crossref]  [PubMed]  [PMC]
  44. Pu H, Luo Y, Zhang L, Li X, Li F, Chen J, et al. Development and validation of nomograms for predicting survival outcomes in patients with T1-2N1 breast cancer to identify those who could not benefit from postmastectomy radiotherapy. Front Oncol. 2023;13:1112687. [Crossref]  [PubMed]  [PMC]
  45. Kunkler IH, Canney P, van Tienhoven G, Russell NS; MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group. Elucidating the role of chest wall irradiation in "intermediate-risk" breast cancer: the MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol). 2008;20(1):31-4. [Crossref]  [PubMed]
  46. Velikova G, Williams LJ, Willis S, Dixon JM, Loncaster J, Hatton M, et al; MRC SUPREMO trial UK investigators. Quality of life after postmastectomy radiotherapy in patients with intermediate-risk breast cancer (SUPREMO): 2-year follow-up results of a randomised controlled trial. Lancet Oncol. 2018;19(11):1516-29. [Crossref]  [PubMed]