VOLUME 31 䡠 NUMBER 36 䡠 DECEMBER 20 2013
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Should Radiotherapy Be Omitted in Women Age 70 Years or Older With Early Breast Cancer? TO THE EDITOR: The important role of adjuvant radiotherapy in locoregional control and survival for patients after breast-conserving surgery has been proven in numerous randomized trials and in a meta-analysis of individual patient data for 10,801 women in 17 randomized trials.1-7 A pivotal study by the Cancer and Leukemia Group B (CALGB; trial 9343)3 suggested that a subset of women age 70 years or older with tumors less than 2 cm in size (T1) might not benefit from adjuvant whole-breast irradiation (WBI) if tamoxifen is given. These conclusions were based on a 3% difference in 5-year locoregional control recurrence rates between the combined WBI-tamoxifen group compared with the tamoxifen-alone group (1% v 4%; P ⬍ .001).2,3 Because there were no statistically significant differences between the two groups with regard to the rates of mastectomy, distant metastases, or 5-year overall survival, this group of patients was considered to be a favorable subgroup of patients given breast-conserving treatment for whom radiation could be avoided.8 Now, an update of the CALGB 9343 study has indicated statistically significant differences of 10% without radiation versus 2% with radiation in 10-year breast cancer recurrence rates.9 However, the authors indicated that these are clinically insignificant results because the findings did not translate into an advantage in overall survival, distant disease–free survival, or breast preservation, suggesting again that these results identify a favorable subgroup of patients administered breast-conserving treatment for whom radiation can be avoided.10 An important issue to understand is that not all patients age 70 years and older are the same. A healthy 70-year-old woman has a high chance of living more than 10 years, risking a one-in-10 rate of local recurrence if radiotherapy is omitted and a one-in-50 rate if radiotherapy is given. Conversely, in patients with significant comorbidities, the benefit of endocrine therapy can be questioned: the survival benefit of systemic treatment in patients with so-called low-risk tumors is mainly seen after 5 years, whereas the benefit of radiotherapy in reducing local recurrence is considerable in the first 5 years. In this subgroup of patients, perhaps endocrine therapy and not radiotherapy can be omitted.10 Moreover, as pointed out in the editorial accompanying the updated CALGB 9343 report, “Radiation treatments are also well tolerated and, when delivered using modern technologies, carry a low risk of serious morbidity”11(p2367): in this subgroup of patients, hypofractionated WBI, partial breast irradiation, or intraoperative irradiation could all be reasonable options for some patients. These modern options impose a much smaller burden on patients than the conventional radiotherapy used in the CALGB study, which must be explained to patients in deciding between treatment options.
The CALGB 9343 trial again highlights the importance of involving patients in the decision-making process. It provides oncologists with data to better identify the recurrence rates that are associated with different treatment options; however, only patients can ultimately decide how much value they place on avoiding the inconveniences and adverse effects of radiotherapy. This balancing of apples and oranges, so to speak, thus obliges us to put patient views high in the decisionmaking hierarchy.
Orit Kaidar-Person and Abraham Kuten Rambam Health Care Campus, Haifa, Israel
Georgina Anastasia Walker Nottingham University Hospitals, Nottingham, United Kingdom
David A.L. Morgan Sherwood Forest Hospitals National Health Service Foundation Trust, Nottinghamshire, United Kingdom
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 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 378:1707-1716, 2011 2. Hughes KS, Schnaper LA, Cirrincione C, et al: Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer. J Clin Oncol 28:69s, 2010 (suppl; abstr 507) 3. 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 351:971-977, 2004 4. 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 351:963-970, 2004 5. 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 20:41414149, 2002 6. 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 366:20872106, 2005 7. 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 49:2294-2302, 2013 8. Smith IE, Ross GM: Breast radiotherapy after lumpectomy: No longer always necessary. N Engl J Med 351:1021-1023, 2004 9. 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 31:2382-2387, 2013 10. Walker GA, Kaidar-Person O, Kuten A, et al: Radiotherapy as sole adjuvant treatment for older patients with low-risk breast cancer. Breast 21:629-634, 2012 11. Smith BD, Buchholz TA: Radiation treatments after breast-conserving therapy for elderly patients. J Clin Oncol 31:2367-2368, 2013
DOI: 10.1200/JCO.2013.51.5312; published online ahead of print at www.jco.org on November 4, 2013
■ ■ ■
Journal of Clinical Oncology, Vol 31, No 36 (December 20), 2013: pp 4569-4573
© 2013 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at GEORGETOWN UNIVERSITY MEDICAL CENTE on Copyright © 2013 American of Clinical Oncology. All rights reserved. March 7,Society 2015 from 141.161.91.14
4569
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Should Radiotherapy Be Omitted in Women Age 70 Years or Older With Early Breast Cancer? TO THE EDITOR: The important role of adjuvant radiotherapy in locoregional control and survival for patients after breast-conserving surgery has been proven in numerous randomized trials and in a meta-analysis of individual patient data for 10,801 women in 17 randomized trials.1-7 A pivotal study by the Cancer and Leukemia Group B (CALGB; trial 9343)3 suggested that a subset of women age 70 years or older with tumors less than 2 cm in size (T1) might not benefit from adjuvant whole-breast irradiation (WBI) if tamoxifen is given. These conclusions were based on a 3% difference in 5-year locoregional control recurrence rates between the combined WBI-tamoxifen group compared with the tamoxifen-alone group (1% v 4%; P ⬍ .001).2,3 Because there were no statistically significant differences between the two groups with regard to the rates of mastectomy, distant metastases, or 5-year overall survival, this group of patients was considered to be a favorable subgroup of patients given breast-conserving treatment for whom radiation could be avoided.8 Now, an update of the CALGB 9343 study has indicated statistically significant differences of 10% without radiation versus 2% with radiation in 10-year breast cancer recurrence rates.9 However, the authors indicated that these are clinically insignificant results because the findings did not translate into an advantage in overall survival, distant disease–free survival, or breast preservation, suggesting again that these results identify a favorable subgroup of patients administered breast-conserving treatment for whom radiation can be avoided.10 An important issue to understand is that not all patients age 70 years and older are the same. A healthy 70-year-old woman has a high chance of living more than 10 years, risking a one-in-10 rate of local recurrence if radiotherapy is omitted and a one-in-50 rate if radiotherapy is given. Conversely, in patients with significant comorbidities, the benefit of endocrine therapy can be questioned: the survival benefit of systemic treatment in patients with so-called low-risk tumors is mainly seen after 5 years, whereas the benefit of radiotherapy in reducing local recurrence is considerable in the first 5 years. In this subgroup of patients, perhaps endocrine therapy and not radiotherapy can be omitted.10 Moreover, as pointed out in the editorial accompanying the updated CALGB 9343 report, “Radiation treatments are also well tolerated and, when delivered using modern technologies, carry a low risk of serious morbidity”11(p2367): in this subgroup of patients, hypofractionated WBI, partial breast irradiation, or intraoperative irradiation could all be reasonable options for some patients. These modern options impose a much smaller burden on patients than the conventional radiotherapy used in the CALGB study, which must be explained to patients in deciding between treatment options.
The CALGB 9343 trial again highlights the importance of involving patients in the decision-making process. It provides oncologists with data to better identify the recurrence rates that are associated with different treatment options; however, only patients can ultimately decide how much value they place on avoiding the inconveniences and adverse effects of radiotherapy. This balancing of apples and oranges, so to speak, thus obliges us to put patient views high in the decisionmaking hierarchy.
Orit Kaidar-Person and Abraham Kuten Rambam Health Care Campus, Haifa, Israel
Georgina Anastasia Walker Nottingham University Hospitals, Nottingham, United Kingdom
David A.L. Morgan Sherwood Forest Hospitals National Health Service Foundation Trust, Nottinghamshire, United Kingdom
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 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 378:1707-1716, 2011 2. Hughes KS, Schnaper LA, Cirrincione C, et al: Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer. J Clin Oncol 28:69s, 2010 (suppl; abstr 507) 3. 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 351:971-977, 2004 4. 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 351:963-970, 2004 5. 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 20:41414149, 2002 6. 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 366:20872106, 2005 7. 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 49:2294-2302, 2013 8. Smith IE, Ross GM: Breast radiotherapy after lumpectomy: No longer always necessary. N Engl J Med 351:1021-1023, 2004 9. 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 31:2382-2387, 2013 10. Walker GA, Kaidar-Person O, Kuten A, et al: Radiotherapy as sole adjuvant treatment for older patients with low-risk breast cancer. Breast 21:629-634, 2012 11. Smith BD, Buchholz TA: Radiation treatments after breast-conserving therapy for elderly patients. J Clin Oncol 31:2367-2368, 2013
DOI: 10.1200/JCO.2013.51.5312; published online ahead of print at www.jco.org on November 4, 2013
■ ■ ■
Journal of Clinical Oncology, Vol 31, No 36 (December 20), 2013: pp 4569-4573
© 2013 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at GEORGETOWN UNIVERSITY MEDICAL CENTE on Copyright © 2013 American of Clinical Oncology. All rights reserved. March 7,Society 2015 from 141.161.91.14
4569
