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Commentary

Clinical practice guidelines for the care and treatment of breast cancer: breast radiotherapy after breast-conserving surgery (summary of the 2003 update)

Timothy Whelan, Ivo Olivotto, Mark Levine and ; The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer
CMAJ February 18, 2003 168 (4) 437-439;
Timothy Whelan
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Ivo Olivotto
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Mark Levine
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This article provides a summary of the changes along with the updated recommendations (Table 1) made by Health Canada's Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer to the article “Clinical Practice Guidelines for the Care and Treatment of Breast Cancer: 6. Breast radiotherapy after breast-conserving surgery,” originally published in 19981 (the 2003 update can be found online at www.cmaj.ca/cgi/content/full/158/3/DC1).

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Table 1.

In the 1998 guideline, irradiation to the whole breast following breast-conserving surgery (BCS) was recommended. This recommendation was based on the results of 5 randomized trials that demonstrated that postoperative breast irradiation substantially reduced the risk of recurrent cancer in the breast compared with no irradiation. In the 2003 update, results of longer follow-up from 2 of these trials are presented.2,3 There continues to be a statistically significant reduction in breast cancer recurrence associated with irradiation. In a Scandinavian trial, at 10 years of follow-up, the rate of local recurrence was 8.5% in the irradiation group compared with 24% in the no treatment group.2 In an Italian trial, at a median of 9 years of follow-up, the corresponding rates were 5.8% and 23.5%.3 There was one new trial reported that compared breast irradiation following BCS with no irradiation. In this trial, from Finland, 152 women over 40 years of age with node-negative breast cancer whose tumours were smaller than 2 cm in diameter were randomly assigned to BCS followed by radiation therapy or BCS alone.4 At 6.7 years of follow-up, the local recurrence rate was 7.5% in the irradiated group and 18.1% in the control group (p = 0.03). Hence, our 1998 recommendation concerning the administration of radiation after BCS has not changed.

A frequently asked question is whether any patients who undergo BCS are at such a low risk of local recurrence (e.g., those with small tumours and older women) that they do not require irradiation. Data recently reported from 3 randomized trials addressed this issue. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-21 trial, 1009 women with node-negative breast cancer and tumours 1 cm in diameter or smaller treated by BCS were randomly allocated to receive tamoxifen alone, breast irradiation alone or tamoxifen plus breast irradiation.5 About 80% of the women were 50 years of age or older. The average follow-up was 7.2 years. The rate of local breast recurrence at 8 years was 16.5% with tamoxifen alone, 9.3% with irradiation alone and 2.8% with tamoxifen plus irradiation (p < 0.01 for all comparisons).

In a Canadian trial, 769 women over 50 years of age (median age 68 years) with tumours less than 5 cm in diameter and pathologically or clinically node-negative were randomly assigned after BCS to receive tamoxifen or tamoxifen plus breast irradiation.6 The median follow-up was 3.4 years. The rate of local recurrence at 4 years was 6% in the tamoxifen group and 0.3% in the tamoxifen plus irradiation group (p = 0.009). In an Intergroup trial, 647 women 70 years of age or older with estrogen-receptor (ER) positive tumours less than 2 cm in diameter and pathologically or clinically node-negative were randomly assigned after BCS to tamoxifen or tamoxifen plus breast irradiation.7 The median follow-up was 2.3 years. The annual rate of local recurrence was 0.9% with tamoxifen alone and 0% with tamoxifen plus breast irradiation (p > 0.05).

The steering committee feels that the results of the NSABP trial indicate that the risk of local breast cancer recurrence in patients who received tamoxifen without irradiation is high. Although the results of the Canadian and Intergroup trials suggest that older women with small ER-positive tumours who receive tamoxifen without breast irradiation may have a lower risk of recurrence, the follow-up is still too short. Thus, breast irradiation should not be omitted.

A commonly used radiation fractionation schedule in Canada has been 50 Gy in 25 fractions to the whole breast without a boost (i.e., without additional radiation to the lumpectomy cavity) when the margins of surgical excision are clear of disease.8 The results of a Canadian trial have recently been reported in which women with node-negative breast cancer who underwent BCS were randomly assigned to either the more traditional, longer course of breast irradiation (50 Gy in 25 fractions administered over 35 days) or a shorter course (42.5 Gy in 16 fractions over 22 days).9 The median follow-up was 5.8 years. No difference was detected in the rates of local recurrence or cosmetic outcome at 5 years between the treatment groups. The rates of local breast recurrence were 3.2% in the long treatment arm and 2.8% in the short treatment arm. The steering committee supports the use of the shorter irradiation schedule in most patients. A number of centres in Canada have already switched to this shorter fractionation course.

The steering committee also considered the issue of boost irradiation to the breast. In the 1998 guideline, the data considered were from case series. In the current update, the results of 3 randomized trials are reported. In a trial from France, 1024 patients with tumours 3 cm in diameter or smaller and clear margins following BCS were randomly allocated to receive breast irradiation plus a boost to the primary site or breast irradiation alone.10 The median follow-up was 3.3 years. The rate of local recurrence at 5 years was 3.6% in the boost group compared with 4.5% in the control group (p = 0.044). More patients in the boost group than in the control group had telangiectasia of the skin of the breast. In another trial from France, 664 patients who underwent BCS were randomly assigned to receive breast irradiation plus a boost or breast irradiation alone.11 At a median follow-up of 6.1 years, the rate of local recurrence was 4.3% among patients who received the boost and 6.8% among those who did not (p = 0.13). The European Organization for Research and Treatment of Cancer (EORTC) conducted a trial involving 5318 women with early breast cancer who underwent BCS.12 The median follow-up was 5.1 years. The rate of local recurrence at 5 years was 4.3% in the boost group compared with 7.3% in the control group (p < 0.001). An excellent or good cosmetic outcome was observed in 71% of the patients treated with a boost, compared with 86% of those in the control group (p < 0.001). Patients less than 50 years of age were at higher risk of local recurrence than older women, and in this group of patients the absolute benefit of a boost appeared greater.

The steering committee feels that the results of these studies support the notion that boost irradiation to the primary site in patients with clear resection margins reduces the risk of local recurrence. However, the absolute benefit is small, and the use of boost irradiation is associated with a decrease in cosmetic outcome. In the recent Canadian trial that compared different radiation therapy regimens,9 when a boost was not administered the rates of local recurrence were very low (3.2% in the long treatment arm and 2.8% in the short treatment arm). These rates were lower than those in the boost arm of the EORTC trial. Hence, the steering committee feels that a boost following breast irradiation is not required in all women who undergo BCS but might be considered in women at particularly high risk of local recurrence (e.g., those less than 40 years of age or those with positive or close resection margins).

The steering committee also considered the topic of brachytherapy implants (i.e., radioactive seeds placed into the tumour bed) or intraoperative radiation. Recently, a number of pilot studies have demonstrated that partial breast irradiation utilizing brachytherapy implants or local intraoperative radiation therapy may provide adequate local control with acceptable cosmetic outcome in selected patients.13,14 However, none of these techniques has been evaluated in randomized trials. Thus, the steering committee feels that data from randomized trials are necessary before definitive recommendations about these treatments can be made.

Since the publication of the 1998 guideline, a number of studies have evaluated the acute and long-term morbidity of breast irradiation. In the Canadian randomized trial,15 breast irradiation was associated with a modest negative impact on quality of life during treatment and 1 month following treatment. This association was attributed to the side effects of fatigue, skin irritation and the inconvenience of daily treatments. In the original guideline, studies of breast irradiation after lumpectomy had not shown an increase in long-term cardiac mortality. A recent Canadian study using data from a cancer registry suggested that the rate of death from myocardial infarction was increased by 1% at 10 years with irradiation of left-sided breast cancer.16 A systematic evaluation of cardiac morbidity in a large number of women in the same cohort showed no increase.17

In summary, trials of breast irradiation following lumpectomy continue to support the evidence that irradiation substantially reduces the risk of local recurrence and prevents the need for mastectomy. Negative effects on acute and long-term morbidity appear to be limited.

Footnotes

  • Contributors: Drs. Whelan, Olivotto and Levine contributed equally to the writing and revising of this commentary.

    Competing interests: None declared.

References

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    Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Clinical practice guidelines for the care and treatment of breast cancer. CMAJ 1998;158(3 Suppl):S1-83.
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    Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabár L, Nordgren H, et al. 10-year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 1999;17(8):2326-33.
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    Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, et al. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 2001;12:997-1003.
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    Holli K, Saaristo R, Isola J, Joensuu H, Hakama M. Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: results of a randomized study. Br J Cancer 2001;84(2):164-9.
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    Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, 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 2002;20:4141-9.
  6. 6.
    Fyles A, McCready D, Manchul L, Trudeau M, Olivotto I, Merante P, et al. Preliminary results of a randomized study of tamoxifen +/- breast radiation in T1/2 N0 disease in women over 50 years of age [abstract]. Prog Proc Am Soc Clin Oncol 2001;20:24a.
  7. 7.
    Hughes KS, Schnaper L, Berry D, Cirrincione C, McCormick B, Shank B, et al. Comparison of lumpectomy plus tamoxifen with and without radiotherapy (RT) in women 70 years of age or older who have clinical stage 1, estrogen receptor positive (ER+) breast carcinoma [abstract]. Prog Proc Am Soc Clin Oncol 2001;20:24a.
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    Whelan T, Marcellus D, Clark R, Levine M. Adjuvant radiotherapy for early breast cancer: patterns of practice in Ontario. CMAJ 1993;149(9):1273-7.
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    Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143-50.
  10. 10.
    Romestaing P, Lehingue Y, Carrie C, Coquard R, Montbarbon X, Ardiet JM, et al. Role of 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol 1997; 15 (3) : 963-8.
  11. 11.
    Teissier E, Hery M, Ramaioli A, Lagrange JL, Courdi A, Bensadoun RJ, et al. Boost in conservative treatment: 6 years results of randomized trial [abstract]. Breast Cancer Res Treat 1998;50:287.
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    Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van Den Bogaert W, Barillot I, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 2001; 345 (19):1378-87.
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    Nag S, Kuske RR, Vicini FA, Arthur DW, Zwicker RD. Brachytherapy in the treatment of breast cancer. Oncology (Huntingt) 2001;15(2):195-202,205; discussion 205-7.
  14. 14.
    Veronesi U, Orecchia R, Luini A, Gatti G, Intra M, Zurrida S, et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. Eur J Cancer 2001;37(17):2178-83.
  15. 15.
    Whelan TJ, Levine M, Julian J, Kirkbride P, Skingley P. The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trial. Ontario Clinical Oncology Group. Cancer 2000;88 (10): 2260-6.
  16. 16.
    Paszat LF, Mackillop WJ, Groome PA, Schulze K, Holowaty E. Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada. Int J Radiat Oncol Biol Phys 1999;43(4):755-62.
  17. 17.
    Vallis KA, Pintilie M, Chong N, Holowaty E, Douglas PS, Kirkbride P, et al. Assessment of coronary heart disease morbidity and mortality after radiation therapy for early breast cancer. J Clin Oncol 2002;20(4):1036-42.

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