Tamoxifen With or Without Breast Irradiation in Women 50 Years of Age or Older With Early Breast Cancer
Objective:
To compare disease-free survival and local relapse in women 50 years of age or older with T1 or T2 node-negative breast cancer treated with tamoxifen alone or tamoxifen and radiation therapy.
Introduction:
The findings of NSABP (National Surgical Adjuvant Breast and Bowel Project) B-06 and other randomized trials suggest that local relapse after lumpectomy alone is lower in women 50 years of age or older than in younger women. Adjuvant tamoxifen also reduces the risk of local relapse. Given the risks of radiation therapy and benefit of tamoxifen in local control, there is interest in identifying a favorable subset of postmenopausal women in whom adjuvant radiation therapy may be unnecessary. This Canadian randomized trial aims to compare outcome in women 50 years of age or older with T1-2 tumors treated with either tamoxifen and radiation or tamoxifen alone.
Methods:
Inclusion criteria:
* years of age or older at diagnosis
* tumor size no greater than 5cm
* pathologically negative axillary lymph nodes or clinically negative nodes in women 65 years old or older, and negative margins.
Patients (N = 769) were randomized to
* breast irradiation (40 Gy/16 fractions plus a 12.5Gy/ 5 fractions tumor bed boost) plus concurrent tamoxifen (20 mg daily for 5 years)
* tamoxifen alone.
Results:
* 5-year disease free survival (DFS) favored those treated with radiation (84% tamoxifen alone versus 91% radiation therapy and tamoxifen, HR relapse 1.7, 95% CI 1.2-2.5, p = .004).
* Ipsilateral breast relapse was 7.7% in women given tamoxifen only versus 0.6% in women who received radiation therapy and tamoxifen (HR 8.3, 95% CI, 3.3-21.2, p < .001).
* Overall survival (93.2% in the tamoxifen group and 92.8% in the tamoxifen and radiation group; p = 0.83) and distant control (4.0% relapse with tamoxifen alone and 4.5% with tamoxifen and irradiation, p = 0.69) were equivalent.
* A planned subgroup analysis of 611 women with T1 tumors and positive hormone receptors demonstrated a 5-year local relapse rate of 5.9% with tamoxifen alone versus 0.4% with tamoxifen and irradiation. These figures increased to 15.2% and 3.6% respectively at 8 years.
Conclusions:
At 5 year follow-up, the results demonstrate that the addition of radiation therapy to tamoxifen significantly decreased local relapse in women 50 years of age or older with T1-2 node-negative breast cancer.
Commentary:
This trial demonstrates that even among women age 50 or older with T1-2 node-negative disease, whom we believe to he at lower risk for relapse, adjuvant irradiation with tamoxifen is needed for optimal local control. With 5 years of follow-up, a statistically significant benefit of adjuvant irradiation in reducing local relapse from 7.7% to 0.6% was noted and the magnitude of this benefit will likely increase over time. Indeed, in the subset of 86 women who were followed for 8-years or more, the respective breast recurrence rates were 17.6% with tamoxifen alone versus 3.5% with tamoxifen and radiation therapy.
Table 1 Select randomized trials in early breast cancer with tamoxifen + / - radiation therapy
A second important finding of this study, is that it confirms that patients with lymph node-negative breast cancer who are treated with tamoxifen and radiation after lumpectomy have an extremely low risk of breast recurrence. In this study, the breast relapse rate for such patients after 5 years was less that 1%.
The data from this trial are consistent with those from the NSABP B-21 trial. This three-arm trial randomized women with pathologically node-negative invasive disease measuring less than or equal to 1 cm to tamoxifen alone, radiation alone, or tamoxifen and irradiation. The main differences from the Canadian trial was that eligibility was restricted to tumors lcm or less in size, did not exclude women under 50 years of age and required all women regardless of age to have pathologically negative axillary nodes. Not surprisingly, the comparative local relapse at 8 years of 16.5% for tamoxifen alone versus 2.8% for tamoxifen with adjuvant irradiation was nearly identical to that reported in the subset of Canadian patients with 8 years follow-up (Table 1). Although Fyles and colleagues enrolled patients with tumors up to 5cm on study, tumors greater than 2 cm made up less than 17% of patients in each arm.
The Canadian trial commented on an unplanned subgroup analysis of women who had tumors 1 cm or less in diameter and positive hormone receptors. Among this favorable subset of 263 women, the local relapse at 5 years was 2.6% in the tamoxifen group and 0% in the tamoxifen and irradiation group (p = 0.02). This difference disappeared when women age 60 years of age or older were examined; however, the number of events was too few and the study not powered to make conclusions on these observations. A simulation model by Punglia et al. demonstrated that the absolute benefit of radiation in postmenopausal women with Stage I breast cancer decreases with increasing age. These findings are supported by the results of the CALGB/ Intergroup trial that compared the outcome in women 70 years of age or older with early breast cancer after lumpectomy and tamoxifen with or without irradiation. This trial was published in the same issue in the New England Journal of Medicine and showed a very low breast recurrence rate in both arms.
Therefore, while it appears prudent at this time to continue offering both tamoxifen and adjuvant radiation therapy to postmenopausal women following lumpectomy, the age cut-off where the benefit of adjuvant irradiation may be eclipsed by competing risks of survival is still poorly understood.
Selected references:
1. Fisher B. 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;16:1233-41
2. Fisher B. 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
3. Punglia R. Radiation therapy plus tamoxifen versus tamoxifen alone after breast conserving surgery in postmenopausal women with Stage 1 breast cancer: a decision analysis. J Clin Oncol 2003;21;12:2260-7
4. Hughes K. 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;10:971-7
Fyles A, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintille M, Weir LM, Olivotto IA. N Engl J Med 2004;351;10:963-970
Commentary by: Julia L. Oh, MD, MD Anderson Cancer Center, Houston, TX, USA
Copyright CRC Press Dec 2004
Source: Women's Oncology Review
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