ATLANTA—A randomized trial finds that most women aged 50 or older who underwent breast-conserving surgery for early-stage breast cancer need radiation therapy (RT) in addition to tamoxifen(Drug information on tamoxifen) to minimize the risk of a breast relapse. However, the data also suggest that selected women aged 60 or older may be able to safely skip radiation therapy. Lead author Anthony W. Fyles, MD, a radiation oncologist at the Princess Margaret Hospital, Toronto, Canada, presented findings of the trial at the 46th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 2). (For a full report, see N Engl J Med 351:963-970, 2004).
Women aged 50 or older were eligible to participate if they had T1 or T2 breast cancer with pathologically negative nodes (clinically negative nodes were allowed in women older than 65) and had undergone lumpectomy or partial mastectomy with clean margins, Dr. Fyles said.
"These patients were stratified on the basis of tumor size (T1 or T2), estrogen-receptor (ER) status, axillary dissection, and participating center (Toronto or British Columbia)," he noted. The patients were assigned to treatment with tamoxifen (20 mg daily for 5 years) with or without radiation therapy (40 Gy to the whole breast plus a boost of 12.5 Gy). The 769 women had a median age of 68 years. Most had small tumors (pT1, 83%), pathologically negative nodes (pN0, 83%), and tumors with a positive or unknown hormone-receptor status (94%), Dr. Fyles said.
With a median follow-up of 5.6 years, the 5-year rate of ipsilateral breast relapse was 4%, but it was markedly higher in the tamoxifen group than in the tamoxifen/RT group—7.7% vs 0.6%; hazard ratio (HR) 8.3; P < .0001. In a multivariate analysis, the factors independently associated with the risk of breast relapse were assignment to tamoxifen alone (HR 9.0), T2 tumor (HR 1.7), and negative hormone-receptor status (HR 3.8). "Age was significant only on univariate analysis," he noted, with those data suggesting that patients aged 50 to 59 years had the highest rate of relapse.
In exploratory analyses, radiation appeared to confer little added benefit among patients aged 60 years or older with favorable features (tumor size 1 cm or less and positive receptor status), Dr. Fyles noted. The 5-year rate of breast relapse in this subgroup did not differ significantly between those treated with tamoxifen only and those treated with tamoxifen plus radiation (1.2% vs 0%).
In the entire study group, compared with patients given only tamoxifen, those given the combined treatment had a significantly lower 5-year rate of axillary failure (0.5% vs 2.5%). "This goes along with the fact that we do include some lower axillary nodes in the breast tangents of radiation therapy," Dr. Fyles noted. "And this was true both in those patients who had an axillary dissection and those who did not." The tamoxifen/radiation group also had a significantly higher rate of disease-free survival (91% vs 84%), which included breast relapse as an event. However, the two groups did not differ with respect to rates of distant relapse (approximately 4% in each) and overall survival (93% in each).
Eight-Year Results
"But, of course, 5-year results are not necessarily the whole picture," Dr. Fyles said, noting that based on a small number of patients, rates of relapse seem to be increasing in both groups. The 8-year rate of local relapse was 18% in patients given only tamoxifen and 3.5% in those given tamoxifen plus radiation, a difference that was significant. "This is true even if we take the best risk group from the stratification factors—T1 tumors that were ER positive," he commented.
Patients who were aged 60 or older and had the favorable features had similar 8-year rates of breast relapse whether they received tamoxifen or tamoxifen/radiation (2.8% vs 0%). However, even among patients aged 70 or older with receptor-positive tumors, Dr. Fyles noted, the rate of relapse was markedly higher among those with tumors larger than 1 cm if they did not receive radiation.
"Admittedly, these are exploratory analyses and really should be considered as hypothesis generating. But they do raise some concerns about the inclusion of patients with intermediate-size T1 tumors in any decision about avoiding radiation therapy," he said.
The investigators concluded that adding radiation therapy to tamoxifen reduces the risk of breast relapse in women aged 50 or older with node-negative breast cancer. "A subgroup that we defined as women 60 and older with tumors of 1 cm or less that were ER positive receiving tamoxifen may—if they are well counseled regarding risks and benefits—consider avoiding radiation treatment, depending on their particular circumstances," Dr. Fyles said. "Further follow-up will give us some better data on the long-term rates of breast control as well as the results of long-term breast salvage, given that these patients are also at further risk of breast relapse."
