ATLANTAA 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 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 group7.7% 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).
"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 factorsT1
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 mayif
they are well counseled regarding risks and benefitsconsider 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."