SALT LAKE CITYWomen with breast cancer who have limited
nodal involvement may be able to safely forego regional radiation therapy after
lumpectomy, according to an analysis of data from 10 randomized trials of the
National Surgical Adjuvant Breast and Bowel Project (NSABP) presented at the
45th Annual Meeting of the American Society for Therapeutic Radiology and
Oncology (ASTRO abstract 74).
In this analysis of women who did not receive regional
radiation therapy, rates of axillary and supraclavicular recurrences after
breast-conserving therapy, and in some cases systemic therapy, were low for
women who had no or only 1 to 3 positive lymph nodes.
"Although axillary and supraclavicular recurrences are
rare, they are difficult to control and are usually associated with significant
morbidity. On the other hand, routine radiation of the axilla and
supraclavicular area can increase the risk of radiation pneumonitis and
lymphedema," said lead author Alphonse Taghian, MD, PhD. Dr. Taghian is
assistant professor, Harvard Medical School, and an associate in radiation
oncology, Massachusetts General Hospital (MGH), Boston, as well as a member of
the Breast Cancer Committee and the Breast Committee Working Group of the NSABP.
To identify patients at higher risk for axillary and/or
supraclavicular recurrences after breast-conserving therapy, Dr. Taghian and
his colleagues analyzed data from 3,788 women enrolled in five trials studying
node-negative cancer and 2,437 women enrolled in five trials studying
All patients were treated with lumpectomy plus radiation
therapy to the breast (50 Gy in 25 fractions, with a boost permitted). Some
patients were also treated with adjuvant chemotherapy (including all women with
node-positive cancer) and/or tamoxifen (including all women aged 50 years and
older), he said. None received regional radiation therapy.
Among patients with node-negative disease, the 10-year
cumulative incidence of regional failure (reported as a first event) was 1% in
patients with estrogen receptor (ER)-positive tumors and 2% in patients with
ER-negative tumors, Dr. Taghian said. Among patients with node-positive
disease, the incidence increased with the extent of nodal involvement: patients
with 1 to 3, 4 to 9, and 10 or more positive nodes had incidences of 4%, 6%,
and 14%, respectively.
The 10-year cumulative incidence of local (in-breast)
failure was 5% and 6% in women with node-negative, ER-positive and
node-negative, ER-negative disease, respectively, Dr. Taghian said. The values
for women with node-positive disease were 10%, 12%, and 8%, respectively, for 1
to 3, 4 to 9, and 10 or more positive nodes.
As expected, the 10-year cumulative incidence of distant
failure (including contralateral breast cancer) increased steadily with the
number of involved nodes, Dr. Taghian noted. It was 10% and 14% in women with
node-negative, ER-positive and node-negative, ER-negative disease,
respectively, but it was 22%, 35%, and 49% in women with 1 to 3, 4 to 9, and 10
or more involved nodes.
The majority of regional recurrences, 59%, occurred in the
supraclavicular area, he said; another 31% occurred in the axilla, and the rest
occurred in parasternal, subclavicular, or multiple sites.
The risk of axillary failure decreased as the number of
nodes removed increased, he said, noting that this analysis did not consider
the status of the nodes. Compared with women who had 10 or more nodes removed,
those who had 1 to 5 and 6 to 9 nodes removed had significant increases5.7-fold
and 2.1-fold, respectivelyin the risk of axillary recurrence. In contrast,
the number of nodes removed was not associated with the risk of supraclavicular
failure, he said.
In an analysis among patients with node-negative disease
that controlled for receptor status, protocol, and therapy, the risk of
regional relapse was increased in patients who were younger at the time of
surgery (P < .01) and marginally increased in patients who had larger
tumors (P = .07), Dr. Taghian said.
"In the patients with positive lymph nodes, the tumor
size did not add much over and above the nodal status: The nodal status
remained the strongest predictor for regional lymph node relapse," he
noted. He added that in patients with node-positive disease, although regional
failure rates were lower for women with ER-positive tumors and marginally lower
for older patients, the indications for tamoxifen therapy used in the trials
prevented any definitive conclusions about these associations.
"Regional recurrences as a first event are extremely
rare in node-negative patients overall," Dr. Taghian said, cautioning that
subgroup analyses in these patients are still ongoing. Even among patients with
1 to 3 positive lymph nodes, only about 4% presented with regional failure,
although the rate was somewhat higher in younger, ER-negative patients, around
6% to 7%, he said.
"In the population of patients with 1 to 3 positive
lymph nodes, the routine use of regional radiation may result in overtreatment,"
Dr. Taghian said. He noted that practices regarding regional radiation vary.
"We know from the MGH survey that probably around 40% to 50% of radiation
oncologists would treat the regional lymph node area in patients with 1 to 3
positive lymph nodes," he said.
Only a large randomized clinical trial can evaluate the worth of regional
radiation in this population, Dr. Taghian concluded. "This study strongly
supports the Canadian MA20 study, which is evaluating the effects of regional
radiotherapy on disease-free survival, overall survival, and toxicity in
patients with high-risk, lymph-node-negative disease and in patients with 1 to
3 or 4 or more positive nodes treated with breast-conserving surgery," he
said. Patients are stratified by number of positive nodes, type of
chemotherapy, and use of hormonal therapy. Randomization is to standard breast
radiotherapy or breast radiotherapy plus regional radiotherapy. MA20 is
supported by the NCI’s Cancer Trial Support Unit and is endorsed by the major
groups that conduct clinical trials in the United States and Canada. "We
strongly encourage physicians to enroll their patients on this important
trial," he said.