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 node-positive cancer.
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(Drug information on 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.