A secondary analysis of the National Surgical Adjuvant Breast and Bowel Project B-32 trial1 indicates that radiation therapy does not increase the incidence of lymphedema in patients with node-negative breast cancer, according to research presented at the American Society for Radiation Oncology’s (ASTRO’s) 56th Annual Meeting.
Original NSABP B-32 Study
The original NSABP B-32 study was a randomized trial of sentinel node biopsy vs sentinel node biopsy plus axillary lymph node dissection in 5,611 women with clinically node-negative breast cancer. The study was initiated to determine if sentinel node biopsy was as effective as axillary lymph node dissection with fewer side effects.
Although designed to assess the impact of type of axillary surgery specifically on lymphedema risk, the NSABP B-32 trial also provided the opportunity to evaluate the impact of radiation therapy on lymphedema risk. Lymphedema is commonly caused by the removal of or damage to lymph nodes and it is a significant concern for women undergoing breast cancer treatment.
Measures of lymphedema were collected at baseline prior to radiation therapy and every 6 months during the 3-year follow-up period. Lymphedema was assessed both by standardized arm measurements by clinicians (objective lymphedema) and via questionnaires completed by patients (subjective lymphedema).
Objective lymphedema (clinician measured) was defined as relative arm volume difference >1%, and was determined by a water displacement method. Subjective lymphedema was defined as patient-reported ipsilateral swelling that was “somewhat,” “quite” or “very” bothersome. Repeated measures analyses, chi-square and Fisher’s exact tests were used to evaluate the association between measures of lymphedema and radiation therapy. Kappa coefficient was used to assess agreement between objective and subjective lymphedema measures at individual time points.
Secondary Analysis
Among 3,916 women in the trial with lymphedema assessments, including 1,936 randomly assigned to sentinel node biopsy plus axillary lymph node dissection and 1,980 randomly assigned to sentinel node biopsy, 82.2% (3,220) received radiation therapy and 17.2% (674) did not undergo radiation therapy. The status was unknown for 0.6% (22) of the patients. The original study results showed that sentinel node biopsy plus axillary lymph node dissection were associated with significantly greater risk of lymphedema vs sentinel node biopsy alone.
Upon secondary analysis, researchers found no greater risk of lymphedema among women receiving radiation therapy vs among women who did not receive radiation therapy. There was no significant difference in standardized arm measurements and no significant difference in patient reports of bothersome arm swelling during 3 years of follow up, suggesting that radiation does not contribute to lymphedema risk beyond surgery over time. Interestingly, although receipt of radiation did not impact either, there was a lack of agreement between patient reports of bothersome swelling (subjective lymphedema) and clinician measurements of arm swelling (objective lymphedema) throughout the 3 years of follow-up.
At 36 months follow-up of the sentinel node biopsy plus axillary lymph node dissection group that had received radiation therapy, 12.4% (147/1,183) had relative arm volume difference >10% (objective lymphedema), and 7.4% (16/216) reported bothersome swelling (subjective lymphedema). Within the sentinel node biopsy plus axillary lymph node dissection group that did not receive radiation therapy, 16.7% (36/216) had relative arm volume difference >1%, and 8.8% (5/57) of the group reported bothersome swelling.
Within the sentinel node biopsy-only group, 7.4% (90/1,218) of radiation therapy recipients had relative arm volume difference >10% (objective lymphedema) at 36 months of follow-up, with only 3.2% (8/250) of radiation therapy patients reporting bothersome arm swelling. For the sentinel node biopsy-only patients who did not undergo radiation therapy, 4.5% (10/220) had relative arm volume difference >1%, whereas 4.8% (3/63) reported bothersome swelling.
Impact of Radiation Therapy on Lymphedema Risk
“These results provide much needed reassurance to breast cancer patients regarding the impact of radiation therapy on lymphedema risk,” said lead study author Susan McCloskey, MD, MSHS, Assistant Professor of Radiation Oncology at The David Geffen School of Medicine at University of California, Los Angeles. “The study findings argue convincingly that radiation therapy to the Level 1 axilla, considered unavoidable “collateral damage” when radiating the whole breast, does not contribute to lymphedema risk beyond surgery. Several recent analyses have suggested that mastectomy rates are on the rise in the United States, and some have suggested that a desire to avoid radiation and its associated toxicities is a contributing factor. This analysis suggests that lymphedema concerns should not be an impediment to women choosing breast conservation and radiation therapy.” ■
References
1. Krag DN, Anderson SJ, Julian TB, et al: Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: Overall survival findings from the NSABP B-32 Randomized Phase 3 trial. Lancet Oncol 11(10): 927-933, 2010.
2. McClosky SA, Bandos H, Julian TB, et al: The impact of radiation therapy on lymphedema risk and the agreement between subjective and objective lymphedema measures: NSABP B32 Secondary Data Analysis. 56th ASTRO Annual Meeting. Abstract CT-06. Presented September 14, 2014.
