SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.

“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.

The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.

In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.

Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).

“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.

The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).

The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.

During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.

The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.

“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”

In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.

“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”

The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.

Dr. McCloskey disclosed no relevant conflicts of interest.

Radiation therapy for early breast cancer did not increase lymphedema risk