Radiation therapy to the internal mammary and medial supraclavicular (IM-MS) lymph nodes can improve overall survival in women with early breast cancer??. European Cancer Conference 2013 (ECCO-ESMO-ESTRO). Abstract BA 2.

Radiation therapy to the internal mammary and medial supraclavicular (IM-MS) lymph nodes can improve overall survival in women with early breast cancer, according to new findings.

At a median follow up 10.9 years, patients who received IMMS radiotherapy had overall better survival than those who did not. This survival benefit was independent of the number of lymph nodes involved.

However, it is not yet the standard of care to radiate the IM-MS lymph nodes, explained lead author Philip Poortmans, MD, a radiation oncologist from the Institute Verbeeten, Tilburg, the Netherlands. "The debate over radiating these lymph nodes has been ongoing for more than 20 years," he said. "In general, the internal lymph nodes are also not treated in the US."

Dr. Poortmans presented his findings during the Presidential Session here at the European Cancer Conference 2013 (ECCO-ESMO-ESTRO).

He noted that a recent Canadian study showed a clear benefit to radiating the internal lymph nodes, although the follow-up time was shorter, at 5.8 years.

The Canadian researchers are currently developing a new study, which will be looking at new surgical techniques for the axilla. "US physicians are going to be participating in the trial, but they have stated that they will only treat the IM-MS lymph nodes in a subgroup with clear involved of axilla," said Dr. Poortmans. "But we have shown that the effect of radiotherapy is also evident in patients who have who no clear involvement, but if the tumor is located centrally in their chest."

Radiation therapy to the IM-MS lymph nodes is also not the standard of practice in his own country, Dr. Poortmans pointed out. "Currently, we are the only center in the Netherlands that routinely radiate the internal lymph nodes in high-risk patients," he said. "This group includes women with stage I - III breast cancer, and we saw the most benefit in patients with either low-risk disease and no node lymph involvement, or those who are treated with both hormonal and chemotherapy."

Although this hypothesis needs further analysis, the researchers believe that the beneficial effect of IM-MS radiation can be explained by the ability of the treatment to eradicate microscopic tumor deposits in the lymph nodes. "The earlier that already present metastases is treated, the more optimal the outcome," he added.

The outcomes appear to be unrelated to the tumor stage, and Dr. Poortmans explained that the benefit is also likely to be related to the positive interaction of the IM-MS treatment with systemic treatment ― chemotherapy, hormonal therapy, and targeted treatment.

Overall Survival Improved

The authors note that although locoregional radiation has improved survival in breast cancer patients with lymph node involvement, it is unclear how much IM-MS radiation contributes to the survival benefit. But because of concerns about increased toxicity when radiating a larger area, many centers do not radiate the IM-MS lymph nodes.

During the study period, 382 women died in the IM-MS group, compared with 429 who did not receive the treatment. Although the causes of death were similar in both groups, breast cancer–related mortality was lower in the IM-MS arm (259 vs 310).To address those questions, Dr. Poortmans and colleagues randomly assigned 4004 women with stage I, II, and III breast cancer. Within this group, 59% were postmenopausal, and 55.6% had involvement of the axillary lymph nodes. About three quarters (76.1%) were treated with breast- conserving surgery, and axillary radiation therapy was given to 6.8% of patients who did not receive IM-MS and 7.8% who did. The majority of patients (99.1%) who were lymph node–positive received adjuvant systemic therapy.

"Only death due to breast cancer was decreased by radiating those lymph nodes," Dr. Poortmans said.

They found that overall survival at 10 years was better for patients who received IM-MS radiation therapy: 82.3% vs 80.7% (P = .0560). Disease-free survival was also improved: 72.1% vs 69.1% (P = .044), as was metastases-free survival (78% vs 75%; P = .020).

Thus far there has been no increase in the number of lethal complications, the authors note.

This topic is quite controversial, as there is no general consensus about radiating internal lymph nodes in breast cancer patients who have no obvious involvement, commented Roberto Orecchia, MD, a professor of radiotherapy at the University of Milan, Italy.

Dr. Orecchia, who discussed the paper after its presentation, also pointed out that there is far more consensus about treatment in more invasive disease and patients with positive nodes.

Results of studies have also not been consistent. "Some data showed no difference in survival after irradiation of internal mammary nodes after mastectomy," he said.

In this study, radiating internal lymph nodes increased overall survival by 1.6%, disease-free survival by 3%, and metastasis-free survival by 3%, Dr. Orecchia reiterated. "In this case, better regional treatment meant less metastases and better survival," he said. "And the most benefit was in patients with lower tumor burden or those who had received both hormonal and chemotherapy."

Looking toward the future, he added that it will be necessary to "improve our capability of selecting patients and to implement more sophisticated imaging examinations," in order to identify the patients who will derive the most benefit from this procedure.