A new study shows that administering radiation therapy to the lymph nodes situated behind the breast bone and above the collar bone to patients with early breast cancer improves overall survival without the risk of increasing side effects.
This new discovery puts an end to the uncertainty regarding whether the advantageous effect of radiation therapy in such patients was merely the result of irradiation of the breast area, or whether it treated in the lymph nodes as well. The study’s findings were presented at the 2013 European Cancer Congress (ECC2013).
Radiation oncologist from the Institute Verbeeten, Tilburg, The Netherlands, and a member of the EORTC Radiation Oncology and Breast Cancer Groups, Dr Philip Poortmans, stated that the results from an international randomized trail, which included 4004 patients from 43 centers, were credible.
"Our results make it clear that irradiating these lymph nodes give a better patient outcome than giving radiation therapy to the breast/thoracic wall alone. Not only have we shown that such treatment has a beneficial effect on locoregional disease control, but it also improves distant metastasis-free survival and overall survival," he said.
Lymphatic drainage from breast cancer means that the cancer has a greater chance of spreading to other areas of the body, usually diverging into two paths; the first and most known is to the axilla (armpit), and these lymph nodes are typically treated by surgery and/or radiation therapy. The second pathway drains to the internal mammary (IM) lymph nodes behind the breast bone, and also to those just above the collar bone, the medial supraclavicular (MS) nodes.
Therefore, due to the uncertainty surrounding the effects of treatment in this region, and growing concerns over the increased toxicity that might be caused by the irradiation of a larger area, many centers do not currently treat the IM-MS lymph nodes.
Moreover, after a median follow-up of 10.9 years, the researchers discovered that patients in the IM-MS treatment group had better overall survival independent of the number of lymph nodes involved. A total of 382 patients in the IM-MS group died during that period, in comparison with 429 in the non IM-MS group, and there was no increase in non-breast cancer related mortality in the first group. As of today, there have been no serious complications related to the treatment.
The researchers also trust that the beneficial effect of IM-MS radiation can be elucidated by the ability of the treatment to abolish microscopic tumor deposits in the lymph nodes.
"With this treatment, we can stop the development of metastases at their source. Interestingly, this effect is irrespective of the stage of the tumour. We believe that this is likely to be related to the positive interaction of the IM-MS treatment with systemic treatment chemotherapy, hormonal therapy and targeted treatment,” said Poortmans.
Patients who are already at a low risk of their cancer spreading anywhere beyond the breast receive less intensive systemic therapy in order to avoid any unnecessary side effects. In such circumstances, utilizing IM-MS radiation therapy can improve their outcome by abolishing any remaining tumor cells in the breast/thoracic wall. Patients with a higher risk of metastases, who receive systemic therapy, the outlook of a cure is also linked to the chance of leaving remaining tumor cells behind throughout the body. Therefore in such circumstances, the definitive outcome can be improved by using effective locoregional treatment to abolish disease at the site where it is most likely to be present.
"The results of our trial, in which the patients received appropriate systemic treatments, contradict the existence of a 'competition' between locoregional and systemic treatments," said Poortmans. "Because there is an interaction between these treatments, in many patients their combination will result in an enhancement of the combined benefits; in other words, one plus one can equal more than two."
As of now the researchers plan on following up on these patients in the long term, roughly over an average follow-up of 20 years, with the next analysis set at 15 years.
"It is of the utmost importance that we record all possible events, including recurrence and toxicity, and such follow-up will also give us the opportunity to continue evaluating our patients in other areas, for example quality of life and wellbeing. But we believe that our trial has already given solid evidence of the benefits of radiation treatment of the IM-MS lymph nodes, and we hope that such treatment will become standard clinical practice for patients with early breast cancer,” said Poortmans.
"In past studies, radiotherapy as an adjunct to surgery has shown important improvements in locoregional control as well as survival, and these further survival benefits without an increase in short and long-term toxicities are a valuable development. The results of this study will help us on the road to the development of yet more personalised treatments, in which we have to find the delicate balance between under-treatment resulting in an increased risk of disease recurrence, and over-treatment accompanied by unnecessary toxicity, in order to provide optimal care for breast cancer patients,” said President of ECCO, Professor Cornelis van de Velde.
