Patients diagnosed with early breast cancer may benefit from radiation therapy to the lymph nodes located behind the breast bone and above the collar bone. New finding show that this approach improves overall survival without increasing unwanted side effects. The study results, presented at the 2013 European Cancer Congress (ECC2013) being held in Amsterdam, The Netherlands, September 27 – October 1, 2013, also ends the uncertainty about whether the beneficial effect of radiation therapy in such patients was simply the result of irradiation of the breast area, or whether it treated cancer cells in the local lymph nodes as well [1][2][3]

Philip Poortmans,MD, Ph.D, a radiation oncologist from the Instituut Verbeeten, Tilburg, The Netherlands, and a member of the EORTC Radiation Oncology and Breast Cancer Groups, noted that results from the international randomised trial, which involved 4,004 patients from 43 centers, were very convincing. ?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 loco-regional disease control, but it also improves distant metastasis-free survival and overall survival,? he said.

Uncertainty and concern
Lymphatic drainage from breast cancer means that the cancer is more likely to spread to other parts of the body. It normally follows two pathways. The best known is to the axilla (armpit), and these lymph nodes are usually treated by surgery and/or radiation therapy. The second pathway drains to the internal mammary or IM lymph nodes behind the breast bone, and also to those just above the collar bone, the medial supraclavicular or MS nodes. Because of uncertainty about the effects of treatment in this area, and particularly concerns about the increased toxicity that might be due to the irradiation of a larger area, many centers do not currently treat the IM-MS lymph nodes.

[The results show that] irradiating these lymph nodes give a better patient outcome than giving radiation therapy to the breast/thoracic wall alone.

Better Overall Survival
After an average follow-up of 10.9 years, the researchers found that patients in the IM-MS treatment group had better overall survival or OS independent of the number of lymph nodes involved. A total of 382 patients in the IM-MS group died during that period, compared with 429 in the non IM-MS group. Furthermore, the researchers found that there was no increase in non-breast cancer related mortality in the first group. To date, there have been no serious complications related to the treatment.

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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. ?With this treatment, we can stop the development of metastases at the source,? Poortmans explained. ?Interestingly, this effect is irrespective of the stage of the tumor. 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.?

Eradicating residual tumor cells
Patients at low risk of their cancer spreading outside the breast will often be given less intensive systemic therapy in order to spare them side effects. In these cases, using IM-MS radiation therapy can improve the outcome by eradicating residual tumor cells in the breast/thoracic wall. For patients at high risk of metastases, who receive systemic therapy, the prospect of cure is also related to the chance of leaving residual tumor cells behind throughout the body. In these cases too, the ultimate outcome can be improved by using effective loco-regional treatment to eradicate 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 loco-regional and systemic treatments,? Poortmans expand. ?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.?

Follow-up analysis
The researchers intend to follow up these patients in the long term and are planning an average follow-up of 20 years, with the next analysis 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,? Poortmans noted. ?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.?

Valuable development
Commenting on these results, Professor Cornelis van de Velde, MD, Ph.D., the current President of ECCO, said: ?In past studies, radiotherapy as an adjunct to surgery has shown important improvements in loco-regional 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.?

For more information
[1]Abstract no: BA 2: Irradiation of the internal mammary and medial spraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC Radiation Oncology and Breast Cancer Groups phase III trial 22922/10925. What:Presidential session I, Date/Time1.45 p.m. CEST, Saturday 28 September, Location: Hall 7.1.

Clinical Trial
[2] EORTC protocol 22922 – 10925 Phase III randomized trial investigating the role of internal mammary and medial supraclavicular (IM-MS) lymph node chain irradiation in stage I-III breast cancer (Joint study of the EORTC Radiotherapy Cooperative Group and the EORTC Breast Cancer Cooperative Group EORTC 22922/10925)
[3]NCT00002851 Lymph Node Radiation Therapy in Patients With Stage I, Stage II, or Stage III Breast Cancer That Has Been Surgically Removed [][Clinical Trials PDQ?]

Note: The Educational Book from ECC 2013 is published as a supplement to the European Journal of Cancer. [Download]

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