ECC 2015

Regional lymph node irradiation in early breast cancer

Prof Philip Poortmans - Radboud University Medical Center, Nijmegen, The Netherlands

Philip, you’ve been looking at breast cancer and specifically regional lymph node irradiation. Can you tell me what it is that you’ve been doing? It’s been reported before but now you’ve got the latest publication out in The New England Journal, what’s been happening?

Well we randomised more than 4,000 patients who had either involved axillary lymph nodes and/or a medially located tumour, medially in the breast so at the inner side of the breast. They were randomised between local treatment to the breast alone with or without irradiation of the internal mammary and medial supraclavicular lymph nodes. We followed patients for a long time, the median follow-up is more than ten years, 10.9 years, and we saw a clear decrease not in the risk of local regional recurrences, there is somewhat, but in the risk for distant metastases. This decrease in the distant metastasis rate translated fully into an improvement in disease free survival, overall disease free survival, of 3% at ten years. Up to now it has been translated into a slight significantly just, not significant, improvement in overall survival of 1.6%.

What is it that this regional lymph node irradiation is doing to hold back the progress of breast cancer then?

There is one very straightforward explanation, and this is probably the right one, that the regional lymph nodes may harbour non-detectable, not clinically detectable, microscopic tumour deposits. By eradicating them with radiation therapy you decrease the risk for subsequent progression and distant metastasis.

Why was it the same whether the patients had breast conserving therapy or mastectomy?

I think the most important is that the risk factors for distant metastases are better before that for having cancer cells in the lymphatics. It’s not the way you treat breast, the risk factor has to do with tumour size, with location of the tumour within the breast, with whether or not systemic therapy was given and so the classical risk factors overall.

You’ve been able to follow this for quite a long time, how much impact on overall survival could this be making?

In the long term I expect that the impact on overall survival will increase because at ten years there are 3% more patients living with distant metastases compared to the group that was treated on the regional lymphatics. Already at ten years we had a benefit of 1.6% so we expect that at 15 years, and we are starting already now with the first phase of the new analysis after 15 years of follow-up, we expect that the difference in overall survival will be greater than at ten years.

Why is it that these regional nodes are so important then, do you think, compared with irradiating other parts of the body and whole breast irradiation?

Breast cancer is typically a disease that spreads, depending on the type of breast cancer it will spread from breast to lymph nodes to distant places. The aggressive forms can spread immediately, you can have a small tumour with immediately a lot of distant metastases but parts of them go via or through the lymph nodes. Those patients can be treated with local regional treatments alone.

What are the clinical messages, then, coming out of this for doctors treating their patients with early breast cancer?

The clinical message is primarily that for patients, especially those with involved lymph nodes, we should always consider the treatment of the regional lymphatics from the axilla up to the internal mammary lymph nodes. This is irrespective of whether or not systemic therapy has been given, as shown in our trial, where even the benefit was larger in those patients who received chemotherapy and hormonal therapy.

Are there any downsides, toxicities, cardio-toxicity for example?

It’s an excellent question. In our study we did not have any increased toxicity at ten years on the level of the heart. We had a slight increase in pulmonary toxicity, however, we also scored the toxicity in a cross-sectional manner and then we demonstrated that most of this toxicity is not permanent. Radio pneumonitis at nine months can complete disappear and does in the majority of the cases.

So the short message for cancer doctors in how best to use their radiotherapy would be what?

To consider regional treatment, regional irradiation, in patients with risk factors. Don’t give it to all the patients, we have to properly select the patients who benefit most. For this we will jointly with other trials that one was jointly published with our paper, the other will come out very soon in another important journal, we will do a meta-analysis to define those subgroups who benefit most.

Thank you very much, Philip.

A pleasure, as usual.