I just presented the ten years result of the AMAROS trial. AMAROS is an acronym for After Mapping of the Axilla Radiotherapy or Surgery. This is about breast cancer patients who have a tumour positive sentinel node and these patients were randomised between either full axillary clearance, what was considered to be standard treatment in those days, and radiotherapy to the axilla, usually together with radiotherapy of the breast. This trial was designed around 1999 in the last century and in those days when a patient had a tumour positive sentinel node axillary clearance was by far the standard of care. We would like to de-escalate side effects further. The main aim of this trial was to show that the axillary occurrence rates of lymph node metastases was equal by both modalities and that the radiotherapy modality would be associated with less side effects.
This trial was up and running between 2001 and 2010. It entered 4,800 patients, 1,400 of them had a positive sentinel node and two times 700 were randomised between either radiation therapy or full axillary surgery of the axilla. We presented five years ago in 2013 the five year results and they showed a very low event rate in the axilla in both groups, very low, and much less side effects in the patients who had radiation therapy. But there was some criticism by then – because of the very low number of events the trial was considered underpowered so the non-inferiority was not statistically shown, albeit that the number of events were extremely low so we were happy for our patients. Secondly the five years follow-up was considered short for breast cancer. Breast cancer is a slow growing disease so it was considered short and people thought that maybe after ten years there will be more events in the radiotherapy group or more side effects.
So, according to the five year results the results were not generally accepted. There were countries where they maintained doing axillary clearance or nothing and radiotherapy only in a limited way. Now we have the ten year results to convince the community that it is really a good thing to do because the number of events is still extremely low. In 2013 there were 4 lymph node metastases in the axillary clearance group after 5 years and 7 in the radiation group; now the figures are 7 and 11 out of 700 in each group so that’s extremely low. So both treatments are, from a cancer point of view, equal. Then, of course, the side effects and the long-term side effects, we don’t have much more extra information because getting the forms was not easy but we have some extra information. The risk of lymphedema, swelling of the arm, is indeed far lower in the radiation group.
So the conclusion is radiation to the axilla, particularly in those patients who will get radiation anyway because of breast conservation or the primary tumour characteristics mandate a chest wall radiation, and the sentinel node is positive, just do radiation of the axilla together with the breast or the chest wall and you have an excellent regional control and less side effects.
Are there any situations where one treatment may be preferable over the other?
For coming Monday should we now irradiate every patient with a tumour positive sentinel node? Well, no, that’s not per se necessary. There are two other trials that randomised between axillary clearance and wait and see and those trials also showed in the wait and see groups very low axillary recurrence rates but these patients got irradiation, tangential field and systemic treatment. So for our practice, in my environment, we have decided the following: isolated tumour cells, micromets, very small deposits – do nothing; low risk breast cancers, smaller than 2cm, one micromet in the lymph node, in the other one, the sentinel lymph node, and the second is free – wait and see; larger tumour, grade 3, heavier or more tumour deposits in the sentinel node – radiation of the axilla. I think this general idea is more and more accepted.
What we observed in this trial is that it looks like there are somewhat more contralateral breast cancers in the radiation of the axilla group as compared to the surgery group. It is in absolute numbers 12 and 22, it’s still very low so one could think that the extra irradiation may have any effect, a small effect, on the risk of contralateral breast cancer. This is, on the other hand, difficult to see because all the patients received tangential field breast irradiation anyway. From the tangential fields it is maybe that some side effects could be on the other breast. There are many studies on this and there is no one study that shows a very large effect on contralateral breast cancer.
In conclusion, with respect to the somewhat more contralateral breast cancer, it is a coincidental finding. We don’t think it is really related to this irradiation of the axilla.
Then a third criticism is that the radiation field we used for AMAROS was not only the axilla but also the supraclavicular fields, which is not standard throughout. In our institute, as well as many other institutes, we only irradiation now the axilla and we don’t use this supraclavicular field anymore.