Most of my research is about harming less while maintaining good survival results. So the SENOMAC trial which I am presenting today is born out of the previous trials, the ACOSOG Z0011 and the AMAROS trial which show that you can actually omit axillary lymph node dissection in people who have sentinel lymph node metastases. But those trials were, at the time, too early and a bit too weak in some things that the Swedish guidelines were not accepting omitting axillary lymph node dissection at the time. So we decided we have to make another trial and actually fill in the gaps so we added patients who have to undergo mastectomy, which were not represented in the other trials, and also those with larger tumours. So the SENOMAC trial is basically just a confirmative trial of previous trials with slight gaps in knowledge really.

Could you outline the methodology?

The SENOMAC trial is a non-inferiority randomised phase III trial. The hypothesis is that not doing an axillary lymph node dissection after two micrometastases in the sentinel lymph node biopsy will not worsen overall survival. So overall survival is the primary endpoint and in non-inferiority trials you have to set a non-inferiority margin, so how much worse can it get? In that case we put the margin at 2.5, which is basically only four statistical power calculations. So it tells us that we needed 3,000 patients for this trial and 190 deaths in order to be able to have statistical power, so really robust results.

What did you find?

We have reported on the secondary endpoint of recurrence free survival in the New England Journal of Medicine 2024 and that already showed that there were no differences between the two groups. So one group being the one standard of care at the time, doing a completion axillary lymph node dissection after a positive sentinel lymph node biopsy, and the other group omitting that completion axillary lymph node dissection. 
Now we’re presenting the primary endpoint, overall survival, and, as before, we now have a median follow-up time of five years which is long; even though it’s a lot of ER+ tumours really in this trial it still is quite a decent follow-up and you can see that the overall curves exactly align with each other. The five-year overall survival is 94.3% in the group that omits axillary lymph node dissection and 93.4% in those who have an axillary lymph node dissection. So we could confirm non-inferiority because it’s also such a big trial that our statistical assumptions can be very well validated in this trial.

What impact could these findings have in the clinic?

In many guidelines people have already started or have omitted axillary lymph node dissection in patients who get breast conserving surgery because the earlier trials had that patient population and, of course, in the meantime we have a very long follow-up from those studies. But there’s really no other trial with a decent number of patients needing mastectomy, and in most countries that is at least a third of patients or something in that vicinity. So for patients who need a mastectomy, this trial is the only one showing that it actually doesn’t matter if they don’t dissect the axilla. But it does matter, of course, for the arm morbidity because we can see very clearly that, looking at all the different timepoints all the way out to five years after surgery, those patients who get an axillary lymph node dissection have much worse problems with their arm in terms of physical arm function but also swelling and pain. That difference is persistent over time so it’s nothing that is just in the early post-operative period but it actually stays like that all the way until five years.

Importantly, asking the patients about their problems after the surgery, you see a very large difference between those who have an axillary dissection and those who don’t have in terms of arm function and arm symptoms. So, of course, the group who has more surgery has much more problems in the early post-operative period, but all the way up to five years the same difference prevails. So it’s nothing that’s disappearing after a while but omitting axillary lymph node dissection in patients with breast cancer like that will actually spare their arm function and that, of course, impacts their quality of life.