BCC 2021 | Prognostic biomarkers in breast cancer – the latest developments

Dr. Michael Knauer (00:03):
Between the last and the current St. Gallen Consensus Conference, we saw the results of RxPONDER, the node-positive subset of patients where the Oncotype DX test has been used, and it clearly showed again that this test is prognostic. It’s reproducible. It’s prognostic. We see that you can rely on multigene test because they are reproducible, and even though they measure different genes if you have several tests, but it remains robust, I would say. In the RxPONDER trial, patients with one to three positive lymph nodes have been evaluated, and you saw that in the postmenopausal set of patients, there has been no benefit at all for adding chemotherapy to endocrine treatment. On the other hand, what we have mentioned before is that in premenopausal women, there appears to be some benefit. And the higher the recurrence score is, the larger it would get, and we don’t have ten-year data of this trial, so the big discussion is really, what are we doing with those patients, and there were several different opinions, I would say.

For example, Fabrice André from Paris said, well, it’s very hard to leave chemotherapy away because this is a potential curing treatment of these patients, and we don’t have the data. It’s only extrapolation, and we think that it’s mainly an endocrine treatment effect, and the panel has voted on that. And more than, I don’t know the number, but 75% or more of the treatment effect is to be felt that it was an endocrine effect of chemotherapy.

Dr. Beat Thürlimann (01:55):
I would agree on that. As you can see in postmenopausal women, where we have, let’s say, an endocrine, clean environment to investigate the magnitude of benefit of chemotherapy, and there has been none. So, prognostic and predictive markers are important, of course, and we are not actually looking for more prognostic markers. We have already dozens of them, and that has been repeated by Dr. Jonas Bergh, and so on. In this regard, actually, only Oncotype DX gives us this information.

Dr. Michael Knauer (02:38):
But not in the RxPONDER trial. So this is different, and the main data comes from the Kathy Albain data from the old trial and a retrospective analysis of a prospective trial, of course. But I think we have to be very careful when we talk of predictive biomarkers in multi-gene signatures. I see that they are really, mainly prognostic on a high level, but predictiveness is still debatable.

Dr. Beat Thürlimann (03:04):
Yes, I think it is also important for which side to take on this issue, and you could see that those are in the panel as you mention that, for example, Fabrice André and Martine Piccart. They would like to have to test to justify withholding chemotherapy, whereas others, in other environments, is the other way around. You need a test. It’s a very strong prediction in justifying chemotherapy. And when you have an overall result, which is negative for chemotherapy, then you need a strong predictor in the individual patient to justify chemotherapy in my view. So that’s, again, escalating and de-escalating, and all starts with where you come from and where you start yourself. So, one important issue, which was discussed, is circulating tumor DNA. And Nicholas Turner gave an excellent lecture, and I recommend you to watch it on the demand lecture, can still be done today. And he elaborated on the different roles. The role could be in diagnosis and detection. Could be in surveillance after primary treatment. Could be in steering neoadjuvant, post-neoadjuvant or adjuvant therapy. And he clearly made the point for which indications situation we have which data. We haven’t got the time to go through all of this.

The bottom line is this is very promising, but it’s not ready for prime time. We use that in daily routine, in lung cancer. But lung cancer is not breast cancer, as the tumor genome is much more unstable there, and here we have a different situation. But we are sure that this will develop very fast. And it will be also first settled in metastatic disease to steer and being able to prove that this is really patient benefit. And not only a benefit related to lead-time bias, and this is a very promising development. And it is, obviously, also a way to implement innovation in countries which have not own the facilities for pathology and gene expression. Such tests can be quite cheap compared to the old technical requirements needed in pathology we are doing today.