BCC 2021 | Genomic predictors for treatment selection in ER+ breast cancer: TAILORx, MINDACT, and RxPONDER

At the St. Gallen Consensus Conference, I was given the task to summarize the huge amount of work that has been done with the use of genomic predictors, as ways to better individualize adjuvant treatment for women with early luminal breast cancers. Hormone receptor-positive, HER2-negative breast cancer.

For these women, it’s very obvious that endocrine therapy plays a major role in order to protect these women from a relapse, but the difficult question has always been who needs to receive chemotherapy in addition to endocrine therapy? And what I think is remarkable is that during the last 15 years or so, there has been a real effort at answering this question with the design of large, well powered, prospective clinical trials that were really designed to demonstrate the clinical utility of the genomic predictor, because that is what is very important; to demonstrate that the genomic predictor brings something in addition to the traditional clinical and pathological factors.

I was very lucky because in 2020, we got very striking results from three large precision medicine trials, two of which have a quite mature follow-up: TAILORx and MINDACT. The median follow-up there is about nine years, which is very relevant in these luminal cancers, because the risk of relapse goes beyond five years, as you know. And the latest trial, the youngest one, RxPONDER was presented with a median follow-up which is already decent, which is five years.

What I think is particularly striking is that there is a very strong message coming out of the three trials in my personal opinion, and the message is that if you are high clinical risk using traditional criteria, clinical and pathological, and we have come up with a nice definition of the high clinical risk patient in MINDACT. If you are high clinical risk, but you have a low genomic signature, favorable genomic signature, either Oncotype or MammaPrint and if you are above the age of 50 and post-menopausal, in the three studies, there is no indication that chemotherapy is beneficial, and this is seen across the three studies. It is seen in high-risk, node-negative patients, because in TAILORx, it was only node-negative patients who were eligible. And it is seen in MINDACT and it is seen in RxPONDER, which is a trial dedicated to women with one to three positive nodes.

The data, in my opinion, are so strong, that it is really time for oncologists to have the courage to change their habit, which has always been, there are positive nodes, I need to prescribe chemotherapy. This is no longer valid. In contrast, what the three studies very powerfully show is that this is not the case for the young women.

For the young women across the three trials, there is a benefit from chemotherapy, highly consistent from one study to the other. It is real. Of course, then there is the question, is it chemotherapy in itself? Is it the indirect endocrine effect of chemotherapy in young women, which is of course ovarian function suppression? This is a question of debate, but the evidence for chemotherapy is very strong and this is what we need to share with our patients.