Expert connection| Pro. Jian Zhang & Pro.Fatima Cardoso: To explore radiotherapy downgrading strategies for early breast cancer
Prof. Jian Zhang: That's great. I think it's an excellent work. Before we have three interview questions, I have one more questions for you. So do you think the ovarian suppression is very important for this kind of patients? Just you have mentioned that in premenopausal patients less than 50 years old, maybe chemotherapy induced ovarian suppression can gain the 5% of the DFS benefit. I just wonder do you have some record for this kind of patients. How many patients have been treated with OFS with LHRH agonists? And because the results have been published for several years. Do you have some record for these patients?
Prof. Cardoso: Please remember that MINDACT enrolled patients almost 15 years ago. So at that time, the use of ovarian function suppression was much lower. So the number of patients who had an ovarian suppression in MINDACT is very low, as well as in Taylor-x. So it's about 15% that received an ovarian function suppression, most of them received tamoxifen alone. So we cannot answer this question in this trial between ovarian function suppression and chemotherapy. We have to go for maybe other trials that have looked into that question.
Prof. Jian Zhang : I guess maybe you can design a new clinical trial for C-high and G-low patients randomize into two groups, The first is for the chemotherapy for premenopausal patients, and other is OFS plus AI and maybe it's a non-inferiority clinical trials. I'm very eager for that.
Prof. Jian Zhang:The first is, At this ASCO annual meeting, you reported a secondary analysis of MINDACT trial with a follow-up of 8.7 years. Compared with the first analysis in 2016, what are the DMFS and OS results of the ITT population in the chemotherapy and non chemotherapy groups of C-High / G-Low patients?
Prof. Cardoso : Thank you. It's good to mention the different the end points that we analyze, just reminding everyone that the primary endpoint of MINDACT was distant metastasis free survival. And this is important because it is very close to overall survival, more than disease free survival. When you look at the primary endpoint that I already explained this long term analysis make the primary endpoint even more positive, stronger with 95.1% of distant metastasis free survival at five years. When we look at the secondary question of chemotherapy versus not, we see for distant metastasis free survival, at five years, the difference is 0.9, and at eight years, the difference is 2.6. At five years, the difference is 1.1 for overall survival. And at eight years 1.4. So we can say that there is a small difference, but there is a difference in distant metastasis free survival, but there is no difference in survival. So chemotherapy does not impact survival in MINDACT at least with 8.7 years follow up.
Prof. Jian Zhang: Thank you. So that is an impressive result. And we have another question for you is that you also reported the exploratory analysis of MINDACT trial at the recent SABCS conference, and got similar results with TAILORx trial, that is, people ≤50y still need to combine chemotherapy with endocrine therapy. Does age and other factors need to be considered in middle risk population?
Prof. Cardoso : So I think this observation both in Tailor-X and in MINDACT, they are very interesting. But I think everyone must remember that they are exploratory analysis. They are not the primary analysis of these trials. So they are very good for us to try to understand the results. But this is not the primary question of these trials. So what these trials show both Tailor-X and MINDACT, if you have a young woman premenopausal, less than 50 years old with a clinical high risk as we define it in MINDACT and then I can explain what that means, but with a clinical high risk, you have a genomic low risk, for example, using mamma print but also using oncotype. In that case, the benefit of giving chemotherapy or not becomes clinically significant. However, most of us believe that is because these women become menopausal because of chemotherapy. And so we believe that if these women had been treated with tamoxifen plus ovarian suppression, or AI plus ovarian suppression, we would not see that difference, but we cannot prove it, not with Tailor-x and not with MINDACT. We would need to do the trial that you suggested that I wish we had financial support to run that trial.
Prof. Jian Zhang: OK, that's great, so another the last question is that In the study of MINDACT and TAILORx, the majority of patients' endocrine therapy was TAM alone. For younger patients under 50 years old, should the benefits come from combination of chemotherapy or OFS?
Prof. Cardoso : So as I just mentioned, we cannot conclude that from the MINDACT or the Tailor-x we cannot answer that question. Is it an ovarian suppression or is it chemotherapy? But my personal opinion is that it's due to the ovarian suppression. And so in these women that have a clinical high risk and you perform a mamma print and is low risk, I would treat them with in the endocrine therapy plus an OFS.
Prof. Jian Zhang : That's great. I just want to ask another question that do you divide the patients less than 50 years old into two or three groups just to less than 35 or 40 and another is 40-50. Because we know the OFS is very important for patients less than 40 years old, maybe chemotherapy induced ovarian suppression is more important in this kind of population. So do you have any results to show us?
Prof. Cardoso : That's a very good question. The problem is that we have very small number of patients below the age of 40, very few patients that were included in MINDACT and also very few in Taylor-x. So for those very young patients, we cannot provide an answer. But if we look between the 40 to 45 and then 45 to 50, indeed, you see that this effect is mostly on the 45 to 50, so exactly on those where chemotherapy is more likely to induce menopause. So you're right. It is linked to the age. It's just that for the very young, we do not have enough patients to conclude that. But for above 40 and above 45, we can see that difference.
Prof. Jian Zhang : Okay, thank you very much for your presentation and answers. I think this is a very impressive and interesting clinical trial result. I think maybe in the near future for five years to 10 years, maybe we could not find another interesting trial impress me. Again thank you very much!