Tamoxifen for Premenopausal Breast Cancer Q&A
-Can you put this in context of all the various functions of prescience studies?
So, this trial was the largest trial that's ever been conducted in premenopausal women with hormone receptor positive breast cancer. There was the important difference between this trial and other trials. There have been other attempts to look at the importance of ovarian suppression. The previous trials have been the effect of ovarian suppression, and it has really been diluted, because some women went into those trials with uncertain hormone receptor status of their breast cancer. So, they were a mixture of hormone receptor positive and negative.
The other thing was that women went into those trials straight after chemotherapy. And many of them were permanently postmenopausal from their chemotherapy. So, any effect from ovarian suppression was diluted. What was different about this trial was that we managed to get agreement from all the major academic cooperative groups from around the world to collaborate on the one trial, which is relatively unique.
We needed all those groups to contribute, because breast cancer in very young women is not common. To get more than 3,000 women in this age group we needed research groups from all around the world. And we were very fortunate in the US that the National Cancer Institute funded this research over many years. So, it shows the importance of federally funded research.
Other women under 35, all of them resemble variant function. Well, to go in this trial you had to resume ovarian function. You were not allowed in the trial unless you resumed. In the women under 35 years old 94 % got chemotherapy, but it is common in that age group for women to resume the function.
-How will you introduce the option to those participating in this study? How did the extended use of hormonal therapy influence your ability to judge the longer follow-up of the soft study?
So, it's crucial that we do get longer follow-up in the soft study, because we don't, actually, have mature survival data. We've followed the women for just over five and a half years. I think you can see that for very young women in that less than 35 years old group already a third of them have had a further breast cancer problem in five years. So, to my way of thinking, the data from, for example, atlas, where they looked at extended hormonal therapy with Tamoxifen for ten years, is much of the benefit coming in even later after ten years. I think that for young women, if they're already having significant number of breast cancer events within the first five years, for that under 35 young women, then it's too long to wait to say that the extended hormonal therapy might benefit them, because they may have already had a distant relapse by that time. So, for those youngest women that have not to say that you might not give them extended therapy in this trial, we only have five years of therapy. Maybe, some of them will choose to go on longer with some type of therapy, but for that youngest group, I think, they're having the events early, whereas the protection from longer Tamoxifen often comes later, as was showed in some prevention study. The protection occurs as many years off and after you finished Tamoxifen. And we needed it earlier for young women.
-Have you calculated the numbers needed for the treatment and for the panel at large? Do you see this as a persuasive practice changing trial?
I believe, it is a practice changing trial. It doesn't answer every question that we have in premenopausal women. But for me, if I go back to my practice on Monday with the woman under 35 with a hormone sensitive breast cancer, then I will now know what to advise that woman. Also, when I see the woman who's 48, who's got a small screen detected and non-aggressive breast cancer, then I will feel more comfortable that she can do very well with Tamoxifen alone. So, I think that there are, certainly, groups, for which this will be practice changing. Number needed to treat would be quite small for the women under 35, because you can see that one in three differences compared to the one in six suffer those very young women, and the number two trip will be small.
As women get older they had the most striking advantage, as the women get older within the premenopausal age group, and the number to treat will be larger. But there is still an advantage. It’s really the incremental advantage, so adding ovarian suppression to Tamoxifen gave a certain amount of advantages. And then, switching the Tamoxifen to the eczema stay in the aromatase inhibitor and keeping the ovarian suppression, there gave a little bit more advantage.
-Exemestane plus ovarian suppression effects sexual functioning. What about all the other arms? How did you measure it and what happened?
So, we thought that, actually, these things were crucial, when we planned the study, and, in fact, we did measure that. So, we have very clear data. And we set out at the start, because we felt this was crucial in a very young population of women.
There are many patients who are right now committed or have started ten years of Tamoxifen. So, maybe one year into it, two years into it, many of them are trading, being on the whole on this drug for a decade, some not.
Would it be reasonable encumber by your data to considering those women adding ovarian suppression now and consider shortening the treatment of ten years? Is that something that would be crazy or reasonable, based on the data you're showing?
Well, I guess the women that were included in our trial, were only the ones, who were premenopausal after chemotherapy. And, I guess, it might depend on the age group of the woman. I think that if the women are very young, and they're on Tamoxifen alone, if they're very young in that under 35 age group, then that's a discussion that needs to be had with them, whether they would want to consider ovarian suppression and eczema stone or an aromatase inhibitor as an alternative, because if they're very young, then it's very likely that they are still producing estrogen.