This is an update of the SOFT trial. The SOFT trial was one of two trials that were launched by the International Breast Cancer Study Group to try to optimise endocrine therapy in pre-menopausal women. The SOFT trial tested the addition of ovarian function suppression to tamoxifen alone or then the use of an aromatase inhibitor – in the case of this trial, exemestane – with ovarian function suppression, and compare that to tamoxifen alone, which had been, and in many cases still is, the only standard endocrine therapy for pre-menopausal women.
At the time that we initially reported the data, about 5.4 years median follow-up, there was no statistically significant advantage to the use of ovarian function suppression in the overall study group. We’re now reporting an eight-year update.
Was that looking at any specific breast cancer types, any biomarkers or indicators?
It is of course in pre-menopausal women, so you had to be pre-menopausal to enter onto the SOFT trial, and that could be either you were having regular menses and they never had chemotherapy, or you had chemotherapy and a documented pre-menopausal oestradiol level after receipt of chemotherapy, and of course you had to have a hormone receptor positive tumour, and for this study it was defined as oestrogen or progesterone receptor greater than 10%, although the majority of women on the study had strongly ER/PR positive tumours.
This is eight years on, findings are consistent with what’s been reported so far?
I think at eight years median follow-up, we now do see a statistically significant benefit to the use of ovarian function suppression, both in the primary endpoint of the trial, which is disease-free survival, as well as a number of the secondary endpoints of the study, and there’s even a small overall survival benefit to the addition of ovarian function suppression to tamoxifen.
You asked about HER2 status, which is a bit of a confounding point in the trial, because it did allow HER2 positive patients to enter, and the treatment of HER2 positive disease changed over the time of the conduct of the trial. We enrolled starting in about 2003, so some of the patients received trastuzumab and some didn’t, so there’s some heterogeneity that we see with respect to HER2 positive disease. But overall there’s a benefit to the use of ovarian function suppression that’s now clear.
I think there is one more point that I’d like to make and that I’ll be emphasising in my talk is that ovarian function suppression, as you can imagine, does add toxicity for young, pre-menopausal women, and many young women, despite the fact that they’re pre-menopausal, are still not at that high a risk of recurrence. In the group of women who did not receive any prior chemotherapy, and this was by patient and physician choice, but it was a stratification factor in the trial, so it was something that was analogous that was planned ahead, there are hardly any distant recurrences and hardly any deaths at this point. So the addition of ovarian function suppression to someone who’s at low risk is not worth it. For someone who is at higher risk I think it’s clearly worth it, and how high a risk is something that is not clearly defined and at this point is going to be a matter of individual decision for each patient and physician.