Dr. Swain: 
This is CME on ReachMD, and I'm Dr. Sandra Swain. 

Dr. Kaklamani:
And I'm Dr. Virginia Kaklamani. 

Dr. Swain: 
Virginia, to start us off, can you provide a quick overview of ovarian function suppression in premenopausal hormone receptor-positive early-stage breast cancer? 

Dr. Kaklamani: 
Yes, absolutely. So, when we're trying to treat patients with breast cancer, a lot of times we talk about ovarian suppression and ovarian suppression really can be achieved by 3 ways. One is giving a GnRH analog, which is most of what we're going to talk about today. But we can also do pelvic radiation as well as surgery to remove the ovaries. Now, we don't really do as much radiation. Radiation is associated with a lot of adverse events and surgery is something permanent that some of our patients don't really want to experience. So, most of what we're doing is GnRH analogs. And there's 2 leading GnRH analogs in the United States, goserelin and leuprolide. Goserelin is the only one that's FDA-approved for breast cancer. The schedule for both of them could be either monthly or 3-monthly. The monthly schedule doses are a little different, obviously, from the 3-monthly doses, and a lot of the data that we're going to talk about is based on the monthly dose. But there actually is information looking at 3-monthly injections, and they seem to be working as well as monthly injections.  

Now, one of the differences between goserelin and leuprolide is the way they're administered. Leuprolide is given as an intramuscular injection, goserelin is given subcutaneously. And when we give these agents, sometimes we actually like monitoring FSH, LH and estradiol levels. I personally don't do that as much. I’ll do it initially to make sure that the patient is premenopausal, but subsequent to that I won't typically do a lot of FSH and LH estradiol testing.  

Now, Sandy, when we talk about all of this data with ovarian suppression in premenopausal women, can you give us an overview of all that data?  

Dr. Swain:
Sure, I'm happy to. I’ll start out by talking about the EBCTCG meta-analysis in 15,000 premenopausal women presented at ASCO a couple years ago. And this analysis that looked at patient-level data did show a very significant benefit of ovarian ablation or suppression in premenopausal patients. And they usually got the suppression with the GnRH agonist. So, this study I think is very important. It also showed that it didn't matter what age of the patient was, if they were premenopausal after chemotherapy then they still got a benefit from ovarian suppression. One caveat was if they got tamoxifen also with ovarian suppression, the benefit wasn't as large. So, they’re getting benefit from basically two kinds of endocrine therapy.  

Another trial, the ASTRRA trial, was done in Korea and that was using ovarian suppression for 2 years after chemotherapy, and it did also show a disease-free survival benefit with ovarian suppression.  

So, there are also the question of giving the GnRH agonist either monthly or 3-monthly. If you look at the ASCO survey that came out recently, more of the physicians actually use it monthly. However, there is a lot of data comparing 3 monthly to monthly from Japan. There are two studies. There’s a study from Korea all showing that the 3-monthly gives you the same suppression as with monthly. So, we really do recommend giving it every 3-monthly since this is much less time for the patient, less toxicity basically.  

Dr. Kaklamani: 
And what we actually found, we did a real-world analysis on the data with goserelin and what we found was that there was better compliance with the 3-monthly schedule compared to the monthly. And obviously, we all know a medication doesn't work unless patients are taking it. 

Dr. Swain:
No, I think that's a great point. And the other issue, too, is a lot of people are concerned that there's not suppression of the estrogen right away. But if you look at the data, especially these Japanese data, the suppression occurs within a couple of weeks. 

Dr. Swain: 
So, really to summarize, we have a lot of data from many years, showing that ovarian suppression does benefit premenopausal patients with ER-positive breast cancer. Well, this has been a very brief but great discussion. I hope we gave you something to think about, and thanks for tuning in.