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Dr. Kaklamani: 
This is CME on ReachMD and I'm Dr. Virginia Kaklamani.  

Dr. Swain: 
And I'm Dr. Sandra Swain.  

Dr. Kaklamani: 
So, Sandy, what is on the horizon for ovarian function suppression in premenopausal HR-positive early-stage breast cancer patients? 

Dr. Swain:
Well, I'm so glad you asked. This is my favorite topic. We really had this question; Do we need to give ovarian suppression and chemotherapy or is the chemotherapy causing ovarian suppression and that's why we're getting a benefit?  

We started the OFSET study in the NRG about a little over a year ago and this study will randomize patients to what we consider a standard of care ovarian suppression and aromatase inhibitor to chemotherapy plus ovarian suppression and an aromatase inhibitor. And we’re looking at invasive disease-free survival benefit in this group of 3,960 patients. So, we’re very excited about it. We're getting good accrual for this study and hopefully someday soon we'll have an answer to this question that we've been asking for so many years.  

The other study that's very interesting, though it's a single-arm study, it is prospective in Korea in patients who have positive nodes. They’re using a NGS-based multi-gene assay, what they have discovered, called OncoFREE. And in those patients who have low genomic risk, they get ovarian suppression plus tamoxifen or an AI for 5 years. So, they're going to compare this to historical control, so we’ll see if this actually also is a benefit in these low risk patients, which is a different kind of question that we’re asking in the OFSET trial.  

Now, something else that was really interesting that was published recently was an ASCO survey on what is going on in the use of ovarian suppression. And it wasn't just in the US, it was throughout the world. And it was amazing findings. So, it was really all over the place on the treatment. And it concluded by saying we really want guidance on what to do with ovarian suppression. So, I think that that was a really important survey and gives us ideas of how we can help guide physicians in the treatment with ovarian suppression.  

Dr. Kaklamani: 
I think the other issue to consider is, now that we have other adjuvant therapies such as CDK 4/6 inhibitors, how do you incorporate CDK 4/6 inhibitors in ovarian suppression. And it's important to remember that if we're going to give ribociclib to our patients, we cannot give ribociclib and tamoxifen because of the prolongation of the QTc. So, if we’re going to use ribociclib adjuvant, we actually have to put a patient on ovarian suppression and then give them an aromatase inhibitor. 

The other issue that also arises even with abemaciclib, is the risk of venous thromboembolic events that increases when you're combining abemaciclib and tamoxifen. So, overall, it's probably a good idea. Plus, these patients have a high enough risk of recurrence because they're going to be on a CDK 4/6 inhibitor that you also want to give them ovarian suppression. But I typically combine those two.  

Now, obviously, we're talking about all this stuff, and we mentioned toxicities as well, and it’s important that we ask our young patients what they want. What is their preference as far as ovarian suppression? How long to take this for? And there was a nice study that asked our young breast cancer patients about extended ovarian suppression and the majority of them, 64% of them, were in favor of continuing. As long as you told them that their absolute benefit as far as risk of recurrence was more than 5%. And so, to me, that seems very fair and that's what I usually discuss with my patients. And most of them will be happy to continue ovarian suppression for more than 5 years.  

Dr. Swain: 
Well, I think this has really been a great discussion. But I want to go back to the OFSET trial, of course, and really, we don't have an absolute answer of whether a chemotherapy needs to be given in addition to ovarian suppression. And that's why this study is so important.  

Dr. Kaklamani: 
You’re right. I was a young faculty at the time. I was looking at the trials that Nancy Davidson runs for ECOG and so forth. There was always one arm missing and finally, that missing arm is going to be used in OFSET to answer this question. So, I’m excited about that trial as well.  

So, well, this is all the time that we have for today. I want to thank you for a great discussion, Dr. Swain, and thank you to our audience for listening. 

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