Rationale for Ovarian Suppression in HR+ Breast Cancer

During a discussion regarding data demonstrated by the RxPONDER trial in HR-positive breast cancer, breast oncologists consider when ovarian suppression is most appropriate and for whom.

Sara Hurvitz, MD: Can you address, Andrew, the use of ovarian suppression in the RxPONDER trial? Let’s dissect out the premenopausal patients a little bit further, if you will. In fact, I saw a patient in clinic yesterday who’s 49 years old, had a 3-cm tumor with a 2.5-mm lymph node metastasis. She is perimenopausal. She had a period a month ago, so truly not yet postmenopausal. We went through these data in great detail, and she’s very willing to do leuprolide with an AI [aromatase inhibitor]. I didn’t feel compelled to give her chemotherapy, though if you look at this trial, it would indicate that her recurrence score was 18. How would you approach a patient like this?

Andrew Seidman, MD: In RxPONDER, ovarian suppression was used in 16% of those patients getting chemotherapy plus endocrine therapy. It was chosen in 4% of those patients getting endocrine therapy alone. This is consistent with the SOFT trial profile; those patients whose risk is high enough to warrant chemotherapy also warrant the use of ovarian suppression. The other interesting piece of data that maybe speaks to your case is that at 6 months, 26% of those premenopausal patients getting chemotherapy had menses at 6 months versus 48% for those who did not. I’m not so sure; this is really provocative. I’m not sure how interpretable it is in terms of whether we really know that the chemotherapy benefit is solely driven by ovarian suppression. I don’t think we know, but I’d be curious to hear if Massimo or Sara Tolaney have thoughts about that.

Sara Hurvitz, MD: Massimo, do you want to weigh in here?

Massimo Cristofanilli, MD: I think the treatment part in this protocol was a little difficult to interpret or to put in the right context. There was the use of TC [docetaxel, cyclophosphamide], for example, and not anthracycline in a good fraction of patients. So, if you say that this postmenopausal patient would not benefit from chemotherapy, they do receive the right chemotherapy or the best chemotherapy that we have available. Of course, for premenopausal, the first thing that comes to mind is ovarian suppression with endocrine therapy, so that you can compare whether it should be a standard of care versus the best chemotherapy.

But I think there are some gray zones where we still, like your patients, don’t know for sure. In that case I think you want to use clinical factors, tumor size, and others. I think the other part of this, frequently we forget, is when you use an AI, you can use bisphosphonate or any bone modeling agent that can perform at the same level of chemotherapy or endocrine therapy. Obviously, a trial cannot answer all the questions, and if you don’t give specific strict direction of therapy, it would never be feasible if you were too strict. But I think this study has given some good direction. As we said, the pre and postmenopausal patient most likely can do well without chemotherapy. For the perimenopausal patient, we probably need to use some of the individual characteristics and consider what the patients could benefit from, what their preference is. For the premenopausal, just looking at the data, chemotherapy is the way to go. But I’m sure there are subsets of patients, but potentially you could do without.

Sara Hurvitz, MD: Sara, is it worthwhile to even check the 21-gene recurrence score if you have a premenopausal woman with 1 to 3 positive nodes?

Sara M. Tolaney, MD, MPH: I had a patient yesterday, too, in clinic where this came up. I think it’s challenging. When I look at the forest plots as was also done on TAILORx, in addition to RxPONDER, and you look at benefit in the premenopausal patients by age, it does seem like the patients who are likely to undergo chemotherapy-induced amenorrhea are the patients who are benefitting. Those patients between ages 45 and 50 are deriving a lot of that benefit. It makes you think, again, as everyone’s pointed out, we don’t really know that the benefit from chemotherapy is due to impact on ovarian function versus the true chemotherapy impact. But there is some suggestion.

It’s kind of consistent if you look at the TAILORx and RxPONDER forest plots and age and benefit. It does make me wonder, and so I guess part of me does want to think about offering some of my premenopausal patients ovarian suppression, AI, and others, potentially chemotherapy. And I think I’d want the recurrence score in my premenopausal patients. I think if the recurrence score is almost 25, I’m going to feel a little different than if the recurrence score is lower. That being said, the data in RxPONDER did not suggest that there was relationship between absolute recurrence score and chemotherapy benefit. I’m sorry, I realize that we cannot directly conclude that, but I think it is also prognostic information that you can meld into your clinical features to help you make those decisions.

Sara Hurvitz, MD: OK, excellent. I think that was a vigorous discussion on those data, and I do think they’re practice-changing, very important data.

Transcript edited for clarity.

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