Stephanie Graff, MD, FACP: Let’s fast-forward with this patient and assume that she has gone through adjuvant chemotherapy and radiation, and is presenting to discuss initiation of adjuvant endocrine therapy. As a premenopausal patient, one of the things that I think is really important that we talk about is the role of ovarian function suppression. The body of evidence far and away supports that ovarian function suppression improves our outcomes for patients with hormone receptor–positive breast cancer. And I think that the body of evidence at this point really supports that that’s true for all comers independent of stage, independent of tumor characteristics.

Obviously, the punishment has to fit the crime. Would I offer ovarian function suppression to a T1AN0? Probably not. Would I offer ovarian suppression to this patient with 5 positive lymph nodes? Yes. So, I would be talking to her about ovarian function suppression in combination with an aromatase inhibitor [AI]. I think adding an AI, rather than tamoxifen again—evidence supports that the AIs improve outcomes over tamoxifen. I think that often when I’m having this conversation 1-on-1 with my patients, I tell them that we can always take steps backward. But sometimes I find once you’re on a therapy that’s working well for you, it’s hard to decide to move up the scale. But if you’re on something that feels bad, it’s really easy to decide to peel back the layers. So I think my tendency is full-court press and then peel back if it’s hard. What do you what’s your approach, Dr Layman?

Rachel Layman, MD: It’s similar. I think in this case, I would offer her ovarian function suppression and an AI, certainly. She’s very young, so the ovarian function suppression seems to have the most benefit, the younger you are. She would be someone who would receive a lot of benefit from ovarian function suppression.

That being said, it’s hard. It is a very hard therapy, especially for these young patients who are used to having a lot of estrogen around. One thing that I sometimes do is if their ovaries are already a little suppressed, or completely suppressed with chemotherapy, I’ll start the ovarian function suppression as quickly as I can after chemotherapy, so they don’t start to recover and then have to go through the withdrawal of estrogen again. I think in the node-negative setting, I often will use tamoxifen. Sometimes in select cases, I would do ovarian function suppression. My experience has been [that] it’s a very difficult therapy to tolerate for some patients, so I try to match the risks and benefits. But I do agree if you were trying to give the most effective therapy to each and every patient, it would be ovarian suppression with an AI.

Stephanie Graff, MD, FACP: I think that prior meta-analysis has shown that in pre-menopausal patients, the addition of an AI over other therapy results in a reduction in recurrence of 21%, and in all comers regardless of menopausal status, the addition of an AI over tamoxifen results in a reduction of occurrence to 31%. So, we’re talking about really substantial reductions in risks switching to AIs from tamoxifen.

That was actually my poster at ASCO [the American Society of Clinical Oncology annual meeting] 2023, looking at distant disease-free survival and invasive disease-free survival for the nonsteroidal AIs vs tamoxifen in patients by menopausal status. And we saw that the group that benefited the greatest from AI over tamoxifen were the premenopausal patients, presumably all of whom were getting the AIs with ovarian function suppression given that in a premenopausal patient, AIs really can’t be used without ovarian function suppression. And their overall survival was the greatest. They have the greatest magnitude of benefit from that change. And that was really great to see.

We had a sort of parallel selection in this real-world analysis that we performed to look at a NATALEE-like population—because in the NATALEE trial [NCT03701334], patients did not receive tamoxifen—to get a sense of how patients did if the focus was really on the AIs, and saw a lot of value in making that change.

So back to our case, we’ve decided to offer her an AI and ovarian function suppression. She’s only 39. I think another thing that’s important to acknowledge is her current pregnancy. I mentioned her husband’s already had a vasectomy, and, of course, we did talk about fertility preservation. She says, “No, my husband had a vasectomy, that ship sailed, 2 and done,” so she declined. But, of course, now we do have the data presented at the San Antonio Breast Cancer Symposium in 2022 on the POSITIVE study, that after 2 years of therapy, it may be reasonable for patients to stop therapy and pursue pregnancies. I think it’s important that we keep that conversation in the dialogue.

Transcript edited for clarity.