Case 3

Management of Ovarian Function in Premenopausal and Perimenopausal Patients With Early or Advanced Breast Cancer


This is Part 3 of Management of Ovarian Function in Premenopausal and Perimenopausal Patients With Early or Advanced Breast Cancer, a three-part video roundtable series.

In this video, Dr. Matthew Goetz (moderator), Dr. Ann Partridge, and Dr. Kathryn Ruddy discuss the clinical considerations in managing higher-risk invasive ductal carcinoma that ultimately becomes metastatic. A 47-year-old, premenopausal woman was diagnosed with invasive ductal breast cancer (estrogen receptor/progesterone receptor–positive, HER2-negative). The Ki67 index was 12%. A 1.6-cm tumor was identified, and one of four lymph nodes removed was positive.

The faculty discuss the treatment options for this patient, including the role of ovarian function suppression and use of tamoxifen. They also review the findings from a recent EBCTCG meta-analysis on the impact of ovarian ablation or suppression on tumor recurrence and survival. After initial therapy, the patient’s disease is found to have spread to the right axillary region and the liver, along with several osseous sites of disease. The experts then explore the role of ovarian function suppression in the metastatic setting, considering it within the context of treatment with fulvestrant plus ribociclib.


Dr. Matthew Goetz:

For the sake of time, we’re going to move on to our final case today. And this is a patient who’s 47 years old, premenopausal, and she presented with a palpable mass and ultimately identified to have an ER/PR-positive, HER2-negative breast cancer. This was invasive ductal. Again, the institution here obtained a Ki67, which was 12%.

She was seen in my clinic as a second opinion later in her disease course, but at this early time point, her pathology was a 1.6-cm tumor, and she had one of four lymph nodes positive on a sentinel lymph node. She ultimately had radiation therapy, and her local oncologist utilized MammaPrint in the decision making. And her multigene panel demonstrated that she was low risk, and so her physician elected for tamoxifen.

I think maybe the first question I’m going to raise for the two of you is in that setting of now a little bit different than that first case that we saw. This is a patient who is a little bit higher risk. She was ER-positive, PR-positive, HER2-negative, MammaPrint low-risk, but she has a positive lymph node.

What would be your thinking in terms of utilizing ovarian function suppression here, Katie?

Dr. Katie Ruddy:

This is a situation where I often do at least start with tamoxifen with ovarian function suppression. And then depending on how she tolerates that and also preferences and values, I would consider whether to go up to a aromatase inhibitor with ovarian function suppression strategy or just to stick with that. I feel a little bit uncomfortable with tamoxifen monotherapy when a lymph node is involved. I prefer an ovarian function suppression–based strategy here.

Dr. Matthew Goetz:

And I think many of us here would feel quite similarly. And just recently, Richard Gray presented an Oxford Overview on this was the EBCTCG meta-analysis looking at the role of ovarian ablation or suppression on recurrence and survival. And I would just say as someone, of course, who’s a member of the EBCTCG, this particular analysis was, I think, very well done. There were some older data published in the past. And the way that this analysis was done was really to divide out, and if you will, sort of sift through some of the data with regard to the issues of whether patients got their chemotherapy.

Whether they got it prerandomization, whether they were actually menopausal or not. But at the end of the day, what this demonstrated of course, was a very large benefit with ovarian function suppression in terms of reducing the risk for recurrence. And we have data, of course, not just at 10 years, but at 20 years, effects on mortality. But I think one of the things that was interesting in this analysis and related to those patients who were treated with tamoxifen, where we did still see benefit out, especially out at 10 and 15 years.

And so your thoughts on this case, Ann, in terms of ovarian function suppression?

Dr. Ann Partridge:

I wholeheartedly agree with you both. I think that it’s tricky these days with the data we have from RxPONDER as well, where I would typically use an Oncotype. And even if a person came out in the MammaPrint, not that there’s perfect correlation in those with a low-risk genomics score, I’d still be worried given the extensive disease in a premenopausal person. And many have even argued recently since RxPONDER that you shouldn’t even check one of these, or at least an Oncotype in this study. Now I still use it, but I’d still worry a little bit just given extensive disease. And I’d be a big fan of using a more escalated hormonal approach with ovarian suppression and choosing the partner. I typically will give them an AI as tolerated and then scale back as needed. But it very much depends on the person’s interest and whether or not I would switch it 2 to 3 years, kind of extrapolating from the postmenopausal setting. But this is a tricky one, Matt, I do like it. It’s what we deal with all the time.

Dr. Matthew Goetz:

And to make it perhaps even a little bit trickier, so this particular patient was treated with tamoxifen monotherapy. She’d actually had a uterine ablation, and so she was amenorrheic, and maybe this was something that perhaps was missed by her and her clinician. But ultimately, when I saw her in the clinic, unfortunately, she did have a recurrence. And this was approximately 3 and a half or 4 years later, she presented with a lump in her right axillary region. Biopsy unfortunately demonstrated recurrence, ER/PR-positive, HER2-negative. And her staging workup demonstrated extensive disease involving not only that region in her right axilla, but also the liver and bone.

And her biopsy, again, proved recurrence in the liver; this indeed was breast cancer ER/PR-positive, HER2-negative. When I saw the patient, it was quite interesting because she was referred to me for a second opinion, and she had already been treated. She had been started on, in this case, fulvestrant plus ribociclib. She remained amenorrheic. And I think one of the first things that I did when I saw this patient was to ask her, “Well, are you premenopausal or not?” Of course, she has been amenorrheic. We assessed her estradiol levels, and indeed she was still premenopausal.

Thinking a little bit about this, Katie, this patient is now on fulvestrant and ribociclib. Your thoughts on utilizing ovarian function suppression in this setting?

Dr. Katie Ruddy:

For a premenopausal woman, I would definitely initiate ovarian function suppression, but I’d be interested in relatively soon moving to bilateral salpingo-oophorectomy just in the metastatic setting. First of all, for convenience such that somebody doesn’t have to continue indefinitely with GnRH agonists, but also because we do know there’s some breakthrough from our GnRH agonists no matter what schedule we administer them in. And for somebody who has metastatic ER-positive disease, we really don’t ever want her to regain ovarian function. We don’t ever want estrogen stimulation to the tumor. So, I often do send people within a few months to receive oophorectomy in this situation.

Dr. Matthew Goetz:

Thanks. I think that’s a really good point. Ann, any additional comments on this particular case?

Dr. Ann Partridge:

I think it speaks to “trust but verify,” especially with someone who has had an ablation. I think it's sloppy at best to have not checked. Especially when she recurred whether or not she truly was suppressed, given she was still in kind of a perimenopausal age and hadn’t gotten chemotherapy, where you’d expect her to be fully shut down at that age. But some aren’t, some of these patients have what I call “ovaries of steel.” So, I think checking and confirming and even confirming again if you’re not sure, I think that’s the moral of the story there.

Dr. Matthew Goetz:

I think that’s a really good point in the sense that this patient obviously, when we saw her, was already in her early 50s but still obviously was premenopausal. And I think suppression of the ovaries, we do have data from the MONALEESA trial, the MONALEESA-7 trial, focusing on premenopausal women who have a diagnosis of metastatic disease. It’s ER-positive, HER2-negative, and obviously in that trial, ovarian function suppression was an integral part. So, we have data, and clearly in this situation, we would want to utilize that.

I know that our time is coming to an end. I would just like to thank my colleagues, Dr. Ann Partridge, Dr. Katie Ruddy, not only for participating, but for your expertise, for your research, for the work that you do for women, and specifically for young women. This is really critically important, so thank you.

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