Dr. Jame Abraham:
Welcome to The ASCO Post Roundtable Series on Ovarian Suppression in Breast Cancer. I'm Dr. Jame Abraham, Department Chair, Hematology and Cedical oncology, Cleveland Clinic. I'm joined by two of my colleagues, Dr. Roesch and Dr. Ali. Dr. Roesch, if you could introduce yourself.
Dr. Erin Roesch:
Yes. Hello, my name is Erin Roesch. I am a breast medical oncologist at Cleveland Clinic.
Dr. Azka Ali:
Hi, my name is Azka Ali. I'm a breast medical oncologist at Cleveland Clinic.
Dr. Abraham:
Thank you. Thank you, Dr. Roesch and Dr. Ali for joining. So let's review the second clinical scenario. She's a young patient, Ms. SM, she's 39 years old, of course, premenopausal with a small tumor, T1aN0M0, ER-positive, PR-positive, HER2-negative breast cancer. She opted for a mastectomy and she did not want to take tamoxifen, adjuvant endocrine treatment, because she was planning to have more children.
She didn't have mammogram for the contralateral breast, but she agrees to have annual MRIs, and she continued that for about 10 years or so, or until this episode. So at the age of 49, 10 years later, she presented with a palpable abnormality on the same side. So she had an ultrasound of the left chest wall, which showed a 6- by 5-mm mass, and she had a biopsy at that point, which confirmed the recurrence.
And then she had a left breast local excision, and she was found to have a multifocal invasive mammary carcinoma with mixed ductal and lobular features. It was grade 2 and it is about 10 mm. The ER was strongly positive, 90%, PR was 80%, and HER2 IHC was 2+. So let me pause. Again, this is not unusual, and she was really young and she did not take an endocrine treatment. And of course, she had a small tumor, node-negative. She had no radiation at that point. So Dr. Ali, what do you think? How do you go from here?
Dr. Ali :
So some of the few things that I would do sounds like were already done here, which would be something like comparison of the morphology to see if we can get any clues to see if this is a true ipsilateral recurrence or if this is a new primary. We know that in about 10% to 15% of patients, they can even have a biomarker change. And we also know breast cancer is very heterogeneous. So I think if that information of morphology is available, I think that can be very helpful.
The pattern and the time, that is obviously very concerning for a true ipsilateral recurrence. In terms of management, I think it's a controversial space, because we don't have a ton of robust data in this situation. I think something to consider here, I would look at this patient and see if this is somebody who would've been able to go on the CALOR trial, which looked at about 150 patients, half of them were randomized to chemotherapy and half were randomized to no chemotherapy. And we know that the ones that did not derive chemotherapy benefit were the ER-positive recurrences that were completely excised. And of course, all the patients were completely excised, all the recurrences that is. So I think based on that, my first thought would be consideration of adjuvant endocrine therapy. I think one could argue that she did not get any tamoxifen, and she's still premenopausal, so that's a clear consideration here.
There may be an unclear role of considering a genomic assay here. I've certainly done that in this space. I may offer that. I don't know if I have a ton of data to back that up, but I think sometimes it can give interesting clues on the tumor biology, which can be very helpful as we are thinking about right-sizing that treatment in that recurrence setting.
Dr. Abraham:
Thank you, that's excellent point. So you talked about many different things, including how do you make sure it's the same tumor or is it something new? And then looking at the biology, you talked about the CALOR data and the risk and benefit of... Or any benefit from cytotoxic chemo vs endocrine treatment only. So Dr. Roesch, is this somebody you'll do a germline testing or is it something you'll focus or...?
Dr. Roesch:
Yes, I think that's a great point. Obviously, I'd want to understand and know her family history, but in a patient like this, very young and with this recurrence, I would consider her for genetic testing.
Dr. Abraham:
So do you repeat? Let's just say she had germline testing done 10 years back, will you repeat or?
Dr. Roesch:
Yeah, I think that's a great question. And because genetic testing has evolved and there are different assays that are available now that weren't perhaps 10, 20 years ago, I think it would be worth... it would be a very relevant discussion of the role of repeating her genetic testing, considering the time interval between then and now.
Dr. Abraham:
Right. I think it's 2013 or so, when they started doing the panel. And you're right. That's a good point. So you're right, we'll obtain the genetic testing and then make sure they did the panel testing. If not, we can ask our genetic counselor and make sure they do the panel testing. Okay, good. So then another thought, again, I don't have a clear idea. Will you do a staging at this point? Are we staging or what do you think? What do you guys think?
Dr. Ali:
I would probably stage this patient just to make sure there's no distant metastasis, but once again, I don't know. I think in a small ipsilateral recurrence in the chest wall, it's likely to be just an isolated recurrence. But I think I would definitely stage this young patient.
Dr. Roesch:
I agree for essentially any of my patients with a recurrence. And in this case as well, I agree with Dr. Ali. I would also do restaging, albeit understanding that the likelihood of finding anything in terms of distant metastatic disease would be low, but I would still favor staging in this case.
Dr. Abraham:
I agree though. I know she's... 10 years. And then of course, unfortunately, at least in some ER/PR-positive patients, you always worry about this delayed some kind of event and a local or distant or so. So that makes sense. That's very reasonable. So Dr. Roesch, Dr. Ali mentioned about genomic testing or do you have any thoughts or what do you think?
Dr. Roesch:
Yeah, I think to Dr. Ali's point, this is a little bit of a controversial space. I think that based on the CALOR data, suggesting that patients with ipsilateral, local recurrences, ER-positive disease would not derive benefit from chemotherapy, and the benefit was really restricted to those with ER-negative disease. I think that the option of proceeding with antiestrogen or endocrine therapy alone is very reasonable.
But to Dr. Ali's point as well, I think that consideration of a genomic assay is something that would certainly, it would cross my mind as well. And I think that it's also reasonable to consider in this situation. But I think, again, based on the data that we have with CALOR, and also this patient had not been exposed to antiestrogen therapy in the past either, which is an important point.
Dr. Abraham:
So here, Dr. Ali, I know you mentioned the choices. How will you make a decision because she never had tamoxifen, right?
Dr. Ali:
Yeah. Yeah, I think it's definitely reasonable to consider tamoxifen, right? Because this is somebody who's essentially endocrine therapy naive. I think if the genomic score is sent, I think the difficult decision is if the score comes back high, if you treat this patient with chemo. I think my kind of thought on genomics testing similar to upfront genomic testing, is once you get the score and once you have that additional information on biology, it's hard to unsee that.
Once again, I think we're not coming from a high-quality evidence space, but this is a space which is a very rare occurrence in terms of breast cancer recurrence, isolated local regional recurrence. So I would factor that in if that is sent. And if based on where that score lands, I think then I would really have that discussion about choosing a treatment option with her.
Now, what I'm not sure if I would offer here is an adjuvant CDK4/6 inhibitor, because that's obviously, we worry. We wonder that if this patient is going to have some benefit from that. And likely yes, but once again, I don't know if this small recurrence would really qualify for any of the eligibility criteria from some of the trials we've seen in the adjuvant space.
Now, there is a trial that's actually ongoing out of University of Chicago, I think after a complete resection with looking at ribociclib in this setting for 3 years. So I think if that was an option, I would certainly recommend that to a patient. But I think if I do do a genomic test, I would look at that score and I would have that discussion accordingly.
Dr. Abraham:
Okay. So our options are either tamoxifen or ovarian suppression with an aromatase inhibitor, so we can consider either leuprolide or goserelin with an AI. So it looks like this patient's story is interesting. Dr. Ali, it looks like she's your patient, she had few other things. You want to go over that?
Dr. Ali:
Yeah, sure. So she did have a genomic test sent and it came back at 20. At that point, the discussion was had with the patient on that potential chemotherapy benefit. Again, borrowing some of that literature from TAILORx data. With that potential benefit of 1.6% and us not understanding if that comes from ovarian ablation effect chemotherapy or if that comes from the chemotherapy itself. Based on that discussion... She also underwent some chest wall radiation and regional lymph node radiation.
Based on the discussion, she opted to choose ovarian functional suppression with leuprolide and exemestane, aromatase inhibitor therapy, and she also started adjuvant zoledronic acid. Four months later, she went ahead and had a bilateral salpingo-oophorectomy and lysis of adhesion. She'd had a previous GI surgery, as we recall for appendix removal. Interestingly, she had some post-surgical complication. Four months after her surgery, she actually started having very heavy bleeding, and of course, she was on ovarian function suppression. She had some GYN imaging which suggested presence of an ovarian remnant. And then she had her-
Dr. Abraham:
Let's pause for a second then. Let's just say, so she had a surgery, right? She had a BSO. Let's just say you put somebody on ovarian suppression and then you started having... Patient started having bleeding. Dr. Roesch, have you seen that or have you had similar occasion or no?
Dr. Roesch:
I have seen that. So we're talking before they have a BSO?
Dr. Abraham:
Right, right, right. Yeah.
Dr. Roesch:
Before they have a BSO, and obviously, and they are started on ovarian suppression, I have seen that. Especially initially when you are first getting them started on ovarian suppression, in those scenarios and I think that, again, working in a multidisciplinary fashion, working with our gynecology colleagues and having the patient seen if they are having bleeding. And then checking hormone levels, checking an estradiol level, and if they are not fully suppressed, noting that. And then trying to achieve that, obviously with modification of the agent you're using or the interval. But it does happen in clinical practice. And personally, like I said, I will often involve my gynecology colleagues in these situations if needed.
Dr. Abraham:
So here, Dr. Ali, you're talking about the patient had an ovarian BSO right?
Dr. Ali:
Yeah.
Dr. Abraham:
Removal of the ovaries. Now she has bleeding, vaginal bleeding. Okay, keep going.
Dr. Azka Ali (13:36):
Yeah. So she had bleeding 4 months after having her ovarian removal, and she had a follow-up GYN imaging with the pelvic ultrasound, which suggested a ovarian remnant. She had her hormones checked, which showed a estradiol of 29 and FSH of 58.6. So at that point, a conversation was had with the gynecology provider that she had seen for her surgery, because she had been receiving exemestane, which can alter the estradiol measurement, the exemestane metabolites. And then the decision was actually made to... I guess I'll leave it open here and see what others would do in this situation.
Dr. Abraham:
So she had her ovaries taken out and now she has high estrogen, she has periods, and as Dr. Roesch was saying, I'll be calling my gynecology colleague and say, "Help me." That's what I do.
Dr. Roesch:
Yeah, no, I completely agree. And then I guess the question would be does she need any resumption of a GnRH analog in the interim until we sort out what's going on here?
Dr. Abraham:
Right.
Dr. Ali:
Yeah. So that's exactly what was done. As we were trying to figure out what to do, we put her back on the GnRH analog. And initially, she was scheduled to go to the following month, but then when her estradiol was checked serially, it actually looked that she was quite suppressed for at least a few months. So the gynecology team wanted to watch her for a little bit, and then she had additional breakthrough. So the decision was made to take her to the OR for the removal of the ovarian remnant.
Dr. Abraham:
How often do you see ovarian remnant?
Dr. Ali:
I don't think it's a very common phenomenon. I don't have the stats off the top of my mind, but I do know that some of the things that put you at risk for it are mostly surgical type things. So having a prior GI surgery, prior GYN surgery, piecemeal removal of ovaries, some of these things can put at a high risk. From the GYN literature, it seems like they are quick to think about it because it's something that they hear about and they see infrequently if so.
Dr. Abraham:
That's really interesting. I haven't had any patients with ovarian remnant, but this really, really fascinating.
Thank you Dr. Ali and Dr. Roesch for joining us for this exciting discussion. So in the key clinical takeaway from this conversation in patients with the chest wall or ipsilateral recurrence. Based upon the randomized CALOR data, if the patient has ER-positive tumor, most benefit is obtained by anti-estrogen treatment. If the patient's tumor is ER-negative, of course, those patients will benefit from chemotherapy or systemic chemotherapy.
In ER-positive patients when we select antiestrogen treatment, endocrine-naive patients, low-risk, tamoxifen is an option. In high-risk patients, so those patients who are exposed to tamoxifen, aromatase inhibitor in premenopausal patients, ovarian function suppression with goserelin or leuprolide with an AI is the treatment of choice. Another option is doing bilateral salpingo-oophorectomy. And if the patient has vaginal bleeding while they are on either goserelin or leuprolide, make sure they're not having a breakthrough bleeding.
About 14% of the patients potentially can have the breakthrough bleeding. In this case in a clinical scenario, Dr. Ali's patient really interesting, she had vaginal bleeding after bilateral salpingo-oophorectomy. So the interesting point in this thing is we should work up that patient for a remnant ovarian tissue. So of course, we can involve a multidisciplinary team to make sure that we are on the right track. Again, thank you for the excellent discussion, Dr. Ali and Dr. Roesch.
So this is the conclusion of the case 2. Please see the other segments for further discussion about the latest data in breast cancer or visit ascopost.com.
