Dr. Jame Abraham:
Welcome to The ASCO Post Roundtable Series on Ovarian Suppression in Breast Cancer. I'm Dr. Jame Abraham. I'm the Department Chair of Hematology and Medical oncology at Cleveland Clinic. Joining me today are two of my colleagues. 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. Abraham:
And Dr. Ali?
Dr. Azka Ali:
Hi, my name is Azka Ali. I am also a breast medical oncologist at Cleveland Clinic.
Dr. Abraham:
So today we'll be discussing ovarian function suppression and it's role in the treatment of breast cancer with three clinical scenarios. And I really thank Dr. Ali and Dr. Roesch for joining this conversation. So let me start with the first case scenario, or patient story.
This is a 46-year-old patient with a history of, she had a hysterectomy for fibroids sometime back, but she had intact ovaries and she had a screening mammogram, which showed a stage I or clinically T1N0M0, ER-positive, PR-positive, HER2-negative invasive tubular carcinoma. And again, that was based upon a screening mammogram in December 2020 or so.
She had a partial mastectomy with sentinel lymph node biopsy, which showed multifocal invasive tubular carcinoma and the size was about 5 mm. And in addition to the tubular carcinoma, she had some atypical ductal hyperplasia, and the pathology showed a grade 1 tumor as expected in tubular carcinoma and six lymph nodes are removed and all were negative for cancer. And the ER was more than 90%, PR was 10% and HER2 negative as per IHC. So this is a really interesting clinical scenario. So Dr. Roesch, in this scenario, it's tubular. So what will you do next? She had lumpectomy, so what will you do next in a similar stage?
Dr. Roesch:
Yeah, so looking at the features from pathology, specifically focusing on things such as the tubular histology, the small size, the low grade, no nodal involvement, estrogen positivity. I think this is a case where I would recommend or favor proceeding with adjuvant endocrine therapy alone. The question of a genomic assay comes to mind as well, but I think considering the favorable features of this particular tumor, I would feel comfortable with endocrine therapy alone and go from there. However, I would say if the patient had requested or wanted a genomic assay to be sent, I would think that's reasonable as well.
Dr. Abraham:
Dr. Ali, is that the way you'll approach too?
Dr. Ali:
Yeah, I would agree. In a young woman, albeit her young age, but a small tumor, tubular histology, very highly ER positive. We don't have Ki67, but very likely to be low in this situation. Clinically low risk disease and very likely to be genomically high risk. So I would very likely also offer adjuvant endocrine therapy and forgo the genomic testing.
Dr. Abraham:
As Dr. Roesch said, again, this is grade 1, this is tubular, so a little more convincing. But if the patient asks, she's only 46, she wants it, I have done it in the past, but as for the guidelines criteria, I think you are absolutely right.
Dr. Ali:
I think one thing I'll mention is the multifocal histology. Sometimes that does worry me. We know that that's an adverse feature. So once again, I think depending on the patient and kind of the nervous level and some of the other features that are things like grade and PR level, I think it's certainly it makes sense to do it, but I think we have to kind of look at everything in context of the clinical picture.
Dr. Abraham:
So let's just say now we are kind of thinking of, because you'll talk about local treatment, radiation therapy, and then let's say she's in our clinic for adjuvant therapy, you're making a decision, you're going to treat her with endocrine treatment. So what things you'll focus at this point?
Dr. Roesch:
Yeah, so I'll weigh in on that. I think some of the questions I would have for this patient or any of our patients coming into our clinic is relevant medical history, things such as other medical issues, medications that patients take on a regular basis. And focusing on medical history, I'd want to know does this patient have any history of blood clots, cardiac risk factors. In terms of medications, one of the things that we often encounter are antidepressants, and those can potentially interact with some of our endocrine therapies, specifically tamoxifen. So I'd start by asking some of those questions to better assess what might be best for the patient.
Dr. Abraham:
Right. And then absolutely. Does she have any other risk like obesity or any other risk factors for DVT and thrombosis? So this is interesting. This patient had a history of DVT after a long flight, after an international flight, and it's about 4 years prior to this diagnosis in 2016 or so. So she had shortness of breath, she had this left leg swelling, and then she had a CT PE protocol, which showed a multifocal segmental PE. So that raises a red flag, right. Azka, what do you think?
Dr. Ali:
Yeah, I think it's tough when we are looking at venous thromboembolism or VTE and the risk factors of patients because there's multiple things that are risk factors and some of those are longstanding provoking risk factors. At least that's how I think about it in my mind. And some of them are kind of transient risk factors. So we don't know her BMI, we don't know her weight and some of the other risk factors like smoking, was she on birth control when this happened? But she did have this big event and it sounds like it might've started from a DVT as well. So I think that presentation does worry me given the elevated risk of VTE with tamoxifen, and tamoxifen carries a boxed warning for that. So that does worry me. I think I would have a discussion with the patient, especially in setting of a low-risk breast cancer and the presence of alternative treatment options.
Dr. Abraham:
So when you look at DVT risk with tamoxifen, so now you're kind of trying to weigh the risk and benefit of what's the endocrine treatment you're choosing. So when you look at the risk and benefit of tamoxifen vs aromatase inhibitors, how do you communicate that with the patient?
Dr. Roesch:
Yeah, so I think in terms from a side effect standpoint, I think that, well, the side effect profiles I'll explain are obviously different. So I agree with Dr. Ali and this patient, particularly with the VTE, the blood clot, knowing other risk factors that the patient might have would certainly be important. I would feel a bit hesitant to treat this patient with tamoxifen in light of that. But on the other hand, the other option would be an aromatase inhibitor plus ovarian function suppression if this patient is not yet menopausal. And the different symptoms or potential side effects, with that approach. I advise patients they differ from tamoxifen in that you can experience hot flashes or vasomotor symptoms, mood symptoms, vaginal dryness or sexual dysfunction. And then osteopenia, osteoporosis in my mind is the more concerning potential risk with ovarian suppression plus the aromatase inhibitor vs tamoxifen. So I'll explain that to the patient and then that of course has to be weighed against the benefit of taking endocrine therapy. And again, in this situation it is a low-risk tumor. And so I think that needs to be weighed against the potential risks with these therapies as well.
Dr. Abraham:
Completely, I completely agree with weighing the risk and benefit. So Dr. Ali, which patients you select for ovarian suppression, let's just say for this patient, she has a contraindication. So I think it's a little more straightforward. We can always talk about the absolute contraindication vs not absolute, but in which patients you select an ovarian suppression and AI in an early stage breast cancer.
Dr. Ali:
I think the more of the SOFT/TEXT data that we see and more we're learning that the patients that are really getting benefit from the aromatase inhibitor/ovarian suppression combination are probably the ones that are slightly higher risk. So we saw a 13-year update this year where we see a disease-free survival improvement of 4.6% with ovarian function suppression and aromatase inhibitor. But I think it must be noted that there's a modest benefit in distant relapse–free survival in those that did not get chemotherapy, which likely represents a low-risk population, a low-risk patient like this one. So typically for a node negative patient, a small tumor like this one, an absence of a genomic score, I would probably discuss that information that's out there and let the patient make that informed decision. And I agree with Dr. Roesch, ovarian function suppression and aromatase inhibitors are not harmless. So some of these side effects of bone health and musculoskeletal events, they can be quite tough on some patients.
Dr. Abraham:
Right. So you're saying that, and of course if the patient is younger, patient with a high risk of relapse and those who receive chemotherapy, those are the patients we may see an absolute benefit from the ovarian suppression. Right.
Dr. Ali:
Yeah, I would agree with that.
Dr. Roesch:
And I think also there was on that the follow-up data after the 12-year mark, there was the OS (overall survival) benefit was really noted in those high-risk patients. The women that were very young, younger than 35, those with larger tumors, and those with higher grade tumors. So I think again pointing to the benefit of this approach, meaning ovarian suppression plus an AI for those higher-risk patients.
Dr. Abraham:
So when you select ovarian suppression, do you usually do monthly or do you do every 3 months or how do you do that?
Dr. Ali:
I think that's a great question and I think when we look at the data, it doesn't seem to be a large efficacy difference, but from some of the subsets that we have seen from SOFT-EST substudy, we do think that there is a higher risk of ovarian escape in some of our younger patients, 35 or younger or those with a higher BMI. So I think once again, I would kind of factor in the high risk status of the tumor and patient's age and some of the other risk factors like BMI and other comorbidities.
Dr. Abraham:
Right, right. Absolutely. Yeah. So it's kind of an evolving data. So Erin, is that what you do too or?
Dr. Roesch:
Yeah, I think it is a great question and something we're learning more about. And I think practice patterns can be different among different institutions and even different providers. But I think that in clinical practice for myself, in those patients who, to Dr. Ali's point who are very young, the BMI consideration is also a notable one, but the very young patients I would adhere to the monthly administration of a GnRH analog, whereas the patients whom I might, I might consider for an every 3 month dosing could be those that are closer to natural menopause, perimenopausal. And so those I think would be the patients that I might feel more comfortable with that approach.
Dr. Abraham:
And COVID changed our mindset too, right? Yeah. Initially we were dogmatic because of the data and now COVID we are kind of saying, okay, less frequent is okay.
Dr. Roesch:
Completely. And I think we had some patients that had started that approach during COVID and kind of going backwards might be challenging sometimes because of convenience then every 3 months vs monthly could be different for our patients.
Dr. Abraham:
Another thing I have seen is insurance. Sometimes the insurance insists you can give only monthly and the next insurance will say you can give only every 3 months. And that is really interesting. I don't know if you had similar experience.
Dr. Roesch:
I have. And even with different GnRH analogs as well. So there's definitely insurance considerations that need to be taken into account and I do find that overall patients are very receptive to all of these things. And many of our patients, they will do what is best and what's recommended to treat their breast cancer. And so it involves modification of plans sometimes and it's very individualized. I don't find myself doing the exact same thing for every single patient.
Dr. Abraham:
Thank you Dr. Roesch and Dr. Ali for the excellent discussion. So the key takeaway of ovarian function suppression in a premenopausal patient with ER-positive breast cancer. In high risk patients, especially young patients, and as per the SOFT/TEXT data under the age of 35, those who received chemotherapy and with larger tumors—they had a clear benefit in disease-free survival and overall survival with ovarian function suppression.
In low-risk patients, we can always have the conversation and discuss about the risk and benefit of ovarian function suppression vs treating the patient with tamoxifen only. Of course, tamoxifen increased the risk for venous thromboembolism. We should have a clear risk assessment of the patients with the history, personal history, and then their past medical history. And of course, we need to screen the patients for thrombosis. Ovarian function by itself or ovarian function with an aromatase inhibitor has its own side effect too. So when we expose a patient for a long-term ovarian function suppression, of course we should be aware of those potential long-term complication. We should have that conversation with the patient. And then some of the side effects such as bone health, cardiac health, and different things, we should be aware and then we should be proactively managing that too.
This brings us to the end of this case. Please see the other segments for further discussion about the latest data in breast cancer or visit ascopost.com.
