Case Study: Managing a High Risk for Recurrence of Early Breast Cancer

Kelsey Martin

Melissa, let’s talk through a case we had recently of a high-risk early breast cancer patient and how we approached the treatment algorithm for her and educated that patient on what to expect. So much has changed in the high-risk early breast cancer space in the last few years, so I think it’d be helpful for us to expand on what those treatments are and how we approach each patient’s care.  

The case we'll talk about today is for Amy, she's a premenopausal 47-year-old woman. She had a mammogram that showed calcifications in her upper inner breast. She had a biopsy of the right breast that showed an invasive ductal carcinoma. It was high-grade ER/PR positive—ER 100% and PR 70% positive. She had a HER2 IHC score of 1+ and a FISH-negative score with a Ki-67 of 20%. She underwent a lumpectomy, which showed she had 8 mm of invasive ductal carcinoma. One out of two sentinel lymph nodes were positive and she had lymphovascular invasion as well. We ordered Oncotype for her, and that came back with a score of 27. We decided to give her adjuvant chemotherapy and she had four cycles of TC. After chemotherapy and then radiation, she came in to discuss what endocrine therapy we would prescribe for her. So Melissa, what treatments are currently available for a patient like Amy in this setting?  

Melissa Rikal

We fortunately have had two new adjuvant therapy approvals in the past few years for our ER+ breast cancer population that allow patients with high-risk ER+ breast cancer to add a CDK4/6 inhibitor to their standard endocrine therapy. For Amy, we would likely recommend an aromatase inhibitor (AI) since she was node positive and we know there is higher efficacy when using an AI over tamoxifen in node-positive patients. Adding a CDK4/6 inhibitor, whether to an AI or to tamoxifen, has shown improved disease-free survival in these patients with high-risk, early breast cancer. 

The two trials that have been approved in the past few years are the monarchE trial and the NATALEE trial. MonarchE actually showed significant improvement in disease-free survival after 2 years of adjuvant therapy with abemaciclib with an AI or tamoxifen.¹This is now approved for those with node-positive disease and high risk of recurrence. So an abemaciclib combination therapy would be an option for Amy. 

We can also look at the NATALEE trial data, which included patients with both stage II and stage III early breast cancer.² These patients received 3 years of ribociclib with an AI adjuvantly, and we did see a significant invasive disease-free survival improvement over an AI alone with a 25% lower risk of invasive disease recurrence or death at the 3-year mark. This trial included node-positive and node-negative patients. We're essentially looking at the stage II and III early breast cancer population here. 

Kelsey Martin

So then which of these options is of greater interest for Amy, and why? Are there certain disease or patient characteristics that make one of these options better for her than the other?  

Melissa Rikal

In our clinic, when we're looking at a patient like Amy, we would consider the side effect profiles of both of these combination therapies. I think, in general, the data from the NATALEE trial are a bit more inclusive in that the study allowed node-negative patients as well as node positive. So we tend to use ribociclib more often for these adjuvant patients. It also can be better tolerated than abemaciclib. 

For Amy, we could use either since she is node positive, but I think we want to look at the whole picture and consider the side effect profile, especially since she is young—she's only 47-years-old. We know that abemaciclib tends to have more diarrhea, which can be a quality-of-life issue in a patient like this when she's probably still working, potentially full-time, and diarrhea can really be a barrier to that lifestyle. We also want to consider a patient’s pre-existing conditions and functionality, and if they can handle something like diarrhea. Are they limited in their physical abilities to get in and out of a bathroom? Are they going to be compliant with taking loperamide when they need to? Are they going to end up in our clinic with dehydration or electrolyte abnormalities because they're not managing it well? 

With ribociclib, we do have to watch EKGs on the front end for the first two cycles. That can be a bit cumbersome, but once they get out of those first couple of cycles, it's pretty easy and then they're just coming in for monthly visits. We do monitor for neutropenia in these patients, but in the adjuvant setting, ribociclib is actually approved at a 400-mg dose. We tend to not see as much neutropenia at this dose as we do in the metastatic setting when the patients are on the 600-mg dose. 

Something else we would consider with Amy is that she is premenopausal, so she would need ovarian suppression with her AI as well. She would come in monthly for blood count monitoring and could have this injection done at that visit, too. 

Kelsey Martin

That's all great data for these patients who we think are higher risk and we think could maybe benefit from additional adjuvant therapy. And it's great that we have multiple options for those patients so we can just tailor it to their needs.  

So if we assume that Amy has completed 3 years of her adjuvant ribociclib with an AI and ovarian suppression, what do we do next for her treatment beyond those 3 years?  

Melissa Rikal

We have the luxury of working in a large research center. So we can always consider clinical trial options when changing therapies for our patients, whether we're thinking about the neoadjuvant, adjuvant, or metastatic setting. Right now in our practice, we actually have the ELEGANT trial ongoing, which compares adjuvant standard endocrine therapy alone vs. elacestrant in our ER+ patients with a high risk of recurrence. This is a trial that's an option for patients after they've completed 2 years of adjuvant endocrine therapy, whether with or without a CDK4/6 inhibitor. So for this patient, once she's finished prior treatment—whether it's 3 years of a ribociclib combination or 2 years of abemaciclib—we would then consider putting her on the ELEGANT trial. When we're talking to patients about pursuing this trial, we explain that elacestrant is well tolerated, but we know that it has improved progression-free survival in the metastatic setting over standard endocrine therapies, which is why we're beginning to study this drug in the adjuvant high-risk setting. 

If I weren't in a research setting, or if Amy were opposed to participating in a trial at this point, I would likely talk to her about doing a breast cancer index (BCI) test to determine the potential benefit of extending her endocrine therapy beyond 5 years. The BCI test shows us if a patient who is high risk would benefit from 10 years vs. the standard 5 years of therapy; this test is available for patients with one to three positive notes, so Amy would qualify for this. 

Kelsey Martin

Is there a benefit for doing BCI testing at, let's say the 3-year mark, for someone like Amy after they finish their CDK4/6 inhibitor vs. waiting until closer to the 5-year mark where they're about to finish their 5 years of AI therapy? Is there a benefit of doing it a little bit sooner for some patients?  

Melissa Rikal

I think knowing the BCI prediction score can really help the patient plan for if they're going to need long-term therapy on an AI because this can really affect their quality of life. If they are going to need 10 years of therapy, maybe they're already struggling with side effects and so we will want to think about finding better symptom management strategies for this patient because we know she's in it for the long haul. If she's on monthly injections for ovarian suppression, for example, and we find out that she's going to need to be on her AI for 10 years, then it might be that she considers having a bilateral salpingo-oophorectomy with her OB/GYN at that point, just to avoid those monthly visits. Also, if her DEXA scans are showing that she has osteopenia or her bones are getting weaker, maybe in planning for those 10 years of therapy, we would recommend that she gets more aggressive with adding on bone-strengthening agents or doing more weight-bearing exercise. I think it is better to know on the front end than to wait until that 5-year mark and then be stunned with that information. 

Kelsey Martin

Sure, that makes a lot of sense. And I think you brought up a lot of the side effects that people can have with AIs. I know that certainly can be a struggle for a lot of patients, but even recently in the last few years, there've been additional medications and strategies that we've used for managing those side effects. Can you discuss what some of those strategies might be? 

Melissa Rikal

We've tried some new strategies recently for hot flashes. We actually had an approval in the past couple of years for a medicine called Veozah. This has actually been really beneficial for several of our patients with hot flashes, but it is still pretty expensive. Some insurance companies won’t authorize it, but I know they do have payment plans for commercially insured patients and financial aid as well. Older but tried and true methods for hot-flash management, of course, are our SSRIs, like escitalopram or paroxetine. But now we also have more natural remedy treatments, such as Relizen or Thermella from Bonafide Pharmaceuticals. These are Swedish pollen extracts, but they can really be quite beneficial for our patients with hot flashes. These drugs can be a little costly as well, as a patient is paying out-of-pocket for these through a monthly payment plan, but they really can improve quality of life. 

For vaginal dryness, there's now Revaree, which is also from Bonafide. This is a vaginal suppository that's a hyaluronic acid. It can be quite helpful for those patients. We also now have incorporated topical estrogens for some of our patients. There was a trial that read out in 2024 that showed that patients with hormone receptor–positive disease did not have a difference in breast cancer mortality when using a topical estrogen vs. those who did not.³So we're being a little bit more open-minded to allowing patients to use those now. 

Kelsey Martin

Those are some great points, Melissa, thank you. It’s encouraging to see how many treatment options and supportive care approaches there are for our patients now.