Refining Treatment Approaches for HER2+ Breast Cancer - Episode 5

Hormone Therapy in HER2+ Breast Cancer

February 5, 2021
Joyce A. O'Shaughnessy, MD, Baylor Charles A. Sammons Cancer Center

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Lisa Carey, MD, FASCO, UNC Lineberger Comprehensive Cancer Center

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Vijayakrishna Gadi, MD, University of Illinois College of Medicine

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William Gradishar, MD, Northwestern Medicine

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Claudine Isaacs, MD, Lombardi Comprehensive Cancer Center

Joyce O’Shaughnessy, MD: Let’s say you have a patient who, for example, comes in and has some bone metastases, de novo metastatic disease. She’s young and triple positive, and she does really well with CLEOPATRA and with a THP [paclitaxel, trastuzumab, pertuzumab], and PETs [positron emission tomography scans] are now clear, with no FDG [F18-fluorodeoxyglucose] uptake. She goes in, gets her ovaries out, gets on an aromatase inhibitor, and continues the HP [trastuzumab, pertuzumab]. Maybe she even has local control because you’re hoping she’s going to be 1 of the ones who goes long term.

Just a show of hands in terms of the HP. The question is, we keep the endocrine therapy going, but how long do we keep the HP going? It depends. Someone’s got multiple mets, for example, or maybe just had like 1 or 2 bone mets or something like that. Who would like to speak from their experience? We obviously don’t have randomized data, but does anybody have any experience on that? What do you tend to do?

William Gradishar, MD: It’s always easy to be an authority when we have no data. Everything is an anecdote, but the reality is the longer a patient maintains stable disease, the more likely I am to probably take 1 of the anti-HER2 therapies away. I don’t know when that is. It’s different with each patient. The younger the patient, if they’re tolerating it, fine. If they start having any gastrointestinal symptoms from the pertuzumab, I’d probably get rid of that first.

Joyce O’Shaughnessy, MD: And probably with lesser disease. This could all be individualized. VK, what were you going to say?

Vijayakrishna Gadi, MD: I know it’s not data. It’s retrospective, and it’s from 2 centers. Rashmi Murthy published a paper not too long ago showing that if your best response to HER2-targeted therapy is a CR [complete response], most of the patients maintain that. They don’t speak to whether they de-escalate or get rid of drugs along the way. It certainly suggests that patients can do really well for a very long period of time, and some may actually be cured in that setting.

I’m just making that point, that we do have a little—not randomized controlled data, but there’s a little bit of—

Joyce O’Shaughnessy, MD: I’ll have to take a look at that, yeah. How about Lisa or Claudine: Any experiences or sense from a practical standpoint of what you do every day?

Claudine Isaacs, MD: We grapple with that. It really is an individual case-by-case situation. The patient’s view of it is obviously of incredible importance as well. For those patients who have a great response—you’re still doing it 2 or 3 years out, and you’re still wondering what you’re doing—if they have adverse effects, I happily get rid of 1. I spread it out a little, so when they can go places, they can go more easily. I’ve had some patients who have been champing at the bit to stop. Others are saying, “There is no way I’m stopping this. I want to come in because it makes me feel better,” and I don’t have any data.

If you want anecdotal experience, I just had a patient who had a great response, and she really wanted to come off. She was convinced that if she did other things it would be a better way to go. She changed her whole diet, and she felt great. She came to see me, and everything was great. I was feeling I should do this more, and her disease just started to grow again. It was 2½ years later, and she got 2½ years without anything, and she has a little lung progression. She was probably right.

We don’t know the answer to that, and it’s obviously something we need to study. We all have these phenomenal responders, and we wonder what we should be doing in that situation. We really don’t know.

Joyce O’Shaughnessy, MD: Lisa, want to add anything?

Lisa Carey, MD, FASCO: I tend to agree. I have to say, this really comes down to the goals of therapy are to control the disease and not to make the patient sick. If you’re doing well 2 years into it, and they’re having diarrhea or they hate coming in—and you’re in the middle of a pandemic—it’s perfectly reasonable to take a break. You’re going to be following them anyway.

That said, I have had very little success in convincing patients who are doing well and having excellent tolerance of these drugs to stop them. I had 1 patient, and it took me years to get her to let me stop the Navelbine she was on. She was on Navelbine-trastuzumab. She was on that. She died of myeloma years later, still taking it. I might have gotten rid of the Navelbine, but it took a long time. She’d say, “I forget about my disease most of the time. I come in to see you guys intermittently, and you give me an infusion. I don’t get sick. I don’t get constipation.” She just happened to tolerate it really well. She said, “Why would I change everything? You know I have metastatic disease.” She had very diffuse visceral symptomatic disease up front. She remembered what it was like to have bad metastatic cancer. You have to individualize it. It wouldn’t surprise me if it never comes back for a few patients we’re able to take off it. We don’t know who they are. The anticipation is that they will, but a holiday isn’t necessarily a terrible thing.

Joyce O’Shaughnessy, MD: Yeah.

Lisa Carey, MD, FASCO: I just wouldn’t count on it. You count on great longevity. I’d be very careful about the patients you choose it in. We know that with chemotherapy you’re better on maintenance doses than you are with intermittent dosing and coming off and on and stuff.

Joyce O’Shaughnessy, MD: I did it in 2, but I won’t do it again. I took 2 off after zillions of years. One came back in the liver in the same spot. She had been on Navelbine—at least it took forever—and she was on it 8 years. Then she did great on trastuzumab for X number more years. It came right back in her liver. Then I got her right back, thank God, to a CR, but now she’s on HP for life.

I had another patient in the pre-pertuzumab, and we stopped after a couple of years. We had 1 solitary bone met. We radiated it, and she was NED [no evidence of disease] 2 years later, so we stopped it. She came back in her brain. She lived a long time, but we couldn’t salvage her back. You know what I mean? I’m like, “That’s it. I’m not doing it anymore.”

Transcript Edited for Clarity