Standard-of-Care Treatment Approaches for HR+/HER2 Early Breast Cancer


A panel of expert oncologists review standard-of-care treatment approaches for HR+/HER2- early breast cancer and genetic testing practices when utilizing PARP inhibitors.


Komal Jhaveri, MD, FACP: Hello, and welcome to this OncLive Peer Exchange® [program], “Evolving Treatment Paradigms and Recent Data Updates in HR-positive/HER2-negative Breast Cancer.” I’m Komal Jhaveri, and I’m a breast medical oncologist at Memorial Sloan Kettering Cancer Center in New York. I’m joined today by an exciting panel of experts in the field of HR [hormone receptor]-positive breast cancer. I’d like to welcome my esteemed fellow panelists to introduce themselves. Why don’t we start with you, Aditya Bardia?

Aditya Bardia, MD, MPH: Hi. Thank you, Komal. I’m Aditya Bardia, breast medical oncologist at Massachusetts General Hospital, Harvard Medical School. Excited to be here today.

VK Gadi, MD, PhD: Hi. VK Gadi; I’m a medical oncologist at the University of Illinois Cancer Center and also the University of Illinois, Chicago.

Timothy Pluard, MD: Hello, I’m Tim Pluard. I’m a breast medical oncologist. I’m in Kansas City, where I direct a metastatic breast cancer center.

Komal Jhaveri, MD, FACP: And then we have Gregory Vidal.

Gregory Vidal, MD, PhD: I’m a breast medical oncologist at the West Cancer Center and Research Institute in Memphis, Tennessee, and also director and chair of the oncology breast program at One Oncology.

Komal Jhaveri, MD, FACP: Thank you all so much for joining me. Today we are going to discuss recent data updates on the treatment and management of HR-positive/HER2-negative breast cancer, including data presented at the…ASCO [American Society of Clinical Oncology] 2023 meeting and how these data may impact practice. Why don’t we get started on our first topic, which will focus on the concept of HER2-negative disease, which has evolved in the most recent years. We’ll focus on early-stage HR-positive/HER2-negative breast cancer. Tim, you can kick us off with this. We’ll [use a] first-name basis, if that’s OK with you. So, as we’re thinking about standard-of-care treatment management for HR-positive disease, maybe walk us through [these questions]: How do we manage these patients in early-stage disease, and how do you think about them when you’re treating patients in clinic?

Timothy Pluard, MD: Well, I think we’ve seen the evolution over the last 10 years with TAILORx [NCT00310180] and RxPONDER [trials; NCT01272037], where we’re using far less chemotherapy and relying more heavily on endocrine therapy. So that’s been a huge benefit. I think we’re now entering an era where we’re trying to optimize that endocrine therapy, identifying those patients who may benefit from a more intensive endocrine regimen, and likewise identifying those who may have a good prognosis and may be able to de-escalate their endocrine therapy. So it’s an exciting time.

Komal Jhaveri, MD, FACP: What about your high-risk or positive patients? Are you thinking about them differently? In addition to chemotherapy and endocrine therapy, what other treatments do you think [of], and how do you think about offering these to your patients?

Timothy Pluard, MD: We now have 2 additional options. With the CDK4/6 inhibitors, based upon the monarchE trial [NCT03155997], we can consider abemaciclib for those high-risk patients who are node positive. Based upon the presentations at ASCO…we now have another option with the NATALEE trial [NCT03701334] and ribociclib, which we’ll talk more about.

Komal Jhaveri, MD, FACP: And VK, maybe you could mention, is there a role for PARP inhibitors in HR-positive breast cancer as well?

VK Gadi, MD, PhD: Absolutely. Patients have BRCA1 and [BRCA2] mutations. Those drugs are very effective, and enalapril in particular is the indication we have in that setting. We know that there are meaningful improvements in DFS [disease-free survival] and potentially other factors as well. So it’s an option. What gets challenging for us is, how are we going to squeeze 1 treatment and where are we going to squeeze it, because all these drug trials were done in an era when the other drugs were not approved. So we’re left at the mess of trying to figure that part out. But we’ll talk about that, of course.

Komal Jhaveri, MD, FACP: Absolutely, I agree. Right now, when you’re thinking about offering these PARP inhibitors to your patients, what patients are you testing, and how are you realizing that this is the patient maybe I should offer PARP inhibitor to?

VK Gadi, MD, PhD: I’m spoiled in that we have a wonderful genetics clinic that does a careful evaluation of every patient [who comes] through the door. I think the theme that you’re seeing at a lot of centers is where you have access to resources. You’re seeing people getting expanded testing beyond sort of the traditional, you’re older than 50, you have a sibling or something. Family cohorts are small. There is a lot of missingness in family history. So having a liberal approach to who you’re going to test is important. I’m being cagey in my answer because I don’t want to say it’s at age 48 or 45 for this, but it really is individualized for that patient sitting in front of you based on that history [and] based on other risk factors. Then you can kind of suss out who needs that testing. In general, I think it’s pretty commonplace at this point for multigene panel testing. We don’t just [test for] BRCA1 and BRCA2. We want to know about ATM, PALB2, and others, because that can really help families in general. Of course, with breast cancer, we really want to know about BRCA1 and BRCA2.

Komal Jhaveri, MD, FACP: [Aditya,] I’ll turn it over to you and ask, when you think about germline BRCA mutations and you’re thinking about offering PARP inhibitors, are you offering them to all? Are you offering them to node-negative patients, node-positive patients? How are you thinking about them? Where do you think PARP inhibitors really fit in for HR-positive disease?

Aditya Bardia, MD, MPH: A good question. At this time, we are considering the use of olaparib based on the clinical trial as how it was done in OlympiA. So, patients who are at high risk, [like the] monarchE population of patients, or patients who have residual disease despite neoadjuvant therapy are the ones [for whom] we are considering olaparib. It’s not very common. BRCA mutations are much more common in TNBC [triple-negative breast cancer] as compared [with] ER-positive. But here and there, you do see a patient.

Komal Jhaveri, MD, FACP: Do you worry about the one thing that we always worried about with PARP inhibitors, with MDS [myelodysplastic syndrome] and AML [acute myeloid leukemia…risk in patients? Is this something that you discuss or you worry about? What have we learned that we can discuss with our patients?

Aditya Bardia, MD, MPH: It’s something to definitely discuss. It was reassuring in the OlympiA trial that you didn’t see a high risk of MDS. Probably, we need more follow-up, but we didn’t see that. There was improvement in overall survival as well. It’s a risk to be aware of. When [a] patient is on olaparib, you do monitor the counts, and even after that’s done, you do monitor counts periodically just to ensure that the patient is not developing MDS.

Komal Jhaveri, MD, FACP: Greg, I’ve also been curious about genetic counseling. So, we do [it], and I know VK mentioned the expanded panels. I think we’re getting more and more availability [with] these panels as well, and we know when to test. We have trial criteria that we want to try to use to offer our patients these therapies. What do you think is the role of genetic counseling with all these expanded panels that we have?

Gregory Vidal, MD, PhD: I would add to that. It becomes more and more difficult because it’s a competitive market. So a lot of practices, like mine, for example, we have 1 genetic counselor. We’ve lost 2 to pharma. With more and more testing, we are overwhelming the system. So we have to find innovative ways to test those patients. The patients who are positive need to have genetic counseling and to know what their risks are, their family risks. Now, what I’ve done in my clinic, actually, is have my nurse practitioners trained so that they’re doing this introduction to the test, to the patients, and the possibilities. When we send the test out, if they are positive, then they get a genetics and counseling visit. If they’re negative, then I have a discussion with them about it.

Komal Jhaveri, MD, FACP: I think it is so important now that we are using these genetic panels, and we want to offer these therapies, but we want to make sure that the patients are counseled, their family members are counseled, and we are able to keep up with the needs of these counseling [sessions]. So thank you for sharing that.

Transcript edited for clarity.

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