Optimizing Breast Cancer Management: Molecular Targets and Platforms for Testing


Expert oncologists identify molecular targets in breast cancer and review available testing platforms in the current treatment paradigm.


Adam Brufsky, MD, PhD: Welcome today to an OncLive® event seminar series titled “New Frontiers in Breast Cancer: Updates and Advances in Treatment.” Today I’ll be speaking with Dr Komal Jhaveri, who is associate attending physician on the Breast Medicine Service, section head of the Endocrine Therapy Research Program, and clinical director of the Early Drug Development Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center and an assistant professor of medicine at Weill Cornell Medicine in New York. I am a professor of medicine, co-director of the Comprehensive Breast Cancer Center at the University of Pittsburgh Cancer Institute in the University of Pittsburgh. The objectives for today's program are to talk about molecular testing practices in patients with early- and late-stage breast cancer, the selection of neoadjuvant and adjuvant treatments in patients with early-stage HER2-negative breast cancers, and strategies for sequencing in patients with HER2-positive metastatic breast cancer. We'll also have some really interesting updates on patients with HER2-low and hormone receptor–positive breast cancer from the recent ASCO [American Society of Clinical Oncology] annual meeting.

Let's start here: where are we with testing for patients with breast cancer? Generally, in early-stage disease, we have a number of tests that we do that are prognostic as well as predictive of various therapies. We have hormone receptor status, HER2, Ki-67, germline genetic testing, and a variety for ER [estrogen receptor]-positive disease, a variety of multiparameter genomic tests that allow us to prognosticate for patients whether they are high risk or low risk or if they need chemotherapy. That's in contrast to late-stage disease, where generally we look into triple-negative disease, at PD-1 and PD-L1 expression in ER-positive disease, and even ER-negative disease for clinical trials. We look at kinase mutations, and we also are starting to look at ESR1 mutations, which is more after several years of therapy, and initially we'll look at germline BRC1, BRC2, and PALB2 mutations.

Adam Brufsky, MD, PhD: Let's stop here, Komal, and talk about this. What do you do in early-stage disease? Are these the kinds of tests that you use, and what platform do you generally use for multiparameter genomic testing?

Komal Jhaveri, MD, FACP: Thanks, Adam, and welcome, everyone, I think all of us definitely want to know the hormone receptor status and the HER2 status for an individual patient such that we can personalize their therapy based on the status of these receptors, and then, germline testing, I think we now that we have data that you'll walk us through—also from the OlympiA trial—where we have approval for PARP inhibitors for patients with BRC1 and BRCA2 mutations. And we'll talk about exactly what that patient population was. I usually follow that trial criteria [for the] patient population for the germline testing as well to offer this.

When it comes to ER-positive patients, we now have 2 different things to think about. We have the multiparametric genomic assays that we use, as you indicated, not only for prognostic information that we give to our patient but also to understand the predictive benefit from chemotherapy. The most common one that I use in my practice is the 21-gene recurrence score; then, for node-negative patients, I also would use RSClin [recurrence scoring] tool, where we combine the clinical pathological information along with the 21-gene recurrence score, and more recently, we also have this Ki-67. I think we'll talk about the monarchE study, where we now have approval for abemaciclib and how we have seen the FDA [United States Food and Drug Administration] guidance and the FDA approval for utilizing Ki- 67 as an assay for these patients. Maybe we'll also talk about the ASCO and the EMA [European Medicines Agency]. I think we're beginning to see a lot of utilization of various ways of helping our patients and providing them the right therapies based on those results.

Adam Brufsky, MD, PhD: I switched over many years ago to the 70-gene prognostic score only because we developed something called the Magee Equations or the Magee Score, which uses immunohistochemistry for ER/PR [progesterone receptor] HER2 as well as Ki-67. The bottom line is because of that, I switched to the 70-gene score which looks at the downstream genes. However, I'm starting to go back to the 21-gene score because of RSClin. I really like RSClin. It gives me and the patient the ability to know with a little bit more precision what their actual recurrence risk is in real numbers as well as the benefit of antihormonal therapy and chemotherapy. I think patients like that. They really like to know the exact number. You said you are using the RSClin a lot. Is it something you use almost all the time now?

Komal Jhaveri, MD, FACP: I have been using RSClin a whole lot and I have continued to do that, and I definitely see the merits of the 70-gene score and the 70-gene assay as well. I know the I-SPY trial [NCT01042379]also utilizes that to assign patients to therapies especially the ER positive patients. We've been using the 21-gene recurrence score at our institution and that's what I've been using.

Adam Brufsky, MD, PhD: The other thing to talk about is HER2. I heard a rumor that Memorial [Sloan Kettering] doesn't use IHC [immunohistochemistry]; it only uses FISH [fluorescence in situ hybridization]. Is your team now required to do IHC? We're going to talk about this in great detail in a few minutes when we talk about the DESTINY-Breast04 trial [NCT03734029], but are is your team going to go back to IHC now?

Komal Jhaveri, MD, FACP: I'm afraid that was just a rumor. We don't do that. I think we definitely follow the ASCO guidelines.

Adam Brufsky, MD, PhD: I see. OK.

Komal Jhaveri, MD, FACP: And we definitely report both on IHC and FISH and use that for HER2 status.

Adam Brufsky, MD, PhD: Right.I wasn't on the ASCO guidelines committee for molecular testing, but I think you were on the ASCO guidelines committee for molecular testing.

Komal Jhaveri, MD, FACP: Yes, I was.

Adam Brufsky, MD, PhD: I know one of the things that they said was that we're not supposed to use CA [cancer antigen] 27-29 [tests]. Do you use that in practice given that or not? I know a lot of people in the community use CA 27-29 as an additional marker in metastatic diseases. Do you use that?

Komal Jhaveri, MD, FACP: I assume that the guidelines that you are referring to are the new ASCO biomarker guidelines that just got published earlier this year.

Adam Brufsky, MD, PhD: Correct.

Komal Jhaveri, MD, FACP: For early stage, I think we're not using tumor markers at all of any kind; maybe CA 27-29, CA 15-3, or CEA [carcinoembryonic antigen], which is what I think many people are utilizing in the metastatic setting. But for early stage, we do not see any survival benefits and so that's not something that I'm using in my practice.

Transcript edited for clarity.

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