Updated Guidelines for the Management of HR+ Breast Cancer

Mark Pegram, MD: ASCO [American Society of Clinical Oncology] has recently updated their guidelines for management of hormone receptor [HR]-positive breast cancer, published by Andre [et al] in the JCO [Journal of Clinical Oncology] this year. Were there any surprises in your read on those guidelines? Is there anything you want to point out?

Lee Schwartzberg, MD, FACP: They continue to refine their experience with genomic classifiers, which we’re going to talk about. As the data mature from some of the seminal trials we have, [such as] TAILORx [NCT00310180], RxPONDER [NCT01272037], and MINDACT [NCT00433589], those continue to slightly change the recommendations for initial decision-making about prediction of chemotherapy and prognosis of HR-positive breast cancer. There were no real surprises. We’ll also talk about high risk. We talked a little about de-escalation, but escalation is also important when necessary. You mentioned the monarchE trial [NCT03155997] that allowed us to add the CDK4/6 inhibitor in the adjuvant setting because of a very substantial benefit, even early on, but there isn’t a long-term follow-up yet on that trial.

Mark Pegram, MD: The ASCO guidelines were certainly very dense on the consideration of multigene assays. They don’t seem to come down strongly on one assay or another. They mention many of them. It still involves clinical decision-making on which approach to use and what you’re more comfortable with—what might be most useful for AJCC [American Joint Committee on Cancer] staging with the newest version of that staging system, for example. There’s a lot to consider for newly diagnosed [HR]-positive early breast cancer. For completeness, we should mention BRCA gene mutations in early breast cancer.

Lee Schwartzberg, MD, FACP: Yes, that’s a great point. We have another opportunity to treat our patients differently based on having a germline BRCA1 or BRCA2 mutation based on the OlympiA trial [NCT02032823], which [randomly assigned patients who are] high risk with BRCA mutations to receive olaparib after adjuvant therapy and showed a very significant benefit in disease-free survival.

It’s frequently forgotten that although we associate BRCA1 mutations more typically with triple-negative breast cancer, both BRCA1 and particularly BRCA2 mutations occur in patients who are HR positive. Because that number is so much larger, it turns out that, at least in the metastatic setting, [approximately] 3% to 5% of all patients might have a BRCA mutation. Now we’re at the point where [patients who are] high risk, and who might qualify for olaparib because they’re high risk, should be tested for BRCA1 and BRCA2 regardless of their family history and hopefully regardless of some guidelines that are a little more restrictive.

Mark Pegram, MD: You find them all the time. It’s surprising. I’ve seen publications where the fraction of BRCA carriers in this country who have yet to be discovered is very high. You’d think almost everybody would’ve been detected by now. That simply isn’t true. [Most] BRCA carriers have yet to be discovered.

Lee Schwartzberg, MD, FACP: Absolutely. A large number of those are in the HR-positive group, because they wouldn’t necessarily get neoadjuvant chemotherapy and be tested for that. They aren’t the patients with triple-negative breast cancer who would do that. And we still don’t know about the influence of HER2 in terms of BRCA treatment; that’s an area of exploration. But 85% of patients might be eligible for testing, certainly if they’re high risk. That brings up lots of other issues in terms of what you do with different therapies. Most of these relate to triple-negative breast cancer and HER2-positive breast cancer. We don’t have the answers to that, but we can safely combine long-term adjuvant endocrine therapy with olaparib without difficulty, so that should be done in combination if a patient qualifies for it with a BRCA mutation. Don’t you agree?

Mark Pegram, MD: Exactly. I believe that’s the study design that was used for the OlympiA trial for the [HR]-positive subset. It was common with antiestrogens, safe, well tolerated, and as you said, it had impressive efficacy results for invasive disease–free survival and distant disease–free survival. With longer follow-up since the first publication, the [overall survival] has become statistically significant. That’s exciting and a breakthrough in the management of early-stage disease.