Selecting Endocrine Therapy in BRCA1/BRCA2+ Breast Cancer


Experts in breast oncology discuss how they select endocrine therapy in BRCA1/BRCA2+ breast cancer.


Stephanie Graff, MD, FACP: One thing I particularly avoided when I defined our case was her genetic testing. I left her paternal lineage undefined. Of course, they’re her patients with missed paternity, which is pretty common. Genetic testing is really important because you don’t know. I certainly, given her young age would have recommended genetic testing anyway. There’s a probability that she could have a genetic mutation. I think that that’s another situation where we could potentially alter the approach. What are you doing for patients that are co-candidates for adjuvant olaparib and CDK4/6 inhibitor?

Rachel Layman, MD: That’s a great question. I don’t know if there is one right answer because there’s a lack of data to guide this but we have seen with the OlympiA trial [NCT02032823] that adjuvant olaparib in patients that have BRCA1 or BRCA2 mutations significantly improves patient outcomes including survival. So depending on the risk and how much the patient is willing to go through, I would start the appropriate adjuvant endocrine therapy for your patient and then also I start with olaparib. I would do olaparib first. Olaparib is for 1 year, so it’s a little bit shorter than the 2 years for abemaciclib and 3 years for ribociclib in their respective clinical trials.

Since olaparib has this survival benefit, and I don’t consider it necessarily an endocrine therapy component, I would give it first. I actually had this situation and I’ve explained to patients that ideally, I would want them to do a year of olaparib and then after that do 2 years of abemaciclib. There’s no data to give abemaciclib that far out but there is data in other settings for patients, for example, that were premenopausal, finished tamoxifen, and then a few years later became postmenopausal that if you started an aromatase inhibitor later, still got benefit. So if you’re considering abemaciclib as part of endocrine therapy, you may be able to extrapolate that the patient might still benefit. I think you have to be very clear with the patient that we don’t have data for this. We have to choose the best that we can and give them the options.

Stephanie Graff, MD, FACP: I think that in both NATALEE [NCT03701334] and monarchE [NCT03155997], patients were eligible for enrollment if they had been on adjuvant endocrine therapy for a pretty long time, actually 6 months to a year. I think you’ve got a pretty good lead-in window with those trials already that extending just a little bit longer so that you can get that year of olaparib in I think is the approach that you hear most experts around the country talk about. I was able to attend the St Gallen [International Breast Cancer] Consensus Conference in 2023. That was the St Gallen panel recommendation as well, which I know isn’t in print yet but hopefully will be soon. We’ll see that as other guidelines come out if that continues to be what’s supported.

Transcript edited for clarity.

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