Optimizing Treatment Strategies in Breast Cancer: Q&A

Transcript:

Joyce A. O’Shaughnessy, MD: We have a couple of minutes, and I want to get to a few questions because folks have been patiently waiting. Sara, if a patient has hormone receptor-positive, HER2-negative, germline BRCA-positive breast cancer with only 1 or 2 positive lymph nodes, and let’s say she had her surgery first and doesn’t quite meet the olaparib criteria in the OlympiA trial, where she had to have 4 or more nodes in this setting. Would you consider olaparib for her if she had fewer nodes but was still node-positive?

Sara A. Hurvitz, MD: It’s a hard question to answer. She wouldn’t have qualified; certainly a triple-negative patient would qualify for olaparib, but for this patient, we don’t have the data to support it. But I’d be tempted to discuss it with her and consider using it. It depends on patient age, grade of the tumor, and if it’s behaving more aggressively like a BRCA-driven tumor. I may be more compelled to do it if it has 1 or 2 positive nodes. But if it’s a low grade or intermediate grade, strongly ER/PR [estrogen receptor/progesterone receptor]-positive BRCA2 mutation that doesn’t seem to be as basal-like, if you will, then I may feel more comfortable sticking with the endocrine therapy option itself. How do you think through this?

Joyce A. O’Shaughnessy, MD: I hear you, the synthetic lethality in a HRD [homologous recombination deficient] cancer as opposed to an ER-driven cancer. We must see if she meets the abemaciclib criteria for monarchE. My hope is that—and we don’t know because we haven’t seen the OlympiA data broken down by luminal A, luminal B, or the other HER2-enriched or basal-like ER-positive—but because it is a germline BRCA, my hope is that it does have homologous recombination deficiency, though it may be more indolent in biology and we still may see synthetic lethality. These patients, I feel like this ER-positive disease always comes back. This node-positive stuff, I’ve been at this a long time, it seems like it comes back and comes back. Node positive, it’s 10 years of AI [aromatase inhibitor] and stop. I’m tempted, regardless of biology, because I don’t see a downside on it either to be honest, I think it’s well-tolerated and safe for these patients. It’s a year of therapy and it has some adverse effects, but it’s not dangerous in any way. I think it’s all hands on deck for these node-positive patients.

Another question is, for a premenopausal patient with TNBC [triple-negative breast cancer] but it’s a T1b, N0, so it’s small, subcentimeter cancer, what’s your choice of chemotherapy? We’ve got ACT [doxorubicin, cyclophosphamide, paclitaxel], ACT/carboplatin, we’re not going to use pembrolizumab, we can use Steve Jones, [MD’s] TC [docetaxel and cyclophosphamide], we can use Priyanka Sharma, [MD’s] docetaxel, carboplatin. What’s your choice for the T1b, N0?

Sara A. Hurvitz, MD: I like Priyanka’s regimen of docetaxel, carboplatin in these patients. In some of these cases, especially T1c, I do the neoadjuvant approach because if they’re not completely responding then I want to give them the opportunity to have AC therapy. But in a T1b, I tend to use the nonanthracycline-based regimen. If you look at that ABC trial that you were a big part of, the node-negative, triple negatives had less benefit from the anthracycline. In that study, they didn’t use the platinum-based regimen. I think that Priyanka’s data are compelling of the activity of this regimen. There have been other studies that have also called into question whether anthracyclines are really needed in those small or node-negative, triple-negative tumors. I think it’s a patient-by-patient discussion, but I would be comfortable with that.

Joyce A. O’Shaughnessy, MD: I do too. If she had surgery first and was found to have a T1b, N0, I’d do 4 cycles generally. For T1c, I’m usually into the 6 cycles. I agree with you, I do the preoperative as well to give the benefit of the doubt on either an AC or a capecitabine.

There was a last question about seeing a lot of HER2 mutations, at least a fair number, coming up on NGS [next-generation sequencing] panels, and if neratinib targets these different mutations. Generally, the reports we get show that folks will have curated these mutations, and they’re felt to be activating mutations that they report, because otherwise they’ll say clinical significance unknown. But they’ll report the ones that are activating, and often they will go into the literature and will write that down about whether there are data preclinically. Neratinib usually covers most, not always lapatinib, but neratinib generally covers most, is my take-home message. I don’t think we know across the board yet, it’s still early days, but I think neratinib’s pretty good at covering most of these HER2 mutations.

With that, I want to thank everybody very much, it’s been a great discussion, Sara, thanks so much, I really enjoyed it, as always. I want to thank OncLive® for putting this OncLive® Events seminar series together, this is a nice way to update us on the new data and the practice implications. Thank you all for being here tonight, I hope it’s been helpful to you and your practice.

Transcript edited for clarity.