Melinda L. Telli, MD, presents a profile of a patient with early stage breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery, whose tumor was initially HER2+ but became triple-negative after treatment.
Sara Hurvitz, MD: We have a second case that I’m going to ask Dr Telli to discuss.
Melinda L. Telli, MD: This is a 54-year-old woman who presents with a palpable mass in her left upper outer breast. On her imaging workup the primary tumor measures about 6 cm. It’s at 2 o’clock, and there are multiple enlarged left axillary nodes. The biopsy shows grade 3 IDC [invasive ductal carcinoma], ER/PR-, HER2+ 3+, with really high FISH [fluorescence in situ hybridization] ratio, and high HER2 copy number. The node is biopsied and [found to be] positive. Ultimately, based on clinical exam and imaging, she staged as a clinical T3N2M0 stage 3a breast cancer. She has systemic staging scans [that] show no evidence of metastatic disease. Her labs are normal. Echocardiogram [results showed] normal left ventricular ejection fraction.
She is treated with preoperative TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab], and has clinical response [found] both by imaging and exam. She moved forward with surgery and ultimately has 1.4 cm of residual disease in the breast and 2 out of 12 x-ray lymph nodes. The nodal deposit is small. [Previously,] the nodes had been very large and are now small at only 5 mm at the largest deposit.
But again here, this time we have the markers repeated and it comes back triple-negative; ER/PR-, HER2 is now 1+ in the residual disease, and FISH-. She [has plans] for post-mastectomy chest wall and regional nodal radiation. Now I think the big question is what do you do at this juncture? HER2+ disease and now we have, at the time of residual disease, biomarkers showing triple-negative disease.
Sara Hurvitz, MD: And were the biomarkers checked only on the breast or did you check them on the lymph nodes as well?
Melinda L. Telli, MD: This was from the breast.Sometimes they do start checking them again on the lymph nodes as well, which often adds more confusion. But this was from the breast.
Sara Hurvitz, MD: Again, I love these cases because they’re a little messy, but they really represent what we struggle with day-to-day. So how would address this? I’m going to go to Heather.
Heather McArthur, MD: This is such a tough case, but you’re right, it does represent our real-world experience. If I was treating her [using] standard of care, I probably would treat her with T-DM1 [trastuzumab emtansine] for all the reasons that we just outlined. The benefits in the subset from KATHERINE [study] still demonstrating benefit. But if I had access to a clinical trial like, DESTINY-Breast05, for example, looking at T-DXd [trastuzumab deruxtecan] vs T-DM1. With all of this growing data for T-DXd and HER2 low, and maybe even HER2 ultra-low, maybe this is the person who would derive benefit from that drug in the curative-intent setting. I would be enthusiastic to get access to that trial if it were available to me.
Sara Hurvitz, MD: Virginia, your thoughts? Would you ever consider immune-based therapy for this triple-negative component?
Virginia G. Kaklamani, MD, DSc: I would consider it, but I don’t know that I would do it. I think here potentially ASTEFANIA might be another option where you do have a 50% of receiving atezolizumab with your T-DM1. So that might be something because we have it open, and I would probably encourage her to go on the trial because of that. But would you give capecitabine in combination? I wouldn’t. But I would definitely think about it.
Sara Hurvitz, MD: But T-DM1 for sure you would do?
Virginia G. Kaklamani, MD, DSc: I would. Yes. Based on the KATHERINE data.
Sara Hurvitz, MD: Debu?
Debu Tripathy, MD: I think the first 3 options are appropriate. Off-study, I’d use T-DM1. We do have the data from the KATHERINE study. Between options 2 and 3, maybe I’d go with T-DXd because they’re getting some topoisomerase-1 inhibitor. So maybe I’d go on that trial, 50-50 chance of getting it to cover that small possibility.
Sara Hurvitz, MD: Would you do it off-label? Would you give T-DXd?
Debu Tripathy, MD: No. I would not give it off-label. I don’t think we have support. In fact, the data we do have suggests otherwise, that [patients] still benefit from a HER2 directive.
Sara Hurvitz, MD: Would any of you want to test the lymph nodes to know if the lymph nodes were HER2+ or triple-negative? Would that help you choose, outside of having a clinical trial available?
Debu Tripathy, MD: I don’t think it would help me, so I wouldn’t do it.
Heather McArthur, MD: I agree.
Melinda L. Telli, MD: I think my overall impression was that it was just a heterogeneous tumor. Her initial core was 3+ by IHC [immunohistochemistry] for a HER2 ratio over 5. HER2 copies were more than 10. And so it was truly HER2-driven disease. [That] was my impression. And so, I really felt that we should remember that. And even though it’s triple-negative on the residual disease, I think it just sort of distorted post-treatment setting. I wanted to make decisions based on the original core, so I talked to her about T-DM1 vs participation and CompassHER2 RD. [Now] she’s making this decision as she’s going through radiation.
Sara Hurvitz, MD: Excellent.
Debu Tripathy, MD: I want to make one additional comment. We look at the residual disease, but that’s a select group of tumors that were resistant to treatment. There may have been a lot of HER2+ around it. What we’re really treating is micro-metastatic disease that was most likely generated before any treatment. So we have to remember that that’s what we’re treating.
Sara Hurvitz, MD: Absolutely. Keeping that in mind is so important in the curative setting.
Transcript edited for clarity.