HER2+ Breast Cancer: Special Challenges and Expert Insight - Episode 1

Patient Case: A 37-Year-Old Woman With HER2+/HR- Breast Cancer

Adam M. Brufsky, MD, PhD

Neil M. Iyengar, MD

Vijayakrishna K. Gadi, MD, PhD

Sara A. Hurvitz, MD

Adam Brufsky, MD, PhD, presents the case of a 37-year-old woman with HER2+/HR- metastatic breast cancer and polls the audience about screening for brain metastases.

Adam Brufsky, MD, PhD: Welcome to this CancerNetwork® Around the Practice presentation, “HER2+ Breast Cancer Special Challenges and Expert Insight.” I am your host, Dr Adam Brufsky, from UPMC [University of Pittsburgh Medical Center] Hillman Cancer Center in Pittsburgh, Pennsylvania. Tonight we have a great panel of very enthusiastic investigators, all of whom are very experienced in this field and have lots to add to this discussion. We have Dr VK Gadi from University of Illinois Cancer Center in Chicago; Dr Sara Hurvitz from UCLA [University of California, Los Angeles] Jonsson Comprehensive Cancer Center in Los Angeles, California; and finally, Dr Neil Iyengar from Memorial Sloan Kettering Cancer Center in New York City.

Tonight, we’re going to talk about 3 challenges we face in our practices. The first is how to optimally treat patients with HER2-positive breast cancer and brain metastases. We’ll also discuss considerations for sequencing therapies and how we make sequencing decisions in second-, third-, and fourth-line HER2+ metastatic breast cancer. I’ll add parenthetically that it’s a comment on how far this field has come that we’re now debating third-, fourth-, and fifth-line therapy in HER2+ metastatic disease. Finally, we’ll talk about the identification and management of interstitial lung disease and how it impacts the next steps for therapy. During this time, we’ll review a single patient case. Instead of 3 cases, we’re going to do 1 case and add to it as we go along during this hour. We’re going to ask the audience several polling questions using an interactive polling platform.

Let’s start. We’d appreciate if people answer this question. How often do you screen asymptomatic patients with metastatic HER2+ breast cancer for brain metastases? Always, sometimes, rarely, or never?

The results show 20% are always screening, 60% sometimes, 20% rarely, and 0% never. 

How often do you treat prophylactically for brain metastases in asymptomatic patients with HER2+ breast cancer? Always, sometimes, rarely, or never? Please fill out the poll.

This is interesting stuff. No one chose always, 25% do sometimes, 25% do rarely, and 2 votes for never. Interesting. Let’s move on and talk about a case. I’ll fill in the details of this case. It is hard to put it all in 1 or 2 slides. This is a 37-year-old woman who 3 or 4 years ago presented with a 5-cm lump in her right breast. She has the typical HER2+, IHC [immunohistochemistry] score of 3+, hormone receptor-negative breast cancer, and no other metastatic disease or LVF [left ventricular failure], and she feels well otherwise. We gave her neoadjuvant TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] for 6 cycles, and she did pretty well with it. Then she had a lumpectomy after being on radiation, had a pCR [pathologic complete response], and then was given trastuzumab and pertuzumab for the remainder of her therapy, which we can debate back and forth.

She did well for about 2.5 years and then came to the clinic complaining of increased fatigue and persistent cough. She had a chest CT scan that showed a 1.5-cm nodule in the left upper—not superior—lobe. She got a lung biopsy, which showed she has adenocarcinoma persistent with the breast primary that is IHC 3+ for HER2 and negative for ER [estrogen receptor] and PR [progesterone receptor]. She had a PET [positron emission tomography]/CT scan that showed no other bone or liver metastases, but did show several lung metastases, not just 1. Had she just had 1, we would have probably taken it out and called it a day. That’s a whole other question. She had 3 or 4 lung metastases, each of which is about 2 to 3 cm.

At this point, she was given a typical first-line regimen. She was given THP [docetaxel, trastuzumab, pertuzumab], and started on bisphosphonates every 3 months. She was given the docetaxel for probably 8 cycles and then complained of neuropathy. At that point, we discontinued that and just continued her on HP [trastuzumab, pertuzumab]. But it’s now 2 years later and a routine CT showed 3 liver metastases, each of which is about 1 or 2 cm in diameter. There is 1 that’s about 3 cm. She has 4 liver metastases, none of which are incredibly damaging to her organs, but she does clearly have visceral disease progression in her liver after THP [docetaxel, trastuzumab, pertuzumab] in the first line.

Here is the first polling question for the audience. You have a woman who has been on THP [docetaxel, trastuzumab, pertuzumab] for 2 years for metastatic disease. Would you screen her for brain metastases at that point? Obviously, she has had PET/CT, but would you actually screen an asymptomatic patient for brain metastases?

Let’s see what we’ve got. Fifty-fifty, right down the middle. This is going to be an interesting discussion with our esteemed audience and our esteemed group of investigators to see what they think.

If you did not know whether she had brain metastases, and you decide not to screen her, what would you give this patient in the absence of an MRI? She has progressive disease in her liver. She has been on HP [trastuzumab, pertuzumab] alone for about 18 months. Would you rechallenge her with THP [docetaxel, trastuzumab, pertuzumab], give her T-DM1 [trastuzumab emtansine], give her trastuzumab deruxtecan, or something else? The results show that 14% would rechallenge with THP [docetaxel, trastuzumab, pertuzumab], which is not a bad idea, 57% would give T-DM1 [trastuzumab emtansine], 29% would give trastuzumab deruxtecan, and 0% would give other.

Transcript edited for clarity.