Early Stage HER2+ Breast Cancer: Overview of Adjuvant Treatment


Expert oncologists review adjuvant treatment strategies in early stage HER2+ breast cancer and consider when observation alone would be appropriate.


Andrew Seidman, MD: Hello, and welcome to this OncLive® Peer Exchange® titled “Updates in the Treatment of HER2+ and HER2-Low Breast Cancer.” I’m Dr Andrew Seidman from Memorial Sloan Kettering Cancer Center in New York [New York]. I’m joined by a panel of my colleagues who treat breast cancer. I’d like to welcome Dr VK Gadi. Please introduce yourself.

Vijayakrishna Gadi, MD, PhD: My name is VK Gadi. I’m a medical oncologist in Chicago [Illinois] at the University of Illinois Chicago in the University of Illinois Cancer Center. I focus on breast cancer, and I have a laboratory also focused on breast cancer.

Andrew Seidman, MD: Thank you. Dr Tiffany Traina?

Tiffany Traina, MD: Hi, I’m Dr Traina. I’m a breast medical oncologist at Memorial Sloan Kettering Cancer Center and a vice chair in the department of medicine.

Andrew Seidman, MD: And we have Dr Bill Gradishar.

William Gradishar, MD: Hi, I’m Bill Gradishar, professor of medicine and chief of hem-onc [hematology-oncology] at Northwestern University in Chicago [Illinois].

Andrew Seidman, MD: And we’re joined by Dr Stephanie Graff.

Stephanie Graff, MD: I’m Dr Stephanie Graff. I’m the director of breast oncology at the Legorreta Cancer Center at Brown University [in Providence, Rhode Island].

Andrew Seidman, MD: Thank you all for joining us. It’s been a remarkable quarter of a century since we began targeting HER2 [human epidermal growth factor receptor 2] in breast cancer. I’d like to start by asking how you approach a patient with early stage HER2-positive disease. When do you think about neoadjuvant therapy vs adjuvant therapy? VK, maybe you can lead off.

Vijayakrishna Gadi, MD, PhD: This is where the principle of precision has 2 meanings. There are precise ways in which we target the cancers and then the optimized way in which we take care of a patient. For patients who have very small-volume disease, we’re drifting toward less is better. We’re looking at simplified regimens, maybe omitting chemotherapy, looking at ways that we can do things like that. Generally speaking, I stick with a taxane and trastuzumab. I try to get that in for a year, but if there’s a clinical trial, I try to deescalate that. For patients unfortunately starting with a little more disease, maybe their lymph nodes are positive or they have a larger breast mass, I’m focused on preoperative therapy on study or standard regimens. Then I optimize the care after that in the adjuvant setting depending on what their response in the tissue might have been.

Andrew Seidman, MD: Stephanie, is there a clinical T or N status that pushes you toward neoadjuvant therapy vs adjuvant therapy?

Stephanie Graff, MD: I try to follow the APHINITY eligibility criteria closely for the most part. I take patients with T2 or larger tumors or N1 or larger disease to treat neoadjuvantly. Obviously there are exceptions to that. The pandemic plays a role as well. There are times when time to the operating room is complicated by the way the pandemic has affected us all. In which case I’ve even done things like give the paclitaxel-trastuzumab regimen neoadjuvantly to patients who I don’t necessarily think need the full forces of TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab], which maybe isn’t the typical approach.

Andrew Seidman, MD: Bill, do you think about the pertuzumab registration criteria as your guidance for neoadjuvant therapy? Do you need a T2 tumor or a node-positive disease to be enthusiastic about preoperative therapy?

William Gradishar, MD: Enthusiastic may not be the right word, but I consider those guardrails. As Stephanie and VK said, there are patients who may not meet those strict criteria. You may have a patient with a smaller breast and at the same time a smaller tumor where, to achieve breast conservation as a goal, you may not meet the criteria for APHINITY but you choose to use neoadjuvant therapy.

Andrew Seidman, MD: We shouldn’t be shackled by those [criteria]. Tiffany, I’m going to bring you to the smallest end of the spectrum. What HER2+ breast cancers should we not treat? Who are those invasive patients for whom we should say, “Let’s leave well enough alone”?

Tiffany Traina, MD: Great question. As VK mentioned, we have data from the APT [adjuvant paclitaxel and trastuzumab] study looking at paclitaxel-trastuzumab. That’s starting to give us comfort in finding ways to deescalate. We have retrospective series that have looked at the teeny-tiny node-negative HER2+ cancers that do extraordinarily well: 5mm, node negative. The challenging area may be in that gray zone of 5 mm to 1 cm. We really need to personalize our choices and have discussions with our patients about risk-benefit balance. We’re certainly also thinking about patients who have strong estrogen receptor–positive disease, or perhaps a more frail patient where we’re concerned about the impact of systemic therapy.

Andrew Seidman, MD: I used to call this the limbo question. How low can you go? Is it 4 mm? Is it 3 mm? We’re going to talk about how low can you go in terms of HER2 expression a little later. So that’s a great place to start.

Transcript edited for clarity.

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