Day 2 of the 42nd Annual Miami Breast Cancer Conference began with an early morning symposium on navigating HER2, HER3, and TROP2 breast cancer (BC) types. From early stage to advanced BC, here’s everything you need to know about the latest treatment advances.

First up: Heather McArthur, MD, MPH, Professor of Internal Medicine and Clinical Director of the Breast Cancer Program at UT Southwestern Medical Center, discussed TROP 2—a protein that antibody-drug conjugates (ADCs) target and bind to, and how it is significantly overexpressed in triple-negative BC.

Looking at TROP2

TROP-2/EGP-1 is a pan-epithelial cancer antigen. It is overexpressed in all breast cancer subtypes, with less expression on normal tissues—and it’s an excellent target for ADCs. It is a marker of poor prognosis (ie, larger tumor size, higher risk of recurrence), and high TROP-2 levels are associated with aggressive tumor resistance to chemotherapy.

Dr. McArthur says all ADCs have different antibodies, linkers, and payloads. She focused on sacituzumab govitecan (SG), a novel ADC, and recommended patients check out the ASCENT trial, which confirms the “clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with metastatic triple-negative breast cancer (mTNBC) in the second line or later.”

She also mentioned datopotamab deruxtecan, another ADC, pointing to the TROPION trial.

There is a high response rate with this antibody drug conjugate [datopotamab deruxtecan]. It’s very impactful data with durable responses, which is very encouraging.

Dr. McArthur also discussed sacituzumab tirumotecan (SKB264) as a potential therapy. “We need to understand mechanisms of resistance, optimal sequencing… but there’s a lot of effort in that space because it’s an area of rapid drug development. We need to understand how best to apply these agents,” Dr. McArthur says. 

The earlier we apply effective drugs, the earlier the benefits.

Diving deep on HER2

Sara Hurvitz, MD, FACP, Professor of Medicine at Fred Hutchinson Cancer Center, discussed targeting HER2 in BC management: “With the emergence of HER2-targeted therapy that only worked in HER2+ disease, it became critical to know whether a tumor was HER2 amplified or overexpressing.” She says there are several available therapies, including lapatinib, neratinib, tucatinib, pertuzumab, trastuzumab, and margetuximab. 

“As of today, the standard is THP (taxane, trastuzumab with pertuzumab). The second line standard is trastuzumab deruxtecan (T-DXd),” Dr. Hurvitz says.

For HER2-low BC, “T-DXd is the only HER2-directed therapy thus far that has shown efficacy in HER2 non-amplified/non-overexpressing breast cancer,” Dr. Hurvitz says. 

Even for small HER2+ tumors, patients should be treated with systemic therapy to improve their outcomes.

Investigating HER3

Jennifer Litton, MD, MHCM, President of Clinical Research and Director of Breast Medical Oncology at MD Anderson Cancer Center, then discussed HER3 biology and treatments. “This is especially fun, because we’re going to talk about an area that is completely investigational at this point. I think we’re going to hear so much more about targeting HER3 in the next few years, so the sooner we have it as part of our discussion, the better,” she says.

HER3 is overexpressed in multiple cancers, she explains, noting positive results of one current therapy: patritumab deruxtecan (HER3-DXd). “The majority of patients are having some sort of tumor shrinkage,” Dr. Litton says.

Another highlight? YL202 BNT326, a HER3-targeted ADC, which she says was found to “demonstrat[e] encouraging efficacy” in BC.