HER2 an ‘Actionable Biomarker’ in Breast Cancer Subset

Over the last few years, new treatments have been approved by the FDA for HER2-positive breast cancer.

Breast cancer is the most common cancer that occurs in women within the U.S., aside from skin cancers. However, approximately 15% to 20% of breast tumors are associated with higher levels of a protein called HER2, according to the American Cancer Society.

“HER2-positive breast cancers are defined by having a high amount of the HER2 growth factor receptor, which is a protein that can drive cancer cell growth and aggressiveness,” Dr. Debu Tripathy, professor and chairman of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center, and CURE®’s editor in chief told CURE®.

Tripathy presented on HER2 as an actionable biomarker at the 2024 Miami Breast Conference and Educated Patient Breast Cancer Summit.

“It is important that every breast cancer case be tested for the HER2 receptor using diagnostic antibodies and sometimes requires confirmation by a technique called in situ hybridization, where the actual DNA encoding the HER2 gene is labeled to see if the HER2 gene is amplified (present in multiple copies of the gene as opposed to the usual single gene copy),” Tripathy explained. “If the breast cancer is HER2-positive, specific regimens would be used, typically including HER2 antibody in combination with chemotherapy. Since HER2-positive breast cancers can be very sensitive to these regimens, it is possible to use less aggressive surgery for early-stage cases.”

He stated that because HER2-positive cancers may respond slower to therapy, the risk for brain metastases could be higher than other breast cancer subtypes.

“[This is] in part because HER2 antibody may not penetrate the brain tissue as readily as some other drugs,” Tripathy said. “HER2-positive brain metastases are typically treated with surgical removal and/or radiation (including highly focused stereotactic radiation), but they can also respond well to some of the newer drugs including kinase inhibitors and HER2 antibody-conjugates.”

Treatments for Patients With HER2-Positive Breast Cancer

Tripathy determined that there are several new therapies to target HER2-positive breast cancer, which have been approved by the Food and Drug Administration (FDA) over the last few years.

“While HER2-positive breast cancers are more aggressive, they can be vulnerable to certain treatments that block the action of the HER2 receptor including HER2-targeting antibodies, such as Herceptin (trastuzumab) and Perjeta (pertuzumab) and other drugs called HER2 kinase inhibitors such as Tukysa (tucatinib),” he said.

Through clinical trials, Tripathy noted, the use of HER2 antibodies resulted in higher cure rates for early-stage HER2-positive breast cancer when added to a chemotherapy regimen, which also demonstrated higher response rates to treatment and better survival outcomes in patients with metastatic breast cancer.

“It continues to be a very active area of research with many newer types of therapies such as antibody-drug conjugate and newer HER2 kinase inhibitors currently being tested,” he elaborated. “There are also drugs designed to activate the immune system against cancer cells that make the HER2 protein that are currently being tested.”

Questions for Patients to Ask Their Care Teams

After receiving a diagnosis, it may be a challenge to know what type of questions to ask medical professionals. Nonetheless, questions about recommended regimens and treatment combinations that are appropriate for patients’ specific cases, along with types of treatments that can target HER2-positive breast cancer cells, can help start the conversation, Tripathy said.

“Patients [can] also ask for the schedule of treatment as well as what further decisions will be made depending on how they respond [to treatment]. They should also be aware of the monitoring tests that are required, such as checking heart function periodically,” he added. “They [can] also inquire about clinical trials and have these explained to them in case they may be interested once they understand the questions being asked by the research study, as well as the potential side effects.

WATCH: What to Expect: Hormonal Side Effects from Breast Cancer Treatment

For patients with HER2-positive breast cancer, Tripathy emphasized that asking about HER2 testing results is important.

“Make sure that HER2 testing has been done and that [patients] know of the HER2 results because sometimes this can be difficult to interpret,” he said. “Make sure that the medical regimen recommended is one that is specific for HER2-positive cases, and that side effects of the treatment are being explained. Especially in the case of metastatic breast cancer that has already progressed on standard treatments, see if any available trials would fit [patients’] situations, or if other centers may have trials open for the type of cancer [they] have.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.