Dr Tarantino on the Role of Genomic Testing in HER2+ Breast Cancer

“We have all these [treatment] options, and we need a [genomic] assay to tell us which [patients] are most likely to achieve a pCR even with an abbreviated and less intensive treatment [regimen].”

Paolo Tarantino, MD, PhD, a research fellow in the Department of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, discussed the role of genomic testing for informing treatment decisions for patients with HER2-positive breast cancer.

The treatment arsenal for patients with HER2-positive breast cancer has seen a rapid expansion in recent years, Tarantino began. Previously, the treatment paradigm included only a few chemotherapy agents and trastuzumab (Herceptin), he continued. However, pertuzumab (Perjeta), adjuvant trastuzumab emtansine (T-DM1; Kadcyla), niraparib (Zejula), fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), and tucatinib (Tukysa) have become available for use in various disease settings, he continued. This wealth of treatment options underscores the need for a genomic assay that can predict pathologic complete response (pCR) with these agents, as well as which patients are most likely to recur, he emphasized.

In the phase 2 CompassHER2 pCR trial (NCT04266249), the HER2Dx assay was used to predict pCR likelihood following treatment with a taxane plus trastuzumab and pertuzumab (THP), Tarantino said. This assay also includes a recurrence risk score, he added.

The HER2Dx assay allows for informed treatment intensity decision-making, Tarantino explained. Patients who are at a lower risk of disease recurrence according to the assay should be considered for the milder THP regimen that was examined in CompassHER2 pCR, he said.

HER2Dx also includes a ERBB2 signature component that can examine the level of HER2 positivity In a tumor, Tarnatino noted. This could be useful in the future because immunohistochemistry and fluorescence in situ hybridization remain imperfect methods for determining HER2 positivity, he added. However, the development of HER2Dx is still in the early days, and the assay will need to be prospectively validated, he concluded.