Targetable Mutations Found in Breast Cancers

Transcript:
Timothy J. Pluard, MD:Ossama, can you talk a little about breast cancer? That’s 1 of your areas of expertise. How have the biomarkers evolved in breast cancer?

Ossama Tawfik, MD: Breast cancer is probably the next success story in molecular markers. It started with our ability to find HER2 [human epidermal growth factor receptor 2]. Because it was the first precision medicine prototype for how to treat diseases, everybody was excited. From a testing point of view, we had the challenge of what type of test to do. Do we do IHC [immunohistochemistry]? Do we do FISH [fluorescence in situ hybridization]? IHC [pathologists] were saying they’re better, while FISH testers were saying they’re much better in detecting molecular changes than pathologists. We also became more efficient in digital pathology and classification of tumors. Hormonal examination and testing also evolved significantly. Recently, PIK3 is picking up, and PD-L1 is joining the club like any other tumor that we can treat with immunotherapy. We’ve evolved significantly. Other things like BRCA come to mind, and all these have transformed the way we practice pathology.

Sujith R. Kalmadi, MD: Tim, 1 thing was the number of actionable markers and how they have increased. Previously, we had a slew of markers but no actionable drugs. With each 1, we’re starting to find that there’s a therapeutical development question and an actionable mutation. That’s the big change. For instance, HER2 low has seen an explosion of patients treated with therapy based on what we’re seeing, which we never thought would happen.

Timothy J. Pluard, MD:Great point.

Samuel K. Caughron, MD, FCAP: In breast cancer, the targetable mutations have been a little more static over the last 10 to 15 years. We’re still going to be testing for estrogen receptors and progesterone receptors as well as HER2, as we have been for some time. PI3K is a newer mutation that you’re going to want to consider evaluating in a metastatic setting, especially in patients who’ve already had first-line therapy. We can talk a little more later about the best strategy for PI3K testing.

The other recent development that those who oversee testing need to be aware of the shift in how HER2 is interpreted. HER2 is moving from a simple positive-negative mentality to a continuum, with HER2-high and HER2-low categories emerging in the specific language. I expect we’ll see that worked out over the next several months, but HER2 is going to be shifting.

Transcript edited for clarity.