Barriers and Breakthroughs Ahead for Personalizing Adjuvant Therapy: Michael Hassett, MD

As breast cancer care becomes increasingly tailored to individual patients, clinicians are grappling with how best to refine treatment decisions using emerging biomarkers and decision support tools. In this interview, Michael Hassett, MD, MPH, chief quality officer at Dana-Farber Cancer Institute in Boston, discusses the evolving landscape of HER2 testing, the challenges of optimizing cyclin-dependent kinases (CDK) inhibitor use, and the need for more precise predictive markers to guide adjuvant therapy, highlighting both the scientific and supportive care innovations that could shape the next era of personalized oncology.

This transcript has been lightly edited; captions were auto-generated.

Transcript

As the field moves toward more personalized care, what innovations in biomarker development or decision-support tools do you foresee being most transformative for selecting adjuvant therapies in breast cancer?

We talked a little bit about it earlier with HER2; we historically have tested HER2 using this immunohistochemistry or IHC test, and in the metastatic setting, we now have found that low and ultra-low IHC-positive cancers benefit from drugs like trastuzumab deruxtecan [T-DXd; Enhertu; Daiichi Sankyo/AstraZeneca]. Do we need to transform the way we test for HER2 in the adjuvant? Should we be thinking differently about how we treat HER2 low positive cases in the adjuvant setting, where they haven't gotten drugs like trastuzumab deruxtecan? And do we need better tests to be more personalized with our delivery of some of these new targeted therapies? So, I think that's one interesting question that we have going forward.

The second thing that I'll talk about is, we talked a lot about the use of CDK inhibition; the cyclin-dependent kinase family of drugs in the cancer space has improved outcomes. But it comes at a cost; more symptoms, more adverse effects are possible. It's a costly treatment. It's being on drugs with monitoring for 2 or 3 years. How can we make the best possible decision about who should be on those medicines, and once they're on those medicines, how they stay on those medicines? And I think that gets back to, you know, are there decision aids or tools that we can use to help personalize and provide supportive care for those types of therapies, and then to manage the symptoms that they could experience when they're on treatment, to keep them on treatment as long as possible.

I think that there's both what I would think of as sort of care delivery, patient supportive care, interventions, but also technical tools that can help us predict benefit. Last thing I'll say in connecting the 2 is that we've really struggled to identify biomarkers that tell us which patients benefit from or don't need CDK inhibition therapy. It's not like the HER2 space, where we have a biomarker, HER2 testing, and we think that helps us understand who benefits from the treatment. With CDK inhibition, I think we're not there yet, and I'd love to see some biomarkers that allow us to be more targeted and personalized with the use of those treatments.