Next-Generation Sequencing in HR+ Metastatic Breast Cancer



Hatem Soliman, MD: The role of NGS, or next-generation sequencing, testing for patients with hormone receptor—positive breast cancer I think will become increasingly important to help us optimally sequence and manage patients through multiple lines of therapy. One could envision that we’re entering a sort of arms race with cancer. In essence, when we apply different therapies up front in the earlier setting, the cancers that emerge from those therapies may become more resistant on the back end and require us to interrogate them more fully to better understand how they developed resistance to the line of therapy that was applied previously, so that we can better tailor our selection of the next line of therapy. So, using assays such as FoundationOne or other tumor-based next-generation sequencing tests when feasible, or blood-based assays as well that can isolate the circulating-free DNA from the blood in order to provide us molecular information, will, I believe, play an increasingly important role in helping us sequence and optimize select agents during the treatment of hormone receptor–positive metastatic breast cancer.

Debu Tripathy, MD: The use of mutational status is still an evolving area. We know that ESR mutations do arise, particularly in patients who have received aromatase inhibitors. And in these patients, there’s a suggestion that ESR mutations do predict relative resistance to aromatase inhibitors, but not to fulvestrant. So, if you were to know that the patient had an ESR mutation—not that we recommend routinely testing for it, but sometimes patients get tested for other reasons—we find out that they have it, then I would certainly prefer to use fulvestrant as opposed to an aromatase inhibitor.

Sara Hurvitz, MD: If I have a patient who has come to me and has been on an aromatase inhibitor for 5 years and about a year ago came off of it, they finished their adjuvant endocrine therapy and they come to me with metastatic disease, I’m really sort of toying with, should I put them on an AI with CDK4/6 inhibitor or with fulvestrant? Sometimes I will do next-generation sequencing to see if they have an ESR1 mutation. If they do, that would push me toward the use of fulvestrant over an AI. But I have to say that’s not yet totally prime time ready for clinical use. And the use of next-generation sequencing to look for AKT mutations, P10 downregulation, PI3-kinase mutations, Cyclin-E amplification and these other mechanisms of resistance, we’re not yet there because we’re not sure how to best treat patients who have these alterations. The best way, in my opinion, to be using next-generation sequencing is to look for patients who are eligible for a given clinical trial of a targeted inhibitor.

Transcript Edited for Clarity

Related Videos
A panel of 3 experts on breast cancer
A panel of 3 experts on breast cancer
Samilia Obeng-Gyasi, MD, MPH,
Nan Chen, MD
Timothy Yap, MBBS, PhD, FRCP
Parul N Barry, MD,
Erin Frances Cobain, MD
Erin Frances Cobain, MD
Video 6 - "Shared Decision Making and Multidisciplinary Collaboration in the Evolving HR+/HER2- Early-Stage Breast Cancer Landscape"
Manmeet Singh Ahluwalia, MD