Breast Cancer Update, Issue 2, 2016 (Video Program) - Video 16Incidence and clinical implications of ESR1 mutations in BC
2:14 minutes.
TRANSCRIPTION:
DR LOVE: At a pretty naïve level, I keep looking for things in hormone therapy that look interesting. And I’m starting to hear things about estrogen receptor mutations. What do we know about that, how frequently they occur and kind of what they mean? DR SLEDGE: They certainly occur. If you look at data from a number of data sets at a patient who’s, say, had adjuvant hormonal therapy and then progressed and then one measures for an estrogen receptor mutation, the studies vary, but most of the data falls somewhere in the range of 10% to 20%, existence of an estrogen receptor mutation, an ESR1 mutation. Up front, before you give that Darwinian pressure, that number is very tiny. It’s probably somewhere in the range of 1% or 2%. So there’s certainly a significant increase, a fairly huge increase, and it’s certainly correlated with a lack of benefit to many standard hormonal therapies. So I think we’re going to see more and more of this. I think it’s reasonably likely, given the dramatically falling prices of genomic analyses, that this will become kind of a standard part of evaluation over the next few years. What you do with that data is a different question, because knowing that someone has an ESR1 mutation doesn’t particularly point me in the direction of a therapy that’s going to work. It does tell me that that patient is going to have a harder time with standard therapies. DR LOVE: Are these similar to tumor mutations that you see, for example, in lung cancer, EGFR tumor mutations? Are they like driver mutations? DR SLEDGE: They’re activating mutations. And that is to say that you can, at least in cell lines — and we don’t have much data in humans yet, but at least in cell lines, if you have one of these mutations, first off you’re less likely, say, to benefit to a drug like tamoxifen that blocks the estrogen receptor. And secondly, there’s certainly some suggestion of cellular autonomy in the absence of estrogen. |