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AACR 2023 | The latest developments in targeted therapies for breast cancer

Paraic Kenny, PhD, Gundersen Medical Foundation, La Crosse, WI, describes advances in identifying molecular subtypes and personalizing care in patients with breast cancer. Following on from the anti-HER2 trastuzumab, trastuzumab deruxtecan and trastuzumab emtansine have provided additional treatment options for HER-positive breast cancer. Novel PI3K inhibitors, which have lower toxicity than alpelisib, have also been developed, and sacituzumab govitecan has been approved following results from the TROPiCS-02 trial (NCT03901339). Elacestrant has also been recently approved, after demonstrating clinical superiority to fulvestrant. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.

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Transcript (edited for clarity)

That’s really clear; we’ve moved far beyond the old days in breast cancer where the routine treatment was just limited to endocrine therapy for hormone receptor positive breast cancer or chemotherapy otherwise. So, you know, all patients up front are screened for estrogen receptor and HER2, which defines the initial stages of therapy. And then in the advanced stage of breast cancer, we have really a range of treatments that are available now starting with trastuzumab but building on to drugs like trastuzumab emtansine and trastuzumab deruxtecan for PI3K mutant breast cancers...

That’s really clear; we’ve moved far beyond the old days in breast cancer where the routine treatment was just limited to endocrine therapy for hormone receptor positive breast cancer or chemotherapy otherwise. So, you know, all patients up front are screened for estrogen receptor and HER2, which defines the initial stages of therapy. And then in the advanced stage of breast cancer, we have really a range of treatments that are available now starting with trastuzumab but building on to drugs like trastuzumab emtansine and trastuzumab deruxtecan for PI3K mutant breast cancers. We have drugs like alpelisib which inhibit PI3K very strongly, probably a little too strongly because hyperglycemia is a big challenge with those drugs. But we’re really excited about the development of newer mutant selective PI3K inhibitors, allosteric inhibitors from Relay Therapeutics and LOXO that offer the opportunity to really squelch the activity specifically of mutant PI3K while sparing wild-type PI3K. So that offers the potential of really hitting the cancer cells very hard in these patients while preventing the pretty significant toxicities that limit the use of those drugs. Beyond those agents, we’ve got sacituzumab govitecan which is an anti-TROP2 antibody drug conjugate in breast cancer which is approved in triple negative breast cancer and following data from TROPiCS-02 is also coming into use in hormone receptor positive cancer. And then post aromatase inhibitors, which we’ve had for a while, we know ESR1 mutations are very important in the escape from those drugs. We’re also quite excited to see new drugs coming on the scene this year, for example, elacestrant, which is an oral estrogen receptor degrader, which offers the potential to have a better easier to deliver more tolerable treatment than fulvestrant, which was the previous leader in this space

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