Dana-Farber Cancer Institute Metastatic Breast Cancer Forum 2016
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Transcript of Dana-Farber Cancer Institute Metastatic Breast Cancer Forum 2016
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Dana-Farber Cancer InstituteMetastatic Breast Cancer Forum 2016Research update for HER2-positive breast cancerShom Goel MD PhDInstructor in Medicine, Harvard Medical SchoolSeptember 24, 2016
What is HER2-positive breast cancer?15-20 percent of breast cancer is HER2-positive
Abundance of HER2 protein on cancer cellsAmplification of the HER2gene in tumor cells
HER2-positive metastatic breast cancer
Relapse after treatment for early stage breast cancer
De novo metastatic breast cancer
How is HER2-positive MBC treated?The primary treatment of HER2-positive MBC is with systemic medical therapyi.e. drugsSurgery and radiotherapy may play a role in specific situations
FDA-approved drugs for HER2-positive MBC
Herceptin(Trastuzumab, 1998)
Perjeta(Pertuzumab, 2012)
Lapatinib(Tykerb, 2005)
IV vs oralImmune effects of antibodiesUnique aspects of T-DM15
FDA-approved drugs for HER2-positive MBC
Kadcyla(T-DM1, 2013)
Perjeta(Pertuzumab, 2012)
Lapatinib(Tykerb, 2005)
IV vs oralImmune effects of antibodiesUnique aspects of T-DM16
FDA-approved drugs for HER2-positive MBC
Perjeta(Pertuzumab, 2012)
Lapatinib(Tykerb, 2005)
IV vs oralImmune effects of antibodiesUnique aspects of T-DM17
FDA-approved drugs for HER2-positive MBC
Perjeta(Pertuzumab, 2012)
Lapatinib(Tykerb, 2005)
IV vs oralImmune effects of antibodiesUnique aspects of T-DM18
The main issue we face today is drug resistanceIn many (not all) situations, HER2-positive MBC will respond well to existing therapies However, over time cancer cells develop resistance to existing therapiesIf we could completely overcome drug resistance, the disease would become chronic and/or curable
What causes treatment resistance?
Growing in certain locationsTumor heterogeneity
Turning off the immune system
Changes in cell signaling
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How can we study treatment resistance?
In cellsIn miceIn our patientsInformation from clinical trialsBiopsies of drug resistant tumors
Two examples from our laboratory (1)
Resistant tumor cells respond to the CDK4/6 inhibitor abemaciclibCyclin D1A new transgenic mouse model of HER2-positive breast cancer
Goel et al Cancer Cell 2016
Combination of Herceptin and abemaciclib overcomes drug resistancePatient-derived xenograft
Goel et al Cancer Cell 2016
Two examples from our laboratory (2)Patient-derived models of HER2-positive brain metastasis
Ni, Ramkissoon, Xie et al Nature Medicine 2016
Updates from our laboratoryBoth of these findings are being translated into clinical trials for patients
New agents on the horizonPI3-kinase inhibitorsCDK4/6 inhibitorsImmune therapiesNew HER2 inhibitorsmTOR inhibitorsAntibody-drug conjugatesProgress is real and continuing
We have every reason to be optimistic
Thanks for your attention