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An Introduction to Breast Cancer Translational Research
Song Yao, PhD Associate Member
Department of Cancer Prevention and Control Roswell Park Cancer Institute
RPN 532 – Oncology for Scientist
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What is translational medicine?• The application of a discovery to the practice of
medicine - from “bench” to “bedside”
http://www.researchamerica.org/advocacy-action/issues-researchamerica-advocates/bench-bedside-drug-development-pipeline
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Translational research cycle
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Timeline of translational oncology in the last 10 years
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Drugs developed on the basis of tumor biology
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Breast cancer translational medicine
• Multi-gene panels (e.g., OncoType Dx)
• CDK4/6 inhibitor – palbociclib
• Breast cancer immunotherapy
• Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)
• Balancing translational research between treatment and prevention
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Breast Cancer Intrinsic Subtypes
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Intrinsic molecular subtypes
Carey 2006; JAMA 295:2492-2502
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21-gene assay (Oncotype Dx)
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21-gene assay (Oncotype Dx)
http://breast-cancer.oncotypedx.com/en-US/Patient-Invasive/WhatIsTheOncotypeDXCancerTest/WhenShouldTheOncotypeDXBreastCancerTestBeUsed.aspx
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Ongoing trial - TAILORx
http://www.oncolink.org/types/article.cfm?id=9643
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SparanoJAetal.NEnglJMed2015;373:2005-2014.
Kaplan–Meier Estimates in the Analyses of Invasive Disease–free Survival, Freedom from Recurrence of Breast Cancer at a Distant Site, Freedom from
Recurrence at Any Site, and Overall Survival.
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CDK4/6 inhibitor - palbociclib
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CDK4/6 inhibitor - palbociclib
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CDK4/6 inhibitor - palbociclib
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Breast cancer immunotherapy
http://www.pharmaceutical-journal.com/news-and-analysis/feature/immune-checkpoint-inhibitors-bring-new-hope-to-cancer-patients/20067127.article
Avelumab
Pembrolizumab
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Breast cancer immunotherapy• Dirix LY, Takacs I, Nikolinakos P, et al: Avelumab (MSB0010718C), an
anti–PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. 2015 San Antonio Breast Cancer Symposium. Abstract S1-04. Presented December 9, 2015.
- overall response rate: 4.8% (8/168) - 5/8 had triple-negative cancer, and 4 had PD-L1 positive immune cells
• Rugo HS, Delord J-P, Im S-A, et al: Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive estrogen receptor–positive/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. 2015 San Antonio Breast Cancer Symposium. Abstract S5-07. Presented December 11, 2015.
- ER-positive HER2 negative PD-L1 expressing - Of 25 evaluable patients, response rate 12%, plus 8% stable disease
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Clinical applications of CTC and ctDNA analyses in cancer care.
Daniel A. Haber, and Victor E. Velculescu Cancer Discovery 2014;4:650-661
©2014 by American Association for Cancer Research
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A pooled-analysis of CTC in breast cancer
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Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease
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Two-way translational cancer research