r5 洪逸平 supervisor 趙大中醫師
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R5 洪逸平 SUPERVISOR 趙大中醫師. Breast Cancer. The most prevalent cancer in female Mortality 4 th in Taiwan. Treatment of Breast Cancer. Breast Cancer. When to change regimen? Unacceptable toxicity Progression disease. Current Tools for Follow-up. Radiologic image Standard serologic test - PowerPoint PPT PresentationTRANSCRIPT
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R5洪逸平SUPERVISOR 趙大中醫師
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Breast Cancer The most
prevalent cancer in female
Mortality 4th in Taiwan
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Treatment of Breast Cancer
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Breast Cancer When to change regimen?
Unacceptable toxicity Progression disease
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Current Tools for Follow-up Radiologic image Standard serologic test Circulating soluble-tumor–associated
protein biomarkers Circulation tumor cells Circulating tumor DNA
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Radiologic image Expensive Time consuming Inconvenient Inconclusive May not informative in several months Reasonably sensitive, not always reflect
tumor response or progression
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Standard serologic test Such as AST and ALT, LDH Inaccurate
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Circulating soluble-tumor–associated protein biomarkers
CEA, CA 15-3 CA 15-3, soluble forms of MUC(cell surface associated )-1 protein
J Clin Oncol 2007 25:5287-5312.
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Circulation tumor cells In 2004, pts with fewer CTC lived longer
than with more CTCN Engl J Med 351(8):781–791.
177 Pts with metastatic breast cancer
Annals of Oncology 22: 86–92, 2011
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CTCs and tumor markers in Breast Cancer
IC 2006-04 enrolled prospectively 267 metastatic breast cancer pts.
Breast Cancer Research 2012, 14:R29
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Circulation tumor DNA
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Circulating tumor DNA In a study in China, 46 of 126 primary
breast cancer pts have p53 mutation in the peripheral blood
Clin Cancer Res 2001;7:2222-2227
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Circulating tumor DNA Specific mutation and structural
variation in primary tumor cell 142 breast cancer pts ( not
disseminated) was analyzed at diagnosis
Clin Cancer Res 2002;8:3761-3766.
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Method Prospective, single-center study Compare circulating tumor DNA, CA 15-3,
circulating tumor cell Tagged-amplicon deep sequencing for PIK3CA
(encoding the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha protein) and TP53 (encoding tumor protein p53) or paired-end whole-genome sequencing p53 mutations are found in 50–75% of breast
carcinoma patients Serial blood samples(30ml) every 3 or more weeksScience (Wash. DC), 253: 49–53, 1991.
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Identification of Genome Alteration
Tagged-amplicon deep sequencing
Paired-end whole-genome sequencing
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22 3 5mutation SV
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CA 15-3 vs ctDNA
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CTCs and ctDNA
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Result
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Result
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Result
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Quartiles of ctDNA and OS
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ctDNA, CTCs and Relative Hazard
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Conclusion Circulating tumor DNA shows superior sensitivity
and has a greater dynamic range that correlates with tumor burden
Circulating tumor DNA provide earliest measure of treatment response
Identification of somatic alteration is needed Target sequencing could be expanded in addition
to PIK3CA and TP53 when the cost reduced There are many ways to identify tumor DNA :
digital PCR assay, targeted deep sequencing, exome sequencing, BEAMing, Safe-SeqS…
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Future Target like BCR/ABL may be found and
develop new target therapy!!
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Thanks for Your Attention!!