Breast Cancer The most prevalent cancer in female

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 Circulating soluble-tumor–associated protein biomarkers Circulation tumor cells Circulating tumor DNA

Radiologic image Expensive Time consuming Inconvenient Inconclusive May not informative in several months Reasonably sensitive, not always reflect tumor response or progression

Standard serologic test Such as AST and ALT, LDH Inaccurate

Circulating soluble-tumor– associated protein biomarkers CEA, CA 15 -3, soluble forms of MUC(cell surface associated )-1 protein J Clin Oncol 2007 25: 5287 -5312.

Circulation tumor cells In 2004, pts with fewer CTC lived longer than N Engl J Med 351(8): 781– 791. with more CTC 177 Pts with metastatic breast cancer Annals of Oncology 22: 86– 92, 201

CTCs and tumor markers in Breast Cancer IC 2006 -04 enrolled prospectively 267 metastatic breast cancer pts. Breast Cancer Research 2012, 14: R

Circulation tumor DNA

Circulating tumor DNA In a study in China, 46 of 126 primary breast cancer pts have p 53 mutation in the peripheral blood Clin Cancer Res 2001; 7: 2222 -2227

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 -376

Method Prospective, single-center study Compare circulating tumor DNA, CA 15 -3, circulating tumor cell Tagged-amplicon deep sequencing for PIK 3 CA (encoding the phosphatidylinositol-4, 5 bisphosphate 3 -kinase, catalytic subunit alpha protein) and TP 53 (encoding tumor protein p 53) or paired-end whole-genome sequencing � p 53 mutations are found in 50– 75% of breast carcinoma patients Science (Wash. DC), 253: 49– 53, 1991. Serial blood samples(30 ml) every 3 or more weeks

Identification of Genome Alteration Tagged-amplicon deep sequencing Paired-end wholegenome sequencing

mutation 22 3 SV 5

CA 15 -3 vs ct. DNA

CTCs and ct. DNA

Result

Result

Result

Quartiles of ct. DNA and OS

ct. DNA, CTCs and Relative Hazard

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 PIK 3 CA and TP 53 when the cost reduced There are many ways to identify tumor DNA : digital PCR assay, targeted deep sequencing, exome sequencing, BEAMing, Safe-Seq. S…

Future Target like BCR/ABL may be found and develop new target therapy!!

Thanks for Your Attention!!