R5洪逸平SUPERVISOR 趙大中醫師

Breast Cancer

The most prevalent cancer in female

Mortality 4th 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 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 with more CTCN Engl J Med 351(8):781–791.

177 Pts with metastatic breast cancer

Annals of Oncology 22: 86–92, 2011

CTCs and tumor markers in Breast Cancer

IC 2006-04 enrolled prospectively 267 metastatic breast cancer pts.

Breast Cancer Research 2012, 14:R29

Circulation tumor DNA

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

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.

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

weeks

Science (Wash. DC), 253: 49–53, 1991.

Identification of Genome Alteration

Tagged-amplicon deep sequencing

Paired-end whole-genome sequencing

22 3 5mutation SV

CA 15-3 vs ctDNA

CTCs and ctDNA

Result

Result

Result

Quartiles of ctDNA and OS

ctDNA, 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 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…

Future

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

Thanks for Your Attention!!