PT  - JOURNAL ARTICLE
AU  - Andrea Li-Ann Wong
AU  - Hui-Ling Yap
AU  - Wee-Lee Yeo
AU  - Richie Soong
AU  - Swee-Siang Ng
AU  - Ling-Zhi Wang
AU  - Maricel Tiemsim Cordero
AU  - Wei-Peng Yong
AU  - Boon-Cher Goh
AU  - Soo-Chin Lee
TI  - Gemcitabine and Platinum Pathway Pharmacogenetics in Asian Breast Cancer Patients
DP  - 2011 Sep 01
TA  - Cancer Genomics - Proteomics
PG  - 255--259
VI  - 8
IP  - 5
4099  - http://cgp.iiarjournals.org/content/8/5/255.short
4100  - http://cgp.iiarjournals.org/content/8/5/255.full
SO  - Cancer Genomics Proteomics2011 Sep 01; 8
AB  - Background/Aim: Gemcitabine/carboplatin is efficacious in breast cancer but results in significant hematologic toxicities. We employed a multi-gene approach to identify variants to predict its toxicities. Patients and Methods: Twenty-six gemcitabine and platinum-based DNA repair pathway polymorphisms were correlated with gemcitabine pharmacokinetics, hematologic toxicities, response and survival in 41 Asian breast cancer patients receiving gemcitabine/carboplatin. Results: The combined effects of solute carrier family (SLC)28A1+1528C>T and thymidylate synthetase (TYMS)+1494del6 significantly influenced hematologic toxicities: 89% of patients who possessed either SLC28A1+1528TT or TYMS+1494ins6/ins6 (n=9) developed grade 4 thrombocytopenia, versus 14% with neither genotype (n=29; p<0.001). In concordance, all patients who possessed either genotype developed grade 3/4 neutropenia, compared to 38% with neither genotype (p=0.001). None of the other genetic variants analyzed correlated with drug pharmacokinetics and pharmacodynamics. Conclusion: Approximately one-quarter of our Asian cohort carried SLC28A1+1528TT or TYMS+1494ins6/ins6, which are associated with increased myelotoxicity from gemcitabine/carboplatin. This has potential utility in treatment selection and genotype-based dosing strategies.