Clinical Research Details

Descriptive Information
Role of genetic polymorphisms of drug metabolizing enzymes and drug transporters in the risk and treatment of breast cancer

Nathalie Khoueiry-Zgheib

Completed- Has Results


Conditions and Keywords
Breast cancer
Breast cancer, pharmacogenetics
Study Design
Basic / Translational
Safety and/or Efficacy Study
Observational Study
N/A: Not Applicable
N/A: Not Applicable
N/A: Not Applicable
Eligibility and IRB

This is a cohort of 300 breast cancer patients who were recruited while they were receiving cytotoxic therapy at AUBMC between 2009 and 2012. The plan was to build a data set coupled with DNA for pharmacogenetics studies. So far 2 manuscripts have been published:

Manuscript 1: Haroun F, Al-Shaar L, Habib RH, El-Saghir N, Tfayli A, Bazarbachi A, Salem Z, Shamseddine A, Taher A, Cascorbi I, Zgheib NK. Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer. Cancer Chemother Pharmacol. 2015 Jan;75(1):207-14. (PMID: 25428516)

This included an analysis of a sub-cohort of 145 breast cancer patients who received cyclophosphamide combination therapy and who were genotyped for CYP2B6. We have shown that CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were however no significant associations with myelo-toxicity. 

Manuscript 2: Awada Z, Haider S, Tfayli A, Bazarbachi A, El-Saghir NS, Salem Z, Shamseddine A, Taher A, Zgheib NK. Pharmacogenomics variation in drug metabolizing enzymes and transporters in relation to docetaxel toxicity in Lebanese breast cancer patients: paving the way for OMICs in low and middle income countries.OMICS. 2013 Jul;17(7):353-67 (PMID: 23758476)

This included an analysis of a sub-cohort of 32 breast cancer patients: 18 who developed febrile neutropenia following docetaxel therapy (cases).  They were age- and treatment- matched with 18 patients who did not develop febrile neutropenia on docetaxel (controls). They were all genotyped using the DMETPLus array from Affymetrix. We found that 12 SNPs in seven genes (ABCC6, ABCG1, ABCG2, CYP1A2, CYP2D6, FMO2 and FMO3) were significantly associated with febrile neutropenia after docetaxel treatment.  

This is a retrospective cohort of women with breast cancer who received all cycles of chemotherapy at the American University of Beirut Medical Center (AUBMC) between 2009 and 2011. 

Physician referrals of patients who approved to be consented for the study.

Adults (age more than 18 years) treated for breast cancer at AUBMC.

Refusal of consent.