Pharmacogenomic Impact on Breast Cancer Survival for Black Zimbabwean Patients on Tamoxifen.

Abstract

About one in three Black Africans carry the African-predominant allele variants CYP2D6*17 and/or CYP2D6*29, which confer a reduced enzymatic activity. CYP2D6 intermediate metabolizers (IM) have a reduced biotransformation rate of tamoxifen compared with its more active metabolite endoxifen. A prospective cohort study of Black Zimbabwean patients with hormone receptor-positive breast cancer on tamoxifen therapy was conducted. Patients were genotyped for CYP2D6 and followed up for event-free survival (EFS) on tamoxifen. In total, 18 CYP2D6 IM and 33 normal metabolizers (NM) were enrolled. At 2 years, the estimated EFS was 40.1% (95% CI, 20.3 to 79.4) for the IM group and 84.0% (95% CI, 72.1 to 97.9) for the NM group (log-rank <i>P</i> = .0021). A Cox proportional hazards model, after adjusting for BMI, stage at diagnosis, and previous breast cancer surgery, estimated about a 5.5-fold higher hazard of recurrence, progression, or death in IM compared with NM. Individuals with hormone receptor-positive breast cancer who are CYP2D6 NM had better disease recurrence and progression-free survival outcomes compared with IM.