A Researcher Is Conducting a Retrospective Study on Breast Cancer

A researcher is conducting a retrospective study on breast cancer recurrence.  Records of a number of patients with hormone receptor-positive, early-stage breast cancer who received adjuvant therapy with tamoxifen were evaluated.  Various clinical, demographic, and drug concentration data were analyzed.  A comparison of patients who had disease recurrence with those who remained cancer free showed that some of the relapsed patients had lower serum concentrations of endoxifen and 4-hydroxytamoxifen, the active metabolites of tamoxifen.  Which of the following is the most likely cause of the drug's ineffectiveness in this subset of patients?

A) Activating mutation affecting a downstream signal transducer
B) Decreased hepatic N-acetyltransferase activity
C) Deficiency of thiopurine methyltransferase enzyme
D) Overexpression of P-glycoprotein in the tumor cells
E) Polymorphism of a cytochrome P450 enzyme

Correct Answer:

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