Trial Information

Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population

OBJECTIVES:

Primary

- To evaluate the change in endoxifen levels after an increase in tamoxifen citrate dose
from 20 mg to 40 mg in women with breast cancer or ductal breast carcinoma in situ with
intermediate-metabolizing CYP2D6 genotypes.

Secondary

- To evaluate the tolerability of increasing the dose of tamoxifen citrate from 20 to 40
mg per day in these patients.

- To assess the feasibility of obtaining pharmacogenomic information from patients in the
clinical setting and using it to guide changes in therapy.

- To examine CYP2D6 allele frequencies and endoxifen levels among African-American women
taking tamoxifen citrate.

- To evaluate the change in plasma endoxifen levels after an increase in the tamoxifen
citrate dose from 20 mg to 40 mg daily in patients with poor-metabolizing genotypes.

- To study patient understanding of pharmacogenomics and obstacles to participation in
clinical trials based upon germline DNA.

OUTLINE: This is a multicenter study.

Blood samples are collected at baseline to determine CYP2D6 genotype and tamoxifen citrate
metabolic status (i.e., poor-metabolizing [PM], intermediate-metabolizing [IM], or
extensive-metabolizing [EM] alleles). Samples are also analyzed for plasma levels of
endoxifen and N-desmethyltamoxifen and for endoxifen/N-desmethyltamoxifen ratio. Patients
found to be IM or PM are notified to increased tamoxifen citrate to 40 mg/day for 4 months
(in the absence of unacceptable toxicity) with repeat endoxifen and N-desmethyltamoxifen
levels (and the ratio) at the end of this time.

All patients complete Quality Of Life (QOL) and Menopausal Symptoms Scale (MSS)
questionnaires at baseline and after 4 months of treatment. Toxicities are assessed at the
end of 4 months. Patients undergo repeat questionnaire assessment of their understanding of
the use of pharmacogenomics in clinical decision-making. Some patients also undergo a
30-minute, baseline interview regarding attitudes and experience towards participation in a
pharmacogenomics study.

Patients who choose to be informed of the results of their genotyping are contacted by
letter, along with their physicians, and offered genetic counseling to discuss the
significance of these results.

After completion of study therapy, patients are followed at 3-6 months, including toxicity
assessment and QOL and MSS questionnaires.