Studying Blood Samples From Women With Breast Cancer or Ductal Carcinoma In Situ Who Are Receiving Tamoxifen
Studying Blood Samples From Women With Breast Cancer or Ductal Carcinoma In Situ Who Are Receiving Tamoxifen
RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help
 doctors learn more about differences in DNA and predict how well patients will respond to
 treatment and plan better treatment.

 PURPOSE: This clinical trial is studying blood samples from women with breast cancer or
 ductal carcinoma in situ who are receiving tamoxifen.
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: 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.
Inclusion:

 Histologically confirmed invasive carcinoma of the breast or ductal breast carcinoma in
 situ Has been receiving tamoxifen citrate at a dose of 20 mg/day for at least 4 months
 either for the treatment of invasive or non-invasive carcinoma of the breast or for breast
 cancer recurrence prevention

 -  Expected duration of tamoxifen citrate treatment at least 6 months Hormone receptor
 status not specified Concurrent participation in non-treatment studies allowed
 provided it will not interfere with participation in this study Menopausal status not
 specified Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life
 expectancy ≥ 6 months Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/L Platelet count ≥
 100 x 10^9/L Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5
 times Upper Limit of Normal (ULN) Total bilirubin ≤ 2.5 times ULN Creatinine clearance
 ≥ 50 mL/min Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 -  No limitations to number of prior therapies

 -  No limitations for prior radiotherapy

 -  More than 14 days since prior and no other concurrent investigational agent

 Exclusion:

 Not pregnant or nursing No active, serious infection or medical or psychiatric illness
 likely to preclude study participation No psychiatric conditions that would preclude study
 compliance or informed consent No history of venous thromboembolism, transient ischemic
 attack, or cerebral vascular accident No history of allergic reaction to tamoxifen citrate
 or any of its reagents No concurrent coumadin

 No concurrent medications known to inhibit CYP2D6, including any of the following:

 -  Amiodarone

 -  Haloperidol

 -  Indinavir

 -  Ritonavir

 -  Quinidine

 No concurrent selective serotonin reuptake inhibitors, except the following:

 -  Venlafaxine

 -  Citalopram