A Phase II Prospective Trial Correlating Progression Free Survival With CYP2D6 Activity in Patients With Metastatic Breast Cancer Treated With Single Agent Tamoxifen

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast

- Stage III (locally advanced), metastatic, or recurrent disease

- Deemed not resectable

- Estrogen-receptor and/or progesterone-receptor positive disease

- Receptor status is based on most recent results

- Receptor testing on metastatic disease is not required

- Measurable or non-measurable disease

- History of CNS metastasis allowed provided it has been treated (surgery,
radiotherapy, or radiosurgery) within the past 4 weeks and does not require
medications to control symptoms

- No known leptomeningeal disease allowed

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Menopausal status not specified

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception

- No medical or psychiatric conditions that would interfere with protocol compliance,
the ability to provide informed consent, assessment of response, or anticipated
toxicities

- More than 5 years since prior invasive malignancies except curatively treated basal
cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior investigational agents in the metastatic setting

- Other prior investigational agents in any setting must have been completed at
least 6 weeks prior to study registration and should be discussed with the study
PI

- Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have
disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last
dose

- Prior tamoxifen for advanced disease is not allowed

- No prior chemotherapy or trastuzumab (Herceptin) for metastatic disease

- Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed
provided it has been completed ≥ 4 weeks before study therapy

- Patients must not have had more than 2 lines of non-hormonal treatment in the locally
advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or
other biologics

- Treatment in the advanced setting must have been completed at least 2 weeks
prior to study initiation

- Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane,
aminoglutethamide) are allowed in the adjuvant or metastatic setting

- At least 2 weeks since prior and no concurrent medications that are strong to
moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including,
but not limited to, any of the following:

- Paroxetine (Paxil)

- Fluoxetine (Prozac)

- Bupropion (Wellbutrin)

- Quinidine (Cardioquin)

- Patients may not initiate bisphosphonate therapy while receiving treatment on this
study

- Patients who have begun receiving bisphosphonate therapy prior to registration
may continue at the same intervals used prior to study registration

- Concurrent radiotherapy to painful sites of bone disease or areas of impending
fractures allowed provided the following criteria are met:

- Radiotherapy was initiated before study entry

- Sites of measurable or non-measurable disease are outside the radiotherapy port

- Recovered from prior radiotherapy

- No other concurrent hormonal therapy

- No concurrent chemotherapy