Tamoxifen Resistance in Women With Stage I, Stage II, Stage IIIA, or Stage IIIB Breast Cancer

OBJECTIVES:

- Identify women who are resistant to tamoxifen citrate and other drugs for the treatment
of breast cancer by testing their plasma for the presence of proteins (e.g., macrophage
migration inhibition factor) encoded by resistance-inducing genes (RIGs).

- Provide retrospective data on the predictive value of RIGs to serve as the basis for a
prospective clinical trial of these genes as predictors of drug resistance.

OUTLINE: This is a multicenter study. Patients are stratified according to response during
tamoxifen citrate (TAM) therapy (resistant group [i.e., those who develop recurrent breast
cancer while being treated with TAM] vs conditionally sensitive group [i.e., those who have
disease-free survival for over 3 years after initial diagnosis while being treated with
TAM]).

Patients undergo blood collection at baseline, within 3 weeks of initiation of TAM therapy,
and then every 6 months for 3 years or until relapse, whichever comes first. Samples are
analyzed by enzyme-linked immunosorbent assay for expression of protein biomarkers (i.e.,
kallikrein gene 10, macrophage migration inhibition factor, prolyl carboxypeptidase, queuine
tRNA-ribosyltransferase, and kinesin) encoded by resistance-inducing genes. An additional
blood sample is obtained from patients at the time of relapse, if available.

Patients also undergo assessment of medical history, personal habits, and characteristics of
breast cancer (e.g., tumor histology, stage, and grade) at baseline.

Inclusion Criteria:

- Histologically confirmed invasive breast cancer

- Initial pathologic stage I-IIIB disease

- No stage IV disease

- Meets the following criteria for breast cancer therapy:

- Received prior primary local therapy for breast cancer

- Scheduled to begin tamoxifen citrate as adjuvant therapy for breast cancer within
3 weeks

- Hormone receptor status:

- Estrogen-receptor positive tumor

- Female

- Pre- or post-menopausal

- Must be able to donate 20 mL of blood

Exclusion Criteria:

- Severe anemia, defined as hemoglobin < 11 g/dL

- Psychiatric history that would preclude obtaining informed consent