Tamoxifen Compared With LY353381 in Treating Women With Newly Diagnosed Breast Cancer

OBJECTIVES:

- Determine whether LY353381 hydrochloride or tamoxifen administered in the interval
between biopsy and re-excision alters the expression of tissue biomarkers relative to
placebo controls in postmenopausal women with newly diagnosed breast cancer.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study.

- Phase I: Patients are randomized to receive either oral LY353381 hydrochloride or oral
placebo daily.

Upon completion of phase I, all treatment centers begin phase II of the study.

- Phase II: Patients are randomized to receive either oral tamoxifen or oral placebo
daily.

Treatment in both phases continues for 2-6 weeks (until scheduled lumpectomy or mastectomy)
in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 and 2 weeks after surgery.

PROJECTED ACCRUAL: A minimum of 120 patients (60 per treatment phase) will be accrued for
this study within 18 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed noninvasive or small invasive breast cancer

- Low or intermediate grade (ductal carcinoma in situ, T1, or T2) OR

- Estrogen and/or progesterone receptor positive

- Largest mass no greater than 5 cm

- Clustered microcalcifications as only abnormality allowed with no upper size
limit

- If no distinction between mass and microcalcifications, size as 1 lesion

- Lumpectomy or mastectomy must be planned for 2-6 weeks from start of study

- No evidence of metastases from any malignancy

- Hormone receptor status:

- Estrogen and progesterone receptor positive (unless low or intermediate grade
tumor)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex:

- Female

Menopausal status:

- Postmenopausal by one of the following:

- Prior oophorectomy

- Over age 50 with prior hysterectomy, ovaries remaining

- Uterus and ovaries intact and no menstrual period for more than 3 months

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Platelet count greater than 100,000/mm^3

- Hemoglobin greater than 10 g/dL

- Absolute granulocyte count greater than 1,000/mm^3

Hepatic:

- Albumin greater than 3 g/dL

- Bilirubin less than 1.5 mg/dL

- AST less than 100 U/L

- Alkaline phosphatase less than 200 U/L

Renal:

- Creatinine less than 1.5 mg/dL

Cardiovascular:

- No history of deep vein thrombosis

Pulmonary:

- No prior pulmonary embolus

Other:

- Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- At least 1 year since prior chemotherapy

Endocrine therapy:

- At least 1 year since prior aromatase inhibitors, antiestrogens, or LH
agonists/antagonists

- No concurrent hormone replacement therapy or oral contraceptives (from time of
randomization)

Radiotherapy:

- Not specified

Surgery:

- See Disease Characteristics

Other:

- No concurrent treatment for other malignancy