Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer

PRIMARY OBJECTIVES:

I. Progression-free survival at 4 months, as measured by Response Evaluation Criteria in
Solid Tumors (RECIST).

SECONDARY OBJECTIVES:

I. Objective response rate (complete response [CR] and partial response [PR]).

II. Clinical benefit (CR, PR, and stable disease >= 6 months).

III. Assessment of toxicity.

IV. Assessment of compliance with medication adherence.

V. Assessment of quality of life.

VI. Assessment of bone health.

TERTIARY OBJECTIVES:

I. Serial measurements of serum estradiol, estrone, and estrone sulfate.

II. To investigate treatment resistance (e.g., expression of amphiregulin, epidermal growth
factor receptor [EGFR]), using molecular and immunohistochemical analyses of blood and tumor
samples of pre- and post- (when available) treatment tissues. Microarray analyses to
quantitate the expression of specific estrogen-responsive genes (e.g. thyroid transcription
factor 1 [TTF1] and PDZK1) will also be performed.

OUTLINE: Patients receive exemestane orally (PO) once daily (QD) on days 1-14. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for 1 year.

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic carcinoma of the breast

- Hormone receptor (estrogen receptor [ER] and/or progesterone receptor [PR]) positive
disease (defined as: ER and/or PR positivity as >= 5% staining), as confirmed by
immunohistochemistry (IHC) based on primary breast tissue or metastatic tissue

- Postmenopausal, as defined by any of the following:

- Natural menopause, with at least 1 year since last menses

- Chemotherapy-induced menopause with at least 1 year from last menses and serum
luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and estradiol levels
within the postmenopausal range

- History of surgical or radiation-induced ovarian ablation

- For women =< 56 years old and with a history of hysterectomy but at least one ovary
intact, serum LH/FSH and estradiol levels must be within the postmenopausal range

- Postmenopausal women with disease recurrence while receiving either tamoxifen or a
non-steroidal aromatase inhibitor (AI) as adjuvant therapy (as long as adjuvant
hormonal therapy was taken for 6 months before disease progression) or with disease
recurrence following the discontinuation/completion of adjuvant hormonal therapy

- Postmenopausal women with disease progression following either 0, 1 or 2 prior
hormonal therapies for metastatic breast cancer, as long as the subject has had no
prior exposure to exemestane (EXE)

- Measurable or non-measurable (but evaluable) disease, as defined by RECIST criteria

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Neutrophil count >= 1.5 X 10^9 cells/L

- Platelet count >= 100 X 10^9 cells/L

- Serum creatinine =< 1.5 times upper limit of normal (ULN)

- Total serum bilirubin =< 1.5 times ULN

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels =< 2.5 x ULN in
patients without liver metastases or =< 5 times ULN in patients with liver metastases

- Alkaline phosphatase =< 2.5 times the ULN for patients without bone or liver
metastases

- Subjects must have an estimated life expectancy of greater than 6 months

Exclusion Criteria:

- Prior exposure to EXE, whether in the adjuvant or metastatic setting

- Prior history of any other cancer with the exception of non-melanoma skin cancer and
treated in situ carcinoma of the cervix

- Active or symptomatic central nervous system (CNS) metastasis (stable or treated brain
metastasis allowed but patients must be off decadron, if given for CNS disease)

- Hormone-receptor negative or unknown breast cancer

- More than two prior chemotherapy regimen for treatment of metastatic disease (any
prior chemotherapy given in the adjuvant setting is permitted)

- Administration of any other anti-cancer therapy within 2 weeks of initiating study
treatment; use of bisphosphonates, however, are permitted for patients with known bone
metastases

- Treatment with any other concurrent investigational agent or anti-tumor drug
(chemotherapy, antibody therapy or other biologic agents), will not be permitted

- Subjects who have had no prior exposure to endocrine therapy

- Any uncontrolled medical co-morbidity or psychiatric disorder which interferes with
the ability to provide informed consent or comply with study procedures