Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer
Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
 exemestane may fight breast cancer by lowering the amount of estrogen the body makes.

 PURPOSE: This phase II trial is studying how well exemestane works 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