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.

Eligibility Criteria:
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