Exemestane and Cyclophosphamide for Metastatic Breast Cancer

Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may
fight breast cancer by blocking the use of estrogen by the tumor cells. Low dose
cyclophosphamide may also stimulate the white blood cells, including natural killer cells,
for instance by decreasing the suppressor (regulatory) T-cells. Giving exemestane with
cyclophosphamide may be an effective treatment for estrogen receptor-positive, progesterone
receptor-positive, and HER2-negative stage IV breast cancer.

Inclusion Criteria:

- Patients must have histologically confirmed breast cancer that is ER positive and/or
PR positive, and HER2/neu negative and have disease that is metastatic (stage IV)

- HER2/neu negative disease determined using commercially available/approved assay
in local institutional or reference laboratory, according to American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (IHC
0-1+ or 2+ with HER2/17 ratio on FISH <= 1.8).

- ER/PR expression performed by standard immunohistochemical assay and classified
as ER and/or PR-positive according to ASCO/CAP guidelines (1-100% expression)

- Histologic and/or cytologic confirmation of metastatic disease is encouraged
whenever feasible, furthermore, if feasible, the biopsy should confirm that the
metastatic tumor is ER and/or PR positive and HER2/neu negative. For patients in
whom histologic biopsy confirmation and/or assessment of ER/PR/HER2 of metastatic
disease is not feasible, it is required that the primary tumor be ER and/or
PR-positive and HER2/neu negative.

- Measurable disease (RECIST 1.1) or non-measurable (assessable) disease

- Patients must have had progressive disease during at least one line of endocrine
therapy for metastatic disease or have recurrent disease while or within 12 months of
receiving adjuvant endocrine therapy. Prior treatments accepted include a
non-steroidal aromatase inhibitor, tamoxifen, fulvestrant or combinations.

- Patients taking bisphosphonates for bone disease are permitted to enter the trial, but
their bone lesions are not considered to be assessable for response, although they are
assessable for progression.

- Female or male subjects age >= 18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

- Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count >= 1,200/mcL

- platelets >= 100,000/mcL

- hemoglobin >= 9g/dl

- total bilirubin <= 2 X upper limit of normal (ULN) [unless due to Gilbert's
disease]

- AST(SGOT) <= 2.5 X ULN

- ALT(SGPT) <= 2.5 X ULN

- creatinine <= 1.5 X ULN

- Patients must be able to swallow and tolerate oral medications.

- Postmenopausal status, defined as 60 years and older, being 45 years and older and
having amenorrhea x 12 months or follicle stimulating hormone levels within
postmenopausal range, OR having undergone a bilateral oophorectomy.

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Patients may not be receiving any other investigational agents.

- Prior treatment for breast cancer with a steroidal aromatase inhibitor; with the
exception of patients who were started on the combination of exemestane with
everolimus less than 4 weeks prior to study entry and discontinued everolimus due to
poor tolerability.

- Presence of life threatening metastatic visceral disease (defined as extensive hepatic
involvement or symptomatic pulmonary lymphangitic spread) or uncontrolled brain
metastases.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.