RATIONALE: Estrogen can cause the growth of tumor cells. Hormone therapy using therapeutic estradiol may fight breast cancer by lowering the amount of estrogen the body makes. Though estradiol initially produces stimulation of ER+ cancer cells, both laboratory and some clinical experience indicate that it may have the opposite effect on such cells, once they have become resistant to estrogen deprivation. In laboratory models, there is death of the "resistant" population after estradiol treatment, followed by restoration of sensitivity of the remaining cells to estrogen deprivation, as with an aromatase inhibitor. Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving therapeutic estradiol together with exemestane may kill more tumor cells. PURPOSE: This clinical trial studies therapeutic estradiol and exemestane in treating post-menopausal patients with hormone receptor-positive metastatic breast cancer
OBJECTIVES: I. To assess feasibility and toxicity associated with estradiol followed by exemestane in the treatment of estrogen receptor positive metastatic breast cancer patients failing prior aromatase inhibitor therapy. II. Exploratory analysis of bio-correlates which will evaluate the mechanism of action of this treatment combination: changes in serum M-30, a marker of mitochondrial apoptosis; changes in number of circulating tumor cells (CTC); changes in CTC expression of ER, IGF1-R, and M-30. III. Exploratory analysis of Progression Free Survival (PFS). OUTLINE: Patients receive oral therapeutic estradiol once daily on days 1-3, twice daily on days 4-7, and thrice daily on days 8-90. Beginning on day 98, patients receive oral exemestane once daily in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Given orally (PO)
Given PO
Correlative studies
Correlative studies
University of Arizona Cancer Center
Tucson, Arizona, United States
Number of Participants With Grade 4 Toxicity
Such as deep vein thrombosis requiring hospitalization or pulmonary embolism
Time frame: By day 90
Patients With Change in Serum M-30 (a Marker of Mitochondrial Apoptosis) With Treatment
Time frame: At baseline and on days, 8, 30, 60, and 90
Patients With Change in Number of Circulating Tumor Cells (CTC) With Treatment
Time frame: At baseline and on days 8, 90, and 180
Patients With Change in Circulating Tumor Cells (CTC) Expression of M-30 With Treatment
Time frame: At baseline and on days 8, 90, and 180
Change in Circulating Tumor Cells (CTC) ER Expression With Treatment
Time frame: At baseline and on days 8, 90, and 180
Change in Circulating Tumor Cells (CTC) IGF1R Expression With Treatment
Time frame: At baseline and on days 8, 90, and 180
Median Time From Entry on Study to Progression of Disease
In weeks
Time frame: Up to 1.5 years
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