Combined Estrogen Blockade of the Breast With Exemestane and Raloxifene in Postmenopausal Women With a History of Breast Cancer Who Have No Clinical Evidence of Disease: A Pilot Chemoprevention Trial
The objectives of this project are to investigate the safety and toxicity of the combination
of raloxifene, a selective estrogen receptor modulator (SERM), with exemestane, a new
steroidal aromatase inhibitor, in postmenopausal women with a history of breast cancer who
have no clinical evidence of disease. The study cohort will consist of postmenopausal women
with a history of AJCC Stage 0, I, II, or III breast cancer after completion of all planned
adjuvant therapy. The study cohort is limited to patients who have not already received
anti-estrogen therapy as part of post-operative adjuvant treatment. Patients with a history
of invasive ER- and/or PR-positive breast cancer are eligible only if they have not received
an anti-estrogen as part of adjuvant therapy, and they are at least 2 years from the time of
their primary surgery.
Tamoxifen has been shown to reduce the incidence of contralateral breast cancer regardless
of the estrogen expression of the primary tumor and may therefore be offered as a
chemopreventive agent to patients who have not received an anti-estrogen in the adjuvant
setting. This population of patients is also a reasonable cohort in which to test other
chemoprevention regimens. Our hypothesis is that the combination of raloxifene and
exemestane may offer an alternative treatment for chemoprevention that may prove to be more
effective than an anti-estrogen alone.
Endpoints of the study are to determine whether the combination of raloxifene and exemestane
is safe and tolerable with respect to:
1. markers of bone turnover and bone mineral density
2. the serum lipoprotein profile
3. quality of life (in particular, symptoms of estrogen deficiency)
4. pharmacokinetics and pharmacodynamics of both drugs.
We will also determine the feasibility of using mammography and breast MRI imaging to assess
the effects of the combination on radiographic breast density.
As part of a correlative laboratory study of breast biopsy material, women may undergo an
optional biopsy of their unaffected breast. Breast biopsy material will be evaluated both
pre- and 3 months post-treatment to determine whether the combination will have an impact on
breast tissue aromatase activity and breast tissue estrogen levels, and potential surrogate
endpoint biological markers.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a hx of AJCC Stage 0, I, II, or III breast cancer, who have no clinical evidence of disease, after completion of all planned adjuvant
Maura Dickler, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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