Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer

Pre/perimenopausal women: exemestane is only effective in post-menopausal women

History of DVT or PE: tamoxifen can increase tendency to blood clot

Endometrial cancer: full-dose tamoxifen is associated with increased risk of endometrial cancers

Macular disorders: tamoxifen is associated with retinal damage

Inability to comply with study procedures: standard

Prior use of antiestrogens within 12 months from the date of the trial consent form signature: there can be long duration effects from antiestrogens that could influence trial drug effects

Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature: similarly, wish to avoid any long lasting effect before alternate effect from study drugs

Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zoledronic acid or denosumab: Exemestane is an aromatase inhibitor which can worsen bone loss (osteoporosis)

Current use of terbinafine, quinidine, cinacalcet, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, warfarin, erythromycin, cyclosporin, nifedipine and any concomitant coumarin-type anti-coagulant therapy: these drugs compete for the Cytochrome P450 metabolic pathways of tamoxifen and exemestane

Moderate or severe renal impairment: Exemestane is eliminated equally by liver and renal metabolism

Known hypersensitivity to study drugs: standard

Screening Eligibility Criteria

To register a participant to the screening phase, the following documents should be provided by the participating site:

Signed participant consent form

Postmenopausal status, and any of the following:

* Histological report of ER-positive DCIS within 12 months, or HRL of the breast within 3 years from date of consent form signature, or;

* Report of risk assessment ≥3% in 5 years or 5% in 10 years of breast cancer according to the selected risk model(s) different criteria within 6 months from screening, or;

* Documentation of women carriers of a germline pathogenic/likely pathogenetic variant in a moderate penetrance gene (CHEK2 or ATM), or;

* Documented history of chest wall radiotherapy before age 30.

Inclusion of Women and Minorities

Only women will be recruited in the study given that breast cancer is much more frequent in women than men and because exemestane is contraindicated in men because of risk of uncontrolled gonadal stimulation. Women of all races and ethnic groups are eligible for this trial. At participating sites, efforts will be made to enroll women from diverse ethnic and socio-economic backgrounds, including recruitment of non-white women in a selected New York city area.

NIH policy requires that women and members of minority groups and their subpopulations be included in all NIH-supported biomedical and behavioral research projects involving NIH-defined clinical research unless a clear and compelling rationale and justification establishes to the satisfaction of the funding Institute \& Center (IC) Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances designated by the Director, NIH, upon the recommendation of an IC Director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research.

What this study is about