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A Trial of Exemestane in Postmenopausal Women With DCIS or at High Risk for Invasive Breast Cancer

Phase 2
Not Enrolling
Breast Neoplasms

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Trial Information

A Trial of Exemestane in Postmenopausal Women With DCIS or at High Risk for Invasive Breast Cancer


Evidence from adjuvant treatment trials of invasive breast cancer with aromatase inhibitors
suggests that these agents are superior to tamoxifen in preventing contralateral breast
cancer and are well tolerated. These agents are promising breast cancer chemopreventive
agents. Data on safety and effect on surrogate biomarkers in a healthy at risk population is



-The primary objective is to evaluate the study drug effects on mammographic density after
one year on treatment.


-Secondary objectives include assessing the effect of the intervention on bone mineral
density, serum hormones and lipids, and breast tissue biomarkers.


Eligible patients are postmenopausal women who meet one of the following criteria:

- History of stage I or II breast cancer 2 years out from definitive therapy.

- Gail model 5 year risk greater than or equal to 1.7%

- History of treated DCIS

- History of high risk lesion on breast biopsy (ADH, ALH, LCIS)

- Known or suspected BRCA1 or BRCA2 mutation

- Subjects must have adequate bone mineral density by DEXA scan in order to enroll.


- This is an open label study of exemestane in postmenopausal women with an elevated risk
of developing invasive breast cancer. Forty five subjects will be enrolled and receive
standard dose exemestane (25 mg QD), calcium and vitamin D.

- Each subject will continue treatment for a total of two years.

- Changes in mammographic breast density and bone mineral density will be evaluated
annually which will provide long term biomarker and safety information about prevention
therapy with exemestane.

Inclusion Criteria


Postmenopausal female.

Postmenopausal defined as no menses for at least 12 months or bilateral oophorectomy. In
unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of
postmenopausal status may be confirmed with FSH greater than 35 U/L.

Elevated risk for developing invasive breast cancer by virtue of one of the following

Gail Model risk of greater than or equal to 1.7% over 5 years from study entry. (This is
the same minimum level of risk required for a subject to be eligible for the recently
completed NSABP-P1 tamoxifen breast cancer prevention trial).

Lobular neoplasia.

Atypical ductal hyperplasia.

DCIS (ductal carcinoma in situ) that has been previously treated with mastectomy or
lumpectomy and radiation, +/- tamoxifen.

Deleterious mutations in BRCA1 or 2 OR A priori risk assessment of 20% chance or greater
of carrying BRCA1/2 gene mutation. The BRCAPRO and Couch model will both be used to asses
this risk. If a woman has a 20% risk of carrying a BRCA1/2 mutation by either model, she
will meet eligibility criteria.

Prior stage I or II breast cancer at least 2 years out from treatment for invasive disease
and no prior use of aromatase inhibitors.

Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen,
hormone replacement therapy, oral contraceptive pills, hormone-containing IUDs. E-string
is acceptable). Venlafaxine will be offered as supportive care for women with menopausal

ECOG performance status 0-1.

Subject has been counseled regarding her options and has signed the informed consent

Baseline DEXA scan with BMD T-score greater than or equal to 2.5 at AP spine.

Hemoglobin greater than or equal to 11 g/dl.

Creatinine less than 1.5 times the upper limits of normal.

ALT or AST less than 2.5 times upper limit of normal.

No investigational agent for the past 30 days.

If history of cancer (other than squamous or basal cell skin cancers), subject must have
no evidence of disease at time of enrollment AND no history of cancer directed treatment
in the 2 years preceding enrollment.


Current or recent chronic use (within 3 months) of hormonal medications, e.g. oral
contraceptive pills, hormone replacement therapy, tamoxifen, raloxifene, IUD with
progestins or corticosteroids. (Subjects on chronic topical or inhaled steroids will be
eligible for the study.) Current use of phenytoin, carbamazepine, rifampin due to
increased estrogen metabolism.

History of clotting or bleeding disorder.

History of allergic reactions attributed to compounds of similar chemical or biologic
composition to exemestane (e.g. anastrozole, letrozole, formestane).

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.

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Effect of exemestane on mammographic density at 1 year

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

November 2003

Completion Date:

February 2010

Related Keywords:

  • Breast Neoplasms
  • Chemoprevention
  • Mammographic Density
  • Bone Mineral Density
  • Biomarkers
  • Safety
  • Breast Cancer
  • Postmenopausal
  • Breast Neoplasms
  • Neoplasms



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