Clinical trial NCT00066586: Exemestane in Reducing Breast Density in Postmenopausal Women at Risk for Breast Cancer
Official title: A Randomized Study Of The Effect Of Exemestane (Aromasin) Versus Placebo On Breast Density In Postmenopausal Women At Increased Risk For Development Of Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-08-07
Enrollment: 98
Sex: FEMALE
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: RATIONALE: High estrogen levels may be associated with dense breast tissue and an increased risk of developing breast cancer. Exemestane may be effective in preventing the development of breast cancer by decreasing estrogen levels and reducing breast density.

PURPOSE: Randomized clinical trial to study the effectiveness of exemestane in preventing the development of breast cancer by decreasing estrogen levels and reducing breast density in postmenopausal women who are at increased risk for breast cancer.

Detailed description: OBJECTIVES:

* Determine the efficacy of exemestane in decreasing breast density at least 1 grade in postmenopausal women with increased radiological breast density at increased risk for breast cancer.
* Determine whether the decrease in breast density is sustained 1 year after the cessation of this drug in these participants.
* Correlate the grade of breast density with bone density at baseline and at 1 year in participants treated with this drug.
* Determine the overall safety of this drug, in terms of bone and lipid metabolism and toxicity, in these participants.
* Determine the menopause-specific quality of life of participants treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to baseline mammographic density grade (2 vs 3 vs 4 vs 5 vs 6). Participants are randomized to 1 of 2 treatment arms.

* Arm I: Participants receive oral exemestane once daily for 1 year.
* Arm II: Participants receive oral placebo once daily for 1 year. In both arms, treatment continues in the absence of disease or unacceptable toxicity.

Quality of life is assessed at baseline and then at 3, 6, 9, 12, 18, and 24 months.

Participants are followed at 18 and 24 months.

PROJECTED ACCRUAL: A total of 120 participants (60 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Radiologically confirmed density occupying at least 25% of the breast tissue on baseline mammogram\*

  * Grade 2, 3, 4, 5, or 6 (Boyd classification)

    * Participants with different grades between the 2 breasts should be classified according to a higher grade NOTE: \*Performed within 6 months before study entry
* Bone mineral density T-score of either posterior-anterior spine or hip (femoral neck) must be no greater than 2.0 standard deviations below the mean value of peak bone mass in young normal women as determined by DEXA scan within the past 6 months
* No concurrent breast cancer
* No prior invasive breast cancer or ductal carcinoma in situ
* No breast implants
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* Postmenopausal

Sex

* Female

Menopausal status

* Postmenopausal, defined as 1 of the following:

  * Over 50 years of age with no spontaneous menses for at least 1 year
  * 50 years of age and under with no menses (e.g., spontaneous or secondary to hysterectomy) within the past year AND a follicle-stimulating hormone level within institution postmenopausal range
  * Bilateral oophorectomy

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Cardiovascular

* No cardiovascular disease
* No history of myocardial infarction
* No history of stroke
* No uncontrolled high blood pressure

Other

* No uncontrolled metabolic or endocrine disease
* No malabsorption syndrome
* No known hypersensitivity to exemestane or its excipients
* No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy
* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy
* No concurrent chemotherapy

Endocrine therapy

* More than 3 months since prior exogenous estrogen and/or progesterone/progestin therapy
* More than 6 months since prior selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or raloxifene)
* No concurrent selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or raloxifene)
* No concurrent steroids
* Vaginal estrogens allowed (e.g., Estring® or Vagifem®)

  * No concurrent compounded creams

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* More than 4 weeks since prior investigational agents
* No other concurrent medications that would preclude study endpoints
* No concurrent over-the-counter products or supplements considered to have an estrogenic effect, including any of the following:

  * Ginseng
  * Ginkgo biloba
  * Black cohosh
  * Dong quai
  * Fortified soy supplements (e.g., phytoestrogen preparations)

Primary outcomes:
measure: Change in breast density as measured by Boyd Scale at 1 year
timeFrame: 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
Study officials:
affiliation: Massachusetts General Hospital
name: Paul E. Goss, MD, PhD
role: STUDY_CHAIR
References:
citation: Cigler T, Richardson H, Yaffe MJ, Fabian CJ, Johnston D, Ingle JN, Nassif E, Brunner RL, Wood ME, Pater JL, Hu H, Qi S, Tu D, Goss PE. A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the effects of exemestane on mammographic breast density, bone density, markers of bone metabolism and serum lipid levels in postmenopausal women. Breast Cancer Res Treat. 2011 Apr;126(2):453-61. doi: 10.1007/s10549-010-1322-0. Epub 2011 Jan 9.