Exemestane in Reducing Breast Density in Postmenopausal Women at Risk for Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: exemestane; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L-4M1
      • Centre Hospitalier de l'Universite de Montreal
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo once daily x 1 year
Active Comparator: Exemestane	Drug: exemestane; exemestane 25 mg once daily x 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in breast density as measured by Boyd Scale at 1 year	6 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2001
• Primary Completion (Actual): November 16, 2007
• Study Completion (Actual): February 10, 2009

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: MAP2; CAN-NCIC-MAP2 (Other Identifier: PDQ Identifier); PFIZER-971-ONC-0028-088 (Other Identifier: Pfizer); CDR0000316328 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No