Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Letrozole in Preventing Breast Cancer in Postmenopausal Women

This study has been completed.
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: September 7, 2004
Last updated: April 10, 2009
Last verified: October 2007

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Letrozole may be effective in preventing the development or recurrence of breast cancer in postmenopausal women who are at increased risk of developing breast cancer because of elevated estradiol levels.

PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women with elevated estradiol levels.

Condition Intervention Phase
Breast Cancer
Drug: letrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Pilot Study of Aromatase Inhibitors for Women at Increased Risk of Breast Cancer Based on Estradiol Levels

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety, acceptability, and adherence
  • Effects on menopausal symptoms

Secondary Outcome Measures:
  • Effects on mammographic percent breast density

Estimated Enrollment: 110
Study Start Date: September 2000
Detailed Description:



  • Compare the safety, acceptability, and adherence to letrozole vs placebo in postmenopausal women at increased risk for the development or recurrence of breast cancer based on elevated plasma estradiol levels.
  • Compare the effects of these regimens on menopausal symptoms (including hot flushes, weight changes, sexual functioning, and genitourinary effects), blood lipid levels, markers of bone turnover, and multidimensional quality of life in patients treated with these regimens.


  • Determine the effect of letrozole-induced reduction of plasma estradiol levels on mammographic percent breast density in these patients.

OUTLINE: This is a pilot, randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily for 1 year. Patients may then receive additional oral letrozole once daily for up to 4 years.
  • Arm II: Patients receive oral placebo once daily for 1 year. Patients may then receive oral letrozole once daily for up to 5 years.

In both arms, treatment continues in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

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

PROJECTED ACCRUAL: A total of 110 patients (73 for arm I and 37 for arm II) will be accrued for this study.


Ages Eligible for Study:   35 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • At increased risk for the development or recurrence of breast cancer, defined as an estradiol level ≥ 9 pg/mL
  • No evidence of suspicious or malignant disease, based on the following examinations:

    • Clinical bilateral breast examination within the past 6 months
    • Bilateral* mammogram within 3 months before randomization OR within 30 days after randomization
    • Pelvic exam normal within the past 5 years
    • General physical exam within the past 6 months NOTE: *Unilateral mammogram of the uninvolved breast for patients with prior invasive breast cancer or ductal carcinoma in situ (DCIS)
  • Bone density scan within 2 standard deviations from normal within the past 30 days

    • Bone density scan ≥ 2 standard deviations below normal allowed if approved by the study physician
  • At least 1 breast that has not been previously treated with radiotherapy or surgery (for patients with prior invasive breast cancer or DCIS)
  • Hormone receptor status:

    • Not specified



  • 35 and over


  • Female

Menopausal status

  • Postmenopausal, defined by any of the following criteria:

    • At least 12 months without spontaneous menstrual bleeding
    • Prior hysterectomy and bilateral salpingo-oophorectomy
    • ≥ 55 years of age with a prior hysterectomy with or without oophorectomy
    • < 55 years of age with a prior hysterectomy without oophorectomy OR the status of the ovaries is unknown AND follicle-stimulating hormone (FSH) level is in the postmenopausal range

Performance status

  • Normal activity must not be restricted for a significant portion of the day

Life expectancy

  • At least 10 years


  • Complete blood count with differential normal

    • Prior benign neutropenia allowed provided the granulocyte count is ≥ 1,500/mm^3


  • Bilirubin normal
  • Alkaline phosphatase normal
  • SGOT and SGPT normal


  • Creatinine normal


  • No uncontrolled cardiovascular disease


  • Not pregnant
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No osteoporosis
  • No hyperlipidemia
  • No mental health status resulting in cognitive or emotional impairment that would preclude study participation


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • More than 30 days since prior AND no concurrent use of any of the following hormonal agents:

    • Estrogen or progesterone replacement therapy
    • Oral contraceptives
    • Raloxifene or other plasma estrogen receptor modulators (SERMs)
    • Androgens (e.g., danazol)
    • Luteinizing hormone-releasing hormone (LHRH) analogs (e.g., goserelin or leuprolide)
    • Prolactin inhibitors (e.g., bromocriptine)
    • Antiandrogens (e.g., cyproterone)
  • More than 60 days since prior AND no concurrent tamoxifen
  • No prior aromatase inhibitors (for patients with prior invasive breast cancer or DCIS)
  • No concurrent phytoestrogenic dietary supplements (e.g., soy, ginseng, or other natural products)

    • Dietary soy allowed


  • See Disease Characteristics


  • See Disease Characteristics
  • No prior bilateral mastectomy


  • More than 60 days since prior treatment for invasive breast cancer or DCIS
  • More than 30 days since prior bisphosphonates or calcitonin
  • No prior or concurrent participation on a treatment study for invasive breast cancer or DCIS
  • No concurrent participation in any other cancer prevention study or osteoporosis prevention study involving pharmacologic agents
  • No concurrent calcitonin
  • No concurrent bisphosphonate therapy
  • Concurrent cholecalciferol (vitamin D) and calcium to augment bone mineral density allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00090857

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Principal Investigator: Judy Garber, MD Dana-Farber Cancer Institute
Principal Investigator: Patricia A. Ganz, MD Jonsson Comprehensive Cancer Center
  More Information Identifier: NCT00090857     History of Changes
Obsolete Identifiers: NCT00165529, NCT00577551
Other Study ID Numbers: CDR0000375585
Study First Received: September 7, 2004
Last Updated: April 10, 2009

Keywords provided by National Cancer Institute (NCI):
breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
breast cancer in situ
ductal breast carcinoma in situ

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on May 25, 2017