Clinical trial NCT00896636: Study of Breast Tissue in Women Not Previously Diagnosed With Breast Cancer Who Are Undergoing Fine Needle Aspiration
Official title: Gene Methylation and Estradiol Levels in Random FNA Samples as Biomarkers for Breast Cancer Risk
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Healthy, no Evidence of Disease
Keywords: breast cancer
healthy, no evidence of disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 385
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women coming in for screening mammography, for diagnostic imaging, for evaluation of benign breast problems, and for breast cancer risk evaluation who have no history of breast cancer.

Brief summary: RATIONALE: Studying samples of blood and breast tissue from healthy women in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to breast cancer risk.

PURPOSE: This research study is looking at breast tissue in women not previously diagnosed with breast cancer who are undergoing fine-needle aspiration.

Detailed description: OBJECTIVES:

Primary

* To determine if breast tissue DNA methylation profile and hormone concentration change across follicular and luteal phase, or across menopause, in random fine needle aspiration samples of women with no prior diagnosis or treatment for breast cancer.
* To determine if DNA methylation profile and breast hormone levels correlate with mammographic density, cytomorphology, or Gail risk estimates.
* To develop a high throughput commercial assay for DNA methylation profiling for assessing breast cancer risk.
* To develop a highly sensitive, specific, and novel nanoassay for estradiol and progesterone.

OUTLINE: This is a multicenter study.

Premenopausal women are stratified by menstrual cycle phase (mid-follicular \[day 5-10\] vs mid-luteal \[day 20-25\]), based on an adjusted 28-day cycle.

Patients undergo breast density measurement by digital mammography. Blood samples are obtained and analyzed for estradiol, progesterone, and follicle-stimulating hormone measurements, to define menstrual/menopausal status, and for DNA extraction. Patients also undergo random fine needle aspiration. Biopsy material from aspiration is analyzed for cytomorphology, steroid radioimmunoassay (RIA), steroid nanoassay, and DNA methylation studies (via polymerase chain reaction). The aspiration samples are also analyzed for estradiol and progesterone levels using high-pressure liquid chromatography and RIA.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Women meeting one of the following requirements:

  * Regularly cycling premenopausal women under 45 years of age
  * Perimenopausal women 45-55 years of age who have had ≥ two periods in the past 6 months
  * Postmenopausal women under 60 years of age (no menstrual period for 12 months and follicle-stimulating hormone (FSH) levels \> 25 IU/dL)
* No history of breast cancer diagnosis or prior treatment for breast cancer
* Negative breast evaluation within the past 3 months

PATIENT CHARACTERISTICS:

* See Disease Characteristics

PRIOR CONCURRENT THERAPY:

* No concurrent oral contraceptives
* At least 2 weeks since prior aspirin, non-steroidal anti-inflammatory drugs, and vitamin E

Primary outcomes:
measure: Differences in DNA methylation profiles between women in different menstrual stages
timeFrame: One time rFNA procedure to collect samples.
measure: Differences in DNA methylation profiles between women in different menstrual stages
timeFrame: One time rFNA procedure to collect samples
measure: Correlation between DNA methylation profiles and mammographic density, cytomorphology, or Gail risk estimate
timeFrame: One time rFNA procedure to collect sample to compare with baseline mammogram and risk info.
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Seema A. Khan, MD
role: PRINCIPAL_INVESTIGATOR
References: