Study of Breast Tissue in Women Not Previously Diagnosed With Breast Cancer Who Are Undergoing Fine Needle Aspiration

Study Overview
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Brief Summary
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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
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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.

Official Title
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Gene Methylation and Estradiol Levels in Random FNA Samples as Biomarkers for Breast Cancer Risk

Conditions
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Breast Cancer, Healthy, no Evidence of Disease

Intervention / Treatment
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* Procedure: Random fine need aspiration (rFNA)
* Other: Mammogram


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Luteal<br>Pre-menopausal women who undergo rFNA procedure during the luteal phase of their menstrual cycle. | Procedure: Random fine need aspiration (rFNA)<br>* Deep infiltration into the tissue of each breast with up to a 21 gauge needle attached to a syringe with about 4-5 passes at each location (up to 8-10 passes per breast) under local anesthesia (lidocaine).<br>Other: Mammogram<br>* Standard mammography of both breasts to obtain images for breast density measurement.<br>|
| Follicular<br>Pre-menopausal women who undergo rFNA procedure during the follicular phase of their menstrual cycle. | Procedure: Random fine need aspiration (rFNA)<br>* Deep infiltration into the tissue of each breast with up to a 21 gauge needle attached to a syringe with about 4-5 passes at each location (up to 8-10 passes per breast) under local anesthesia (lidocaine).<br>Other: Mammogram<br>* Standard mammography of both breasts to obtain images for breast density measurement.<br>|
| Menopause<br>Women who have entered menopause. | Procedure: Random fine need aspiration (rFNA)<br>* Deep infiltration into the tissue of each breast with up to a 21 gauge needle attached to a syringe with about 4-5 passes at each location (up to 8-10 passes per breast) under local anesthesia (lidocaine).<br>Other: Mammogram<br>* Standard mammography of both breasts to obtain images for breast density measurement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in DNA methylation profiles between women in different menstrual stages |  | One time rFNA procedure to collect samples. | 
| Differences in DNA methylation profiles between women in different menstrual stages |  | One time rFNA procedure to collect samples | 
| Correlation between DNA methylation profiles and mammographic density, cytomorphology, or Gail risk estimate |  | One time rFNA procedure to collect sample to compare with baseline mammogram and risk info. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, healthy, no evidence of disease