Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Disease Susceptibility

All Drugs and Chemicals

Antineoplastic Agents

Estrogens

3,3'-diindolylmethane

Protective Agents

women will receive DIM 100mg\*1/d, a nutritional supplement for 24 months.

DIM-Avail 100mg

David Margel, MD, PhD

Rinat Yerushalmi, MD

The purpose of this study is to determine whether adding DIM supplement will decrease breast density among female BRCA mutation carriers in two years.

The Research Question: In female BRCA mutation carriers, will adding DIM (100mg\*1/d, a nutritional supplement), decrease breast density in two years?

Study design: A single center single arm prospective interventional study of the use of DIM to decrease risk of breast cancer among female BRCA carriers.

Study population: Subjects will be female carriers of a BRCA mutation and have more than 10% mammographic breast density at baseline.

Intervention: DIM supplement (100mg\*1/d).

Study Time line: This will be a 2 years study. At initiation a breast mammography will be performed and eligibility assessed. Follow-up visits will occur every 4 months and quality of life questionnaires as well as adherence to DIM supplementation will be assessed. At the initiation and every 4 months blood and urine samples will be collected for Estrogen profile. At 12 and 24 months a mammography will be performed to verify changes in breast density.

Primary Endpoint: A decrease of more than 10% in breast density compared to baseline, following DIM supplementation intervention among female BRCA carriers.

Study impact: Decrease in mammographic breast density was shown to be a good marker for lower risk of breast cancer. This study has the potential to dramatically impact the management of female BRCA carriers. If we prove that by adding a food supplement breast density is decreased, we will change standard of care in these woman. In addition, the urine and blood samples collected during the study will be used for future translational research on the pathogenesis of breast cancer.

A Nutritional Intervention to Decrease Breast Density Among Female BRCA (BReast CAncer Susceptibility Gene) Carriers

A Nutritional Intervention to Decrease Breast Density Among Female BRCA Carriers -A Prospective Clinical Trial

The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI)

changes in TSH (Thyroid Stimulating Hormone), FSH (Follicle Stimulating Hormone), LH (Luteinizing Hormone), Estrogen, Prolactin, Progesterone and Testosterone compare to baseline

changes in the 2, 4, and 16 alpha- hydroxyderivative of estrone and the 2 and 4 methoxyestrone compare to baseline

Quality of life will be evaluate using the Revised Illness Perception Questionnaire.

Rabin Medical Center

Nutritional and Metabolic Diseases

Obesity

Breast Diseases

Skin Diseases

Overweight

Overnutrition

Nutrition Disorders

Body Weight

exercise

Mindy Kurzer

RATIONALE: Exercising regularly may lower the risk of breast cancer.

PURPOSE: This randomized clinical trial is studying how well exercise prevents breast cancer in healthy young women.

OBJECTIVES:

Primary

* Compare the changes in urine levels of a stable marker of oxidative stress (F_2-isoprostanes) in healthy young women who undergo exercise training during 4 menstrual cycles vs no exercise.

Secondary

* Assess the changes in other metabolic factors that explain the association between physical activity and breast cancer, including:

Estrogen metabolism (estrone, estradiol, estriol, 2-OHE_1, 2-OHE_2, 2-MeOHE_1, 2-MeOHE_2, 4-OHE_1, 4-OHE_2 \[as well as ratios of these metabolites\], insulin-like growth factor (IGF)-1 (as well as IGF-binding proteins-1, -2, and -3, insulin, glucose, body composition (including body mass index, lean mass, and body fat \[DEXA scan\]).

OUTLINE: This is a randomized, controlled study. Participants are stratified according to baseline body fat percentage and age (18 to 24 years vs 25 to 30 years). Participants are randomized to 1 of 2 intervention arms.

* Arm I: Participants exercise for 30 minutes 5 times a week. The intensity of exercise is increased every 4 weeks. The exercise regimen continues for up to 4 menstrual cycles.
* Arm II: Participants are observed for 4 menstrual cycles. Participants in both arms undergo 24-hour collection of urine on days 7, 8, and 9 of menstrual cycles 1 and 6. F_2-isoprostanes are measured via gas chromatography-mass spectrometry (GC/MS). Estrogens are also measured by GC/MS and include E_1, E_2, E_3, 2-OHE_1, 2-OHE_2, 4-OHE_1, 4-OHE_2, 2-MeE_1, 2-MeE_2, 4-MeE_1, 4-MeE_2, and 16OHE_1.

Participants undergo blood collection, body mass measurement by dual-energy x-ray absorptiometry, and a fitness assessment twice during the 6-month study.

PROJECTED ACCRUAL: A total of 400 participants will be accrued.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Nutritional Intervention to Decrease Breast Density Among Female BRCA (BReast CAncer Susceptibility Gene) Carriers	NCT02197000	BRCA1 Gene Muta... BRCA2 Gene Muta...	DIM-Avail 100mg	18 Years - 70 Years	Rabin Medical Center
Women in Steady Exercise Research [Formerly Women, Oxidative Stress, Exercise and Estrogens (WOSEE)]	NCT00393172	Breast Cancer Obesity	exercise	18 Years - 30 Years	University of Minnesota

Spots Global Cancer Trial Database for estrogen metabolism