Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Dysbiosis

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Estrogens

Endocrine Disruptors

Women's age will range 25-70 years. Cases will be women diagnosed and surgically intervened of breast cancer, stages I and II.

Controls will be women surgically intervened of breast augmentation or reduction.

Luis Fontana, Ph.D.

Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. The hypothesis of this study is that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter the microbiota.

This is a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered.

Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed.

This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.

The study will follow the Declaration of Helsinki and the Spaniard legislation regarding clinical research. Data obtained will be confidential and only the researchers and participants, upon request, will have access to them. The study will also follow the data protection legislation of Spain to guarantee data confidentiality, treatment and availability.

Participation is volunteer. Participants will be informed about the nature of the research and the usage of biological samples. In addition to verbal information, participants will be presented and read an informed consent. Permission has been granted by the Ethics Committee of Andalusia (Spain).

Inclusion and exclusion criteria. Women's age will range 25-70 years. Cases will be women diagnosed and surgically intervened of incident breast cancer, stages I and II. Controls will be women surgically intervened of breast augmentation or reduction. Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded of the study. Women with oncological, gynecological or endocrine antecedents and those who have received of antibiotic treatment 3 months prior to recruitment will be also excluded. Controls will be matched to cases by age (± 2 years), category of body mass index and hospital of recruitment.

Sample size. The number of breast cancer cases will include at least 100 women, matched with 100 control women. Three hospitals will participate in the recruitment: The University Hospital of Jaén, Spain; the University Hospital Campus de la Salud of Granada, Spain; and Ana Moreno Clinic (Granada, Spain).

Biological samples. Blood, breast tissue, stool and urine samples from cases and controls will be collected. Serum will be separated from blood by centrifugation. Breast tissue samples will be taken during surgery, from a marginal area 3-5 cm apart from the tumor. For controls, samples will be taken from any available breast tissue during breast reduction or augmentation surgery.

Breast and intestinal microbiota. Bacteria, archaea, fungi and viruses will be investigated in feces and breast tissue samples. Samples will be pre-treated with pathogen lysis tubes L and S (QIAGEN, Barcelona, Spain). DNA will be extracted with the QIAamp cador Pathogen Mini kit (QIAGEN, Barcelona, Spain).

DNA quantification. The DNA concentration of the samples will be evaluated in a NanoDrop2000c (Thermo Fisher Scientific, Waltham, MA, USA).

Metagenomic library construction and sequencing. The Nextera XT DNA Library Preparation Kit (Illumina, San Diego, CA, USA) will be used for metagenomic library construction. The amplicon tagment mix (ATM) in Nextera XT, which includes the enzyme used for tagmentation, will be diluted 1:10 in nuclease-free water for library construction using 1 to 100 pg input DNA. Each 20 μL of the tagmentation reaction mixture consists of 10 μL TD buffer, 5 μL of input DNA, and 5 μL of diluted ATM. PCR cycles for library construction will be 12, 14, 17, and 20 cycles for 1,000, 100, 10, and 1 pg DNA, respectively, following the manufacturer's protocol. The manufacturer recommends 12 cycles of the PCR reaction for no less than 1 ng input DNA. Amplified libraries will be purified using AMPure XP (Agencourt, Brea, CA, USA). The quality of the purified libraries will be assessed using an Agilent High Sensitivity DNA Kit on an Agilent 2100 Bioanalyzer (Santa Clara, CA, USA). The sequencing libraries will be further quantified using the KAPA Library Quantification Kit. Metagenomic libraries will be mixed with PhiX Control v3 (Illumina) at a ratio of 9:1 and sequenced with an Illumina MiSeq Reagent Kit v3 (600 cycles). All samples to be analyzed will be combined in a pool before starting the massive sequencing. The latter will be done with the MiSeq apparatus (Illumina).

Data processing for metagenomic libraries. Metagenomic reads will be subjected to adaptor clipping and quality trimming using Trimmomatic v0.3. The first three nucleotides with quality scores less than 20 will be cut from the 3' and 5' read ends. Reads will be processed using a sliding window method, cutting once the average quality within the window (4 base) fell below the threshold (Q20). Reads with a length of fewer than 100 nucleotides will be then removed. Low-complexity reads will be filtered out using PRINSEQ version 0.20.4. PCR duplicates will be removed with Picard version 2.8.0 (http://broadinstitute.github.io/picard). The processed high-quality and clean reads in each library will be used in subsequent analyses. In the community analysis based on metagenomic sequences, small subunit (SSU) rRNA gene sequences will be identified using Metaxa2 software. Taxonomy assignments will be performed based on the results of a BLAST search against the SILVA123 database, using the MEGAN program \[23\] with the following settings: Min Support 1, Min Score 50, Max Expected 1xe-5, Top Percent 10.0. SSU rRNA gene community compositions were compared among the metagenomic libraries.

Metabolomic study. Sample preparation. The samples will be prepared using the automated MicroLab STARR (Hamilton Company, Salt Lake City, UT, USA) robot system. For quality control (QC) purposes, a recovery standard will be added to 100 L of the serum samples before the first step in the extraction process. The proteins will be precipitated with methanol by vigorously shaking for 2 min. Next, the samples will be centrifuged to remove the proteins, dissociate the small molecules bound to the proteins or trapped in the precipitated protein matrix, and to recover chemically diverse metabolites (Glen Mills GenoGrinder 2000, Lebanon, USA). Then, the samples will be placed on a TurboVapR (Zymark, California, USA) to remove the organic solvent. For liquid chromatography (LC) analysis, the samples will be stored overnight in nitrogen before preparation. For gas chromatography (GC) analysis, each sample will be dried overnight under vacuum before preparation.

Quality controls. Several types of control experiments will be performed in parallel with the experimental samples. A pooled matrix sample, generated by taking a small volume of each experimental sample, will serve as a technical replicate throughout the extracted data set. Water aliquots will serve as process blanks. Moreover, a cocktail of QC standards carefully chosen not to interfere with the measurement of endogenous compounds will be spiked into every analyzed sample. This will allow instrument performance monitoring and aid in the chromatographic alignment. The instrument variability will be determined by calculating the median relative standard deviation (RSD) for the standards that will be added to each sample before injection into the mass spectrometers (MS). The entire process variability will be determined by calculating the median RSD for all the endogenous metabolites (i.e., non-instrument standards) present in 100% of the pooled matrix samples. The experimental samples will be randomized across the platform run with the QC samples spaced every 5 or 10 injections to verify overall assay performance. The internal standards will be used to measure the instrument variability and will have a median RSD of 3%. Additionally, the total process variability will be 8%.

Ultra-performance liquid chromatography-tandem mass spectrometry. The liquid chromatography/mass spectrometry (LC/MS) portion of the platform to be used will employ a Waters ACQUITY ultra performance liquid chromatography (UPLC), a Thermo Scientific Q-Exactive high-resolution/accurate MS interfaced with a heated electrospray ionization (HESI-II) source, and an Orbitrap mass analyzer operated at a 35,000 mass resolution. The sample extract will be dried and reconstituted in acidic or basic LC-compatible solvents, each of which will contain eight or more injected QC standards at fixed concentrations to ensure injection and chromatographic consistency. One aliquot will be analyzed using acidic, positive ion-optimized conditions, and another will be performed using basic, negative ion optimized conditions in two independent injections using separate dedicated columns (Waters UPLC BEH C18-2.1 × 100 mm, 1.7 m). The extracts reconstituted in acidic conditions will be gradient-eluted from a C18 column using water and methanol containing 0.1% formic acid. A second aliquot, from the basic extract, will be similarly eluted from a C18 column using methanol, water, and 6.5 mM ammonium bicarbonate. A third aliquot will be analyzed via negative ionization following elution from a hydrophilic interaction chromatography column (Waters UPLC BEH Amide 2.1 × 150 mm, 1.7 m) using a gradient consisting of water and acetonitrile with 10 mM ammonium formate.

Gas chromatography-mass spectrometry. The samples destined for analysis by GC-MS will be dried under a vacuum for a minimum of 18 h before being derivatized under dried nitrogen with bistrimethylsilyltrifluoroacetamide. The derivatized samples will be separated on a 5% diphenyl/95% dimethyl polysiloxane fused silica column (20 m × 0.18 mm id; 0.18 m film thickness) with helium as the carrier gas and a temperature ramp from 60C to 340C over a 17.5-min period. The samples will be analyzed on a Thermo-Finnigan Trace DSQ fast-scanning single-quadrupole MS using electron impact ionization (EI) operated at unit mass resolving power. The scan range will be 50-750 m/z.

Data extraction and compound identification. The raw data will be extracted, and the peaks will be aligned and identified. QCs will be processed using specific hardware and software. The peaks will be quantified using the area-under-the-curve (AUC) calculation. The compounds will be identified comparing the data to library entries of purified standards or recurrent unknown entities. The biochemical identifications will be based on three criteria: the retention index (RI) within a narrow RI window of the proposed identification, an accurate mass match to the library ± 0.005 amu, and the MS/MS forward and reverse scores between the experimental data and authentic standards. The MS/MS scores will be based on a comparison of the ions present in the experimental spectrum with the ions present in the library spectrum. Although there may be similarities between these molecules based on one of these factors, the use of all three data points can be utilized to distinguish and differentiate the biochemicals with precision.

Quantitation of the exposure to EDCs in urine samples. Analysis of non-persistent EDCs will be carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Briefly, urine samples are thawed completely at room temperature, centrifuge at 2600 x g for 10 min to sediment particulate matter and 0.75 mL are taken to carry out the analysis. In order to determine total EDCs amount (free plus conjugated), each sample is spiked with 50 μL of enzyme solution (β-glucuronidase/sulfatase) and incubated at 37 °C for 24 h. The treated urine is placed in a 15 mL screw-cap glass tube and spiked with 30 μL of the surrogate standard solution (1.25 mg/L of BPA-d16). Urine is diluted to 10.0 mL with 5% NaCl aqueous solution (w/v) and the pH is adjusted to 2.0. Next, 0.75 mL of acetone and 0.75 mL of trichloromethane are mixed and injected rapidly into the aqueous sample with a syringe. After manual shaking, centrifugation and evaporation of the extract, the residue is dissolved with 100 μL of a mixture consisting of water (0.1% ammonia)/acetonitrile (0.1% ammonia), 70:30 (v/v), and finally 10 μL is injected in the LC system. Urinary creatinine concentration is determined using an automated colorimetric determination in the same urine samples in which the environmental chemical is assessed.

Quantitation of urinary concentrations of the parent estrogens and estrogen metabolites. Concentrations of estrone, estradiol and 13 estrogen metabolites will be determined adjusting for urinary creatinine levels (mg/dl). The quantitation of urinary estrogens will be assessed by gas chromatography tandem mass spectrometry using a triple quadrupole analyzer. Briefly, one mL of urine with 25 µL of internal standards solution is extracted using C18 SPE cartridge (Sep-Pack C18) previously conditioned with 4 mL of methanol and 4 mL of water. After loading the urine sample, the cartridge is washed with 4 mL of water. The treated urine is then evaporated. Three mL of acetate buffer 0.1 M (pH 4.5) and 3 µL of β-glucuronidase are added to the evaporated, and the mixture is incubated for 3 h at 55 °C. After cooling to room temperature, pH was increased to approximately 9.5. Then, samples are extracted with 6 mL of tert-butyl methyl ether by shaking and centrifuged. Finally, the organic layer is evaporated to dryness under a stream of nitrogen.

Other sources of information and covariables. Participants' anthropometric, sociodemographic and reproductive features will be recorded. They will also grant permission to access their clinical history. Tumor features and dietary habits will be recorded.

Breast Cancer and Its Relationship With the Microbiota

Association of Breast and Gut Microbiota Dysbiosis and the Risk of Breast Cancer

Composition of bacteria, archaea, fungi and viruses present in breast tissue of women with breast cancer compared with that of women without breast cancer.

Composition of bacteria, archaea, fungi and viruses present in stool samples of women with breast cancer compared with that of women without breast cancer.

Universidad de Granada

Full Professor, Ph. D., Department of Biochemistry and Molecular Biology II, School of Pharmacy, Campus de Cartuja s/n, 18071 Granada, Spain. Phone: +34958241000 Extension 20322 / +34958242318. E-mail: fontana@ugr.es

Behaviors and Mental Disorders

Rare Diseases

Alcohol Drinking

Menopause

Acute Graft Versus Host Disease

Anti-Infective Agents

Central Nervous System Depressants

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Ethanol

Ibuprofen

Hormones

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Ibuprofen Tab 400 MG

A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Placebo tab

Lars O Dragsted, PhD

Postmenopausal women, stratified by a peroxisome proliferator-activated receptor gamma-2 (PPARG) polymorphism, were given the following treatments in a random order with a 5w wash-out period: a 400mg ibuprofen tablet or a placebo tablet; both treatments were followed after 30min by a single acute dose of 0.4g alcohol per kg bw. Serum estrogen levels were measured before and at three timepoints after alcohol intake. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

In a pilot human intervention trial we aimed to determine the effect of the PPARG Pro12Ala polymorphism and the PPARγ stimulator, Ibuprofen, on sex-hormone levels following alcohol intake in postmenopausal women. Seven women with PPARG Pro12Ala and 18 PPARG wildtype women were included.The study was performed as a randomised, double-blinded, placebo controlled 2x24 h crossover study. The volunteers were randomised to 1 of 2 groups who got the two treatments in different orders. Treatment 1 was a placebo tablet with water followed after 30min by an alcoholic drink providing 0,4g alcohol per kilogram bw and treatment 2 was an Ibuprofen tablet (400mg) with water followed by the same alcoholic drink. The two treatments were separated by a 5-7 weeks washout period. Alcohol was supplied as 7.7% ethanol in a lime-flavoured drink and was consumed over 15 min. EDTA-plasma was collected 40min before and 30, 60 and 90 min after ethanol intake as well as after 24 hours. Ibuprofen (400mg) was provided together with 100mL water 30min before the ethanol. Urine was collected throughout the 24 hour interval. Serum estrone, estrone sulphate, serum estrogen-binding globulin (SHBG), and ethanol were determined. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

Participants are randomized to an ibuprofen or placebo pill in the first period and are then provided with placebo or ibuprofen pills, respectively, in the second period in a crossover fashion. Alcohol (0.4g/kg bw) is provided as a challenge 30min after the pill has been swallowed.

Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women

Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage

Plasma estrone sulfate concentration after acute ethanol intake by Ibuprofen intake and/or PPARG genotype

Plasma estrone decrease after acute ethanol intake by ibuprofen intake and/or PPARG genotype

Plasma SHBG concentration after acute ethanol ingestion by ibuprofen intake and/or PPARG genotype

Plasma ethanol concentration after acute ethanol ingestion

The plasma metabolome profile by time after alcohol intake

The urine metabolome profile by time after alcohol intake

Technical University of Denmark

Professor Lars Ove Dragsted

Professor, Head of Section

Amy Trentham Dietz, PhD

Mammographic density is sensitive to estorgen exposure and constitutes a strong intermediate maker of breast cancer risk. We hypothesize that women with higher serum xenoestrogen levels will have greater mammographic density.

Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Rlisk

Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Risk

United States Department of Defense

University of Wisconsin, Madison

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Vasoconstrictor Agents

Respiratory System Agents

Reproductive Control Agents

Imidazole

Estradiol

Anti-Bacterial Agents

Methyltestosterone

Androgens

Epinephrine

Antibiotics, Antitubercular

Leuprolide

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Goserelin

Bicalutamide

Androgen Antagonists

Clotrimazole

Miconazole

Racepinephrine

Epinephryl borate

Ketoconazole

Antifungal Agents

Nonsteroidal Anti-Androgens

Anabolic Androgenic Steroids

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

Cytochrome P-450 CYP3A Inhibitors

leuprolide and goserelin are gonadotropin-releasing hormone analogues

GnRH

An imidazole antifungal agent. reduces adrenal and testicular androgen production in men

Testosterone transdermal gel

Estradiol is the primary and most potent estrogen

Estrogen transdermal patch

Howard Scher, MD

Objective: To determine the response to rapid hormonal cycling in patients with non-castrate prostate cancer.

Rapid Hormonal Cycling as Treatment for Patients With Prostate Cancer: The Men's Cycle

Complete Response: Normalization of the PSA (\< or = to 4.0 for patients with castrate metastatic disease, or \< 0.5 for patients with a rising PSA) that is maintained on 3 successive evaluations a minimum of 2 weeks apart. Partial Response: Decrease in PSA value by \> or = to 50% from baseline value (without normalization) for 3 successive evaluations a minimum of 2 weeks apart. Stabilization: Patients who do not meet the criteria for PR or PROG for at least 90 days will be considered stable.

Memorial Sloan Kettering Cancer Center

Rapid Hormonal Cycling as Treatment for Patients with Prostate Cancer

All Participants

Age, Categorical

Sex: Female, Male

Dr. Howard Scher

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Response

Overall Study

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Heart and Blood Diseases

Digestive System Diseases

Osteoporosis

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Heart Diseases

Ischemia

Colonic Neoplasms

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Vascular Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Micronutrients

Bone Density Conservation Agents

Vitamins

Vitamin D

Cholecalciferol

Calcium

Progestins

Calcium, Dietary

Trace Elements

Vitamin D3

Calciferol

hormone replacement therapy

estrogens

progestins

estrogen replacement therapy

diet, fat-restricted

calcium

vitamin D

dietary supplements

Ross Prentice

To address cardiovascular disease, cancer, and osteoporosis, the most common causes of death, disability, and impaired quality of life in postmenopausal women. The three major components of the WHI are: a randomized controlled clinical trial of hormone replacement therapy (HRT), dietary modification (DM), and calcium/vitamin D supplementation (CaD); an observational study (OS); and a community prevention study (CPS). On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).

BACKGROUND:

Prior to 1991, little research had focused on health issues unique to, or more common for, women. This was especially the case for studies of chronic diseases and their prevention in mature women. These conditions (coronary heart disease, cancer, and osteoporosis) are the leading causes of impairment of quality of life, morbidity, and mortality in post-menopausal United States women. The WHI, mandated by Congress, was established in 1991 by the National Institutes of Health and located in the Office of the Director (OD). The Clinical Coordinating Center for the clinical trial/observational study was funded in September 1992 and the 16 Vanguard Clinical Centers were funded in March 1993. The initial protocol was developed jointly by the Clinical Coordinating Center and the Program Office and was reviewed and approved by the Investigators Committee on April 20, 1993. Additional clinical centers were funded in 1994.

On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).

DESIGN NARRATIVE:

As has been described in the objective, the WHI has three major components: a randomized controlled clinical trial, an observational study, and a study of community approaches to developing healthful behaviors. Recruitment for the WHI began in September 1993 and ended in December 1998. Six clinical centers completed recruitment in January 1997. The remaining 34 centers completed recruitment in December 1998.

CLINICAL TRIAL COMPONENT

The clinical trial component consists of three subtrials: the hormone replacement trial, the dietary modification trial, and the calcium /vitamin D supplementation trial. Approximately 27,500 women aged 50 to 79 are participating in the HRT, which tests whether long-term HRT reduces coronary heart disease and fractures without increasing breast cancer risk. Women with a uterus were randomized to receive either estrogen plus progestin or a placebo. Progestin was added to protect women with a uterus from endometrial cancer. Women who have had a hysterectomy were randomized to receive either estrogen alone or a placebo. The estrogen plus progestin trial was stopped early on July 8, 2002 after an average follow-up of 5.2 years on the recommendation of the Data and Safety Monitoring Board. The estrogen alone study continued unchanged until March 2, 2004 when the NIH instructed participants to stop taking their study pills and to begin the follow-up phase of the study. . Participants in the estrogen alone study will be followed for eight to 12 years and have clinic visits every six months to assure safety and assess their health.

The dietary modification trial component studies the effect of a low-fat, high fruit, vegetable and grain diet on breast cancer, colorectal cancer and heart disease in 48,000 postmenopausal women. Participants are randomized to a comparison group which maintains usual dietary habits or to a dietary change group. Women in the dietary change group decrease their fat intake to 20 percent of total daily calories, increase fruit and vegetable consumption to five or more servings per day, and increase grains to six or more servings per day. Additionally, they monitor their food intake and attend nutrition group meetings to learn more about changing their diets in the first year. Thereafter they attend four meetings per year.

The calcium/vitamin D supplementation subtrial tests whether calcium and vitamin D supplements reduce the risk of hip and other fractures and colorectal cancer in postmenopausal women. Women in the hormone replacement therapy and the dietary modification trials are encouraged to join the calcium/vitamin D supplementation study. Approximately 45,000 postmenopausal women are randomized into one of two study groups. One group was randomly assigned to receive 1,000 mg of elemental calcium (as calcium carbonate) and 400 International Units of vitamin D₃daily. The second group received a matching placebo.

Women already taking calcium supplements can continue to take them. Participants will be followed for eight to 11 years and contacted by their clinical center every six months to assure their safety and assess their health.

Total number of trial participants in all three subtrials is 68,135.

OBSERVATIONAL STUDY

The several goals of the study include: to give reliable estimates of extent to which known risk factors predict heart disease, cancers, and fractures; to identify new risk factors for these and other diseases in women; to compare risk factors, presence of disease at the start of the study and new occurrences of disease during the WHI in all study components; and to create a future resource to identify biological indicators of disease, especially substances and factors found in blood. The study enrolled 93,726 postmenopausal women and will track them for an average of nine years. Participants fill out periodic health forms and visit the clinic three years after enrollment. They take no medication and do not change their health habits.

COMMUNITY PREVENTION STUDY

The community prevention study consists of 12 separate studies conducted at eight of the Centers for Disease Control and Prevention's (CDC) University-based Prevention Research Centers through a cooperative agreement between NIH and CDC. The 12 studies began in October 1995 and continue for an additional five years. The collaboration supports health promotion and disease prevention research and demonstration projects that are community-based and focus on healthy behaviors that prevent the major causes of death and disability and that promote health practices that lead to more effective public health interventions. Each project provides research dissemination and translation of findings into community interventions. Topics under study include: attitudes towards hysterectomy, oophorectomy, and surgical menopause among African Americans; reducing cardiovascular disease risk among Black women; environmental and policy interventions to increase physical activity among minority women ages 40 to 75; peer support intervention for cardiovascular disease risk among African American women, aged 40 and older; assessing the effectiveness of a brief medical-provider educational intervention for osteoporosis in minority women aged 40 and older; improving the delivery of diabetes care to women in minority groups; and assessment of moderate physical activity among women.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Breast Cancer and Its Relationship With the Microbiota	NCT03885648	Breast Cancer		25 Years - 70 Years	Universidad de Granada
Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women	NCT02463383	Breast Cancer	Ibuprofen Tab 4... Placebo tab	50 Years - 70 Years	University of Copenhagen
Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Rlisk	NCT00839696	Breast Cancer R...		55 Years - 70 Years	University of Wisconsin, Madison
Breast Cancer and Its Relationship With the Microbiota	NCT03885648	Breast Cancer		25 Years - 70 Years	Universidad de Granada
Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Rlisk	NCT00839696	Breast Cancer R...		55 Years - 70 Years	University of Wisconsin, Madison
Rapid Hormonal Cycling as Treatment for Patients With Prostate Cancer: The Men's Cycle	NCT00586898	Prostate Cancer Hormonal Cyclin...	GnRH Ketoconazole Bicalutamide Testosterone tr... Estrogen transd...	18 Years -	Memorial Sloan Kettering Cancer Center
Women's Health Initiative (WHI)	NCT00000611	Bone Diseases Breast Neoplasm... Cardiovascular ... Colonic Neoplas... Coronary Diseas... Heart Diseases Myocardial Isch... Osteoporosis Postmenopause	hormone replace... estrogens progestins estrogen replac... diet, fat-restr... calcium vitamin D dietary supplem...	50 Years - 79 Years	National Heart, Lung, and Blood Institute (NHLBI)
Women's Health Initiative (WHI)	NCT00000611	Bone Diseases Breast Neoplasm... Cardiovascular ... Colonic Neoplas... Coronary Diseas... Heart Diseases Myocardial Isch... Osteoporosis Postmenopause	hormone replace... estrogens progestins estrogen replac... diet, fat-restr... calcium vitamin D dietary supplem...	50 Years - 79 Years	National Heart, Lung, and Blood Institute (NHLBI)
Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women	NCT02463383	Breast Cancer	Ibuprofen Tab 4... Placebo tab	50 Years - 70 Years	University of Copenhagen

Spots Global Cancer Trial Database for estrogens

Every month we try and update this database with for estrogens cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for estrogens

Every month we try and update this database with for estrogens cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for estrogens cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.