Phytoestrogens and Breast Cancer - Effects of Phytoestrogens on Markers of Disease Progression and Gene Expression

Study Overview
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Brief Summary
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The aim is to investigate if soy isoflavones and lignans affect markers of disease progression and gene expression among breast cancer patients receiving neo-adjuvant treatment in a three arm, double-blinded, randomized placebo-controlled trial (RCT) comparing: soy isoflavone supplementation, lignan supplementation, and placebo.

Official Title
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DAGMAR: Phytoestrogens and Breast Cancer - Effects of Phytoestrogens on Markers of Disease Progression and Gene Expression

Conditions
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Breast Cancer, Breast Neoplasms, Breast Cancer Female

Intervention / Treatment
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* Dietary Supplement: Soy isoflavones
* Dietary Supplement: Lignans
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with breast cancer at Brystkirurgisk Afdeling at Rigshospitalet and Herlev Hospitals (within the last 30 days). Advised (and accepted) to receive neo-adjuvant treatment Primary unilateral breast cancer Treatment is expected to be curative Is expected to be able to attend surgery Exclusion Criteria: Allergic to soy Celiac disease Inflammatory bowel disease Not understanding Danish (patient material and questionnaires are in Danish) Prior diagnosis of breast cancer Use of dietary supplements containing lignans or isoflavones three months prior to diagnosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study planned to include 150 women.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lignan capsule<br>1 capsule/day from baseline to end-of-follow-up (approx. 4 months) | Dietary Supplement: Lignans<br>* Commercially available dietary supplement (capsule) containing 63 mg lignans (secoisolaricirecinol)<br>|
| Experimental: Isoflavones capsule<br>1 capsule/day from baseline to end-of-follow-up (approx. 4 months) | Dietary Supplement: Soy isoflavones<br>* Commercially available dietary supplement (capsule) containing 60 mg isoflavones (genistein, daidzein and glycitein).<br>|
| Placebo Comparator: Placebo capsule<br>1 capsule/day from baseline to end-of-follow-up (approx. 4 months) | Dietary Supplement: Placebo<br>* The placebo capsules are supplied and packaged by Region Hovedstadens Apotek (Denmark) and will contain lactose monohydrate, potato starch, gelatin, magnesium stearate and talc.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki-67 | Ki-67 can be measured using immunohistochemistry (IHC) and using the transcript from gene expression data (see secondary outcomes). As the latter is superior and less biased, the Ki-67 based on the transcript will be used as primary measure of Ki67. | Change from baseline (diagnosis of breast cancer) to end-of-study (surgery): Approx. four months (neo-adjuvant setting) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis marker caspase-3 |  | Change from baseline (diagnosis of breast cancer) to end-of-study (surgery): Approx. four months (neo-adjuvant setting) | 
| Proliferation Index | Based on expression data from 79 genes encoding proliferative and cell cycle markers. Gene expression will be analyzed using a microarray (GeneChip® Human Genome U133 Plus 2.0 Array, Affymetrix, USA) | Change from baseline (diagnosis of breast cancer) to end-of-study (surgery): Approx. four months (neo-adjuvant setting) | 
| Patient reported outcomes | Well-being | Change for completion of first questionnaire (shortly after diagnosis) to second questionnaire (close to time of surgery). Approx. four months (neo-adjuvant setting) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phytoestrogens, Isoflavones, Lignans, Gene expression, Breast cancer