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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Breast Neoplasms; Breast Cancer Female
• Intervention / Treatment: Dietary supplement: Lignans; Dietary supplement: Soy isoflavones; Dietary supplement: Placebo

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbiome:	The microbial community composition will be characterized using the 16sRNA method (Illumina MiSeq Platform).	Change measured in first fecal sample (shortly after diagnosis) to second fecal sample (close to time of surgery). Approx. four months (neo-adjuvant setting)

Collaborators and Investigators

• Sponsor: Danish Cancer Society
• Collaborators: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2021
• Primary Completion (Estimated): July 1, 2022
• Study Completion (Estimated): December 1, 2022

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Gene expression; Isoflavones; Phytoestrogens; Lignans
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Disease Progression; Breast Neoplasms
• Other Study ID Numbers: R174-A11507-17-S52

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon approval from relevant authorities and in accordance with the law
• IPD Sharing Access Criteria: Please request this information from PI Cecilie Kyrø, Ceciliek@cancer.dk
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes