Low Dose Tamoxifen With or Without Omega-3 Fatty Acids for Breast Cancer Risk Reduction

NCT06195306 | Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2023-10830UMICC 2024.076UMI23-14-02P30CA046592UG1CA242632
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial evaluates tamoxifen, with or without omega-3 fatty acids, for reducing risk of breast cancer among postmenopausal and overweight or obese women who are at increased risk of developing breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen is approved by the Food and Drug Administration for prevention of breast cancer in women at increased risk. Omega-3 fatty acids have been shown to decrease the amount of fats made in the liver. Omega-3 fatty acids may work to prevent cancer in overweight or obese individuals. Tamoxifen with or without omega-3 fatty acids may be effective at reducing risk of breast cancer among women who are postmenopausal, overweight or obese, and at increased risk.

Conditions

Breast Carcinoma; Breast Atypical Hyperplasia; Breast Ductal Carcinoma In Situ; Breast Lobular Carcinoma In Situ

Outcome Measures

Primary Outcomes (1)

• Change in serum adiponectin

  An analysis for difference between the two arms will be conducted to document a beneficial effect of addition of high dose omega-3 fatty acids to low dose tamoxifen. Paired and unpaired t-tests will be used.

  From baseline up to end of treatment (6 months)

Secondary Outcomes (4)

• Change in insulin resistance

  From baseline up to end of treatment (6 months)

• Change in insulin sensitivity

  From baseline up to end of treatment (6 months)

• Change in insulin secretory function

  From baseline up to end of treatment (6 months)

• Estrogen response gene index (ERGI)

  From baseline up to end of treatment (6 months)

Other Outcomes (12)

• Effect of change in red blood cell omega-3:omega-6 fatty acid ratio on within arm change in blood adiponectin

  From baseline to end of treatment (6 months)

• Effect of change in red blood cell omega-3:omega-6 fatty acid ratio on within arm change in tissue ERGI

  From baseline to end of treatment (6 months)

• Effect of baseline bioavailable estradiol on within arm change in blood adiponectin

  From baseline to end of treatment (6 months)

Study Arms (2)

Group 1 (tamoxifen)

EXPERIMENTAL

Participants receive tamoxifen PO QD for 180 days in the absence of unacceptable toxicity. Participants may continue to receive tamoxifen PO QD for up to 60 additional days in the case of scheduling delays. Participants also undergo mammography at screening and undergo RPFNA and collection of blood samples at screening and on study.

Procedure: Biospecimen Collection; Procedure: Mammography; Other: Questionnaire Administration; Procedure: Random Periareolar Fine-Needle Aspiration; Drug: Tamoxifen

Group 2 (tamoxifen, omega-3 fatty acids)

EXPERIMENTAL

Participants receive tamoxifen PO QD and omega-3 fatty acids PO BID for 180 days in the absence of unacceptable toxicity. Participants may continue to receive tamoxifen PO QD and omega-3 fatty acids PO BID for up to 60 additional days in the case of scheduling delays. Participants also undergo mammography at screening and undergo RPFNA and collection of blood samples at screening and on study.

Procedure: Biospecimen Collection; Procedure: Mammography; Drug: Omega-3-Acid Ethyl Esters; Other: Questionnaire Administration; Procedure: Random Periareolar Fine-Needle Aspiration; Drug: Tamoxifen

Interventions

Random Periareolar Fine-Needle Aspiration PROCEDURE

Undergo RPFNA

Also known as: Random Periareolar Fine Needle Aspiration, RPFNA

Group 1 (tamoxifen); Group 2 (tamoxifen, omega-3 fatty acids)

Mammography PROCEDURE

Undergo mammography

Also known as: MG

Group 1 (tamoxifen); Group 2 (tamoxifen, omega-3 fatty acids)

Omega-3-Acid Ethyl Esters DRUG

Given PO

Also known as: Lovaza

Group 2 (tamoxifen, omega-3 fatty acids)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Group 1 (tamoxifen); Group 2 (tamoxifen, omega-3 fatty acids)

Questionnaire Administration OTHER

Ancillary studies

Group 1 (tamoxifen); Group 2 (tamoxifen, omega-3 fatty acids)

Tamoxifen DRUG

Given PO

Also known as: TMX

Group 1 (tamoxifen); Group 2 (tamoxifen, omega-3 fatty acids)

Eligibility Criteria

• Age: 45 Years - 74 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 45 - 74
• Postmenopausal female
• Postmenopausal is defined as either
• Prior removal of the ovaries, or if ovaries intact amenorrhea for \>= 12 months and not on any form of contraception, or
• Amenorrhea for greater than 2 months with serum follicle-stimulating hormone (FSH) in postmenopausal range (\>= 25 IU/L). Women with ovaries and a prior hysterectomy or endometrial ablation \< age 55 must have a FSH \>= 25 IU/L. Women may be on vaginal low dose estrogen preparations for vaginal dryness. Women over age 50 with a levonorgestrel intrauterine device in place for 2 or more years and not planning removal in the next 6 month are also eligible if FSH \>= 25 IU/L
• Note: FSH will be done at time of screening
• Women with intact ovaries and uterus \< age 55 must have a negative pregnancy test prior to randomization
• Overweight or obese (body mass index \[BMI\] \>= 25 kg/m\^2)
• Note: BMI must be calculated within 28 days of randomization
• Willing to undergo a fasting blood draw and non-fasting RPFNA with fixed and frozen aliquots sent to University of Kansas Medical Center (KUMC)
• At increased risk of breast cancer per at least one of the following:
• Personal medical history
• History of atypical hyperplasia or lobular carcinoma in situ (LCIS) found on breast biopsy
• History of unilateral ductal carcinoma in situ treated with unilateral mastectomy, lumpectomy, or local excision with or without radiation and this treatment was completed at least 3 months prior to the screening RPFNA
• High mammographic density determined by one of the following:

You may not qualify if:

• Bilateral breast implants (danger of implant puncture with RPFNA)
• Prior invasive breast cancer
• Prior invasive uterine cancer
• Other prior invasive cancer and haven't completed cancer related therapy or with evidence of disease (other than non-melanoma skin cancer) within the past 2 years
• Currently breastfeeding (concern that tamoxifen may be in breast milk) or nursing within past 12 months (concern about milk fistula with RPFNA)
• Type I or type II diabetes mellitus requiring current pharmacologic treatment (including metformin, glucagon-like peptide 1 agonists, insulin, sulfonylurea)
• Prior deep vein thrombosis, pulmonary embolus, or stroke
• Prior gastric bypass surgery
• History of chronic liver disease including NASH (nonalcoholic steatohepatitis) or cirrhosis
• Pathogenic or likely pathogenic germline mutation in BRCA1 or TP53
• Current use of prescription anticoagulants such as Coumadin (warfarin), direct-acting oral anticoagulants such as Xarelto (rivaroxaban) or Eliquis (apixaban) or heparin
• Women who would not be able to or do not wish to discontinue daily use of aspirin (81mg or higher) and aspirin containing products (81 mg or higher) at least 3 weeks prior to each RPFNA
• Note: Women may resume daily use of aspirin and aspirin containing products 3 days after each RPFNA procedure
• Current use of a levonorgestrel intrauterine device if in place less than 2 years or if there is planned removal within the next 6 months
• Current use of hormone therapy (oral, transdermal, or injectable)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Specimen Handling; Omacor; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Lauren Nye

  University of Kansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 8, 2024
• Study Start: July 28, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)