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

About the Study

Tamoxifen is a medication that blocks the effects of estrogen in breast tissue. It is approved to help reduce breast cancer risk in some women at increased risk. Omega-3 fatty acids, found in fish oil, may affect how the body processes fats and may influence factors related to cancer risk.

This phase 2 study is evaluating whether adding omega-3 fatty acids to low-dose tamoxifen affects changes in the body that may be associated with breast cancer risk. Researchers will measure changes in adiponectin, a hormone involved in regulating metabolism, as well as other markers in blood and breast tissue.

The study will compare two groups of participants over approximately six months: one group taking low-dose tamoxifen alone and another taking low-dose tamoxifen with omega-3 fatty acids.

What the Study Involves

Participants will be randomly assigned to one of two groups:

• Group 1: Take low-dose tamoxifen by mouth once daily for approximately six months.

• Group 2: Take low-dose tamoxifen by mouth once daily and omega-3 fatty acids by mouth twice daily for approximately six months.

Participants in both groups will also:

• Have a mammogram as part of screening.
• Provide blood samples, including a fasting blood sample. 
• Have breast tissue collected using a procedure called random periareolar fine-needle aspiration (RPFNA). A thin needle is used to collect cells from breast tissue.
• Complete study assessments and attend follow-up visits as required.

The study medications may be continued for up to 60 additional days if scheduling delays occur. Participants will be followed for approximately one month after completing the six-month study.

Women age 45 to 74 may be eligible if they meet all of the following requirements.

• Have gone through menopause
• Are overweight or obese (body mass index of 25 or higher), and meet at least one of the following breast cancer risk criteria:
  • Previous breast biopsy or diagnosis: A history of atypical hyperplasia, lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS). Previous DCIS must have been treated, with treatment completed at least three months before breast tissue sampling.
  • Dense breast tissue: Mammograms showing a high level of breast density.
  • Inherited genetic mutation in ATM, BARD1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D or STK11. 
  • Family history of breast cancer: Breast cancer in a first- or second-degree relative before age 50; breast cancer in two or more first- or second-degree relatives; or a close relative with breast cancer in both breasts or with both breast and ovarian cancer.
  • Elevated breast cancer risk based on risk models or family history. 

Additional requirements include:

• Must not have had a double mastectomy and are able to undergo breast tissue sampling and has not been treated for cancer.

People are not eligible to participate if they:

• Have a history of invasive breast cancer or uterine cancer, or any another invasive cancer that is active or was treated within the past two years. Non-melanoma skin cancer is an exception.
• Have a BRCA1 or TP53 inherited mutation.
• Have type 1 or type 2 diabetes requiring medication, a history of blood clots, blood clots in the lungs, stroke, gastric bypass surgery, or long-term liver disease.
• Are currently breastfeeding or having breastfed within the past 12 months.
• Are taking blood thinners; daily aspirin that cannot be safely paused as required for breast tissue sampling; hormone therapy other than permitted low-dose vaginal estrogen; immunosuppressive medications; metformin; certain medications that affect how tamoxifen works; or GLP-1 medications currently being used or planned during the study period.
• Have taken tamoxifen or raloxifene in the past for more than two months. People who used these medications for less than two months must have stopped them at least six months before starting the study.
• Are taking high-dose omega-3 supplementation, more than 1 gram daily within the past six months.
• Have breast implants in both breasts as these may interfere with the required breast tissue sampling.
• Have a history of allergic reactions to tamoxifen, omega-3 fatty acids, or related products, or other circumstances that could make study participation unsafe or difficult.