Study of Moderate Dose Omega 3 Fatty Acid Supplement in Premenopausal Women at High Risk for Breast Cancer

Pregnancy and breast feeding are protective when they occur at an early age, typically at an
age less than 30. The influence of pregnancy on breast cancer risk is not fully understood,
and little is known about modulation of the breast microenvironment during pregnancy and its
influence on risk. Hormones, including rising estrogen levels, play a role in fatty acid
synthesis. In pre-clinical models, a rise in omega-3:omega-6 ratio occurs naturally in the
breast of pregnant mice. This may be able to be accentuated in human breast tissue with
omega-3 fatty acid supplementation. Omega-3 fatty acid supplementation has been shown to
favorably modulate breast cancer risk and risk biomarkers in pre-menopausal women at high
risk for breast. Omega-3 fatty acid supplementation during pregnancy has also been found to
have positive outcomes for the offspring, making it an ideal intervention to study in this
population.

This pilot study of omega-3 supplementation in pre-menopausal women at high risk for breast
cancer who are still considering pregnancy is addressing a potential prevention strategy in a
population otherwise excluded from breast cancer prevention trials and not eligible for
standard of care chemoprevention. With this pilot, the intent is to establish feasibility,
document tolerability, determine number of women needed to enroll based on pregnancy rate and
identify biomarkers for future investigation. This information will provide necessary data to
apply for future extramural funding for a larger randomized trial. In a larger randomized
trial with longer follow up, we will be able to assess post-pregnancy breast tissue and
biomarkers to examine efficacy of omega-3 fatty acid supplementation in breast cancer risk
reduction.

Inclusion Criteria:

- Women age 21 - 40 must be pre-menopausal as defined as having intact ovaries with
regular menses or if not menstruating, have a premenopausal status confirmed by serum
follicle-stimulating hormone (FSH) and estradiol.

- Women must be considered at high risk for breast cancer based on family history (first
or second degree relative diagnosed with breast cancer under the age of 60), prior
precancerous biopsy or a 5-year Gail model risk estimate of ≥ 1.7% or 10 year
Tyrer-Cuzick risk of 2x population risk as listed in the model.

- Women must indicate that they are still considering future pregnancy and childbearing.

- Women must be one year from pregnancy and breast-feeding.

- Women must be willing to take supplemental omega-3 fatty acids provided by the study.

Exclusion Criteria:

- Women actively undergoing in-vitro fertilization or fertility treatments are excluded.

- Women currently pregnant or breast-feeding at time of study consent.

- Women with an active malignancy.

- Women on anticoagulation.

- Women with bilateral breast implants or tram flap reconstruction.

- Women who have had radiation to both breasts.

- Women with current mammographic or clinical breast exam mass which is suspicious for
breast cancer and malignancy has not been ruled out.