• biomarkers of oxidative stress (Urinary 8-(isoprostane) F-2α and 8OHdG, Lymphocyte 8-OHdG, DNA etheno adducts) [ Time Frame: baseline, q6 months for two years ] [ Designated as safety issue: No ]
• Urinary 2-OHE1, 4-OHE1, and 16α-OHE1 [ Time Frame: baseline, q6 months for two years ] [ Designated as safety issue: No ]
• Serum level of C-reactive protein and IL-6 [ Time Frame: baseline, q6 months for two years ] [ Designated as safety issue: No ]
• Serum level of IGF-I and IGFBP-3 [ Time Frame: baseline, q6 months for two years ] [ Designated as safety issue: No ]
• lipid panel and complete blood count [ Time Frame: yearly ] [ Designated as safety issue: Yes ]

The overall hypothesis is that the combination of a low dose of the antiestrogen Raloxifene with omega-3 fatty acids will exert a synergistic breast cancer chemopreventive effect due to the crosstalk of their downstream cellular effects leading to decreased proliferation and increased apoptosis of premalignant mammary cells. Based on the investigators hypothesis that upregulation of functional estrogen receptors in the premalignant lesions is also responsible for the development of hormone independent tumors, the investigators postulate that the combination of antiestrogens and omega-3 fatty acids will reduce the development of both hormone-dependent and -independent tumors. At present, there are no known interventions able to decrease the development of hormone-independent tumors, which are more prevalent, more aggressive, leading to the patient's demise. In addition, the investigators postulate that this approach will be safe since it will combine a lower and hence a less toxic dose of Raloxifene with the administration of omega-3 fatty acids which are known to have health benefits, i.e., reduction in cardiovascular risk, beyond their possible chemo preventive effect in breast cancer.

The main objectives of this study are to determine the individual and combined effects of Raloxifene and omega-3 fatty acids on surrogate markers of breast cancer development in healthy, postmenopausal women. The primary endpoint will be mammographic density for which the study has been powered. Breast density is a major risk factor for breast cancer and hence it is chosen to evaluate the potential chemopreventive efficacy of our interventions. Secondary endpoints would include markers of oxidative stress, parameters of estrogen metabolism, markers of inflammation, and markers of IGF-I signaling, all of which have been shown in the literature to have an influence on mammary carcinogenesis.

Study Population: Healthy, postmenopausal women between the ages of 35-70 years, undergoing yearly mammograms as part of routine screening practice.

Method of Identification of Subjects/Samples/Medical Records: Women reporting for yearly mammograms will be considered for this protocol. They will be given first a screening questionnaire to rule out any co-existing medical condition that would predispose them to thromboembolic events.

• Dietary Supplement: Lovaza
• Drug: Raloxifene
• Drug: Raloxifene 30 mg
• Drug: Lovaza plus Raloxifene

• No Intervention: Control
• Experimental: Raloxifene 60 mg
• Experimental: Raloxifene 30 mg
• Experimental: Lovaza 4 gm
• Experimental: Lovaza 4 gm plus Raloxifene 30 mg

Inclusion Criteria:

• Postmenopausal status defined as history of at least 12 months without spontaneous menstrual bleeding or a documented hysterectomy and bilateral salpingo oophorectomy
• Breast density greater than 25%
• No hormone replacement therapy for at least six months prior to entry into this study
• Non-smokers.

Exclusion Criteria:

• History of stroke, pulmonary embolism or deep vein thrombosis
• History of atherosclerotic heart disease
• Presence of any known hypercoagulable state either congenital (e.g., protein S deficiency) or acquired (e.g., corticosteroid treatment)
• Diabetes mellitus
• Uncontrolled hypertension (BP ≥140/90)
• Presence of a psychiatric condition that would interfere with adherence to the protocol.