Clinical trial NCT00723398
Conditions: Breast Cancer
Keywords: omega-3 fatty acids antiestrogens breast cancer prevention breast density biomarkers of mammary carcinogenesis
Sponsor: Milton S. Hershey Medical Center
Start date: 2009-03-01; Completion date: 2015-04-01
Enrollment: 266 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Control, no intervention arm 2: Raloxifene 60 mg Orally Daily arm 3: Raloxifene 30 mg Orally Daily arm 4: Lovaza 4 gm/day Orally with Meals arm 5: Lovaza 4 gm/day oral capsule with meals plus Raloxifene 30 mg oral tablet daily
Interventions: intervention 1: Lovaza 4gm oral intervention 2: Raloxifene 60 Mg Oral Tablet intervention 3: Raloxifene 30 Mg Oral Tablet intervention 4: Lovaza 4gm & Raloxifene 30mg
Intervention descriptions: intervention 1: Dietary supplement; Take 4 mg oral capsules daily intervention 2: 60 mg orally every day for two years intervention 3: 30 mg orally daily for two years intervention 4: Lovaza 4gm and Raloxifene 30 Mg orally once per day for 2 years

Protocol documents: