Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention

NCT ID: NCT00723398

Last Updated: 2018-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 266 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2015-04-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1: Control

Control, no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Group 2: Raloxifene 60 Mg Oral Tablet

Raloxifene 60 mg Orally Daily

Group Type: EXPERIMENTAL

Raloxifene 60 Mg Oral Tablet

Intervention Type: DRUG

60 mg orally every day for two years

Group 3: Raloxifene 30 Mg Oral Tablet

Raloxifene 30 mg Orally Daily

Group Type: EXPERIMENTAL

Raloxifene 30 Mg Oral Tablet

Intervention Type: DRUG

30 mg orally daily for two years

Group 4: Lovaza 4 gm oral

Lovaza 4 gm/day Orally with Meals

Group Type: EXPERIMENTAL

Lovaza 4gm oral

Intervention Type: DIETARY_SUPPLEMENT

Dietary supplement; Take 4 mg oral capsules daily

Group 5: Lovaza 4gm & Raloxifene 30mg

Lovaza 4 gm/day oral capsule with meals plus Raloxifene 30 mg oral tablet daily

Group Type: EXPERIMENTAL

Lovaza 4gm & Raloxifene 30mg

Intervention Type: DRUG

Lovaza 4gm and Raloxifene 30 Mg orally once per day for 2 years

Interventions

Lovaza 4gm oral

Dietary supplement; Take 4 mg oral capsules daily

Intervention Type: DIETARY_SUPPLEMENT

Raloxifene 60 Mg Oral Tablet

60 mg orally every day for two years

Intervention Type: DRUG

Raloxifene 30 Mg Oral Tablet

30 mg orally daily for two years

Intervention Type: DRUG

Lovaza 4gm & Raloxifene 30mg

Lovaza 4gm and Raloxifene 30 Mg orally once per day for 2 years

Intervention Type: DRUG

Other Intervention Names

Omega-3 Fatty Acid Capsules; Fish Oil capsules; Triklo; Evista 60 Mg Oral Tablet; Evista 30 Mg Oral Tablet; Pitavastatin 4 gm and Evista 30 mg oral tablet

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Andrea Manni

Professor and Chief Division of Endocrinology, Diabetes, and Metabolism

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Manni, MD

Role: PRINCIPAL_INVESTIGATOR

Penn State University

Locations

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

References

Manni A, Richie JP, Schetter SE, Calcagnotto A, Trushin N, Aliaga C, El-Bayoumy K. Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women. Eur J Clin Nutr. 2017 Jun;71(6):762-765. doi: 10.1038/ejcn.2016.273. Epub 2017 Feb 1.

Reference Type: DERIVED

PMID: 28145413 (View on PubMed)

Other Identifiers

26970

Identifier Type: -

Identifier Source: org_study_id