Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention - Full Text View

Sponsored by:	Penn State University
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00723398

Purpose

The investigators 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.

Condition	Intervention
Breast Cancer	Dietary Supplement: Lovaza Drug: Raloxifene Drug: Raloxifene 30 mg Drug: Lovaza plus Raloxifene

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Dietary Supplements

Drug Information available for: Raloxifene Raloxifene hydrochloride Omacor Fish oil

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Combination of Low Dose Antiestrogens With Omega-3 Fatty Acids for Prevention of Hormone-Independent Breast Cancer

Further study details as provided by Penn State University:

Primary Outcome Measures:

breast density [ Time Frame: baseline, q6 months for two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	372
Study Start Date:	September 2008
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: No Intervention Control
2: Experimental Raloxifene 60 mg	Drug: Raloxifene 60 mg orally every day for two years
3: Experimental Raloxifene 30 mg	Drug: Raloxifene 30 mg 30 mg orally daily for two years
4: Experimental Lovaza 4 gm	Dietary Supplement: Lovaza dietary supplement
5: Experimental Lovaza 4 gm plus Raloxifene 30 mg	Drug: Lovaza plus Raloxifene Lovaza 4 gm daily plus Raloxifene 30 mg daily for two years

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.

Eligibility

Ages Eligible for Study:	35 Years to 70 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723398

Contacts

Contact: Andrea Manni, M.D.

717-531-8395

amanni@hmc.psu.edu

Locations

United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033

Sponsors and Collaborators

Penn State University

Investigators

Principal Investigator:

Andrea Manni, MD

Penn State University

More Information

Responsible Party:	Penn State College of Medicine ( Andrea Manni, M.D., Professor of Medicine )
Study ID Numbers:	26970
Study First Received:	July 24, 2008
Last Updated:	July 24, 2008
ClinicalTrials.gov Identifier:	NCT00723398
Health Authority:	United States: Institutional Review Board

Keywords provided by Penn State University:

omega-3 fatty acids
antiestrogens
breast cancer prevention
breast density
biomarkers of mammary carcinogenesis

Study placed in the following topic categories:

Raloxifene
Skin Diseases
Breast Neoplasms
Breast Diseases

Additional relevant MeSH terms:

Estrogen Receptor Modulators
Estrogen Antagonists
Neoplasms
Neoplasms by Site
Hormone Antagonists

Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009