Clinical trial NCT00723398: Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention
Official title: Combination of Low Dose Antiestrogens With Omega-3 Fatty Acids for Prevention of Hormone-independent Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: omega-3 fatty acids
antiestrogens
breast cancer prevention
breast density
biomarkers of mammary carcinogenesis
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2008-07-28
Enrollment: 266
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Change in Absolute Breast Density
timeFrame: 2 years
Secondary outcomes:
measure: Changes in Biomarkers for Oxidative Stress:Urinary 8-(Isoprostane) F-2α
timeFrame: 1 year
measure: Changes in Biomarkers for Oxidative Stress: Urinary 8-hydroxy-deoxyguansine
timeFrame: 1 year
measure: Changes in Biomarkers for Estrogen Metabolism: 2-hydroxy Estrone (Urinary 2-OHE1) and 16-α-hydroxy Estrone (16α-OHE1)
timeFrame: 1 year
measure: Changes in Serum Biomarkers for Inflammation From Levels of High Sensitivity C-reactive Protein (hsCRP) and Interleukin 6 (IL-6)
timeFrame: 1 Year
measure: Changes in Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor-1 Binding Protein-3 (IGFBP-3)
timeFrame: 1 year
measure: Changes in Serum Lipid Levels
timeFrame: 2 years
measure: Changes in Complete Blood Count: Red Blood Cells
timeFrame: 2 years
measure: Changes in Complete Blood Count: Hemoglobin
timeFrame: 2 years
measure: Changes in Complete Blood Count: Hematocrit
timeFrame: 2 years
measure: Changes in Complete Blood Count: White Blood Cells and Platelets
timeFrame: 2 years
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Andrea Manni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.