Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/3/2019 |
| Start Date: | June 2009 |
| End Date: | March 2013 |
An in Vivo Proof of Principle Trial to Determine Whether the Nutritional Supplement Conjugated Linoleic Acid (CLA, Clarinol™) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
Conjugated Linoleic Acid (CLA) is obtained in the human diet by consumption of foods
containing ruminant fat. Milk and dairy products have shown the highest amounts of CLA.
Clarinol (CLA), is considered a natural supplement and is not regulated by the Food and Drug
Administration (FDA). CLA is known to inhibit proliferation of human breast cancer cells and
tumors in rodent breast cancer models and reduced Spot 14 (THRSP, S14) and Fatty Acid
Synthase (FASN) gene expression in breast cancer cells and tht the two major CLA isomers used
in nutritional supplements (C9, t11 and t10, c12) were equipotent in reducing breast cancer
cell growth. This study looks at the hypothesis that S14 expression is decreased by CLA and
will characterize the major pharmacodynamic (PD) effects of CLA in newly diagnosed Breast
cancer patients on Tumor tissue lipogenic pathway. FASN, S14 and Lipoprotein Lipase (LPL),
Ki67 and apoptotic index expression will be assessed by quantitative immunohistochemistry
(IHC) in initial breast cancer biopsies and compared to that in resected breast tumor tissue
after the study subject has been taking CLA for ten to twenty-eight days. Tissue from
adjacent breast adipocytes will also be analyzed to determine whether adipose tissue effects
can serve as a surrogate marker for those in tumor tissue. A sample of the original biopsy
will be compared to the tumor resection sample to determine the levels of CLA in the breast
cancer cells.
containing ruminant fat. Milk and dairy products have shown the highest amounts of CLA.
Clarinol (CLA), is considered a natural supplement and is not regulated by the Food and Drug
Administration (FDA). CLA is known to inhibit proliferation of human breast cancer cells and
tumors in rodent breast cancer models and reduced Spot 14 (THRSP, S14) and Fatty Acid
Synthase (FASN) gene expression in breast cancer cells and tht the two major CLA isomers used
in nutritional supplements (C9, t11 and t10, c12) were equipotent in reducing breast cancer
cell growth. This study looks at the hypothesis that S14 expression is decreased by CLA and
will characterize the major pharmacodynamic (PD) effects of CLA in newly diagnosed Breast
cancer patients on Tumor tissue lipogenic pathway. FASN, S14 and Lipoprotein Lipase (LPL),
Ki67 and apoptotic index expression will be assessed by quantitative immunohistochemistry
(IHC) in initial breast cancer biopsies and compared to that in resected breast tumor tissue
after the study subject has been taking CLA for ten to twenty-eight days. Tissue from
adjacent breast adipocytes will also be analyzed to determine whether adipose tissue effects
can serve as a surrogate marker for those in tumor tissue. A sample of the original biopsy
will be compared to the tumor resection sample to determine the levels of CLA in the breast
cancer cells.
Inclusion Criteria:
- All study patients must have histologically confirmed invasive adenocarcinoma of the
breast. Their breast cancer must be resectable clinical stage I or II breast cancer as
defined by the current AJCC TNM Staging System (Greene FL, Page DL, Fleming ID, et
al.: editors. AJCC cancer staging manual, 6th edition. New York: Springer; 2002).
- All patients must be able to and give informed consent indicating they are aware of
the investigational nature of this treatment, prior to entry into the study.
- All subjects must be Age >18 years.
- All subject must have adequate hepatic and renal function documented prior to study
entry to include: hepatic transaminases (AST or ALT) ≤ 1.5 times the upper limits of
normal, total bilirubin ≤ 1.5 times the upper limits of normal, serum creatinine ≤ 1.5
times the upper limit of normal or eCRCl ≥ 60 mL/min.
Exclusion criteria:
- Patients who have received prior or be receiving radiation therapy for their breast
cancer will be excluded.
- Patients who have received prior chemotherapy or receiving chemotherapy or hormonal
therapy for their breast cancer will not be included.
- Women must be surgically sterilized or post-menopausal or women of childbearing
potential must be using an adequate method of contraception. Women of childbearing
potential must be using at least one of the following: oral, implanted, injectable
contraceptive hormones, or mechanical products such as an intrauterine device or
barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing
abstinence or have a partner that is sterile (e.g., vasectomy). Women of childbearing
potential must have a negative serum or urine pregnancy test within 72 hours prior to
start of study therapy. Women who are pregnant or breast-feeding and women of
childbearing potential not using an adequate method of birth control will be excluded.
- Patients with gastrointestinal abnormalities including: inability to take oral
medication, requirement for intravenous alimentation, or prior surgical procedures
affecting nutrient /drug absorption will be excluded.
- A serious uncontrolled medical disorder or active infection which would impair their
ability to receive study treatment will be excluded. Significant cardiac disease,
including uncontrolled high blood pressure, unstable angina, and congestive heart
failure, myocardial infarction within the previous 3 months or serious cardiac
arrhythmias will be excluded. Dementia or significantly altered mental status that
would prohibit the understanding or rendering of informed consent and compliance with
the requirements of this protocol will be excluded.
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