Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Micronutrients

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Vitamins

Vitamin D

Cholecalciferol

Celecoxib

Prostaglandin Antagonists

Trace Elements

Hormones

Calcium

Calcium, Dietary

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Vitamin D3

Calciferol

In this arm, the placebo is in place of celecoxib and the current RDA for cholecalciferol is used the control of the cholecalciferol higher dose.

celecoxib 400 mg \& cholecalciferol2,000 IU

Take 1 capsule from each bottle (1 bottle containing either placebo/celecoxib and 1 bottle containing either cholecaliferol 400 IU/cholecaliferol 2,000 IU) for 30 days

placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU

Edward R. Sauter, MD, PhD, M.H.A

This is a biomarker study with the goal of measuring changes in proteins and gene methylation. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.

The purpose of this study is to determine if Vitamin D (cholecalciferol) alone and in combination with celecoxib (Celebrex, a non-steroidal anti-inflammatory drug, or NSAID), act together to decrease breast cancer risk by their effect on certain biological indicators (biomarkers) of breast cancer risk (called PGE2, COX-2, and 15-PGDH) and cell changes in the breast.

This is a biomarker study with the goal of measuring changes in protein and rna expression. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.

66 women at normal risk for developing breast cancer will be recruited and enrolled. 22 women will be randomized into each arm, with anticipation of 2 women in each group will not be evaluable, leaving 20 in each group for evaluation.

A combination of vitamin D and celecoxib act synergistically to decrease breast cancer risk by decreasing cell proliferation in the mammary epithelium through their action on prostaglandin synthesis and metabolism.

Specific Aims:

-Evaluate vitamin D metabolism, through the measurement of CYP24 in the breast.

2-Evaluate breast specific levels of vitamin D and celecoxib, and assess if the levels of these compounds correlate with response to markers which influence prostaglandin synthesis and metabolism. Additionally, in women without active breast cancer , we will determine the effect of vitamin D, with or without celecoxib, on 1) PG synthesis and metabolism, through the measurement of PGE2, COX-2 and 15-PGDH in the breast, 2) proliferative activity in the breast,, and 3) circulating levels of vitamin D and celecoxib, to determine if levels of these compounds correlate with response to markers of PG production, metabolism, or cell proliferation.

Changes in Biomarkers Using Prostaglandin Inhibitors

Prostaglandin Inhibition to Prevent Breast Cancer

This will be measured from both baseline and completion samples

1. PG synthesis and metabolism, through the measurement of 15-PGDH, COX-2, and PGE2 in the breast

Rationale: 1,25(OH)2D, the active form of vitamin D, has been shown in vitro to decrease PGE2 both by interfering with its production and by increasing its breakdown, leading to lower cell proliferation. Celecoxib potentiated the antiproliferative effect, allowing a much lower dose of each agent when used in combination than in isolation.

This will be measured from both baseline and completion samples.

2. Proliferative activity in the breast, as measured by MD cell morphology

Rationale: Both MD and NAF contain ductal epithelial cells, but MD samples contain more cells for cytologic review than NAF. Findings on MD cytology correlate with likelihood of breast cancer, NAF cytology relates to breast cancer risk and improves risk stratification, and bioactive food components can alter NAF cytology

Susan G. Komen Breast Cancer Foundation

Hartford Hospital

MD, PhD, M.H.A

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Changes in Biomarkers Using Prostaglandin Inhibitors	NCT01769625	Biomarker Chang...	placebo/celecox...	18 Years -	Hartford Hospital
Changes in Biomarkers Using Prostaglandin Inhibitors	NCT01769625	Biomarker Chang...	placebo/celecox...	18 Years -	Hartford Hospital

Spots Global Cancer Trial Database for biomarker change linked to breast cancer