Changes in Biomarkers Using Prostaglandin Inhibitors

• PG synthesis and metabolism, through the measurement of PGE2, COX-2 and 15-PGDH in the breast [ Time Frame: approximately 30 days ] [ Designated as safety issue: No ]

  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.

  
  

• proliferative activity in the breast and 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. [ Time Frame: approximately 30 days ] [ Designated as safety issue: No ]

  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

  
  

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.