Faculty Collaboration Database

Pilot study of rosiglitazone therapy in women with breast cancer: effects of short-term therapy on tumor tissue and serum markers. Clin Cancer Res 2007 Jan 01;13(1):246-52

Date

01/04/2007

Pubmed ID

17200362

DOI

10.1158/1078-0432.CCR-06-1947

Scopus ID

2-s2.0-33846334043 (requires institutional sign-in at Scopus site)   86 Citations

Abstract

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARgamma is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARgamma ligand therapy might inhibit tumor growth and progression in human breast cancer.

EXPERIMENTAL DESIGN: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (T(is)-T(2), N(0-1), M(0)) breast cancer, administered between the time of diagnostic biopsy and definitive surgery.

RESULTS: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARgamma by immunohistochemistry, down-regulation of nuclear PPARgamma expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events.

CONCLUSION: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARgamma signaling that may be relevant to breast cancer.

Author List

Yee LD, Williams N, Wen P, Young DC, Lester J, Johnson MV, Farrar WB, Walker MJ, Povoski SP, Suster S, Eng C

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Agents
Breast Neoplasms
Cell Proliferation
Disease Progression
Female
Humans
Hypoglycemic Agents
Ki-67 Antigen
Middle Aged
PPAR gamma
Pilot Projects
Signal Transduction
Thiazolidinediones