effect of fluvastatin on biomarkers in women who are undergoing surgery for ductal carcinoma in situ or stage i breast cancer

Conditions: Breast Cancer

Summary: rationale: collecting samples of blood and tissue from patients with cancer to study in the laboratory may help doctors learn how fluvastatin effects biomarkers related to breast cancer. purpose: this randomized phase ii trial is studying how fluvastatin effects biomarkers in women undergoing surgery for ductal carcinoma in situ or stage i breast cancer.

objectives: primary * determine differences between measures of cell proliferation (ki-67) in women with ductal carcinoma in situ (dcis) or stage i breast cancer receiving neoadjuvant fluvastatin sodium. secondary * determine whether statin use differentially affects specific types of dcis/early-stage breast cancer (comedo, estrogen receptor \[er\]-positive, er-negative). * compare differences between tissue staining of cd68, circulating macrophages, and regulatory t cells in these patients. * assess the feasibility of using inherent susceptibility (mrna polymerase chain reaction testing) to predict response to statins in these patients. outline: this is a randomized, controlled, single-blind, multicenter, pilot study. patients are randomized to 1 of 2 treatment arms (arms i or ii). patients accrued as control participants are assigned to arm iii. * arm i: patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity. * arm ii: patients receive oral fluvastatin sodium as in arm i at a higher dose. * arm iii (control): patients do not receive fluvastatin sodium. all patients then undergo definitive surgery. patients in arms i and ii undergo blood collection at baseline and at the time of surgery for biomarker analysis. patients in arm iii undergo blood collection at baseline and then approximately 1 month later. tissue is collected from patients in all arms at the time of surgery. blood and tissue samples are examined for biological markers, including ki-67, c-reactive protein, cleaved caspase 3, her2, cd68 gene, and estrogen and progesterone receptors by immunohistochemistry. markers of inflammation (e.g., comedo necrosis macrophages and cd25-positive t cells), low-density lipoprotein, and cholesterol are also analyzed. serum mrna is measured by polymerase chain reaction. projected accrual: a total of 60 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed ductal carcinoma in situ (dcis) or stage i breast cancer by stereotactic core or incisional biopsy * planning to undergo surgery in 3-6 weeks * patients undergoing re-excision due to evidence of tumor present at surgical margins are eligible * hormone receptor status not specified patient characteristics: * female * menopausal status not specified * alt and ast ≤ 10% above upper limit of normal * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * able to tolerate statins * willing to undergo 2 blood draws (separated by approximately 3-4 weeks) during study participation (control arm) prior concurrent therapy: * no other concurrent statins * no concurrent chemotherapy * no concurrent administration of any of the following: * niacin * propranolol * cholestyramine * cyclosporine * digoxin * erythromycin * itraconazole * gemfibrozil * phenytoin * diclofenac * tolbutamide * glyburide * losartan * cimetidine * ranitidine * omeprazole * rifampin * warfarin * no initiation of new hormonal therapy during study participation * concurrent participation in other clinical trials (e.g., for dcis or prevention) is allowed

Keywords: breast cancer in situ ductal breast carcinoma in situ stage ia breast cancer stage ib breast cancer