Effect of Fluvastatin on Biomarkers in Women Who Are Undergoing Surgery for Ductal Carcinoma In Situ or Stage I Breast Cancer

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