SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.
While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.
A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.
The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m2. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.
Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.
A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.
Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).
Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.
Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.
The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.
"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote
Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).