The Association of Valproic Acid and Incident Breast Cancer in a Managed Care Cohort
Abstract
The possible role of histone deacetylase inhibitors (HDACi) in breast cancer treatment is an area of active investigation. However, its potential as a preventive agent has not been studied . Valproic acid (VPA) is an HDACi which has been used for many decades to safely treat neurological disorders. The rationale for the use of HDACi in breast cancer prevention is a previously unexplored area of research that is based on compelling preclinical data. Epidemiologic studies showing an association between HDACi use and breast cancer incidence would be important evidence to support future prospective clinical trials of HDACi in cancer prevention. We sought to ascertain whether the risk of incident breast cancer is reduced in patients with a history of VPA use, and if so, to determine whether this effect is proportional to the duration of VPA use and whether all breast cancer subtypes are impacted similarly. We developed a database using de-identified data from the Kaiser Permanente of Northern California (KPNC) clinical and pharmacy records of members of the KPNC Healthplan between 1997 and 2007. 20,864 breast cancer cases and 208,640 controls matched for birth year and duration of KNPC pharmacy coverage were identified. 68 incident breast cancers were seen among women with history of VPA use; 486 were in women without history of VPA use. Mean age at diagnosis of the cohort was 61 .8 years; mean years of prescription drug coverage was 7.4 years. Among cases, 73% of the cohort was non-hispanic white, 7.6% were African American, and 10.5% were Asian/Pacific Islander. When compared to never users, patients with at least 2 years of VPA use had an increased odds of a breast cancer diagnosis (OR 1.37; 95% Cl 1.06-1.76). This effect was only significant for HR-positive incident tumors, although the numbers of HR-negative cases was small (n=12). These findings support that VPA use is not associated with reduction of breast cancer incidence.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA587680
Entities
People
- Eun-sil S. Hwang
- Veronica Shims
Organizations
- University of California, San Francisco