Oral Bisphosphonate and Breast Cancer: Prospective Results from the Women's Health Initiative (WHI).
Chlebowski RT, Chen Z, Cauley JA, Rodabough RJ, McTiernan A, Lane DS, Manson JE, Snetselaar L, Yasmeen S, O'Sullivan MJ, Stafford M, Hendrix SL, Wallace RB Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torance, CA; University of Arizona, Tucson, AZ; University of Pittsburgh, Pittsburgh, PA; Fred Hutchinson Cancer Research Center, Seattle, WA; State University of New York, Stony Brook, NY; Brigham and Women's Hospital and Harvard Medical School, Boston, MA; University of Iowa, Iowa City, IA; University of California at Davis, Sacramento, CA; University of Miami, Miami, FL; University of Alabama School of Medicine, Birmingham, AL; Wayne State University School of Medicine and Hutzel Hospital, Detroit, MI; University of Iowa Hospitals and Clinics, Iowa City, IA
Background: Emerging clinical evidence suggest intravenous bisphosphonates may directly inhibit breast cancer (Gnant SABCS 2008) while oral bisphosphonates in US clinical practice have received limited evaluation regarding breast cancer influence.
Methods: To investigate associations between oral bisphosphonates and invasive breast cancer we examined data for 151,592 postmenopausal women enrolled in the WHI. Information was collected on breast cancer risk factors and oral bisphosphonate use. To control for bone mineral density (BMD) we employed a published hip fracture prediction model which did not incorporate BMD (Robbins 2007) against the 10,296 WHI participants who had baseline total hip BMD determination. Breast cancers were centrally adjudicated by pathology report review. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).
Results: Of the 151,592 participants, 2,216 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). An analysis comparing hip fracture risk score to BMD in those with both found a significant correlation (regression line = .79-.0478 log predicted hip fracture, r=0.43). As a result, the hip fracture risk score was used to control for potential BMD group differences. HRs for invasive breast cancer by bisphosphonate use are outlined below after 7.8 (1.7) mean years (SD).
|No||Yes||Breast Cancer Incidence **|
|Invasive Breast Cancer||N||Rate*||N||Rate||HR||95% CI||P-value|