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).

    Bisphosphonate Use         
  No Yes Breast Cancer Incidence **   
Invasive Breast Cancer Rate* Rate HR 95% CI P-value 
Total 5092 4.38 64 3.29 0.68 (0.52-0.89) < .01 
ER positive 3829 3.28 50 2.56 0.70 (0.52-0.95) 0.02 
ER negative 717 0.61 0.41 0.66 (0.31-1.39) 0.27 
    Bisphosphonate Use         
  No Yes Breast Cancer Incidence **   
Invasive Breast Cancer Rate* Rate HR 95% CI P-value 
Total 5092 4.38 64 3.29 0.68 (0.52-0.89) < .01 
ER positive 3829 3.28 50 2.56 0.70 (0.52-0.95) 0.02 
ER negative 717 0.61 0.41 0.66 (0.31-1.39) 0.27 

 

* Rate/1000 women years of follow-up**Cox proportional hazards analyses adjusted for age, ethnicity, smoking, alcohol use, physical activity, BMI, mammograms, prior hormone use, calcium, vitamin D, hip fracture risk score, Gail risk score and stratified on WHI trial randomization arm.Conclusion: There was a statistically significant association between oral bisphosphonate use and lower invasive breast cancer incidence with fewer ER positive breast cancers and a non-significant trend for ER negative breast cancers in bisphosphonate users. This result suggests oral bisphosphonates may have direct inhibiting effects on breast cancer.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 21.