Oral bisphosphonate use and breast cancer incidence in postmenopausal women

Abstract

Purpose: Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence.

Patients and methods: The association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations. To adjust for potential BMD difference based on bisphosphonate use, the hip fracture prediction score was included in multivariant analyses as a BMD surrogate.

Results: Of the 154,768 participants, 2,816 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). As calculated hip fracture risk score was significantly associated with both BMD (regression line = 0.79 to 0.0478 log predicted fracture; P < .001; r = 0.43) and breast cancer incidence (P = .03), this variable was incorporated into regression analyses to adjust for BMD difference between users and nonusers of bisphopshonate. After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) -positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). A similar but not significant trend was seen for ER-negative invasive cancers. The incidence of ductal carcinoma in situ was higher in bisphosphonate users (HR, 1.58; 95% CI, 1.08 to 2.31; P = .02).

Conclusion: Oral bisphosphonate use was associated with significantly lower invasive breast cancer incidence, suggesting bisphosphonates may have inhibiting effects on breast cancer.

Fig 1.

The 5-year predicted probability of hip fracture was calculated from an 11-item algorithm, which does not incorporate bone mineral density (BMD). The log of the predicted probability of hip fracture is compared with total hip BMD at baseline in the 10,418 women who had both determinations. A significant correlation is seen (regression line = 0.79, 0478 log predicted hip fracture; P < .001; r = 0.43). The predicted probability of hip fracture was also significantly associated (hazard ratio, 0.95; 95% CI, 0.90 to 0.99; P = .025) with breast cancer incidence when considered as a continuous variable in a model adjusted for age and race/ethnicity and stratified by Women's Health Initiative trial component.

Fig 2.

The cumulative incidence of invasive breast cancer after entry into the cohort by bisphosphonate use at baseline. Hazard ratio (HR) and 95% CI from a multivariate-adjusted Cox proportional hazards analysis.