Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer

J Natl Cancer Inst. 2011 Dec 7;103(23):1752-60. doi: 10.1093/jnci/djr399. Epub 2011 Oct 21.

Abstract

Background: A growing body of evidence suggests that nitrogenous bisphosphonates may reduce the risk of developing a first breast cancer and may prevent metastases among breast cancer survivors. However, their impact on risk of second primary contralateral breast cancer is uncertain.

Methods: Within a nested case-control study among women diagnosed with a first primary estrogen receptor-positive invasive breast cancer at ages 40-79 years, we assessed the association between post-diagnostic bisphosphonate use and risk of second primary contralateral breast cancer. We used multivariable-adjusted conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) comparing 351 contralateral breast cancer case subjects with 662 control subjects (ie, breast cancer patients not diagnosed with contralateral breast cancer) who were incidence density-matched on county; race/ethnicity; and age at, year of, and stage at first breast cancer diagnosis. We performed sensitivity analyses with respect to bisphosphonate type and confounding by indication. All statistical tests were two-sided.

Results: Current use of any nitrogenous bisphosphonate and use specifically of alendronate were both associated with reduced risks of contralateral breast cancer compared with never use (OR = 0.41, 95% CI = 0.20 to 0.84 and OR = 0.39, 95% CI = 0.18 to 0.88, respectively). The risk of contralateral breast cancer further declined with longer durations of bisphosphonate use among current users (P(trend) = .03). Results were similar in analyses restricted to patients with a history of osteoporosis or osteopenia.

Conclusions: Bisphosphonate use was associated with a substantial reduction in risk of contralateral breast cancer. If this finding is confirmed in additional studies, nitrogenous bisphosphonate therapy may be a feasible approach for contralateral breast cancer risk reduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Bone Density Conservation Agents / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / prevention & control*
  • Case-Control Studies
  • Confidence Intervals
  • Confounding Factors, Epidemiologic
  • Diphosphonates / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Incidence
  • Logistic Models
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasms, Second Primary / epidemiology
  • Neoplasms, Second Primary / prevention & control
  • Nitrogen Compounds / therapeutic use
  • Odds Ratio
  • Receptors, Estrogen / analysis*
  • Risk Assessment
  • SEER Program
  • Secondary Prevention* / methods
  • Washington / epidemiology

Substances

  • Biomarkers, Tumor
  • Bone Density Conservation Agents
  • Diphosphonates
  • Nitrogen Compounds
  • Receptors, Estrogen