Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer.
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.
SD, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. gmonsees@fhcrc.org
Genevieve M
GM
Monsees
Kathleen E
KE
Malone
Mei-Tzu C
MT
Tang
Polly A
PA
Newcomb
Christopher I
CI
Li
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016022:Case-Control Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D004164:Diphosphonates / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000517:prevention & control; D017672:Nitrogen Compounds / Q000627:therapeutic use; D016017:Odds Ratio; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D018426:SEER Program; D055502:Secondary Prevention / Q000379:methods; D014861:Washington / Q000453:epidemiology
D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D017672:Nitrogen Compounds; D011960:Receptors, Estrogen