Bisphosphonate Use After Estrogen Receptor-Positive Breast Cancer and Risk of Contralateral Breast Cancer

• Published in: JNCI : Journal of the National Cancer Institute 2011-12, Vol.103 (23), p.1752-1760
• Main Authors: MONSEES, Genevieve M, MALONE, Kathleen E, TANG, Mei-Tzu C, NEWCOMB, Polly A, LI, Christopher I
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Biological and medical sciences; Biomarkers, Tumor - analysis; Bisphosphonates; Bone Density Conservation Agents - therapeutic use; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Breast Neoplasms - prevention & control; Cancer; Case-Control Studies; Clinical trials; Confidence Intervals; Confounding Factors (Epidemiology); Diphosphonates - therapeutic use; Dose-Response Relationship, Drug; Estrogens; Ethnic groups; Female; Gynecology. Andrology. Obstetrics; Historical account; Humans; Incidence; Logistic Models; Mammary gland diseases; Medical sciences; 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; Osteoporosis; Receptors, Estrogen - analysis; Risk Assessment; Risk factors; Risk reduction; Secondary Prevention - methods; SEER Program; Sensitivity analysis; Tumors; Washington - epidemiology
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djr399

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. 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. 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. 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.