br c Division of Pulmonary Critical Care and
c Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
d Department of Internal Medicine, Maimonides Medical Center, 4802 10th Avenue, Brooklyn, NY, 11219, USA
Received in revised form
Background: Cardiovascular disease (CVD) is a leading cause of mortality in early-stage breast cancer survivors. Recent studies suggest that bisphosphonates may decrease CVD risk in older patients. Objective: This study sought to assess whether bisphosphonate use is associated with lower rates of incident CVD events among early-stage breast cancer survivors.
Methods: Longitudinal, population-based cohort study was conducted by using data from the Surveil-lance, Epidemiology and End Results registry linked to Medicare claims. We identified women >65 years with no history of CVD who were diagnosed with stage 0-III primary breast cancer between 2007 and 2010. Our primary outcome was a composite of incident KX2-391 pectoris, myocardial infarction, atrial fibrillation/flutter, heart failure, or stroke within 36 months of cancer diagnosis. Bisphosphonate use was defined as the presence of 1 pharmacy claim from 6 months prior to cancer diagnosis to the incident CVD event. We used propensity scores to create a matched group of breast cancer survivors without bisphosphonate exposure to compare rates of incident CVD events.
Results: A total of 2178 breast cancer survivors had 1 bisphosphonate prescription; the average length of bisphosphonate use was 15 months. Analyses of the matched data showed that 13.0% of bisphosph-onate users and 23.4% of non-bisphosphonate users experienced an incident CVD event (p < 0.0001) after breast cancer diagnosis. Bisphosphonate use was significantly associated with fewer incident CVD events (hazard ratio: 0.51, 95% confidence interval: 0.44 to 0.59).
Conclusions: Bisphosphonate use is associated with lower incidence of CVD events among older early-stage breast cancer survivors. Future studies should prospectively evaluate whether bisphosphonate use can decrease CVD incidence.
Published by Elsevier Ltd.
More than half of breast cancer patients in the United States are diagnosed at >60 years of age, and older cancer survivors have an increased risk of developing cardiovascular disease (CVD) . Moreover, CVD is one of the major causes of competing mortality in women with early-stage breast cancer . Hooning et al. found breast cancer patients had a 30% increased incidence of CVD events compared to women from the general population. Moreover, some
* Corresponding author. Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1087, New York, NY, 10029. E-mail address: [email protected] (N. Gegechkori).
of this increased risk is a consequence of cardiotoxicity due to some anticancer treatments .
Bisphosphonates inhibit bone resorption and are broadly used in clinical practice for the treatment and prevention of skeletal conditions characterized by increasing osteoclast-mediated bone remodeling [4,5]. Adjuvant use of bisphosphonates has been shown to reduce rates of cancer recurrence and death in patients with early-stage breast cancer . Recent studies also suggest that bisphosphonates may modulate CVD risk in older patients; how-ever results have been mixed [7,8]. Wolfe at al. reported a sub-stantial risk reduction in myocardial infarction (MI) among patients with rheumatoid arthritis who were treated with bisphosphonates . An analysis of participants in a retrospective cohort study
investigating the safety profile of risedronate found a tendency toward a lower cardiovascular mortality, driven mainly by a reduction in stroke mortality . Conversely, concerns have been raised regarding associations between bisphosphonate use and increased rates of atrial fibrillation [11,12]. However, it is not known whether bisphosphonate use impacts CVD risk among breast can-cer survivors.
In this study, we used population-based cancer data to evaluate the association between bisphosphonate use and incident CVD events after cancer diagnosis in older women diagnosed with pri-mary breast cancer.
We used the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare data. This database combines two large population-based data sources that provide detailed information about Medicare beneficiaries with cancer. We excluded individuals in health care maintenance organizations or those without Part B Medicare insurance due to lack of complete claims data and those without Part D coverage for whom we could not ascertain outpa-tient medication use.
2.2. Study participants
We identified women >65 years who were diagnosed primary early-stage (0-III) breast cancer between January 1, 2007, and December 31, 2010. We excluded women who had CVD prior to breast cancer diagnosis, including those who had undergone heart transplant surgery, cardiac valve surgery, coronary artery bypass grafting (CABG), patients with uncorrected atrial or ventricular septal defects (congenital heart disease), or anyone with a history of angina, atrial fibrillation/flutter, heart failure, myocarditis, myocardial infarction or stroke. We also excluded patients with end-stage renal disease as these patients have a significantly higher risk for CVD or those who were diagnosed with breast cancer on autopsy or at death.