Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy.

PURPOSE: Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts. METHODS: In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006-2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores. RESULTS: Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02-1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84-1.30). CONCLUSIONS: Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women. IMPLICATIONS FOR CANCER SURVIVORS: Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.

Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United States: Lessons From Medicare Part D.

Background: Drug utilization under Medicare Part D varies significantly by geographic region. This study examined the extent to which geographic variation in Part D plan characteristics contributes to the variation in choice of initial endocrine therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses were applied to the 16,541 women identified from Medicare claims as having incident breast cancer in 2006-2007. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine therapy. The second stage provided estimates of the impact of state-specific Part D plan characteristics on variation in choice of initial therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as initial endocrine therapy, despite controlling for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia. Results from the second stage revealed that variation in characteristics of Part D plans across states explained approximately one-third (30%) of the state-level variability in endocrine therapy. A higher number of plans with cost-sharing above the mean, greater spread in deductibles, and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost-sharing (in dollars) were both positively associated with likelihood of starting on an AI. Conclusions: Study findings suggest that variation in benefit design of Part D plans accounts for an important share of the large and persisting variability in use of AIs-the preferred oral therapy for breast cancer.

Erratum to: Patient costs of breast cancer endocrine therapy agents under Medicare Part D vs with generic formulations.

[This corrects the article DOI: 10.1186/s40064-015-0827-8.].

The introduction of generic aromatase inhibitors and treatment adherence among Medicare D enrollees.

BACKGROUND: Aromatase inhibitors (AIs) substantially reduce breast cancer mortality in clinical trials, but high rates of nonadherence to these long-term oral therapies have reduced their impact outside of trials. We examined the association of generic AI availability with AI adherence among a large national breast cancer cohort. METHODS: Using a quasi-experimental prepost design, we examined the effect of generic AI introductions (7/2010 and 4/2011) on adherence among a national cohort of women with incident breast cancer in 2006 and 2007 who were enrolled in the Medicare D pharmaceutical coverage program. Medicare D claims were used to calculate AI adherence, defined as a medication possession ratio of 80% or more of eligible days, over 36 months. Multivariable logistic regression models estimated with generalized estimating equations were applied to longitudinal adherence data to control for possible confounders, including receipt of a Medicare D low-income subsidy, and to account for repeated measures. All statistical tests were two-sided. RESULTS: Sixteen thousand four hundred sixty-two Medicare D enrollees were eligible. Adherence declined throughout the study. However, among women without a subsidy, the median quarterly out-of-pocket cost of anastrozole fell from $183 in the fourth quarter of 2009 to $15 in 2011, and declines in adherence were attenuated with generic AI introductions. Regression-adjusted adherence probabilities were estimated to be 5.4% higher after generic anastrozole was introduced in 2010 and 11% higher after generic letrozole/exemestane was introduced in 2011. Subsidy recipients had higher adherence rates throughout the study. CONCLUSIONS: The introduction of generic medications attenuated the decline in adherence to AIs over three years of treatment among breast cancer survivors not receiving low-income subsidies for Medicare D coverage.

Patient costs of breast cancer endocrine therapy agents under Medicare Part D vs with generic formulations.

PURPOSE: The high expense of newer, more effective adjuvant endocrine therapy agents (aromatase inhibitors [AIs]) for postmenopausal breast cancer contributes to socioeconomic disparities in breast cancer outcomes. This study compares endocrine therapy costs for breast cancer patients during the first five years of Medicare Part D implementation, and when generic alternatives became available. METHODS: The out of pocket patient costs for AIs and tamoxifen under Medicare Part D drug plans were determined for 2006-2011 from the CMS Website for the 50 US states and District of Columbia. RESULTS: Between 2006 and 2010, the mean annual patient drug cost under Medicare Part D in the median state rose 19% for tamoxifen, 113% for anastrozole, 89% for exemestane, and 129% for letrozole, resulting in median annual out of pocket costs in 2010 of $701, $3050, $2804, and $3664 respectively. However, the 2011 availability of generic AI preparations led to median annual costs in 2011 of $804, $872, $1837, and $2217 respectively. Not included in the reported patient costs, the mean monthly drug premiums in the median state increased 58% in 2011 compared to 2007. CONCLUSIONS: The more effective AI agents became considerably more expensive during the first several years of the Medicare Part D program. Cost decreased with the introduction of generic agents, an intervention that was independent of the Part D program. It is unlikely that the Part D program ameliorated existing socioeconomic disparities in survival among breast cancer patients, but the availability of generic agents may do so.