Jessica B. Long

Incidence of Heart Failure or Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer

OBJECTIVES The purpose of this study was to estimate heart failure (HF) and cardiomyopathy (CM) rates after adjuvant trastuzumab therapy and chemotherapy in a population of older women with early-stage breast cancer. BACKGROUND Newer biologic therapies for breast cancer such as trastuzumab have been reported to increase HF and CM in clinical trials, especially in combination with anthracycline chemotherapy. Elderly patients, however, typically have a higher prevalence of cardiovascular risk factors and have been underrepresented in trastuzumab clinical trials. METHODS Using Surveillance, Epidemiology, and End Results-Medicare data from 2000 through 2007, we identified women 67 to 94 years of age with early-stage breast cancer. We calculated 3-year incidence rates of HF or CM for the following mutually exclusive treatment groups: trastuzumab (with or without nonanthracycline chemotherapy), anthracycline plus trastuzumab, anthracycline (without trastuzumab and with or without nonanthracycline chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy or trastuzumab therapy. HF or CM events were ascertained from administrative Medicare claims. Poisson regression was used to quantify risk of HF or CM, adjusting for sociodemographic factors, cancer characteristics, and cardiovascular conditions. RESULTS We identified 45,537 older women (mean age: 76.2 years, standard deviation: 6.2 years) with early-stage breast cancer. Adjusted 3-year HF or CM incidence rates were higher for patients receiving trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per 100 patients) compared with no adjuvant therapy (18.1 per 100 patients, p < 0.001). Adding trastuzumab to anthracycline therapy added 12.1, 17.9, and 21.7 HF or CM events per 100 patients over 1, 2, and 3 years of follow-up, respectively. CONCLUSIONS HF or CM are common complications after trastuzumab therapy for older women, with higher rates than those reported from clinical trials.

Risk Prediction Model for Heart Failure and Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer

Background Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2‐positive breast cancer, but increases risk for heart failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate HF/CM risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of HF or CM after trastuzumab. Methods and Results Using the Surveillance, Epidemiology and End Results (SEER)‐Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split‐sample design, we used a proportional hazards model to identify candidate predictors of HF/CM in a derivation cohort. A risk score was constructed using regression coefficients, and HF/CM rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3‐year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify HF/CM risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3‐year rates of 16.2%, 26.0%, and 39.5%, respectively. Conclusions A 7‐factor risk score was able to stratify 3‐year risk of HF/CM after trastuzumab between the lowest and highest risk groups by more than 2‐fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for HF/CM for breast cancer patients of all ages.

Assessing the Impact of a Cooperative Group Trial on Breast Cancer Care in the Medicare Population

PURPOSE The Cancer and Leukemia Group B (CALGB) C9343 trial found that adjuvant radiation therapy (RT) provided minimal benefits for older women with breast cancer. Although treatment guidelines were changed to indicate that some women could forego RT, the impact of the C9343 results on clinical practice is unclear. PATIENTS AND METHODS We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare data set to assess the use of adjuvant RT in a sample of women ≥ 70 years old diagnosed with stage I breast cancer from 2001 to 2007 who fulfilled the C9343 inclusion criteria. We used log-binomial regression to estimate the relation between publication of C9343 and use of RT in the full sample and across strata of patient and health system characteristics. RESULTS Of the 12,925 Medicare beneficiaries in our sample (mean age, 77.7 years), 76.5% received RT. Approximately 79% of women received RT before study publication compared with 75% after (adjusted relative risk of receiving RT postpublication v prepublication: 0.97; 95% CI, 0.95 to 0.98). Although use of RT was lower after the trial within all strata of age and life expectancy, the magnitude of this decrease did not differ significantly by strata. For instance, among patients with life expectancy less than 5 years, RT use decreased by 3.7%, from 44.4% prepublication to 40.7% postpublication. Among patients with life expectancy ≥ 10 years, RT use decreased by 3.0%, from 92.0% to 89.0%. CONCLUSION The C9343 trial had minimal impact on the use of RT among older women in the Medicare population, even among the oldest women and those with shorter life expectancies.

Patterns of Use and Short-Term Complications of Breast Brachytherapy in the National Medicare Population From 2008-2009

PURPOSE Brachytherapy has disseminated into clinical practice as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer; however, current national treatment patterns and associated complications remain unknown. PATIENTS AND METHODS We constructed a national sample of Medicare beneficiaries ages 66 to 94 years who underwent breast-conserving surgery from 2008 to 2009 and were treated with brachytherapy or WBI. We used hospital referral regions (HRRs) to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics. We compared overall, wound and skin, and deep-tissue and bone complications between brachytherapy and WBI at 1 year of follow-up. RESULTS Of 29,648 women in our sample, 4,671 (15.8%) received brachytherapy. The percent of patients receiving brachytherapy varied substantially across HRRs, ranging from 0% to over 70% (interquartile range, 7.5% to 23.3%). Of women treated with brachytherapy, 34.3% had a complication compared with 27.3% of women undergoing WBI (P < .001). After adjusting for patient and clinical characteristics, 35.2% of women treated with brachytherapy (95% CI, 28.6 to 41.9) had a complication compared with 18.4% treated with WBI (95% CI, 15.5 to 21.3; P value for difference, <.001). Brachytherapy was associated with a 16.9% higher rate of wound and skin complications compared with WBI (95% CI, 10.0 to 23.9; P < .001), but there was no difference in deep-tissue and bone complications. CONCLUSION Brachytherapy is commonly used among Medicare beneficiaries and varies substantially across regions. After 1 year, wound and skin complications were significantly higher among women receiving brachytherapy compared with those receiving WBI.

The Cost of Breast Cancer Screening in the Medicare Population

BACKGROUND Little is known about the cost to Medicare of breast cancer screening or whether regional-level screening expenditures are associated with cancer stage at diagnosis or treatment costs, particularly because newer breast cancer screening technologies, like digital mammography and computer-aided detection (CAD), have diffused into the care of older women. METHODS Using the linked Surveillance, Epidemiology, and End Results-Medicare database, we identified 137 274 women ages 66 to 100 years who had not had breast cancer and assessed the cost to fee-for-service Medicare of breast cancer screening and workup during 2006 to 2007. For women who developed cancer, we calculated initial treatment cost. We then assessed screening-related cost at the Hospital Referral Region (HRR) level and evaluated the association between regional expenditures and workup test utilization, cancer incidence, and treatment costs. RESULTS In the United States, the annual costs to fee-for-service Medicare for breast cancer screening-related procedures (comprising screening plus workup) and treatment expenditures were

The cost implications of prostate cancer screening in the Medicare population

1.08 billion and

The adoption of new adjuvant radiation therapy modalities among Medicare beneficiaries with breast cancer: clinical correlates and cost implications.

1.36 billion, respectively. For women 75 years or older, annual screening-related expenditures exceeded

Impact of the 2008 US Preventive Services Task Force recommendation to discontinue prostate cancer screening among male Medicare beneficiaries.

410 million. Age-standardized screening-related cost per beneficiary varied more than 2-fold across regions (from

Variation in receipt of radiation therapy after breast-conserving surgery: assessing the impact of physicians and geographic regions.

42 to

Examining the Cost-Effectiveness of Radiation Therapy Among Older Women With Favorable-Risk Breast Cancer

107 per beneficiary); digital screening mammography and CAD accounted for 65% of the difference in screening-related cost between HRRs in the highest and lowest quartiles of cost. Women residing in HRRs with high screening costs were more likely to be diagnosed as having early-stage cancer (incidence rate ratio, 1.78 [95% CI, 1.40-2.26]). There was no significant difference in the cost of initial cancer treatment per beneficiary between the highest and lowest screening cost HRRs (