Racial disparities in treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer.

Data characterizing demographics, treatment patterns, and clinical outcomes in black patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. registHER is a large, observational cohort study of patients (n = 1,001) with HER2-positive MBC diagnosed ≤6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up of 27 months). Demographics, treatment patterns, and clinical outcomes were described for black (n = 126) and white patients (n = 793). Progression-free survival (PFS) following first-line therapy and overall survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Black patients were more likely than white patients to be obese (body mass index ≥30), to have diabetes, and to have a history of cardiovascular disease; they were also less likely to have estrogen receptor or progesterone receptor positive disease. In patients treated with trastuzumab, the incidence of cardiac safety events (grade ≥3) was higher in black patients (10.9 %) than in white patients (7.9 %). Unadjusted median OS and PFS (months) were significantly lower in black patients than in white patients (OS: black: 27.1, 95 % confidence interval [CI] 21.3-32.1; white: 37.3, 95 % CI 34.6-41.1; PFS: black: 7.0, 95 % CI 5.7-8.2; white: 10.2, 95 % CI 9.3-11.2). The adjusted OS hazard ratio (HR) for black patients compared with white patients was 1.29 (95 % CI 1.00-1.65); adjusted PFS HR was 1.29 (95 % CI 1.05-1.59). This real-world evaluation of a large cohort of patients with HER2-positive MBC shows poorer prognostic factors and independently worse clinical outcomes in black versus white patients. Further research is needed to identify potential biologic differences that could have predictive impact for black patients or that could explain these differences

Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study.

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65-74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS

Potential misinterpretations caused by collapsing upper categories of comorbidity indices: An illustration from a cohort of older breast cancer survivors

BACKGROUND: Comorbidity indices summarize complex medical histories into concise ordinal scales, facilitating stratification and regression in epidemiologic analyses. Low subject prevalence in the highest strata of a comorbidity index often prompts combination of upper categories into a single stratum (\u27collapsing\u27). OBJECTIVE: We use data from a breast cancer cohort to illustrate potential inferential errors resulting from collapsing a comorbidity index. METHODS: Starting from a full index (0, 1, 2, 3, and \u3e/=4 comorbidities), we sequentially collapsed upper categories to yield three collapsed categorizations. The full and collapsed categorizations were applied to analyses of (1) the association between comorbidity and all-cause mortality, wherein comorbidity was the exposure; (2) the association between older age and all-cause mortality, wherein comorbidity was a candidate confounder or effect modifier. RESULTS: Collapsing the index attenuated the association between comorbidity and mortality (risk ratio, full versus dichotomized categorization: 4.6 vs 2.1), reduced the apparent magnitude of confounding by comorbidity of the age/mortality association (relative risk due to confounding, full versus dichotomized categorization: 1.14 vs 1.09), and obscured modification of the association between age and mortality on both the absolute and relative scales. CONCLUSIONS: Collapsing categories of a comorbidity index can alter inferences concerning comorbidity as an exposure, confounder and effect modifier

HOP Queue: Hyperspectral Onboard Processing Queue Demonstration

The HOP Queue (Hyperspectral Onboard Processing Queue) demonstration leverages emerging COTS AI accelerators and GPUs to perform on-board processing of hyperspectral imagery data, with the aim of providing near- real time conservation-oriented data and metrics from Low Earth Orbit (LEO). These include forest health, fire detection, and coastal water health. Phase 1 of this project is currently underway, including a completed lab demonstration of this technology and ongoing flight testing. The data from this mission will support Northrop Grumman’s enterprise “Technology for Conservation” campaign and will be provided to NASA’s Surface Biology and Geology (SBG) organization, as well as other conservation efforts

Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study

Background: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM. Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results: Among 12 500 women (mean age = 60 years, range = 22–99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions: Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety

Statin use and risk of hepatocellular carcinoma in a U.S. population

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population

Treatment patterns and clinical outcomes for patients with de novo versus recurrent HER2-positive metastatic breast cancer

Improvements in screening and adjuvant therapy for breast cancer are associated with decreased recurrence, which may have the effect of increasing the proportion of patients presenting with first-line de novo versus recurrent metastatic breast cancer (MBC). Here, we describe and compare patients with de novo versus recurrent human epidermal growth factor 2 (HER2)-positive MBC. registHER was a prospective observational cohort study (late 2003–early 2006) of 1,023 patients with HER2-positive MBC. Baseline characteristics, treatment patterns, and clinical outcomes were examined in patients with newly diagnosed de novo (n = 327) compared with recurrent HER2-positive MBC after prior treatment for early-stage disease (n = 674). Patients with de novo HER2-positive MBC were less likely to have lung metastases, more likely to have lymph node, bone, and/or liver metastases and >4 sites of metastases and more likely to receive combined or concurrent chemotherapy and hormonal therapy with or without trastuzumab than those with recurrent HER2-positive MBC. Median follow-up was 29 months. Median progression-free survival was 12.1 versus 9.3 months [hazard ratio = 0.716 (95 % confidence interval (CI) 0.617–0.831)], and overall survival was 41.7 versus 32.8 months [hazard ratio = 0.766 (95 % CI 0.633–0.928)] for patients with de novo versus recurrent HER2-positive MBC, respectively. Patients with recurrent HER2-positive MBC had similar outcomes regardless of whether they received prior adjuvant therapy, excluding hormonal therapy. Despite presenting with more advanced-stage disease and higher tumor burdens, patients with de novo HER2-positive MBC have more favorable clinical outcomes than those with recurrent HER2-positive MBC. These differences may be due to effects of prior drug exposure and could have implications for designing and interpreting clinical trials

Statin use and risk of multiple myeloma: An analysis from the cancer research network

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998–2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48–72 months prior to diagnosis/index date was associated with a suggestive 20–28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90–0.99 with 0–36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67–0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis