Angela M. Capra

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients

IntroductionThe Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting.MethodsA case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score.ResultsAfter adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7–3.9%), 10.7% (95% CI 6.3–14.9%), and 15.5% (95% CI 7.6–22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5–7.9%), 17.8% (95% CI 11.8–23.3%), and 19.9% (95% CI 14.2–25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values.ConclusionIn this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.

Misunderstanding of Asthma Controller Medications: Association with Nonadherence

Objective. Nonadherence to regular inhaled anti-inflammatory medication use is a frequent contributor to poor control of persistent asthma and may result from misunderstanding of the preventive role of such medications. This studys aims are to 1) test the hypothesis that misunderstanding is associated with decreased adherence to its daily use and 2) identify factors associated with increased risk of misunderstanding. Study Design. A sample of parents of children with asthma insured by Medicaid and enrolled in managed care programs in Northern California, Washington, and Massachusetts were interviewed by telephone. This analysis focused on the subset that reported having an inhaled anti-inflammatory medication and whose medication use and symptom frequency in the 2 weeks before the interview suggested persistent asthma. Misunderstanding of the role of inhaled anti-inflammatory medication was defined as identifying it as being for treatment of symptoms after they begin and not for prevention of symptoms before they start. Results. A total of 1663 parents of children with asthma (63% response rate) were interviewed. Of those, 571 subjects (34%) reported use of an inhaled anti-inflammatory medication and met our criteria for persistent asthma. Among those with persistent asthma, 23% (131 parents) misunderstood the role of their childs inhaled anti-inflammatory. Misunderstanding of inhaled anti-inflammatory medication was associated with decreased adherence to its daily use (odds ratio [OR] 0.18, 95% confidence interval [CI], 0.11–0.29). The risk for misunderstanding was lower if the patient had seen a specialist (OR 0.42, 95% CI, 0.24–0.75) or had graduated high school (OR = 0.54, 95% CI, 0.34–0.84). Conclusion. Misunderstanding of the role of inhaled anti-inflammatory medication is associated with reduced adherence to its daily use.

Effectiveness and Cost-effectiveness of Letters, Automated Telephone Messages, or Both for Underimmunized Children in a Health Maintenance Organization

Background. Immunization rates have improved in the United States, but are still far from the national 90% goal for the year 2000. There is scant evidence about the effectiveness and costs of automated telephone messages to improve immunization rates among privately insured children. Objective. To evaluate the effectiveness and cost-effectiveness of sending letters, automated telephone messages, or both to families of underimmunized 20-month-olds in a health maintenance organization (HMO). Methods. In this randomized trial, underimmunized 20-month-olds identified by the HMOs computerized immunization tracking system were assigned to one of four interventions: 1) an automated telephone message alone; 2) a letter alone; 3) an automated telephone message followed by a letter 1 week later; and 4) a letter followed by an automated telephone message 1 week later. The primary outcome was receipt of any needed immunization by 24 months of age. Decision analysis was used to evaluate the projected cost-effectiveness of the alternative strategies. Results. A total of 648 children were randomized. A letter followed by a telephone message (58% immunized) was significantly better than either a letter alone (44% immunized) or a telephone message alone (44% immunized). A telephone message followed by a letter (53% immunized) also was more effective than either alone, although the differences were not statistically significant. Among a similar comparison group that received no systematic intervention, 36% were immunized. The estimated cost per child immunized was

Mammographic density in a multiethnic cohort

7.00 using letters followed by automated telephone messages,

Distant Invasive Breast Cancer Recurrence Risk in Human Epidermal Growth Factor Receptor 2-Positive T1a and T1b Node-Negative Localized Breast Cancer Diagnosed From 2000 to 2006: A Cohort From an Integrated Health Care Delivery System

9.80 using automated telephone messages alone, and

Computer-Based Models to Identify High-Risk Adults with Asthma: Is the Glass Half Empty or Half Full?

10.50 using letters alone. Under alternative cost assumptions for automated telephone messages and mailed messages, the cost per child immunized ranged from

Varicella serology among school age children with a negative or uncertain history of chickenpox.

2.20 to

Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente.

6.50. Conclusions. For underimmunized 20-month-olds in this HMO setting, letters followed by automated telephone messages were more effective and cost-effective than either message alone. The cost-effectiveness of automated telephone messages and letters may vary widely depending on the setting, and choices among strategies should be tailored to the populations being served.

Thiazolidinedione Therapy Is Not Associated With Increased Colonic Neoplasia Risk in Patients With Diabetes Mellitus

Objectives:To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. Design:The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese participants in the Study of Womens Health Across the Nation, a multisite study of US women transitioning through menopause. Mammograms done when women were premenopausal or early perimenopausal were assessed for area of dense breast tissue and the percent of the breast occupied by dense tissue (percent density). Information on race/ethnicity, acculturation, and other factors was obtained from standardized instruments. Multiple linear regression modeling was used to examine the association between race/ethnicity or acculturation and density measures. Results:Age-adjusted mean percent density was highest for Chinese (52%) and lowest for African American (34%) women. After additional adjustment for body mass index, menopause status, age at first birth, breast-feeding duration, waist circumference, and smoking, African Americans had the highest mean percent density (51%) and Japanese women had the lowest (39%). In contrast, the area of dense tissue was highest for African Americans and similar for white, Japanese, and Chinese women. Less acculturated Chinese and Japanese women tended to have a larger area of density and a higher percent density. Conclusions:Neither the age-adjusted nor fully adjusted results for percent density or area of dense tissue reflected current differences in breast cancer incidence rates among similarly aged African American, Japanese, Chinese, and white women. In addition, mammographic density was higher in less acculturated Asian women.

Mammographic Density and Risk of Second Breast Cancer after Ductal Carcinoma In situ

PURPOSE To determine the invasive recurrence (IR) risk among patients with small, node-negative human epidermal growth factor receptor 2 (HER2) -positive breast cancer. PATIENTS AND METHODS Among 16,975 consecutive patients with invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in a large, integrated health care system, we identified a cohort of 234 patients with HER2-positive T1aN0M0 or T1bN0M0 (T1abN0M0) disease with a median follow-up of 5.8 years. Kaplan-Meier methods were used to estimate the percentage of patients who were free of invasive recurrence (recurrence-free interval [RFI]) at 5 years for both distant (DRFI) and local (LRFI) recurrences. RESULTS Of 15 IRs, 47% were locoregional only. Among T1ab patients not treated with adjuvant trastuzumab or chemotherapy (n = 171), the 5-year invasive DRFI was 98.2% (95% CI, 94.5% to 99.4%); it was 99.0% (95% CI, 93.0% to 99.9%) for T1a patients, and 97.0% (95% CI, 88.6% to 99.2%) for T1b patients. Locoregional plus distant 5-year invasive RFI was 97.0% (95% CI, 90.9% to 99.0%) for T1a and 91.9% (95% CI, 81.5% to 96.6%) for T1b patients; it was 89.4% (95% CI, 70.6% to 96.5%) for T1b tumors reported at 1.0 cm. T1b tumors reported at 1.0 cm accounted for 24% of the T1ab cohort, 61% of the cohort total tumor volume, and 75% of distant recurrences. Invasive RFI for T1b 1.0 cm tumors was lower than that for T1a tumors: 84.5% versus 97.4% (P = .009). CONCLUSION The distant IR risk of T1a HER2-positive breast cancer appears quite low. The distant IR risk in T1b patients, particularly those with 1.0-cm tumors, is higher. Potential risk differences for T1a and T1b, including the 1.0-cm tumors, should be considered when making treatment decisions.