A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone.

The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2- early breast cancer with high-risk clinicopathologic features.

Comparison of recording of pericarditis and lung disorders at routine meat inspection with findings at systematic health monitoring in Danish finisher pigs.

BACKGROUND: The use of secondary data is widespread in a range of surveillance and monitoring applications because of the low cost and high availability associated with this form of data. However, as they are often collected for quite unrelated purposes, they are not necessarily fit for the new purpose that is required of them. Routine meat inspection data were originally collected with the purpose of safeguarding food, but have been re-tasked to also include animal welfare assessment. The objective of the present study was to compare the recording of pericarditis, pleuritis and lungs with lesions at routine meat inspection (RMI) with those performed at systematic health monitoring (SHM) in Danish pigs at slaughter, in order to assess the usefulness of RMI for monitoring the prevalence of these diseases. Data originating from 165 Danish pig herds were collected in the period September 2011 to November 2013. From each herd, a batch consisting of all pigs slaughtered on a specific day from a specific farm were included as the RMI data, while lungs and hearts sampled from the batches were used for the SHM. The RMI data and SHM data included recordings related to a) chronic pericarditis, b) chronic pleuritis and c) lung lesions. The proportion of carcases with a specific disease recording was estimated for each batch of pigs, and linear regression was used to relate the RMI-proportion to the SHM-proportion for the conditions mentioned above. RESULTS: The coefficients of determination (R(2)) were estimated as R(2),pericarditis = 0.16; R(2),pleuritis = 0.67; R(2),lungs with lesions = 0.40. R(2),pericarditis changed to 0.42 when the regression analysis included inspection type at the abattoir (with purely visual inspection of the hearts versus traditional inspection including an incision into the heart). CONCLUSIONS: Overall, the results suggest that the correlation between findings at RMI and SHM was moderate for pleuritis and lungs with lesions, but poor for pericarditis. The latter could partly be explained by the type of meat inspection conducted at the abattoir. We conclude that caution should be used whenever RMI data are used for purposes other than those for which they were originally intended.