期刊
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
卷 30, 期 4, 页码 237-245出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAI.0000000000001009
关键词
assay validation; CDK 4 and 6 inhibitor; early breast cancer; immunohistochemistry; Ki-67
资金
- Eli Lilly and Company
The objective of this study was to develop a standardized Ki-67 immunohistochemistry method for precise assessment of patients with early breast cancer and to evaluate the prognostic value of Ki-67 expression in these patients. The results showed that patients with high Ki-67 expression had a higher risk of developing invasive disease within 2 years compared to those with low Ki-67 expression.
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.
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