Development of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancer
| Autor: | Rodrigo Franco Gonçalves, Souzan Sanati, Yu Tao, Maggie C.U. Cheang, D. C. Allred, Erika C. Crouch, Michael Barnes, Katherine DeSchryver, Jeremy Hoog, Matthew J. Ellis, John Olson, Cynthia X. Ma, Luis Octavio Zanatta Sarian, Neha Dahiya |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal medicine.medical_treatment Concordance Clinical Decision-Making Breast Neoplasms Kaplan-Meier Estimate 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Endocrine system Humans Neoadjuvant therapy biology business.industry Endocrine therapy Reproducibility of Results medicine.disease Prognosis Triage Clinical Trial Neoadjuvant Therapy 3. Good health Clinical trial Ki-67 proliferation marker 030104 developmental biology Ki-67 Antigen Treatment Outcome ROC Curve Chemotherapy Adjuvant 030220 oncology & carcinogenesis Ki-67 biology.protein Female business Biomarkers |
| Zdroj: | Breast Cancer Research and Treatment |
| ISSN: | 1573-7217 |
| Popis: | Purpose The recent publication of the ACOSOG Z1031 trial results demonstrated that Ki-67 proliferation marker-based neoadjuvant endocrine therapy response monitoring could be used for tailoring the use of adjuvant chemotherapy in ER+HER2-negative breast cancer patients. In this paper, we describe the development of the Ki-67 clinical trial assay used for this study. Methods Ki-67 assay assessment focused on reproducing a 2.7% Ki-67 cut-point (CP) required for calculating the Preoperative Endocrine Prognostic Index and a 10% CP for poor endocrine therapy response identification within the first month of neoadjuvant endocrine treatment. Image analysis was assessed to increase the efficiency of the scoring process. Clinical outcome concordance for two independent Ki-67 scores was the primary performance metric. Results Discordant scores led to a triage approach where cases with complex histological features that software algorithms could not resolve were flagged for visual point counting (17%). The final Ki-67 scoring approach was run on T1/2 N0 cases from the P024 and POL trials (N = 58). The percent positive agreement for the 2.7% CP was 87.5% (95% CI 61.7–98.5%); percent negative agreement 88.9% (95% CI: 65.3–98.6%). Minor discordance did not affect the ability to predict similar relapse-free outcomes (Log-Rank P = 0.044 and P = 0.055). The data for the 10% early triage CP in the POL trial were similar (N = 66), the percentage positive agreement was 100%, and percent negative agreement 93.55% (95% CI: 78.58–99.21%). The independent survival predictions were concordant (Log-rank P = 0.0001 and P = 0.01). Conclusions We have developed an efficient and reproducible Ki-67 scoring system that was approved by the Clinical Trials Evaluation Program for NCI-supported neoadjuvant endocrine therapy trials. Using the methodology described here, investigators are able to identify a subgroup of patients with ER+HER2-negative breast cancer that can be safely managed without the need of adjuvant chemotherapy. Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4329-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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