Development of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancerReportar como inadecuado

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Breast Cancer Research and Treatment

pp 1–10

First Online: 13 June 2017Received: 29 May 2017Accepted: 01 June 2017DOI: 10.1007-s10549-017-4329-y

Cite this article as: Goncalves, R., DeSchryver, K., Ma, C. et al. Breast Cancer Res Treat 2017. doi:10.1007-s10549-017-4329-y


PurposeThe 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.

MethodsKi-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.

ResultsDiscordant 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.

ConclusionsWe 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.

KeywordsBreast cancer Biomarkers Ki-67 proliferation marker Electronic supplementary materialThe online version of this article doi:10.1007-s10549-017-4329-y contains supplementary material, which is available to authorized users.

Rodrigo Goncalves, Katherine DeSchryver and Cynthia Ma contributed equally to the manuscript.

Autor: Rodrigo Goncalves - Katherine DeSchryver - Cynthia Ma - Yu Tao - Jeremy Hoog - Maggie Cheang - Erika Crouch - Neha Dahiya


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