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dc.contributor.authorGoncalves, Ren_US
dc.contributor.authorDeSchryver, Ken_US
dc.contributor.authorMa, Cen_US
dc.contributor.authorTao, Yen_US
dc.contributor.authorHoog, Jen_US
dc.contributor.authorCheang, Men_US
dc.contributor.authorCrouch, Een_US
dc.contributor.authorDahiya, Nen_US
dc.contributor.authorSanati, Sen_US
dc.contributor.authorBarnes, Men_US
dc.contributor.authorSarian, LOZen_US
dc.contributor.authorOlson, Jen_US
dc.contributor.authorAllred, DCen_US
dc.contributor.authorEllis, MJen_US
dc.identifier.citationBreast Cancer Res Treat, 2017, 165 (2), pp. 355 - 364en_US
dc.description.abstractPURPOSE: 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.en_US
dc.format.extent355 - 364en_US
dc.subjectBreast canceren_US
dc.subjectKi-67 proliferation markeren_US
dc.subjectAntineoplastic Agents, Hormonalen_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectChemotherapy, Adjuvanten_US
dc.subjectClinical Decision-Makingen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectKi-67 Antigenen_US
dc.subjectNeoadjuvant Therapyen_US
dc.subjectROC Curveen_US
dc.subjectReproducibility of Resultsen_US
dc.subjectTreatment Outcomeen_US
dc.titleDevelopment of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancer.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBreast Cancer Res Treaten_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials
pubs.embargo.termsNo embargoen_US
icr.researchteamGenomic Analysis – Clinical Trialsen_US
dc.contributor.icrauthorCheang, Chonen_US

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