Journal Article

The use of automated Ki67 analysis to predict Oncotype DX risk-of-recurrence categories in early-stage breast cancer

Tudor, Roxana, Li, Haocheng, Bigras, Gilbert, Enwere, Emeka K., Yang, Hua, Chan, Angela M. Y., Morris, Don, Thakur, Satbir Singh

2018

Overview

Ki67 is a commonly used marker of cancer cell proliferation, and has significant prognostic value in breast cancer. In spite of its clinical importance, assessment of Ki67 remains a challenge, as current manual scoring methods have high inter- and intra-user variability. A major reason for this variability is selection bias, in that different observers will score different regions of the same tumor. Here, we developed an automated Ki67 scoring method that eliminates selection bias, by using whole-slide analysis to identify and score the tumor regions with the highest proliferative rates. The Ki67 indices calculated using this method were highly concordant with manual scoring by a pathologist (Pearson's r = 0.909) and between users (Pearson's r = 0.984). We assessed the clinical validity of this method by scoring Ki67 from 328 whole-slide sections of resected early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. All patients had Oncotype DX testing performed (Genomic Health) and available Recurrence Scores. High Ki67 indices correlated significantly with several clinico-pathological correlates, including higher tumor grade (1 versus 3, P<0.001), higher mitotic score (1 versus 3, P<0.001), and lower Allred scores for estrogen and progesterone receptors (P = 0.002, 0.008). High Ki67 indices were also significantly correlated with higher Oncotype DX risk-of-recurrence group (low versus high, P<0.001). Ki67 index was the major contributor to a machine learning model which, when trained solely on clinico-pathological data and Ki67 scores, identified Oncotype DX high- and low-risk patients with 97% accuracy, 98% sensitivity and 80% specificity. Automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy, in a manner that integrates readily into the workflow of a pathology laboratory. Furthermore, automated Ki67 scores contribute significantly to models that predict risk of recurrence in breast cancer.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Automation / Bias / Biology and Life Sciences / Breast cancer / Cell proliferation / Chemotherapy / Computer and Information Sciences / Epidermal growth factor / Estrogens / Gene expression / Growth factors / Health risks / Laboratories / Learning algorithms / Machine learning / Medicine and Health Sciences / Methods / Oncology / Pathology / Patients / Progesterone / Progesterone receptors / Receptors / Research and Analysis Methods / Risk / Tumors / Variables / Workflow