MRI-based Quantification of Intratumoral Heterogeneity for Predicting Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer

Background Breast cancer is highly heterogeneous, resulting in different treatment responses to neoadjuvant chemotherapy (NAC) among patients. A noninvasive quantitative measure of intratumoral heterogeneity (ITH) may be valuable for predicting treatment response. Purpose To develop a quantitative measure of ITH on pretreatment MRI scans and test its performance for predicting pathologic complete response (pCR) after NAC in patients with breast cancer. Materials and Methods Pretreatment MRI scans were retrospectively acquired in patients with breast cancer who received NAC followed by surgery at multiple centers from January 2000 to September 2020. Conventional radiomics (hereafter, C-radiomics) and intratumoral ecological diversity features were extracted from the MRI scans, and output probabilities of imaging-based decision tree models were used to generate a C-radiomics score and ITH index. Multivariable logistic regression analysis was used to identify variables associated with pCR, and significant variables, including clinicopathologic variables, C-radiomics score, and ITH index, were combined into a predictive model for which performance was assessed using the area under the receiver operating characteristic curve (AUC). Results The training data set was comprised of 335 patients (median age, 48 years [IQR, 42–54 years]) from centers A and B, and 590, 280, and 384 patients (median age, 48 years [IQR, 41–55 years]) were included in the three external test data sets. Molecular subtype (odds ratio [OR] range, 4.76–8.39 [95% CI: 1.79, 24.21]; all P < .01), ITH index (OR, 30.05 [95% CI: 8.43, 122.64]; P < .001), and C-radiomics score (OR, 29.90 [95% CI: 12.04, 81.70]; P < .001) were independently associated with the odds of achieving pCR. The combined model showed good performance for predicting pCR to NAC in the training data set (AUC, 0.90) and external test data sets (AUC range, 0.83–0.87). Conclusion A model that combined an index created from pretreatment MRI-based imaging features quantitating ITH, C-radiomics score, and clinicopathologic variables showed good performance for predicting pCR to NAC in patients with breast cancer. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Rauch in this issue. An earlier incorrect version appeared online. This article was corrected on July 12, 2023.