Simple SummaryDiscordance and conversion of receptor expressions in metastatic lesions and primary tumors is often observed in patients with brain metastases from breast cancer. Personalized therapy requires continuous monitoring of receptor expressions and dynamic adaptation of applied targeted treatment options. This study sought to evaluate if quantitative MR image features can predict the receptor status of brain metastases from breast cancer using machine learning algorithms. Results indicate that receptor status can be differentiated non-invasively based on routine MR imaging data. The proposed approach could allow non-invasive expression tracking at high frequencies, and may support dynamic treatment optimization for personalized therapies.AbstractDiscordance and conversion of receptor expressions in metastatic lesions and primary tumors is often observed in patients with brain metastases from breast cancer. Therefore, personalized therapy requires continuous monitoring of receptor expressions and dynamic adaptation of applied targeted treatment options. Radiological in vivo techniques may allow receptor status tracking at high frequencies at low risk and cost. The present study aims to investigate the potential of receptor status prediction through machine-learning-based analysis of radiomic MR image features. The analysis is based on 412 brain metastases samples from 106 patients acquired between 09/2007 and 09/2021. Inclusion criteria were as follows: diagnosed cerebral metastases from breast cancer; histopathology reports on progesterone (PR), estrogen (ER), and human epidermal growth factor 2 (HER2) receptor status; and availability of MR imaging data. In total, 3367 quantitative features of T1 contrast-enhanced, T1 non-enhanced, and FLAIR images and corresponding patient age were evaluated utilizing random forest algorithms. Feature importance was assessed using Gini impurity measures. Predictive performance was tested using 10 permuted 5-fold cross-validation sets employing the 30 most important features of each training set. Receiver operating characteristic areas under the curves of the validation sets were 0.82 (95% confidence interval [0.78; 0.85]) for ER+, 0.73 [0.69; 0.77] for PR+, and 0.74 [0.70; 0.78] for HER2+. Observations indicate that MR image features employed in a machine learning classifier could provide high discriminatory accuracy in predicting the receptor status of brain metastases from breast cancer.