Background: Functional tumor volume (FTV), measured from dynamic contrast-enhanced MRI, is an imaging biomarker that can predict treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The FTV-based predictive model, combined with core biopsy, informed treatment decisions of recommending patients with excellent responses to proceed to surgery early in a large NAC clinical trial.
Methods: In this retrospective study, we constructed models using FTV measurements. We analyzed performance tradeoffs when a probability threshold was used to identify excellent responders through the prediction of pathology complete response (pCR). Individual models were developed within cohorts defined by the hormone receptor and human epidermal growth factor receptor 2 (HR/HER2) subtype.
Results: A total of 814 patients enrolled in the I-SPY 2 trial between 2010 and 2016 were included with a mean age of 49 years (range: 24 to 77). Among these patients, 289 (36%) achieved pCR. The area under the ROC curve (AUC) ranged from 0.68 to 0.74 for individual HR/HER2 subtypes. When probability thresholds were chosen based on minimum positive predictive value (PPV) levels of 50%, 70%, and 90%, the PPV-sensitivity tradeoff varied among subtypes. The highest sensitivities (100%, 87%, 45%) were found in the HR-/HER2+ sub-cohort for probability thresholds of 0, 0.62, and 0.72; followed by the triple-negative sub-cohort (98%, 52%, 4%) at thresholds of 0.13, 0.58, and 0.67; and HR+/HER2+ (78%, 16%, 8%) at thresholds of 0.34, 0.57, and 0.60. The lowest sensitivities (20%, 0%, 0%) occurred in the HR+/HER2- sub-cohort.
Conclusions: Predictive models developed using imaging biomarkers, alongside clinically validated probability thresholds, can be incorporated into decision-making for precision oncology.
Keywords: breast cancer; dynamic contrast-enhanced MRI; functional tumor volume; neoadjuvant chemotherapy; pathologic complete response; therapy decision.