Domain Shift in Breast DCE-MRI Tumor Segmentation: A Balanced LoCoCV Study on the MAMA-MIA Dataset

<b>Background and Objectives:</b> Accurate breast tumor segmentation in dynamic contrast-enhanced MRI (DCE-MRI) is crucial for treatment planning, therapy monitoring, and quantitative studies of breast cancer response. However, deep learning models often have worse performance when applied to new hospitals because scanner hardware, acquisition protocols, and patient populations differ from those in the training data. This study investigates how such center-related domain shift affects automated breast DCE-MRI tumor segmentation on the multi-center MAMA-MIA dataset. <b>Methods:</b> We trained a standard 3D U-Net for primary tumor segmentation under two evaluation settings. First, we constructed a random patient-wise split that mixes cases from the three main MAMA-MIA center groups (ISPY2, DUKE, NACT) and used this as an in-distribution reference. Second, we designed a balanced leave-one-center-out cross-validation (LoCoCV) protocol in which each center is held out in turn, while training, validation, and test sets are matched in size across folds. Performance was assessed using the Dice similarity coefficient, 95th percentile Hausdorff distance (HD95), sensitivity, specificity, and related overlap measures. <b>Results:</b> On the mixed-center random split, the best three-channel model achieved a mean Dice of about 0.68 and a mean HD95 of about 19.7 mm on the held-out test set, indicating good volumetric overlap and boundary accuracy when training and test distributions match. Under balanced LoCoCV, the one-channel model reached a mean Dice of about 0.45 and a mean HD95 of about 41 mm on unseen centers, with similar averages for the three-channel variant. Compared with the random split baseline, Dice and sensitivity decreased, while HD95 nearly doubled, showing that boundary errors become larger and segmentations less reliable when the model is applied to new centers. <b>Conclusions:</b> A model that performs well on mixed-center random splits can still suffer a substantial loss of accuracy on completely unseen institutions. The balanced LoCoCV design makes this out-of-distribution penalty visible by separating center-related effects from sample size effects. These findings highlight the need for robust multi-center training strategies and explicit cross-center validation before deploying breast DCE-MRI segmentation models in clinical practice.