We have studied in vivo responses of ''spontaneous'' Brca1-and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer.multidrug resistance ͉ P-glycoprotein ͉ cancer stem cells

MRI during NAC to monitor response is effective in triple-negative or HER2-positive disease but is inaccurate in ER-positive/HER2-negative breast cancer.

Contrast-enhanced magnetic resonance imaging (MRI) of the breast is known to reveal breast cancer with higher sensitivity than mammography alone. The specificity is, however, compromised by the observation that several benign masses take up contrast agent in addition to malignant lesions. The aim of this study is to increase the objectivity of breast cancer diagnosis in contrast-enhanced MRI by developing automated methods for computer-aided diagnosis. Our database consists of 27 MR studies from 27 patients. In each study, at least four MR series of both breasts are obtained using FLASH three-dimensional (3D) acquisition at 90 s time intervals after injection of Gadopentetate dimeglumine (Gd-DTPA) contrast agent. Each series consists of 64 coronal slices with a typical thickness of 2 mm, and a pixel size of 1.25 mm. The study contains 13 benign and 15 malignant lesions from which features are automatically extracted in 3D. These features include margin descriptors and radial gradient analysis as a function of time and space. Stepwise multiple regression is employed to obtain an effective subset of combined features. A final estimate of likelihood of malignancy is determined by linear discriminant analysis, and the performance of classification by round-robin testing and receiver operating characteristics (ROC) analysis. To assess the efficacy of 3D analysis, the study is repeated in two-dimensions (2D) using a representative slice through the middle of the lesion. In 2D and in 3D, radial gradient analysis and analysis of margin sharpness were found to be an effective combination to distinguish between benign and malignant masses (resulting area under the ROC curve: 0.96). Feature analysis in 3D was found to result in higher performance of lesion characterization than 2D feature analysis for the majority of single and combined features. In conclusion, automated feature extraction and classification has the potential to complement the interpretation of radiologists in an objective, consistent, and accurate way.

Automatic segmentation of medical images is an important task for many clinical applications. In practice, a wide range of anatomical structures are visualised using different imaging modalities. In this paper, we investigate whether a single convolutional neural network (CNN) can be trained to perform different segmentation tasks. A single CNN is trained to segment six tissues in MR brain images, the pectoral muscle in MR breast images, and the coronary arteries in cardiac CTA. The CNN therefore learns to identify the imaging modality, the visualised anatomical structures, and the tissue classes. For each of the three tasks (brain MRI, breast MRI and cardiac CTA), this combined training procedure resulted in a segmentation performance equivalent to that of a CNN trained specifically for that task, demonstrating the high capacity of CNN architectures. Hence, a single system could be used in clinical practice to automatically perform diverse segmentation tasks without task-specific training.