Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

The number of attentional foci and their precision are dissociated in the posterior parietal cortex.

Many everyday tasks require us to track moving objects with attention. The demand for attention increases both when more targets are tracked and when the targets move faster. These 2 aspects of attention-assigning multiple attentional foci (or indices) to targets and monitoring each focus with precision-may tap into different cognitive and brain mechanisms. In this study, we used functional magnetic resonance imaging to quantify the response profile of dorsal attentional areas to variations in the number of attentional foci and their spatiotemporal precision. Subjects were asked to track a specific spoke of either 1 or 2 pinwheels that rotated at various speeds. Their tracking performance declined both when more pinwheels were tracked and when the tracked pinwheels rotated faster. However, posterior parietal activity increased only when subjects tracked more pinwheels but remained flat when they tracked faster moving pinwheels. The frontal eye fields and early visual areas increased activity when there were more targets and when the targets rotated faster. These results suggest that the posterior parietal cortex is specifically involved in indexing independently moving targets with attention but not in monitoring each focus with precision.