Treatment patterns, healthcare resource utilization and outcomes for early stage triple-negative breast cancer in Japan.

Aim: There is limited information regarding the treatment and outcomes of early stage triple-negative breast cancer (esTNBC) in real-world settings in Japan. Materials & methods: Retrospective analyses of the Medical Data Vision database assessed treatment patterns, healthcare resource utilization (HCRU), patient characteristics, outcomes and prognostic factors among four groups (neoadjuvant therapy+surgery+adjuvant therapy; neoadjuvant therapy+surgery; surgery+adjuvant therapy; surgery only) of esTNBC patients. Results: Treatment patterns, HCRU and demographics varied among the four groups. HCRU was greater and prognosis tended to be worse in the neoadjuvant+surgery+adjuvant therapy group. Conclusion: Our results provide insights into the treatment practices, HCRU and prognosis of esTNBC in Japan. The treatment practices were heterogeneous, reflecting the decision-making process in Japan during the study period.

Triple-negative breast cancer (TNBC) is a cancer type that does not express three biomarkers (estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2), which results in a lack of targeted treatment strategies. Early stage TNBC (esTNBC) is mainly treated by anticancer drugs before (neoadjuvant) and/or after (adjuvant) surgery and adjuvant radiotherapy. New therapies including an immune checkpoint inhibitor which helps better immune system and a PARP inhibitor which helps repair DNA damage were approved for esTNBC in 2022 in Japan, and they are expected to change the treatment options for TNBC. However, there are limited data about the treatment patterns, healthcare resource utilization (HCRU) and outcomes for esTNBC in real-world clinical practice in Japan. Therefore, a hospital-based administrative database was analyzed to understand the treatment patterns for patients with esTNBC in Japan, the HCRU, treatment outcomes (overall survival and event free survival), and the associated factors. Patients received a large variety of treatments before and after surgery. Patients who received both neoadjuvant and adjuvant therapies tended to have more severe disease and required greater HCRU, and their outcomes were worse than patients who received neoadjuvant treatment only, adjuvant treatment only or neither neoadjuvant nor adjuvant treatment. Our findings will help us understand how new treatments will impact the treatment practices and patient outcomes in the future.

Control of postnatal apoptosis in the neocortex by RhoA-subfamily GTPases determines neuronal density.

Apoptosis of neurons in the maturing neocortex has been recorded in a wide variety of mammals, but very little is known about its effects on cortical differentiation. Recent research has implicated the RhoA GTPase subfamily in the control of apoptosis in the developing nervous system and in other tissue types. Rho GTPases are important components of the signaling pathways linking extracellular signals to the cytoskeleton. To investigate the role of the RhoA GTPase subfamily in neocortical apoptosis and differentiation, we have engineered a mouse line in which a dominant-negative RhoA mutant (N19-RhoA) is expressed from the Mapt locus, such that all neurons of the developing nervous system are expressing the N19-RhoA inhibitor. Postnatal expression of N19-RhoA led to no major changes in neocortical anatomy. Six layers of the neocortex developed and barrels (whisker-related neural modules) formed in layer IV. However, the density and absolute number of neurons in the somatosensory cortex increased by 12-26% compared with wild-type littermates. This was not explained by a change in the migration of neurons during the formation of cortical layers but rather by a large decrease in the amount of neuronal apoptosis at postnatal day 5, the developmental maximum of cortical apoptosis. In addition, overexpression of RhoA in cortical neurons was seen to cause high levels of apoptosis. These results demonstrate that RhoA-subfamily members play a major role in developmental apoptosis in postnatal neocortex of the mouse but that decreased apoptosis does not alter cortical cytoarchitecture and patterning.

Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.

Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.