Treatment of residual disease following neoadjuvant therapy in breast cancer.

Substantial advances have been made in the systemic treatment of breast cancer with residual disease following neoadjuvant therapy. We reviewed recent and ongoing studies informing the standard clinical management of residual disease by subtype: HER2+, TNBC, and HR+/HER2-, as well as strategies for BRCA+ disease. We conclude with a discussion of ongoing clinical trials and current controversies regarding the treatment of residual disease in breast cancer.

Psychosocial needs of older patients with metastatic breast cancer treated at community centers.

INTRODUCTION: Psychosocial status contributes to overall quality of life (QOL) for patients with cancer as psychosocial distress is commonly seen in this population. We sought to describe the psychosocial needs of older adults with metastatic breast cancer (MBC) treated in the community. We evaluated the correlation between the patient's psychosocial status and the presence of other geriatric abnormalities in this patient population. MATERIALS AND METHODS: This is a secondary analysis of a completed study evaluating older adults (≥65 years) with MBC treated at community practices who received a geriatric assessment (GA). This analysis evaluated psychosocial factors collected during GA, including depression assessed by Geriatric Depression Scale (GDS), perceived social support (SS) assessed by Medical Outcomes Study Social Support Survey (MOS), and objective social supportassessed by demographic variables (living situation and marital status). Perceived SS was further subdivided into tangible social support (TSS) and emotional social support (ESS). Kruskal-Wallis tests, Wilcoxon tests, and Spearman's correlations were used to assess the relationship between psychosocial factors, patient characteristics, and geriatric abnormalities. RESULTS: One hundred older patients with MBC were enrolled and completed GA with a median age of 73 years (65-90). Almost half of the participants (47%) were either single, divorced, or widowed and 38% lived alone, demonstrating a significant number of patients with objective social support deficits. Patients with HER2+ or triple negative MBC had lower overall SS scores compared to patients with ER/PR+ or HER2- MBC (p = 0.033). Patients on fourth line of therapy were more likely to screen positive for depression compared to patients on earlier lines of therapy (p = 0.047). About half (51%) of the patients indicated at least one SS deficit on the MOS. A higher GDS and lower MOS score correlated with greater total GA abnormalities (p = 0.016). Evidence of depression correlated with poor functional status, decreased cognition, and a high number of co-morbidities (p < 0.005). Abnormalities in functional status, cognition, and high GDS are associated with lower ESS (p = 0.025,0.031,0.006 respectively). DISCUSSION: Psychosocial deficits are common among older adults with MBC treated in the community and are associated with the presence of other geriatric abnormalities. These deficits require a thorough evaluation and management to optimize treatment outcomes.

Sepsis survivor mice exhibit a behavioral endocrine syndrome with ventral hippocampal dysfunction.

Severe acute stressors are known to trigger mood disorders in humans. Sepsis represents one such stressor, and survivors often suffer long term from psychiatric morbidity. We hypothesized that sepsis leads to lasting changes in neural circuits involved in stress integration, altering affective behavior and the stress response. To investigate this hypothesis, sepsis was induced in male C57Bl/6 mice using cecal ligation and puncture (CLP), and control mice underwent sham surgery. Mice recovered from acute illness within 2 weeks, after which they exhibited increased avoidance behavior and behavioral despair compared with sham, with behavioral changes observed more than 5 weeks after recovery. Sepsis survivors also showed evidence of enhanced hypothalamic-pituitary-adrenal (HPA) axis activity, with increased corticosterone after a novel stressor and increased adrenal weight. In the brain, sepsis survivor mice showed decreased stress-induced cfos mRNA and increased glucocorticoid receptor immunoreactivity specifically in the ventral hippocampus, a brain region known to coordinate emotional behavior and HPA axis activity. We conclude that murine sepsis survivors exhibit a behavioral neuroendocrine syndrome of negative affective behavior and HPA axis hyperactivity, which could be explained by ventral hippocampal dysfunction. These findings could contribute to our understanding of the human post-intensive care syndrome.