The author discusses 3 variables that assess different aspects of social relationships—social support, social integration, and negative interaction. The author argues that all 3 are associated with health outcomes, that these variables each influence health through different mechanisms, and that associations between these variables and health are not spurious findings attributable to our personalities. This argument suggests a broader view of how to intervene in social networks to improve health. This includes facilitating both social integration and social support by creating and nurturing both close (strong) and peripheral (weak) ties within natural social networks and reducing opportunities for negative social interaction. Finally, the author emphasizes the necessity to understand more about who benefits most and least from socialconnectedness interventions.

/pdf/social-relationships-and-health-3l9d7bp4y3.pdf

Social relationships and health.

https://cdr.lib.unc.edu/downloads/nz8061892

Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013

Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

Insulin and insulin-like growth factors (IGFs) are well known as key regulators of energy metabolism and growth. There is now considerable evidence that these hormones and the signal transduction networks they regulate have important roles in neoplasia. Epidermiological, clinical and laboratory research methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling. Pharmacological strategies under study include the use of novel receptor-specific antibodies, receptor kinase inhibitors and AMP-activated protein kinase activators such as metformin. There is evidence that insulin and IGF signalling may also be relevant to dietary and lifestyle factors that influence cancer risk and cancer prognosis. Recent results are encouraging and have justified the expansion of many translational research programmes.

Insulin and insulin-like growth factor signalling in neoplasia

Breast cancer (BC) prognosis and outcome are adversely affected by increased body weight, obesity, and the obesity-associated type 2 diabetes. Hyperinsulinemia, common in the obese state, has been associated with higher risk of death and recurrence in BC. Up to 80% of breast cancers overexpress the insulin receptor (INSR), which correlates with worse prognosis. To directly probe the role of insulin signaling in mammary tumorigenesis, we generated the MMTV-driven polyoma middle T (PyMT) and ErbB2/Her2 BC mouse models, respectively, with coordinate mammary epithelium restricted deletion of the INSR. In both models, deletion of either one or both copies of the INSR in the mammary gland led to a marked delay in tumor onset and burden, including in mice fed to mimic conditions of human obesity. Phenotypic characterization and longitudinal monitoring of mouse tumours, and ex vivo analysis of mammary cells from the generated mouse models revealed that tumor initiation, rather than progression and metastasis, were impacted by INSR deletion. Mechanistically, INSR deficiency in non-transformed mammary epithelial cells led to diminished bioenergetic fitness. The similarity of phenotypes elicited by the deletion of one or both copies of INSR indicates that there is a dose-dependent threshold for the contribution of INSR to mammary tumorigenesis.

/pdf/insulin-receptor-loss-impairs-mammary-tumorigenesis-in-mice-39sojtx5.pdf

Insulin Receptor Loss Impairs Mammary Tumorigenesis in Mice

BACKGROUND
Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT).


METHODS
In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area.


RESULTS
Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89).


CONCLUSION
Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.

/pdf/body-composition-and-endometrial-cancer-outcomes-1qpenfoe.pdf

Body composition and endometrial cancer outcomes.

1028 Background: Tissue biopsy is recommended to confirm breast cancer (BC) recurrence. Liquid biopsy [including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA)] is a non-invasive approach for detecting cancer that may provide information to identify treatment choices and replace invasive biopsies. This ongoing study aims to assess the concordance between tissue and liquid biopsy testing in subjects presenting with suspicion of distant recurrence from BC. Methods: Patients with suspected metastatic BC were enrolled; tumour characteristics and treatment were recorded. Blood samples were collected within 30 days before tissue biopsy, or within 7-28 days after tissue biopsy and before any systemic or radiation treatment. Samples were shipped to EPIC Sciences and processed within 96 hours; after plasma isolation, nucleated cells were plated; slides and plasma were banked. CTCs were identified using Epic Sciences digital imaging and machine learning algorithms. Single-cell isolation for genomic ctDNA analysis was performed. Cell free DNA was analyzed using a validated NGS panel to detect ctDNA alterations. The presence of metastases was classified as suspicious, highly suspicious, definitely metastatic BC or other by the treating oncologist based on the patient's clinical presentation and biopsy pathology results. Epic Sciences classified samples into similar categories based on CTC and ctDNA assay results. These classifications were performed independently. Sensitivity of the Epic Sciences methodology to detect metastatic BC (as determined by the treating oncologist), and its false positive rate were calculated. Results: 100 patients were enrolled from June 2020 to October 2022; shipping delays precluded EPIC assays in six patients; 94 patients were analyzed. Of 83 cases deemed suspicious, highly suspicious, or definitely metastatic BC by the treating oncologist, 61 were also deemed so by Epic Sciences (sensitivity of 73.5%, 95% confidence interval, CI 63.1% - 81.9%). Of 66 cases assigned as suspicious, highly suspicious, or definitely metastatic BC by the Epic Sciences, 4 had new primary cancers (3 lung cancer, 1 hepatocarcinoma), for a false positive rate of 6.1% (95% CI 1.9% - 15.0%). One additional case was classified as un-specified adenocarcinoma (possibly breast) by the treating oncologist; resolution awaits further follow-up. Conclusions: Preliminary results show that 73.5% of distant BC recurrences were correctly identified by liquid biopsy. A small number of false positive results occurred in patients with other new primary cancers. Additional analyses with CTC characterization are ongoing. [Table: see text]

Concordance between liquid and tissue biopsy in participants with newly diagnosed recurrent breast cancer.

Abstract An interim analysis is commonly used in phase III superiority trials to compare treatment arms, with the goal of terminating exposure of patients to ineffective or unsafe drugs or to identify highly effective therapies for earlier public disclosure. Traditionally, interim analyses have been designed to identify early evidence of extremely large benefit of the experimental approach, potentially leading to early dissemination of effective treatments. Increasingly, interim analysis has also involved analysis of futility, which may lead to early termination of a trial that will not yield additional useful information. This presents an important challenge in early stage hormone receptor–positive breast cancer, where recurrence often occurs late, with a steady annual event rate up to 20 years. Early analysis of events may miss late treatment effects that can be observed only with longer follow-up. We discuss approaches to futility analysis in adjuvant clinical trials in hormone receptor–positive breast cancer, the role of the Data Safety Monitoring Committee in such analyses, considerations of the potential harms vs benefits of treatment, and the risks of continuing vs early termination of a trial.

/pdf/the-futility-of-futility-analyses-in-adjuvant-trials-in-2wz39qno.pdf

Marguerite Ennis

Papers

Insulin Receptor Loss Impairs Mammary Tumorigenesis in Mice

Body composition and endometrial cancer outcomes.

Concordance between liquid and tissue biopsy in participants with newly diagnosed recurrent breast cancer.

The Futility of Futility Analyses in Adjuvant Trials in Hormone Receptor–Positive Breast Cancer