An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

PURPOSE: Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. METHODS: This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. RESULTS: The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. CONCLUSIONS: This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Abdominal CT metrics in 17,646 patients reveal associations between myopenia, myosteatosis, and medical phenotypes: a phenome-wide association study.

BACKGROUND: Deep learning facilitates large-scale automated imaging evaluation of body composition. However, associations of body composition biomarkers with medical phenotypes have been underexplored. Phenome-wide association study (PheWAS) techniques search for medical phenotypes associated with biomarkers. A PheWAS integrating large-scale analysis of imaging biomarkers and electronic health record (EHR) data could discover previously unreported associations and validate expected associations. Here we use PheWAS methodology to determine the association of abdominal CT-based skeletal muscle metrics with medical phenotypes in a large North American cohort. METHODS: An automated deep learning pipeline was used to measure skeletal muscle index (SMI; biomarker of myopenia) and skeletal muscle density (SMD; biomarker of myosteatosis) from abdominal CT scans of adults between 2012 and 2018. A PheWAS was performed with logistic regression using patient sex and age as covariates to assess for associations between CT-derived muscle metrics and 611 common EHR-derived medical phenotypes. PheWAS P values were considered significant at a Bonferroni corrected threshold (α = 0.05/1222). FINDINGS: 17,646 adults (mean age, 56 years ± 19 [SD]; 57.5% women) were included. CT-derived SMI was significantly associated with 268 medical phenotypes; SMD with 340 medical phenotypes. Previously unreported associations with the highest magnitude of significance included higher SMI with decreased cardiac dysrhythmias (OR [95% CI], 0.59 [0.55-0.64]; P < 0.0001), decreased epilepsy (OR, 0.59 [0.50-0.70]; P < 0.0001), and increased elevated prostate-specific antigen (OR, 1.84 [1.47-2.31]; P < 0.0001), and higher SMD with decreased decubitus ulcers (OR, 0.36 [0.31-0.42]; P < 0.0001), sleep disorders (OR, 0.39 [0.32-0.47]; P < 0.0001), and osteomyelitis (OR, 0.43 [0.36-0.52]; P < 0.0001). INTERPRETATION: PheWAS methodology reveals previously unreported associations between CT-derived biomarkers of myopenia and myosteatosis and EHR medical phenotypes. The high-throughput PheWAS technique applied on a population scale can generate research hypotheses related to myopenia and myosteatosis and can be adapted to research possible associations of other imaging biomarkers with hundreds of EHR medical phenotypes. FUNDING: National Institutes of Health, Stanford AIMI-HAI pilot grant, Stanford Precision Health and Integrated Diagnostics, Stanford Cardiovascular Institute, Stanford Center for Digital Health, and Stanford Knight-Hennessy Scholars.

Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status.

Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.

Predictive Role of Leptin Receptor (Ob-R) Overexpression in Patients with Early Breast Cancer Receiving Neoadjuvant Systemic Treatment.

The primary aim of this retrospective study was to investigate the correlation between the immunohistochemical expression of Ob-R (leptin receptor) with pCR (pathological complete response) in early breast cancer patients receiving neoadjuvant systemic treatment (NST). A total of 100 women with breast cancer receiving NST (2017-2020) followed by surgical resection were retrospectively obtained. Demographic parameters and clinicopathological factors (e.g., treatment modalities, immunohistochemistry (IHC), and cancer subtype) were obtained from the patient's clinical records. In the analyzed breast cancer cohort, high expression of Ob-R was found in 52% of tumors and there was a significantly higher incidence in the HER2+ and TNBC subgroups. Overall, a significantly greater percentage of patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients (57.7% vs. 27.1%; p = 0.002). This result was observed in most breast cancer subtypes. In patients with HER2+ breast cancer, there was no difference in Ob-R expression in relation to the HR status. Ob-R cell positivity was significantly higher in younger breast cancer patients (p = 0.008), those who were premenopausal (p = 0.011), and in those with a BMI > 25 kg/m2 (p = 0.019). A significantly greater percentage of early breast cancer patients with Ob-R positive tumors achieved pCR compared with Ob-R negative patients. Furthermore, breast cancer patients with positive Ob-R expression were significantly younger than those with negative Ob-R expression. This association was not explained by differences in BMI between young and old patients.

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

BACKGROUND: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. PATIENTS AND METHODS: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. RESULTS: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia. CONCLUSIONS: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

Contextualizing pertuzumab approval in the treatment of HER2-positive breast cancer patients.

The use of adjuvant pertuzumab in HER2-positive early-stage breast cancer has recently been approved by the EMA on the basis of data from the APHINITY trial. Accordingly, we have produced this opinion article with the aim of putting the study data in perspective against other add-on therapeutic strategies, to clarify methodological or statistical doubts about the study, and to define the population of high-risk patients with hormone receptor-negative breast cancer that we agree, in general, should be treated. With this approval, physicians must be well prepared to place the APHINITY study data in context. It is now up to each country to ratify the EMA-approved indications and to agree on reimbursement, and doctors must optimize their use based on knowledge and discussion with patients.

Clima organizacional y satisfacción del usuario externo en los servicios de hospitalización del Instituto Nacional de Salud del Niño, 2017 / Organizational climate and satisfaction of the external user in the hospitalization services of the Instituto Nacional de Salud del Niño, 2017

Introducción. El clima organizacional dentro de las instituciones de salud y la satisfacción del paciente se utilizan para evaluar y mejorar la calidad de los servicios de salud. Objetivo. Determinar el clima organizacional y la satisfacción del usuario externo sobre la atención medica recibida en los servicios de hospitalización del Instituto Nacional Salud del Niño (INSN). Métodos. En el año 2017 se aplicó una encuesta para calificar el clima organizacional a los trabajadores de los servicios de hospitalización del Departamento de Medicina del INSN. La satisfacción del usuario externo se midió mediante la encuesta SERVQUAL aplicada a los usuarios externos. Resultados. La calificación del clima organizacional fue de 76,3%, considerada como mejorable; y la satisfacción global del usuario externo fue de 64,4%. El clima organizacional en las dimensiones de identidad, comunicación organizacional y estructura lograron el calificativo de saludable y la dimensión remuneración obtuvo el calificativo de no saludable. La dimensión mejor valorada por los usuarios externos fue: ¿durante su hospitalización recibió visita médica todos los días?; y la menos valorada: ¿los trámites para el alta fueron rápidos?. Conclusión. La calificación global del clima organizacional fue de 76,3% y la satisfacción global del usuario externo fue de 64,4% en el INSN.

Introduction. The organizational climate within health institutions and patient satisfaction are used to evaluate and improve the quality of health services. Objective. Determine the organizational climate and the satisfaction of the external user regarding the medical care received in the hospitalization services of the Instituto Nacional Salud del Niño (INSN). Methods. In the year 2017 a survey was applied to qualify the organizational climate to the workers of the hospitalization services of the Department of Medicine of the INSN. The satisfaction of the external user was measured through the SERVQUAL survey applied to external users. Results. The qualification of the organizational climate was 76,3%, considered as improvable; and the overall satisfaction of the external user was 64,4%. The organizational climate in the dimensions of identity, organizational communication and structure achieved the qualification of healthy and the remuneration dimension obtained the qualification of unhealthy. The dimension best valued by external users was: during your hospitalization did you receive a medical visit every day? and the least valued: were the procedures for discharge high?. Conclusion. The overall rating of the organizational climate was 76,3% and the overall satisfaction of the external user was 64,4% in the INSN.

Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies.

BACKGROUND: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients. OBJECTIVE: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice. METHODS: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered. RESULTS: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02-12.25), median OS 21.9 months (95% CI: 17.2-26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8-50.7). Median time to PR was 3.8 months (95% CI: 3.86-5.99) and to CR 8.2 months (95% CI: 4.75-9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05) Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment.

In silico and in vitro analysis of small breast epithelial mucin as a marker for bone marrow micrometastasis in breast cancer.

Molecular signatures associated with malignant phenotype would be useful for detection of micrometastatic carcinoma cells. The small breast epithelial mucin (SBEM) gene is predicted to code for a low molecular weight glycoprotein. To evaluate its potential role as a marker for bone marrow (BM) micrometastasis in breast cancer (BC) patients, we have studied in silico and in vitro expression profiles of SBEM gene. Digital SBEM expression in libraries obtained from normal and neoplastic tissues and cell-lines (CL) were displayed and counted on the SAGE Anatomic Viewer. Profiles for cytokeratin-19 and mammaglobin (hMAM), commonly targets used for detection of disseminated BC cells were obtained and compared with SBEM data. Human breast and haematopoietic cancer CL and normal BM were examined by RT-PCR for SBEM and hMAM. Bioinformatics tools were used to gain further insights about the biological role of SBEM in normal breast and BC. Genes with expression patterns in breast libraries correlating with SBEM were identified using two-dimensional display. SBEM tag was detected in 40 libraries (21 BC; 8 non-cancerous breast tissues). Intermediate to high expression was found on 15/21 BC libraries and 7/8 non-tumor breast tissue. SBEM tag count was correlated with ERBB2 (0.662), hMAM (0.409), and RRM2 (-0.379). A model system based on RT-PCR for SBEM mRNA was highly sensitive and specific in order to detect isolated tumor cells. Our results demonstrate that SBEM mRNA may be an imp ortant marker for targeting BC micrometastasis.

Severidad al ingreso a las Unidades de Cuidados Intensivos Neonatales / Income severity of Neonatal Intensive Care Units

Objetivos: Identificar la severidad al ingreso en las Unidades de Cuidados Intensivos Neonatales (UCI neo) del grupo participante en el estudio multicéntrico y comparar la severidad al ingreso con la duración de la estancia, mortalidad, oxigenoterapia y soporte nutricional. Material y Métodos: Se realizó un estudio descriptivo, prospectivo y multicéntrico en 3 UCI neo, nivel IV, en Lima, Perú. Entre enero y mayo del 2002 se tomaron datos de los pacientes ingresados durante dos meses consecutivos en cada UCI neo participante, que equivale aproximadamente a un 20% de los neonatos ingresados el año anterior. se utilizó la segunda versión del Score for Neonatal Acute Physiology (SNAP II) con su extensión perinatal (SNAPPE II), y se recopiló información sobre estancia hospitalartia, mortalidad, oxigenoterapia y soporte nutricional. Resultados: De un total de 216 neonatos, 12 tuvieron criterios de exclusión. De los 204 incluidos para el análisis, 57 (28%) tuvieron un puntaje SNAP II > 10, el cual estuvo relacionado con una mayor estancia hospitalaria, el doble de riesgo de mortalidad y una mayor demanda de Ventilación Mecánica; no hubo diferencia significativa en el peso al egreso, ni en el inicio o incremento de la alimentación oral, en comparación con los neonatos que tuvieron un puntaje SNAP II > 10 fue de 31%. Conclusiones: La severidad al ingreso a las UCI neo puede ser cuantificada fácilmente con un puntaje como el SNAP II y permite comparar desenlaces en lugares diferentes. La calificación de este puntaje permite seleccionar los neonatos con más severidad, y puede predecir una estancia hospitalaria más prolongada, un riesgo de mortalidad aumentado, y una mayor demanda de ventilación mecánica.

Introduction: The measurement of illness severity on admission to Neonatal Intensive Care Unit (NICU) permits more appropriate outcome classification, use of resources, and therefore, the effectiveness of these units. Material and Methods: We carried out a descriptive, prospective multi-center study at three NICUs, level IV, in Lima, Peru. We used the Score for Neonatal Acute Physiology (SNAP II) to capture illness severity on admission for a sequential cohort of all newborn infants admitted to the 3 neonatal intensive care units. Data on patient characteristics and outcomes of the patients were obtaines in each NICU paticipating, during a period of two months of data collection between January and June 2002. Results: The three NICUs at Lima cared form 216 patients in two months, which is equivalent to about 20% from last year. After exclusion of 12 patients because them have died or left the NICU before 24 hours of admission, we anlyzed 204 newborns. Fifty seven on them (28%) had a significant severity, that is to say SNAP II >_ 10. These high severity patients had and increased length of hospital stay, higher mortality risk, and greater use of resources such as Mechanical Ventilation. There were no significant differences in weight achieved by discharge, nor in the timing and escalation of the oral feeding, when comparing newborns with a SNAP II less than 10 points. For SNAP II > 10, the positive predictive for mortality is 23% and their negative predictive value is 90%. Conclusions: Illness severity for newborns can be quantified easily using a scale like the SNAP II. Such scores allow for risk adjusted comparisons of outcomes among different NICUs. The quantitative scoring allows identification of newborns with greater severity, a group that, in every NICU, tend to have longer hospital styays, an increased mortality risk, and greater demand for mechanical ventilation.