Narrative Review of Multidisciplinary Management of Central Nervous Involvement in Patients with HER2-Positive Metastatic Breast Cancer: Focus on Elderly Patients.

The tumor biology of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) promotes the development of central nervous system (CNS) metastases, with 25% of patients with HER2-positive BC developing CNS metastases. Furthermore, the incidence of HER2-positive BC brain metastases has increased in the last decades, likely because of the improved survival with targeted therapies and better detection methods. Brain metastases are detrimental to quality of life and survival and represent a challenging clinical problem, particularly in elderly women, who comprise a substantial proportion of patients diagnosed with BC and often have comorbidities or an age-related decline in organ function. Treatment options for patients with BC brain metastases include surgical resection, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy, and targeted agents. Ideally, local and systemic treatment decisions should be made by a multidisciplinary team, with input from several specialties, based on an individualized prognostic classification. In elderly patients with BC, additional age-associated conditions, such as geriatric syndromes or comorbidities, and the physiologic changes associated with aging, may impact their ability to tolerate cancer therapy and should be considered in the treatment decision-making process. This review describes the treatment options for elderly patients with HER2-positive BC and brain metastases, focusing on the importance of multidisciplinary management, the different points of view from the distinct disciplines, and the role of oncogeriatric and palliative care in this vulnerable patient group.

Breast cancer, placing drug interactions in the spotlight: is polypharmacy the cause of everything?

Breast cancer is the most prevalent and lethal cancer among women. Forty-one percent of cases occur in people ≥ 70 years, hindering their treatment given its comorbidities and polypharmacy (PP). Potential drug–drug interactions (PDDI) were analyzed in elderly breast cancer patients between daily and oncospecific treatments and their associations with Age, BMI, Mini Nutritional Assessment (MNA), Frailty categorization, PP, and adverse effects. Patients/methods A cohort of 77 patients ≥ 70 years with breast cancer who underwent a Comprehensive Geriatric Assessment (CGA) were included. Clinical characteristics were collected using medical records. PDDI between treatments were analyzed using two databases. Data were assessed using linear regression, Chi-square, Mann–Whitney U, and Kruskal–Wallis tests. Finally, a multivariate logistic regression model was built and tested to predict adverse effects. Results From 719 PDDI, 530 (74%) were moderate (r2 = 0.72) and the median number of drugs during oncospecific treatment (r2 = 0.73) was 9 (range 3–26). Overall, 59 patients (77%) had adverse effects associated with Frailty categorization and MNA (p < 0.05). The distribution of major, moderate, minor, and total PDDI was associated with PP at CGA and during oncospecific treatment (p < 0.05). Moreover, it was verified that Frailty categorization protects from adverse effects given the intervention made at CGA. Conclusions CGA should be applied in oncologic elderly patients to assess clinical outcomes and categorize them according to their frailty but also to analyze PDDI. Furthermore, we encourage the use of the model in clinical practice for predicting the occurrence of adverse effects, improving therapeutic conciliation (AU)

Breast cancer, placing drug interactions in the spotlight: is polypharmacy the cause of everything?

PURPOSE: Breast cancer is the most prevalent and lethal cancer among women. Forty-one percent of cases occur in people ≥ 70 years, hindering their treatment given its comorbidities and polypharmacy (PP). Potential drug-drug interactions (PDDI) were analyzed in elderly breast cancer patients between daily and oncospecific treatments and their associations with Age, BMI, Mini Nutritional Assessment (MNA), Frailty categorization, PP, and adverse effects. PATIENTS/METHODS: A cohort of 77 patients ≥ 70 years with breast cancer who underwent a Comprehensive Geriatric Assessment (CGA) were included. Clinical characteristics were collected using medical records. PDDI between treatments were analyzed using two databases. Data were assessed using linear regression, Chi-square, Mann-Whitney U, and Kruskal-Wallis tests. Finally, a multivariate logistic regression model was built and tested to predict adverse effects. RESULTS: From 719 PDDI, 530 (74%) were moderate (r2 = 0.72) and the median number of drugs during oncospecific treatment (r2 = 0.73) was 9 (range 3-26). Overall, 59 patients (77%) had adverse effects associated with Frailty categorization and MNA (p < 0.05). The distribution of major, moderate, minor, and total PDDI was associated with PP at CGA and during oncospecific treatment (p < 0.05). Moreover, it was verified that Frailty categorization protects from adverse effects given the intervention made at CGA. CONCLUSIONS: CGA should be applied in oncologic elderly patients to assess clinical outcomes and categorize them according to their frailty but also to analyze PDDI. Furthermore, we encourage the use of the model in clinical practice for predicting the occurrence of adverse effects, improving therapeutic conciliation.

Valoración geriátrica y factores pronósticos de mortalidad en pacientes muy ancianos con neumonía extrahospitalaria / Geriatric Assessment and Prognostic Factors of Mortality in Very Elderly Patients With Community-Acquired Pneumonia

Introducción: Analizar la relación de parámetros Obtenidos en la valoración geriátrica con la mortalidad en ancianos con neumonía extrahospitalaria (NEH) en una unidad de geriatría de agudos (UGA). Método: Un total de 456 pacientes (≥ 75 años). Variables: edad, sexo, procedencia, antecedentes, nivel de conciencia, frecuencia cardíaca y respiratoria, presión arterial, datos de laboratorio, derrame pleural, afectación multilobar, capacidad funcional (independencia para actividades de la vida diaria) previa al ingreso (índice de Lawton [IL], índice de Barthel previo [IBp]) y en el momento del ingreso (IBi), función cognitiva (test de Pfeiffer [TP]), comorbilidad (índice de Charlson [ICh]) y nutrición (proteínas totales, albúmina). Resultados: Los 110 pacientes que fallecieron durante el ingreso (24,2%) tuvieron mayor edad (86,6 ± 6,4 vs 85,1 ± 6,4; p < 0,04), mayor comorbilidad (ICh 2,35 ± 1,61 vs 2,08 ± 1,38; p < 0,083), menor capacidad funcional (IL: 0,49 ± 1,15 vs 1,45 ± 2,32; p < 0,001; IBp: 34,6 ± 32,9 vs 54,0 ± 34,1; p < 0,001; IBi: 5,79 ± 12,5 vs 20,5 ± 22,9; p < 0,001), mayor porcentaje de pérdida funcional al ingreso (85,9 ± 23,2 vs 66,4 ± 28,6; p < 0,0001), mayor deterioro cognitivo (TP: 7,20 ± 3,73 vs 5,10 ± 3,69; p < 0,001) y mayor desnutrición (albúmina 2,67 ± 0,54 vs 2,99 ± 0,49; p < 0,001). Hubo también mayor mortalidad con alteración de conciencia (49,2%; p < 0,01), taquipnea (33,3%; p < 0,01), taquicardia (44,4%; p < 0,002), urea elevada (31,8; p < 0,001), anemia (44,7%; p < 0,02), derrame pleural (42,9%; p < 0,002) y afectación multilobar (43,2%; p < 0,001). En el análisis multivariado resultaron significativos: edad ≥ 90 años (OR: 3,11 [IC 95%: 1,31-7,36]), alteración de conciencia (3,19 [1,66-6,15]), hematocrito < 30% (2,87 [1,19-6,94]), derrame pleural (3,77 [1,69-8,39]) y afectación multilobar (2,76 [1,48-5,16]). El sexo femenino y la capacidad funcional más conservada previa (IL ≥ 5) y en el momento del ingreso (IBi ≥ 40) fueron protectores de mortalidad (0,40 [0,22-0,70]; 0,09 [0,01-0,81] y 0,11 [0,02-0,51]). Conclusiones: Los parámetros de valoración geriátrica y las variables clínicas habituales estuvieron relacionados con la mortalidad

Introduction: To assess the relationship between the parameters obtained in the geriatric assessment and mortality in elderly people with community-acquired pneumonia in an acute care geriatric unit.MethodsFour hundred fifty-six patients (≥ 75 years). Variables: age, sex, referral source, background, consciousness level, heart rate, breathing rate, blood pressure, laboratory data, pleural effusion, multilobar infiltrates, functional status (activities of daily living) prior to admission [Lawton index (LI), Barthel index (BIp)] prior to and at admission (BIa), cognitive status [Pfeiffer test (PT)], comorbidity [Charlson index (ChI)] and nutrition (total protein, albumin). Results: A hundred ten patients died (24.2%) during hospitalization. These patients were older (86.6 ± 6.4 vs 85.1 ± 6.4, P < 0.04), had more comorbidity (ChI 2.35 ± 1.61 vs 2.08 ± 1.38; P < 0.083), worse functional impairment [(LI: 0.49 ± 1.15 vs 1.45 ± 2.32, P < 0.001) (BIp: 34.6 ± 32.9 vs 54.0 ± 34.1, P < 0.001) (BIa: 5.79 ± 12.5 vs 20.5 ± 22.9, P V< 0.001)], a higher percentage of functional loss at admission (85.9±23.2 vs 66.4 ± 28.6; P < 0.0001), worse cognitive impairment (PT: 7.20 ± 3.73 vs 5.10 ± 3.69, P < 0.001) and malnutrition (albumin 2.67 ± 0.54 vs 2.99 ± 0.49, P < 0.001). Mortality was higher with impaired consciousness [49.2% (P < 0.01)], tachypnea [33.3% (P < 0.01)], tachycardia [44.4% (P < 0.002), high urea levels [31.8 (P < 0.001)], anemia [44.7% (P < 0.02)], pleural effusion [42.9% (P < 0.002)], and multilobar infiltrates [43.2% (P < 0.001)]. In the multivariate analysis, variables associated with mortality were: age ≥ 90 years [OR: 3.11 (95% CI: 1.31-7.36)], impaired consciousness [3.19 (1.66-6.15)], hematocrit < 30% [2.87 (1.19-6.94)], pleural effusion [3.77 (1.69-8.39)] and multilobar infiltrates [2.76 (1.48-5.16)]. Female sex and a preserved functional status prior (LI ≥ 5) and during admission (BIa ≥ M40) were protective of mortality [0.40 (0.22-0.70), 0.09 (0.01-0.81) and 0.11 (0.02-0.51)]. Conclusions: Geriatric assessment parameters and routine clinical variables were associated with mortality

Geriatric assessment and prognostic factors of mortality in very elderly patients with community-acquired pneumonia.

INTRODUCTION: To assess the relationship between the parameters obtained in the geriatric assessment and mortality in elderly people with community-acquired pneumonia in an acute care geriatric unit. METHODS: Four hundred fifty-six patients (≥75years). VARIABLES: age, sex, referral source, background, consciousness level, heart rate, breathing rate, blood pressure, laboratory data, pleural effusion, multilobar infiltrates, functional status (activities of daily living) prior to admission [Lawton index (LI), Barthel index (BIp)] prior to and at admission (BIa), cognitive status [Pfeiffer test (PT)], comorbidity [Charlson index (ChI)] and nutrition (total protein, albumin). RESULTS: A hundred ten patients died (24.2%) during hospitalization. These patients were older (86.6±6.4 vs 85.1±6.4, P<.04), had more comorbidity (ChI 2.35±1.61 vs 2.08±1.38; P<.083), worse functional impairment [(LI: 0.49±1.15 vs 1.45±2.32, P<.001) (BIp: 34.6±32.9 vs 54.0±34.1, P<.001) (BIa: 5.79±12.5 vs 20.5±22.9, P<.001)], a higher percentage of functional loss at admission (85.9±23.2 vs 66.4±28.6; P<.0001), worse cognitive impairment (PT: 7.20±3.73 vs 5.10±3.69, P<.001) and malnutrition (albumin 2.67±0.54 vs 2.99±0.49, P<.001). Mortality was higher with impaired consciousness [49.2% (P<.01)], tachypnea [33.3% (P<.01)], tachycardia [44.4% (P<.002), high urea levels [31.8 (P<.001)], anemia [44.7% (P<.02)], pleural effusion [42.9% (P<.002)], and multilobar infiltrates [43.2% (P<.001)]. In the multivariate analysis, variables associated with mortality were: age ≥90years [OR: 3.11 (95%CI: 1.31 to 7.36)], impaired consciousness [3.19 (1.66 to 6.15)], hematocrit <30% [2.87 (1.19 to 6.94)], pleural effusion [3.77 (1.69 to 8.39)] and multilobar infiltrates [2.76 (1.48 to 5.16)]. Female sex and a preserved functional status prior (LI≥5) and during admission (BIa≥40) were protective of mortality [0.40 (0.22 to 0.70), 0.09 (0.01 to 0.81) and 0.11 (0.02 to 0.51)]. CONCLUSIONS: Geriatric assessment parameters and routine clinical variables were associated with mortality.

[Paraoxonase 1 gene 192 polymorphism, physical activity and lipoprotein in women]. / Polimorfismo 192 del gen de la paraoxonasa 1, actividad física y lipoproteínas de alta densidad en la mujer.

BACKGROUND AND OBJECTIVE: Regular physical activity is associated with an increase in high-density lipoprotein cholesterol (HDL-C), whose antioxidant and protective effect for coronary artery disease is well known. Paraoxonase-1 (PON1) is an enzyme related with the antioxidant activity of HDL. The PON1 gene has several genetic polymorphisms; one of them locates in codon 192, whose alleles Q and R are associated with low and high PON1-activity, respectively. The objective of this study was to determine whether physical activity has different effects on the lipid profile in women depending on the PON1-192 genotype. PATIENTS AND METHOD: Six hundred and fifty-one women from a cross-sectional risk-factor study were included in this retrospective cohort study. We analyzed anthropometrical characteristics, serum lipids and lipoproteins, blood pressure, PON1-192 genotypes and menopause. We used the Minnesota Leisure Time Physical Activity Questionnaire to assess the daily physical activity in the previous year. RESULTS: Women included in the study were classified into three categories by tertiles of daily physical activity. Although no differences in the lipidic parameters were found, we observed an increasing trend in HDL-C concentration and a decreasing trend in log-triglyceride-to-HDL-cholesterol ratio with increasing physical activity in RR homozygous women. In subgroup analyses, we observed that the association of high physical activity and increased HDL-C concentration or decreased log-triglyceride-to-HDL-cholesterol ratio were exclusive for RR homozygous non-menopausal women. CONCLUSIONS: The results of this study suggest that PON1-192 polymorphism could modulate the effect of physical activity on HDL-C concentration and on triglyceride-rich lipoprotein catabolism in non-menopausal women.