RESUMO
PURPOSE: The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). METHODS: We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). RESULTS: Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). CONCLUSION: SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience.
RESUMO
PURPOSE: Breast cancer-related arm lymphedema (BCRL) is a common chronic and debilitating condition that involves accumulation of lymphatic fluid in the arm or hand. Limited data are available on BCRL in African American women. Lack of physical activity (PA) and poor physical functioning (PF) are both associated with increased morbidity and mortality among breast cancer survivors. We examined the association of BCRL with PA and PF among African American breast cancer survivors. METHODS: 323 African American women who previously participated in a case-only study in three states (TN, GA, SC) completed a survivorship-focused questionnaire (mean: 4.2 years post-diagnosis) in 2015-2016. Validated measures were used to determine BCRL, PF, and PA. Adjusted binary logistic regression models estimated ORs and 95% CIs for the association of BCRL and meeting PA guidelines (≥ 150 min/week), while multinomial logistic regression was used for PF and PA (minutes/week) categorized based on tertiles. RESULTS: Approximately 32% reported BCRL since diagnosis; 25.4% reported BCRL in the last 12-months. About 26% and 50% reported that BCRL interfered with exercise and ability to do daily activities, respectively. The mean PF among those with BCRL was 51.0(SD:29.0) vs. 68.5(SD:30.1) among those without BCRL. BCRL was associated with lower PF (adjusted-OR for tertile 2: 2.12(95% CI:1.03-4.36) and adjusted-OR for tertile 1: 2.93(95% CI:1.44-5.96)). CONCLUSIONS: BCRL was associated with lower PF among long-term African American breast cancer survivors. Continued monitoring by health care professionals and increased education and behavioral interventions to support PA and improved PF among survivors living with BCRL are warranted.
Assuntos
Braço , Negro ou Afro-Americano , Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Sobreviventes de Câncer , Exercício Físico , Humanos , Feminino , Pessoa de Meia-Idade , Negro ou Afro-Americano/estatística & dados numéricos , Exercício Físico/fisiologia , Idoso , Neoplasias da Mama/complicações , Linfedema Relacionado a Câncer de Mama/etiologia , Inquéritos e Questionários , Adulto , Linfedema/etiologia , Modelos LogísticosRESUMO
Biomass and waste power generation holds the promise to secure electricity supply for a growing population and mitigate global warming simultaneously. Along with the increasing commission and installation of biomass/waste power units (BWPUs) across the globe, some BWPUs failures have been observed, including the cancellation of planned/commissioned BWPUs and the termination of those in operation before reaching their natural retirement. While empirical evidence suggests that factors like feedstock accessibility and policy instruments might affect the feasibility and performance of BWPUs, there is a lack of comprehensive investigation about why some BWPUs failed at the global scale. To fill this knowledge gap, this study quantifies the hazard ratio of BWPUs via a parametric survival analysis using a panel dataset covering a total of 12,829 BWPUs (relying on woody, non-woody, and waste biomass as raw feedstocks) located in 164 countries/regions worldwide for the period of 2001-2021. The analytical results suggest that large unit size is conducive to BWPUs failure, while feedstock accessibility and the implementation of policy instruments (including Feed-in-Tariff and carbon pricing) could largely reduce the hazard ratio of BWPUs, with varying impacts on BWPUs at the planned/commissioned stage or the operation stage, located in developed or developing countries. Our findings not only shed additional light on the fate of BWPUs, which is crucial to enriching our understanding about the development of the bioenergy sector worldwide, but also provide salient empirical evidence for policy-making in terms of ensuring feedstock accessibility, overcoming diseconomies of scale, and making fiscal instruments available and transparent to boost the confidence of investors and entrepreneurs in support of BWPUs development.
Assuntos
Biomassa , Centrais ElétricasRESUMO
Importance: Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective: To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants: A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions: Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures: The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. Results: A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance: Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02927249.
Assuntos
Anti-Inflamatórios não Esteroides , Aspirina , Neoplasias da Mama , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Sobreviventes de Câncer/estatística & dados numéricos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Seguimentos , Adulto Jovem , Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Asiático/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Brancos/estatística & dados numéricos , Estados Unidos/epidemiologia , Canadá/epidemiologia , Administração OralRESUMO
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting. METHODS: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P. RESULTS: Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations. CONCLUSION: The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores da Aromatase , Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Fulvestranto , Piperazinas , Piridinas , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Piridinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Pessoa de Meia-Idade , Fulvestranto/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/análise , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Adulto , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso de 80 Anos ou mais , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Intervalo Livre de ProgressãoRESUMO
Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC. SIGNIFICANCE: Nonmalignant luminal progenitor cells expressing pleiotrophin promote angiogenesis by activating NRP1 and induce a prometastatic tumor microenvironment in inflammatory breast cancer, providing potential therapeutic targets for this aggressive breast cancer subtype.
Assuntos
Proteínas de Transporte , Citocinas , Neoplasias Inflamatórias Mamárias , Neovascularização Patológica , Microambiente Tumoral , Humanos , Feminino , Citocinas/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Animais , Camundongos , Neovascularização Patológica/patologia , Neovascularização Patológica/metabolismo , Neoplasias Inflamatórias Mamárias/patologia , Neoplasias Inflamatórias Mamárias/metabolismo , Neoplasias Inflamatórias Mamárias/genética , Neuropilina-1/metabolismo , Neuropilina-1/genética , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Metástase Neoplásica , AngiogêneseRESUMO
We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.
Assuntos
Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Humanos , Metformina/uso terapêutico , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Incidência , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Estudos Prospectivos , Estados Unidos/epidemiologia , Fatores de Risco , Enfermeiras e Enfermeiros/estatística & dados numéricos , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND & AIMS: Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in patients with breast cancer. However, they were not typically combined to develop an overall risk score, which can identify patients at high risk of death and prioritize patients in need of dietary and lifestyle interventions. Thus, we aimed to develop a novel composite body composition risk score (B-Score). METHODS: We included 3105 patients with stage II or III breast cancer at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we assessed areas and radiodensity of muscle and adipose tissue at the third lumber vertebrae. We considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent prognostic factors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (<40.1 cm2/m2), high SATI (≥75.7 cm2/m2), and high SAT radiodensity (≥-97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. RESULTS: Mean (standard deviation) age was 53.9 (11.8) years, 70.3% were Non-Hispanic White, and 60.5% were stage II. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). CONCLUSIONS: More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may improve risk stratification and inform dietary and lifestyle interventions following breast cancer diagnosis.
Assuntos
Neoplasias da Mama , Sarcopenia , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/complicações , Músculo Esquelético/patologia , Fatores de Risco , Composição Corporal , Tecido Adiposo/patologia , Prognóstico , Estudos Retrospectivos , Sarcopenia/etiologiaRESUMO
Urban trees have attracted increasing attention to serve as a green prescription for addressing various challenges facing human society like climate change and environmental deterioration. However, without healthy growth of urban trees, they cannot service any environmental, social, and economic benefits in a sustainable manner. By monitoring the canopy development, the tree growth dynamics in different urban habitats can be detected and appropriate management approaches can be executed. Using the Kowloon Peninsula, Hong Kong, as a case, this study explores how remote sensing data can help monitor and understand the impacts of heterogeneous urban habitats on tree canopy dynamics. Four algorithms based on WorldView-2 satellite image are compared to optimize the canopy segmentation. Then the individual tree canopy is integrated with Sentinel-2 satellite data to obtain canopy growth dynamics for each season from 2016 to 2020. Three indicators are applied to reflect tree canopy status, including the fluorescence correction vegetation index (FCVI, tracking leaf chlorophyll density), the soil adjusted total vegetation index (SATVI, measuring the density of woody branches and twigs), and the normalised difference phenology index (NDPI, capturing canopy water content). And four heterogeneous habitats where urban trees stand are specified. The results revealed that urban trees show varying canopy growth status, in a descending order from natural terrains, parks, residential lands, to road verges, suggesting that urban habitats curtail trees' growth significantly. Additionally, two super-typhoons in 2017 and 2018, respectively, caused serious damages to tree canopy. Relevant resiliency of tree varies, echoing the sequence of canopy growth status with those in road verges the least resilient. This study shows how remote sensing data can be used to provide a better understanding of long-term tree canopy dynamics across large-scale heterogeneous urban habitats, which is key to monitoring and maintaining the health and growth of urban trees.
Assuntos
Tecnologia de Sensoriamento Remoto , Árvores , Humanos , Estudos Longitudinais , Ecossistema , SoloRESUMO
BACKGROUND: Olive oil consumption may reduce breast cancer risk, but it is unclear whether olive oil is beneficial for breast cancer prevention in populations outside of Mediterranean regions, namely in the U.S., where the average consumption of olive oil is low compared with Mediterranean populations. We examined whether olive oil intake was associated with breast cancer risk in two prospective cohorts of U.S. women. METHODS: We used multivariable-adjusted time-varying Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence interval (CI) for breast cancer among 71,330 (Nurses' Health Study, 1990-2016) and 93,295 women (Nurses' Health Study II, 1991-2017) who were free of cancer at baseline. Diet was assessed by a validated semi-quantitative food frequency questionnaire every 4 years. RESULTS: During 3,744,068 person-years of follow-up, 9,638 women developed invasive breast cancer. The multivariable-adjusted HR (95% CI) for breast cancer among women who had the highest consumption of olive oil (>1/2 tablespoon/d or >7 g/d) compared with those who never or rarely consumed olive oil, was 1.01 (0.93, 1.09). Higher olive oil consumption was not associated with any subtype of breast cancer. CONCLUSION: We did not observe an association between higher olive oil intake and breast cancer risk in two large prospective cohorts of U.S. women, whose average olive oil consumption was low. Prospective studies are needed to confirm these findings and to further investigate whether different varieties of olive oil (e.g., virgin and extra virgin olive oil) may play a role in breast cancer risk.
Assuntos
Neoplasias da Mama , Enfermeiras e Enfermeiros , Humanos , Feminino , Azeite de Oliva , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Estudos Prospectivos , Óleos de PlantasRESUMO
BACKGROUND: The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints. METHODS: We examined serial samples from 40 older women with triple-negative or hormone receptor-positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks). RESULTS: CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02). CONCLUSIONS: Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.
Assuntos
Neoplasias da Mama , Hematopoiese Clonal , Humanos , Feminino , Idoso , Hematopoiese Clonal/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Estudos Retrospectivos , Hematopoese/genética , MutaçãoRESUMO
PURPOSE: Physical activity (PA) is associated with many health benefits. While PA has been associated with reduced mortality after breast cancer diagnosis in many studies, few studies have examined the role of PA in breast cancer survival among underserved and minority populations, including Black women. We investigated PA in association with mortality among Black predominantly low-income breast cancer survivors in the Southern Community Cohort Study (SCCS). METHODS: Study participants were women diagnosed with incident breast cancer (n = 949) in the SCCS, which is a prospective cohort study of predominantly low-income adults aged 40-79 years recruited from 12 Southeastern states between 2002 and 2009. Participants completed a detailed baseline questionnaire, with annual follow-up for mortality via registry linkages. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of pre-diagnosis PA (measured via a validated questionnaire) with all-cause and breast cancer-specific mortality. RESULTS: Breast cancer survivors had a mean age of 61.1 years and most (79.3%) had a household income of < $25,000. In adjusted models, higher levels of total PA (MET-hours/day) were inversely associated with all-cause mortality with HRs (95% CIs): 0.79 (0.59-1.06), 0.66 (0.49-0.90), and 0.60 (0.43-0.84), for Q2, Q3, and Q4 (reference: Q1), respectively, ptrend ≤ 0.01. A similar inverse association was found for breast cancer-specific mortality. CONCLUSION: Higher levels of pre-diagnosis PA were associated with improved survival among low-income Black breast cancer survivors. Resources to reduce barriers to PA participation and increase support for education and intervention efforts to promote PA among Black women are needed.
Assuntos
Neoplasias da Mama , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Estudos Prospectivos , Neoplasias da Mama/diagnóstico , Exercício Físico , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at high risk for poor outcomes and are underrepresented in clinical trials. The ADVANCE (ADjuVANt Chemotherapy in the Elderly) trial evaluated the feasibility of two neo/adjuvant chemotherapy regimens in parallel-enrolling cohorts of older patients with human epidermal growth factor receptor 2-negative breast cancer: cohort 1-triple-negative; cohort 2-hormone receptor-positive. MATERIALS AND METHODS: Adults age ≥ 70 years with stage I-III breast cancer warranting neo/adjuvant chemotherapy were enrolled. Cohort 1 received weekly carboplatin (area under the curve 2) and weekly paclitaxel 80 mg/m2 for twelve weeks; cohort 2 received weekly paclitaxel 80 mg/m2 plus every-three-weekly cyclophosphamide 600 mg/m2 over twelve weeks. The primary study endpoint was feasibility, defined as ≥80% of patients receiving ≥80% of intended weeks/doses of therapy. All dose modifications were applied per clinician discretion. RESULTS: Forty women (n = 20 per cohort) were enrolled from March 25, 2019 through August 3, 2020 from three centers; 45% and 35% of patients in cohorts 1 and 2 were age > 75, respectively. Neither cohort achieved targeted thresholds for feasibility. In cohort 1, eight (40.0%) met feasibility (95% confidence interval [CI] = 19.1-63.9%), while ten (50.0%) met feasibility in cohort 2 (95% CI = 27.2-72.8). Neutropenia was the most common grade 3-4 toxicity (cohort 1-65%, cohort 2-55%). In cohort 1, 80% and 85% required ≥1 dose holds of carboplatin and/or paclitaxel, respectively. In cohort 2, 10% required dose hold(s) for cyclophosphamide and/or 65% for paclitaxel. DISCUSSION: In this pragmatic pilot examining chemotherapy regimens in older adults with breast cancer, neither regimen met target goals for feasibility. Developing efficacious and tolerable regimens for older patients with breast cancer who need chemotherapy remains an important goal. CLINICALTRIALS: gov Identifier: NCT03858322.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Idoso , Neoplasias da Mama/tratamento farmacológico , Carboplatina , Projetos Piloto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel , Quimioterapia Adjuvante , CiclofosfamidaRESUMO
A 72-Year-Old Woman with Fatigue and Shortness of BreathA 72-year-old woman presented for evaluation of fatigue, dyspnea on exertion, and weight loss. How do you approach the evaluation, and what is the most likely diagnosis?
Assuntos
Ecocardiografia , Fadiga , Feminino , Humanos , Idoso , Dispneia , Diagnóstico DiferencialRESUMO
BACKGROUND: Research on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival. METHODS: 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors). RESULTS: Mean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality. CONCLUSIONS: High fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.
Assuntos
Neoplasias da Mama , Diabetes Mellitus , Humanos , Feminino , Pessoa de Meia-Idade , LDL-Colesterol , Neoplasias da Mama/terapia , Fatores de Risco , Triglicerídeos , HDL-Colesterol , GlucoseRESUMO
BACKGROUND & AIMS: Computed tomography (CT) scans can measure quantity and distribution of adipose tissue, which are associated with breast cancer prognosis. As a novel prognostic marker, radiodensity of adipose tissue has been examined in multiple cancer types, but never in breast cancer. Lower density indicates larger adipocytes with greater lipid content, whereas higher density can reflect inflammation, fibrosis, vascularity, or even metabolic changes; and both may impact breast cancer prognosis. METHODS: We included 2868 nonmetastatic patients with breast cancer diagnosed between January 2005 and December 2013 at Kaiser Permanente Northern California, an integrated healthcare system. From CT scans at diagnosis, we assessed the radiodensity of subcutaneous (SAT) and visceral adipose tissue (VAT) at the third lumbar vertebra and categorized their radiodensity into three levels: low (<1 standard deviation [SD] below the mean), middle (mean ± 1 SD), and high (>1 SD above the mean). Using multivariable Cox proportional hazards regression with adjustment for clinicopathological characteristics including body mass index, we calculated hazard ratios (HRs [95% confidence intervals]) for the associations of adipose tissue radiodensity with overall mortality and breast-cancer-specific mortality. RESULTS: Median age at diagnosis of breast cancer was 56.0 years, most (63.3%) were non-Hispanic White and nearly half (45.6%) were stage II. Compared to middle SAT radiodensity, high SAT radiodensity was significantly associated with increased risk of overall mortality (HR: 1.45 [1.15-1.81]), non-significantly with breast-cancer-specific mortality (HR: 1.32 [0.95-1.84]). Neither low SAT radiodensity nor high or low VAT radiodensity was significantly associated with overall or breast-cancer-specific mortality. CONCLUSIONS: High radiodensity of SAT at diagnosis of nonmetastatic breast cancer was associated with increased risk of overall mortality, independent of adiposity and other prognostic factors. Considering both radiodensity and quantity of adipose tissue at different locations could deepen understanding of the role of adiposity in breast cancer survival.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Adiposidade , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Prognóstico , ObesidadeRESUMO
BACKGROUND: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diets with higher insulinemic potential increase the risk of invasive breast cancer. OBJECTIVES: We aimed to prospectively evaluate the association between a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer. METHODS: We prospectively followed 76,686 women from the Nurses' Health Study (NHS; 1984-2016) and 93,287 women from the Nurses' Health Study II (NHSII; 1991-2017). Diet was assessed by food-frequency questionnaires every 4 y. The insulinemic potential of diet was evaluated using the previously established EDIH based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential of the diet. Covariates included reproductive, hormonal, and anthropometric factors (height and BMI at age 18 y); race; socioeconomic status; total alcohol intake; total caloric intake; and physical activity. RESULTS: During 4,216,106 person-years of follow-up, we documented 10,602 breast cancer cases (6689 NHS, 3913 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIH quintile (Q) were at higher breast cancer risk (HRQ5 vs. Q1 = 1.15; 95% CI: 1.07, 1.24; P-trend < 0.01). Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association between EDIH and breast cancer was observed for ER-negative tumors (HRQ5 vs. Q1 = 1.21; 95% CI: 1.00, 1.46; P-trend = 0.02). Among tumor molecular subtypes, the strongest associations were observed for human epidermal growth factor receptor 2 (HER2)-enriched tumors (HRQ5 vs. Q1 = 1.62; 95% CI: 1.01, 2.61; P-trend = 0.02). CONCLUSIONS: A dietary pattern contributing to hyperinsulinemia and insulin resistance was associated with greater breast cancer risk, especially ER-negative and HER2-enriched tumors. Our findings suggest that dietary modifications to reduce insulinemic potential may reduce the risk of breast cancer.
Assuntos
Neoplasias da Mama , Hiperinsulinismo , Resistência à Insulina , Feminino , Humanos , Adolescente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Dieta , Ingestão de Energia , Fatores de RiscoRESUMO
BACKGROUND: The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiologic cohorts. METHODS: We followed women with invasive breast cancer from the Nurses' Health Studies with available data on tumor PTEN expression (n = 4,111) and PIK3CA mutation (n = 2,930). PTEN expression was evaluated by IHC and digitally scored (0%-100%). Pyrosequencing of six hotspot mutations of PIK3CA was performed. RESULTS: We found loss of PTEN expression (≤10%) occurred in 17% of cases, and PIK3CA mutations were detected in 11% of cases. After adjusting for clinical and lifestyle factors, PTEN loss was not associated with worse breast cancer-specific mortality among all samples [HR, 0.85; 95% confidence intervals (CI), 0.71-1.03] or among estrogen receptor (ER)-positive tumors (HR, 0.99; 95% CI, 0.79-1.24). However, among ER-negative tumors, PTEN loss was associated with lower breast cancer-specific mortality (HR, 0.68; 95% CI, 0.48-0.95). PIK3CA mutation was not strongly associated with breast cancer-specific mortality (HR, 0.89; 95% CI, 0.67-1.17). Compared with tumors without PTEN loss and without PIK3CA mutation, those with alterations (n = 540) were not at higher risk (HR, 1.07; 95% CI, 0.86-1.34). However, women with both PTEN loss and PIK3CA mutation (n = 38) were at an increased risk of breast cancer-specific mortality (HR, 1.65; 95% CI, 0.83-3.26). CONCLUSIONS: In this large epidemiologic study, the PTEN-mortality association was more pronounced for ER-negative tumors, and the joint PTEN loss and PIK3CA mutation may be associated with worse prognosis. IMPACT: Further studies with a larger sample of ER-negative tumors are needed to replicate our findings and elucidate underlying mechanisms.
Assuntos
Neoplasias da Mama , Enfermeiras e Enfermeiros , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Estrogênio/metabolismoRESUMO
China, the world's largest CO2 emitter, is making every effort to transition to a low-carbon economy and fulfill its part of a concerted global commitment to combating climate change. In tandem with decarbonizing energy and industries, feasible supplementary measures are urgently needed to help remove anthropogenic CO2 from the atmosphere. A burgeoning literature has emphasized the CO2 removal capability of land re-naturalization (such as afforestation and wetland restoration), thereby regarding cognate land-use conversions as Nature-based Solutions (NbS) and potential climate policy options. However, little empirical evidence exists concerning the effectiveness of different land re-naturalization pathways (such as converting wetlands to forests or agricultural lands to grasslands), and it also remains unclear how NbS alternatives (i.e., land-use conversions resulting in negative CO2 emission) and non-NbS options (i.e., land-use conversions resulting in positive CO2 emission) could affect the social cost of carbon (SCC), a conventional measurement for prescribing carbon mitigation approaches. This study aims to fill in this knowledge gap via embedding NbS into the dynamic integrated climate-economics (DICE) model to quantify their impacts on the SCC. Using the Pearl River Delta region (south China) as a case study for the temporal horizon during 2000-2020, we find that both positive and negative CO2 fluxes have been brought by different natural/semi-natural land conversions, affecting the SCC correspondingly. A total of 7 out of 17 types of land-use conversions could be identified as feasible NbS interventions, including forest restoration, forest-to-wetland, grassland-to-forest, grassland-to-wetland, grassland-to-cropland, cropland-to-forest, and cropland-to-wetland conversions, which could reduce the SCC values (comparing 2020 base-year with 2000 base-year) by 0.0132, 0.0009, 0.0033, 0.0030, 0.0001, 0.0082, and 0.0001 (USD/tCO2), respectively. While the SCC is mainly determined by energy and industrial structure, the overall effect of NbS is larger than the sum of land urbanization and non-NbS land-use conversions. Via embedding the real-world inter-dynamics of land-use conversions into the SCC quantification, this study presents a pioneer assessment of the impacts of NbS on the SCC in an integrated framework, sheds important insights into the effectiveness of NbS, and offers practical implications for policy-makers to devise comprehensive policies covering all feasible CO2 abatement options.
Assuntos
Dióxido de Carbono , Carbono , Sequestro de Carbono , Mudança Climática , Conservação dos Recursos Naturais , FlorestasRESUMO
Human health risks brought by fine atmospheric particles raise scholarly and policy awareness about the role of urban trees as bio-filters of air pollution. While a large number of empirical studies have focused on the characteristics of vegetation leaves and their effects on atmospheric particle retention, the dry deposition of particles on branches, which plays a significant role in capturing and retaining particles during the defoliation period and contributes substantially to total removal of atmospheric particles, is under-investigated. To fill in this knowledge gap, this case study examined the dry deposition velocities (Vd) of submicron particulate matters (PM1) on the branches of six common deciduous species in Shanghai (China) using laboratory experiments. And the association between Vd and key branch anatomical traits (including surface roughness, perimeter, rind width proportion, lenticel density, peeling, and groove/ridge characteristics) was explored. It was found that surface roughness would increase Vd, as a rougher surface significantly increases turbulence, which is conducive to particle diffusion. By contrast, peeling, branch perimeter, and lenticel density would decrease Vd. Peeling represents the exfoliated remains on the branch surfaces which may flutter considerably with airflow, leading to particle resuspension and low Vd. When branch perimeter increases, the boundary layer of branches thickens and a wake area appears, increasing the difficulty of particles to reach branch surface, and reducing Vd. While lenticels can increase the roughness of branch surface, their pointy shape would uplift airflow and cause a leeward wake area, lowering Vd. This finely wrought study contributes to a better understanding of branch dry deposition during leaf-off seasons and potential of deciduous trees serving as nature-based air filters all year round in urban environments.