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PURPOSE: Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease. METHODS: 3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell fraction within the TME was calculated by QuantiSeq and MCP-counter. RESULTS: Compared to BrT, more LvM samples had a high TMB (≥ 10 mutations/Mb) and fewer LvM samples had PD-L1+ expression. Evaluation of the TME revealed that LvM sites harbored lower infiltration of adaptive immune cells, such as CD4+, CD8+, and regulatory T-cells compared with the BrT foci. We saw differences in innate immune cell infiltration in LvM compared to BrT, including neutrophils and NK cells. CONCLUSIONS: LvMs are less likely to express PD-L1+ tumor cells but more likely to harbor high TMB as compared to BrTs. Unlike AxMs, LvMs represent a more immunosuppressed TME and demonstrate lower gene expression associated with adaptive immunity compared to BrTs. These findings suggest biopsy site be considered when interpreting results that influence ICI use for treatment and further investigation of immune composition and biomarkers expression by metastatic site.
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Antígeno B7-H1 , Biomarcadores de Tumor , Neoplasias de la Mama , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Mutación , Metástasis Linfática , Persona de Mediana Edad , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
PURPOSE: Financial reimbursement programs (FRPs) offset out-of-pocket (OOP) expenses from therapeutic clinical trial (TCT) participation. The study explores patients' experience in TCTs after enrollment in a FRP at two academic medical centers, including barriers and opportunities to improve trial participation. METHODS: From May 2019 to January 2020, adults diagnosed with cancer and eligible for TCTs and FRP were recruited from the Improving Patient Access to Cancer Clinical Trials randomized trial at the University of California San Francisco and University of Southern California. Patients with income ≤ 700% of national poverty guidelines were eligible. Semistructured interviews were conducted in patients' preferred language. Qualitative analysis was performed by site and preferred language by two independent coders. RESULTS: Of 65 trial patients, 53 participated (38%, University of California San Francisco; 62%, USC). The median age was 59 (IQR, 46-65) years, and 58% were female. Nearly half (49%) identified as Latinx/Hispanic compared with 32% non-Hispanic White, 10% Asian, 4% Black, 1% Native American, and 4% Others. A third were non-English speakers, 42% had college education or more, and 55% were retired/unemployed. Most common malignancies were gastrointestinal (42%), breast (19%), and genitourinary (13%), and 66% had metastatic disease. Patients experienced long travel time (1-4.5 hours) among 57% and financial toxicity from OOP costs (68%). High acceptability of the FRP was reported (81%). Although 30% of patients reported willingness to discuss finances of cancer treatment/trial with physicians, majority (87%) preferred discussion with social workers or TCT staff. Proposed modifications to TCTs included decentralization, recruitment strategies, voucher structure, and established rates for OOP expenses. CONCLUSION: Patients' experience with TCTs reveal financial and logistical stressors that may be lessened by the Improving Patient Access to Cancer Clinical Trial reimbursement program. FRPs may address inequities in clinical trial access among low-income and diverse populations.
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Neoplasias , Mecanismo de Reembolso , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros Médicos Académicos , Hispánicos o Latinos , Neoplasias/terapia , Gastos en Salud , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Exploring the relationship between various neurotransmitters and breast cancer cell growth has revealed their likely centrality to improving breast cancer treatment. Neurotransmitters play a key role in breast cancer biology through their effects on the cell cycle, epithelial mesenchymal transition, angiogenesis, inflammation, the tumor microenvironment and other pathways. Neurotransmitters and their receptors are vital to the initiation, progression and drug resistance of cancer and progress in our biological understanding may point the way to lower-cost and lower-risk antitumor therapeutic strategies. This review discusses multiple neurotransmitters in the context of breast cancer. It also discusses risk factors, repurposing of pharmaceuticals impacting neurotransmitter pathways, and the opportunity for better integrated models that encompass exercise, the intestinal microbiome, and other non-pharmacologic considerations. Neurotransmitters' role in breast cancer should no longer be ignored; it may appear to complicate the molecular picture but the ubiquity of neurotransmitters and their wide-ranging impacts provide an organizing framework upon which further understanding and progress against breast cancer can be based.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Neurotransmisores/metabolismo , Transición Epitelial-Mesenquimal , Microambiente TumoralRESUMEN
BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.
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Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Estudios Retrospectivos , Pruebas Genéticas/métodos , Genes BRCA2 , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Mutación de Línea GerminalRESUMEN
Introduction: There is accumulating information of the effects of chemotherapy and weight changes on the gut microbiome of breast cancer patients. Methods: In this 1-year follow-up study, we investigated gut microbiome of 33 breast cancer patients who donated fecal samples at baseline and after completion of treatment. We compared alpha diversity and mean taxa abundance at baseline and absolute taxa abundance changes (final-baseline) by treatment (16 neoadjuvant [neoADJ], 13 adjuvant [ADJ], 4 no chemotherapy [noC]) and specific chemotherapy agent using Wilcoxon rank sum and negative binomial mixed model (NBMM) analysis. Results: All four gut alpha diversity measures changed in association with chemotherapy treatment; they increased in the neoADJ (+16.4% OTU p = 0.03; +51.6% Chao1 p = 0.03; +7.0% Shannon index p = 0.02; +11.0% PD whole tree p = 0.09) but not in the ADJ and noC group (ADJ+noC). The difference in Chao1 index change between groups was statistically significant (pneoADJ vs. ADJ+noC=0.04). Wilcoxon p values of 0.03-0.003 were observed for five taxa. In NBMM analysis, changes in taxa abundance differed (Bonferroni-adjusted p ≤ 0.0007) for two Bacteroidetes taxa (g_Alistipes, f_S24-7) and two Firmicutes taxa (g_Catenibacterium, g_Eubacterium). NBMM analysis results remained unchanged with adjustment for weight changes. Alpha diversity changes were also found by receipt of chemotherapy agents. Consistent increases in alpha diversity were observed among those treated with TCHP (OTU p = 0.009; Chao1 p = 0.02; Shannon p = 0.02; PD whole tree p = 0.05) but not AC, Taxol or Herceptin. Those treated with TCHP or Herceptin showed increases in Verrucomicrobia (g_Akkermansia) but decreases of Bacteroidetes(g_Alistipes); the differences in changes in taxa abundance were statistically significant. Conclusion: Results from this pilot longitudinal study support an effect of chemotherapy, particularly neoADJ on the gut microbiome of breast cancer patients even after adjustment for weight changes. Further investigations are needed to confirm these findings in larger studies and with longer follow-up and to assess the impact of these microbiome changes on patient outcome.
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PURPOSE: Cancer clinical trial participants face considerable indirect costs associated with participation, such as travel and lodging, which may contribute to poor enrollment. Here, we report the findings in IMproving Patient Access to Cancer clinical Trials, a pilot feasibility study investigating the efficacy of offering a financial reimbursement program (FRP) during a therapeutic clinical trial discussion with or without additional outreach in improving patient enrollment. METHODS: Study participants for this study were recruited at two National Cancer Institute-designated comprehensive cancer centers (CCCs) from April 8, 2019, to September 19, 2019. Eligible participants were adults with a cancer diagnosis being approached to consider enrollment in a clinical trial. Participants were randomly assigned 1:1 to receive no follow-up (usual care) or a follow-up telephone call to facilitate FRP utilization stratified by study site. The target enrollment was 132 patients, with 66 patients in each study arm. The primary outcome was the consent rate to the multisite interventional study on the FRP among participants enrolling in clinical trials. RESULTS: The study had a 78% consent rate and enrolled a total of 132 participants, of whom 51% were non-White compared with 28% of CCC treatment clinical trial participants in 2019. No difference in enrollment in clinical trials between the two study arms was observed as the proportion of enrollment was 70% for both study arms. The most common reason for not enrolling in a clinical trial was due to ineligibility determined through screening procedures (75%). CONCLUSION: The current study observed that implementation of FRP at CCCs is feasible and serves a diverse patient population. Future studies will measure the impact of programs on overall clinical trial accrual and among racial/ethnic minorities.
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Neoplasias , Navegación de Pacientes , Adulto , Estudios de Factibilidad , Humanos , National Cancer Institute (U.S.) , Neoplasias/epidemiología , Neoplasias/terapia , Proyectos Piloto , Estados UnidosRESUMEN
Metastatic breast cancer (mBC) patients have a high risk of progression and face poor prognosis overall, with about one third (34%) surviving five years or more. In rare instances (2-4% of cases) patients with mBC have ERBB2 (HER2) activating mutations but are ERBB2 non-amplified. Neratinib is a potent, irreversible inhibitor that binds HER2 and inhibits downstream signaling. We used the previously validated high-definition single cell assay (HDSCA) workflow to investigate the clinical significance of the liquid biopsy in ERBB2 mutant, non-amplified, post-menopausal mBC patients starting neratinib and fulvestrant combination therapy. Characterization with a comprehensive liquid biopsy methodology (HDSCA) included genomic analysis of both the cell-free DNA (cfDNA) and single circulating tumor cells (CTCs) to monitor tumor evolution and identify potential mutational variants unique to the patient's clinical response. A limited series of five sequentially enrolled patients presented here were from the MutHER ( https://www.clinicaltrials.gov , NCT01670877) or SUMMIT ( https://www.clinicaltrials.gov , NCT01953926) trials. Patients had an average of 5.4 lines of therapy before enrollment, variable hormone receptor status, and ERBB2 mutations at diagnosis and during treatment. CTC enumeration alone was not sufficient to predict clinical response. Treatment pressure was shown to lead to an observable change in CTC morphology and genomic instability (GI), suggesting these parameters may inform prognosis. Single cell copy number alteration (CNA) analysis indicated that the persistence or development of a clonal population of CTCs during treatment was associated with a worse response. Hierarchical clustering analysis of the single cells across all patients and timepoints identified distinct aberrant regions shared among patients, comprised of 26 genes that are similarly affected and may be related to drug resistance. Additionally, the genomic analysis of the cfDNA, identified new mutations in ERBB2, PIK3CA, and TP53 that arose likely due to treatment pressure in a patient with poor response, further providing insights on the dynamics of the cancer genome over the course of therapy. The data presented in this small cohort study demonstrates the feasibility of real-time molecular profiling of the cellular and acellular fractions of the liquid biopsy using the HDSCA methodology. Additional studies are necessary to determine the potential use of morphometric and genomic analysis as a prognostic tool to advance personalized oncology.
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STUDY OBJECTIVES: Poor sleep quality affects nearly one-third of breast cancer survivors and is associated with insulin resistance. The purpose of this secondary analysis was to examine the effects of a 16-week exercise intervention on patient-reported sleep quality among breast cancer survivors and assess whether changes in patient-reported sleep quality were associated with cardiometabolic biomarkers. We explored Hispanic ethnicity as a moderator of the effects of exercise on patient-reported sleep quality. METHODS: Breast cancer survivors who were overweight or obese were randomized to exercise (n = 50) or usual care (n = 50). The 16-week intervention included aerobic and resistance exercise. Patient-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and biomarkers of cardiometabolic health were assessed at baseline and post-intervention. Within- and between-group differences were assessed using general linear models repeated-measures analyses of variance and mixed-model repeated-measure analysis, respectively. Associations between changes in PSQI and cardiometabolic biomarkers were computed using Pearson correlations. Linear mixed-models were used to evaluate effect modification by ethnicity. RESULTS: Participants were 52 ± 10.4 years old, and over half were of Hispanic ethnicity. As compared to usual care, PSQI global scores improved significantly in the exercise group (mean between-group difference -2.2; 95% CI -3.2 to -0.6). Change in PSQI was inversely associated with changes in all cardiometabolic biomarkers (p < 0.01) among the exercise group. Ethnicity was found to moderate the effects of exercise training on global sleep quality (p < 0.001). CONCLUSIONS: An aerobic and resistance exercise intervention effectively improved patient-reported sleep quality in breast cancer survivors. Hispanic ethnicity as a moderator showed greater improvement in patient-reported sleep indicating Hispanic versus non-Hispanic breast cancer survivors may derive larger sleep benefits. CLINICAL TRAIL INFORMATION: NCT01140282.
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Neoplasias de la Mama , Supervivientes de Cáncer , Enfermedades Cardiovasculares , Entrenamiento de Fuerza , Adulto , Biomarcadores , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Ejercicio Físico , Femenino , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/terapia , Sobrepeso/terapia , Medición de Resultados Informados por el Paciente , Calidad de Vida , SueñoRESUMEN
BACKGROUND: Exercise can profoundly affect physical fitness and quality of life in breast cancer survivors; however, few studies have focused on minorities. This secondary analysis examines Hispanic ethnicity as a moderator of the effects of a 16-week aerobic and resistance exercise intervention on physical fitness and quality of life in breast cancer survivors. METHODS: Eligible breast cancer survivors (n = 100) were randomized to exercise (n = 50) or usual care (n = 50). The exercise intervention consisted of supervised moderate-vigorous aerobic and resistance exercise thrice weekly for 16 weeks. Physical fitness and quality of life were measured at baseline, post-intervention, and 28-week follow-up (exercise only). Linear mixed-models adjusted for baseline value of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity. RESULTS: The study sample included 57% Hispanic and 43% non-Hispanic breast cancer survivors. Hispanic breast cancer survivors were younger, less fit, and diagnosed with more advanced cancers compared with non-Hispanic breast cancer survivors (p < 0.001). Ethnicity was found to moderate the effects of exercise training on all physical fitness and quality-of-life measures including VO2max (8.4 mL/kg/min; 95% confidence interval (95% CI) 3.2 to 13.4), physical well-being (12.3; 95% CI 4.2 to 18.4), and emotional well-being (11.4; 95% CI 5.9 to 15.5). In all cases, Hispanics experienced larger benefits than non-Hispanics. CONCLUSIONS: Hispanic breast cancer survivors have poorer cardiorespiratory fitness, muscle strength, and quality-of-life and therefore may derive larger benefits from exercise than non-Hispanic breast cancer survivors. Clinical exercise interventions may attenuate existing health disparities among minority breast cancer survivors. IMPLICATION OF CANCER SURVIVORS: Here we report psychosocial and fitness-related disparities among Hispanic breast cancer survivors when compared with their non-Hispanic counterparts. Our exercise intervention highlights the importance of exercise for minority cancer survivors and the need for distinct, culturally tailored exercise intervention approaches to reduce psychosocial and fitness-related disparities among this understudied population of cancer survivors.
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Neoplasias de la Mama , Supervivientes de Cáncer , Entrenamiento de Fuerza , Neoplasias de la Mama/terapia , Etnicidad , Ejercicio Físico , Terapia por Ejercicio , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Aptitud Física , Calidad de VidaRESUMEN
BACKGROUND: Cancer treatment clinical trials face major challenges with patient recruitment. Strategies to address patient indirect costs associated with clinical trial participation may accelerate accrual overall. The current study examined the effect of the IMproving Patient Access to Clinical Trials (IMPACT) intervention on patient accrual to cancer treatment clinical trials at an academic medical center. The IMPACT intervention was an onsite patient navigator combined with a financial reimbursement program to address patient out of pocket costs and began on September 2018. METHODS: This analysis measured frequency of patient enrollment in cancer treatment clinical trials and available cancer treatment clinical trials per month between January 1, 2016 and March 31, 2020. An interrupted time-series analysis (ITSA) was conducted to estimate changes in patient enrollment attributable to the IMPACT intervention. RESULTS: During the study period, a mean of 69 patients enrolled in clinical trials per month (standard deviation (SD = 13), with 27 (SD = 7) in early phase vs 41 (SD = 12) in late phase clinical trials. The number of available clinical trials per month was 51 (SD = 2) overall, with 23 (SD = 1) in early phase vs 28 (SD = 1) in late phase context. A total of 3470 patients were enrolled in cancer treatment clinical trials during the evaluated time period, the majority of whom were men (1895, 55 %) and racially white (2267, 65 %). A statistically significant increase in the number of patients accrued as compared to the pre-intervention trend was observed; with approximately 1 additional patient accrued per month, with a larger effect on increase patient accrual for late phase clinical trials. DISCUSSION: This study observed that the IMPACT intervention accelerated clinical trial recruitment, especially among late phase clinical trials. Future research will examine strategies to leverage this infrastructure to optimize recruitment among underrepresented patients. POLICY SUMMARY: To improve clinical trial recruitment and ensure that trial results are representative of a diverse population it is critical for health policies consider patient out-of-pocket costs and potential reimbursement to alleviate financial burden associated with clinical trial participation. Furthermore, policies for facilitating clinical trial recruitment and participant retention should budget for and incorporate a navigation component to assist patients who may not be familiar with the healthcare system and available financial assistance.
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Neoplasias , Navegación de Pacientes , Femenino , Gastos en Salud , Humanos , Análisis de Series de Tiempo Interrumpido , Masculino , Neoplasias/terapia , Selección de PacienteRESUMEN
OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors. METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity. RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors. CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/epidemiología , Mama/patología , Microbioma Gastrointestinal/fisiología , Adulto , Factores de Edad , Anciano , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Índice de Masa Corporal , Neoplasias de la Mama/patología , Neoplasias de la Mama/fisiopatología , Estudios Transversales , ADN Bacteriano/aislamiento & purificación , Heces/microbiología , Femenino , Firmicutes/genética , Firmicutes/aislamiento & purificación , Humanos , Menarquia/fisiología , Persona de Mediana Edad , Paridad/fisiología , Proyectos Piloto , ARN Ribosómico 16S/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factores de RiesgoRESUMEN
PURPOSE: Breast density is an important risk factor for breast cancer and varies substantially across racial-ethnic groups. However, determinants of breast density in Vietnamese immigrants in the United States (US) have not been studied. We investigated whether reproductive factors, immigration history, and other demographic and lifestyle factors were associated with breast density in Vietnamese Americans. METHODS: We collected information on demographics, immigration history, and other lifestyle factors and mammogram reports from a convenience sample of 380 Vietnamese American women in California aged 40 to 70 years. Breast Imaging Reporting and Data System (BI-RADS) breast density was abstracted from mammogram reports. Multivariable logistic regression was used to investigate the association between lifestyle factors and having dense breasts (BI-RADS 3 or 4). RESULTS: All participants were born in Viet Nam and 82% had lived in the US for 10 years or longer. Younger age, lower body mass index, nulliparity/lower number of deliveries, and longer US residence (or younger age at migration) were associated with having dense breasts. Compared to women who migrated at age 40 or later, the odds ratios and 95% confidence intervals for having dense breasts among women who migrated between the ages of 30 and 39 and before age 30 were 1.72 (0.96-3.07) and 2.48 (1.43-4.32), respectively. CONCLUSIONS: Longer US residence and younger age at migration were associated with greater breast density in Vietnamese American women. Identifying modifiable mediating factors to reduce lifestyle changes that adversely impact breast density in this traditionally low-risk population for breast cancer is warranted.
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Asiático , Densidad de la Mama/etnología , Emigrantes e Inmigrantes , Estilo de Vida , Adulto , Anciano , Índice de Masa Corporal , Neoplasias de la Mama/epidemiología , California , Estudios Transversales , Emigración e Inmigración , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Paridad , Factores de Riesgo , Estados Unidos , Salud de la MujerRESUMEN
BACKGROUND: Adverse upper limb musculoskeletal effects occur after surgical procedures and radiotherapy for breast cancer and can interfere with activities of daily living. OBJECTIVE: The objective of this study was to examine the effects of a 16-week exercise intervention on shoulder function in women who are overweight or obese and have breast cancer. DESIGN: This study was a randomized controlled trial. SETTING: The study was performed at the Division of Biokinesiology and Physical Therapy at the University of Southern California. PARTICIPANTS: One hundred women with breast cancer were randomly allocated to exercise or usual-care groups. The mean (SD) age of the women was 53.5 (10.4) years, 55% were Hispanic white, and their mean (SD) body mass index was 33.5 (5.5) kg/m2. INTERVENTION: The 16-week exercise intervention consisted of supervised, progressive, moderate to vigorous aerobic and resistance exercise 3 times per week. MEASUREMENTS: Shoulder active range of motion, isometric muscular strength, and patient-reported outcome measures (including Disabilities of the Arm, Shoulder, and Hand and the Penn Shoulder Scale) were assessed at baseline, after the intervention, and at the 3-month follow-up (exercise group only). Differences in mean changes for outcomes were evaluated using mixed-model repeated-measures analysis. RESULTS: Compared with the usual-care group, the exercise group experienced significant increases in shoulder active range of motion (the mean between-group differences and 95% confidence intervals (CIs) were as follows: shoulder flexion = 36.6° [95% CI = 55.2-20.7°], external rotation at 0° = 23.4° [95% CI = 31.1-12.5°], and external rotation at 90° = 34.3° [95% CI = 45.9-26.2°]), improved upper extremity isometric strength, and improved Disabilities of the Arm, Shoulder, and Hand and Penn Shoulder Scale scores. LIMITATIONS: Limitations include a lack of masking of assessors after the intervention, an attention control group, and statistical robustness (shoulder function was a secondary end point). CONCLUSIONS: A 16-week exercise intervention effectively improved shoulder function following breast cancer treatment in women who were overweight or obese, who were ethnically diverse, and who had breast cancer.
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Neoplasias de la Mama/rehabilitación , Supervivientes de Cáncer/estadística & datos numéricos , Terapia por Ejercicio/estadística & datos numéricos , Obesidad/rehabilitación , Entrenamiento de Fuerza/estadística & datos numéricos , Actividades Cotidianas , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Femenino , Humanos , Persona de Mediana Edad , Obesidad/psicología , Rango del Movimiento Articular/fisiología , Articulación del HombroRESUMEN
IMPORTANCE: The Framingham Risk Score (FRS) is a valid method for predicting the 10-year risk of developing cardiovascular disease. Higher FRS is reported in patients with early-stage breast cancer who are overweight than in healthy, age-matched women, but whether exercise reduces FRS in this patient population is unclear. OBJECTIVE: To examine the effects of a 16-week aerobic and resistance exercise intervention on the FRS in women with early-stage breast cancer and with overweight condition or obesity. DESIGN, SETTING, AND PARTICIPANTS: This single-center, prospective randomized clinical trial included 100 women with stage I to III breast cancer who were sedentary, with overweight condition or obesity (body mass index of ≥25.0 or body fat of ≥30%), and completed cancer treatment within 6 months prior to enrollment. Participants were randomized to either the usual care or exercise group. Differences in mean changes for outcomes were evaluated using mixed-model repeated-measures analyses. Data were collected from August 1, 2012, through July 1, 2017. Data analysis, which followed the intention-to-treat approach, was performed from May 24 to October 2, 2018. INTERVENTIONS: The exercise group underwent supervised aerobic and resistance exercise sessions thrice weekly for 16 weeks. MAIN OUTCOMES AND MEASURES: The FRS was calculated for each participant using preset points for each of the 6 FRS categories: age, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes presence, and smoking status. RESULTS: In total, 100 women were randomized to either the exercise group (n = 50) or usual care group (n = 50). Of these women, 55 (55%) were of Hispanic white race/ethnicity and the mean (SD) age was 53.5 (10.4) years. The mean (SD) total FRS scores postintervention were 2.0 (1.5) in the exercise group and 13.0 (3.0) in the usual care group. The postintervention FRS was significantly reduced in the exercise group compared with the usual care group (mean, -9.5; 95% CI, -13.0 to -6.0), which corresponds to an 11% (95% CI, -15.0 to -5.0) decrease on the FRS-predicted 10-year risk of developing cardiovascular disease. CONCLUSIONS AND RELEVANCE: A 16-week supervised aerobic and resistance exercise intervention appeared to reduce the FRS-predicted 10-year risk of cardiovascular disease in women with early-stage breast cancer with overweight condition or obesity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01140282.
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Neoplasias de la Mama/terapia , Enfermedades Cardiovasculares , Terapia por Ejercicio , Adulto , Anciano , Neoplasias de la Mama/patología , Ejercicio Físico , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Obesidad/patología , Obesidad/terapia , Factores de RiesgoRESUMEN
BACKGROUND: Metabolic syndrome (MSY) is associated with an increased risk of cardiovascular disease, type 2 diabetes, and recurrence in breast cancer survivors (BCS). MSY is 1.5 times more common in Hispanic women compared with non-Hispanic women. Although exercise mitigates MSY in BCS, to the best of the authors' knowledge, few studies to date have focused on minorities. This secondary analysis examined ethnicity as a moderator of the effects of a 16-week aerobic and resistance exercise intervention on MSY, sarcopenic obesity, and serum biomarkers in BCS. METHODS: A total of 100 eligible BCS were randomized to exercise (50 BCS) or usual care (50 BCS). The exercise intervention promoted moderate to vigorous aerobic and resistance exercise 3 times a week for 16 weeks. MSY z scores, sarcopenic obesity, and serum biomarkers were measured at baseline, after the intervention, and at the 28-week follow-up (exercise group only). Linear mixed models adjusted for baseline values of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity. RESULTS: The study sample was 57% Hispanic BCS (HBCS) and 43% non-Hispanic BCS (NHBCS). HBCS were younger, of greater adiposity, and had been diagnosed with more advanced cancers compared with NHBCS (P<.001). Ethnicity was found to moderate the mean differences in exercise training on triglycerides (-36.4 mg/dL; 95% confidence interval [95% CI],-64.1 to -18.8 mg/dL), glucose (-8.6 mg/dL; 95% CI, -19.1 to -3.0 mg/dL), and C-reactive protein (-3.3 mg/L; 95% CI, -7.3 to -0.9 mg/L). CONCLUSIONS: HBCS appear to have poorer metabolic profiles and therefore may derive relatively larger metabolic changes from exercise compared with NHBCS. Clinical exercise interventions may attenuate existing health disparities across diverse groups of BCS.
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Neoplasias de la Mama/rehabilitación , Hispánicos o Latinos/estadística & datos numéricos , Entrenamiento de Fuerza/métodos , Sarcopenia/rehabilitación , Adulto , Anciano , Biomarcadores/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/etnología , Supervivientes de Cáncer , Ejercicio Físico , Femenino , Humanos , Persona de Mediana Edad , Obesidad/sangre , Obesidad/etiología , Obesidad/rehabilitación , Sarcopenia/sangre , Sarcopenia/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Exercise is an effective strategy to improve quality of life and physical fitness in breast cancer survivors; however, few studies have focused on the early survivorship period, minorities, physically inactive and obese women, or tested a combined exercise program and measured bone health. Here, we report the effects of a 16-week aerobic and resistance exercise intervention on patient-reported outcomes, physical fitness, and bone health in ethnically diverse, physically inactive, overweight or obese breast cancer survivors. METHODS: One hundred breast cancer survivors within 6 months of completing adjuvant treatment were assessed at baseline, post-intervention, and 3-month follow-up (exercise group only) for physical fitness, bone mineral density, serum concentrations of bone biomarkers, and quality of life. The exercise intervention consisted of moderate-vigorous (65-85% heart rate maximum) aerobic and resistance exercise thrice weekly for 16 weeks. Differences in mean changes for outcomes were evaluated using mixed-model repeated measure analysis. RESULTS: At post-intervention, the exercise group was superior to usual care for quality of life (between group difference: 14.7, 95% CI: 18.2, 9.7; p < 0.001), fatigue (p < 0.001), depression (p < 0.001), estimated VO2max (p < 0.001), muscular strength (p < 0.001), osteocalcin (p = 0.01), and BSAP (p = 0.001). At 3-month follow-up, all patient-reported outcomes and physical fitness variables remained significantly improved compared to baseline in the exercise group (p < 0.01). CONCLUSIONS: A 16-week combined aerobic and resistance exercise program designed to address metabolic syndrome in ethnically-diverse overweight or obese breast cancer survivors also significantly improved quality of life and physical fitness. Our findings further support the inclusion of supervised clinical exercise programs into breast cancer treatment and care. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010.
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Neoplasias de la Mama/rehabilitación , Supervivientes de Cáncer/estadística & datos numéricos , Ejercicio Físico/fisiología , Obesidad/rehabilitación , Entrenamiento de Fuerza , Adulto , Densidad Ósea/fisiología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Ejercicio Físico/psicología , Femenino , Humanos , Persona de Mediana Edad , Obesidad/psicología , Medición de Resultados Informados por el Paciente , Aptitud Física/fisiología , Aptitud Física/psicología , Calidad de Vida , Resultado del TratamientoRESUMEN
Endocrine therapy has historically formed the basis of treatment of metastatic hormone receptor-positive breast cancer. The development of endocrine resistance has led to the development of newer endocrine drug combinations. Use of the CDK4/6 inhibitors has significantly improved progression-free survival in this group of patients. There are multiple studies of the use of P13K inhibitors and mTOR inhibitors for use as subsequent lines of therapy, particularly for endocrine resistance. The optimal sequencing of therapy should be based on medical comorbidities, prior adjuvant therapies, quality of life, side-effect profile, and disease-free interval.
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Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Sistema Endocrino/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Humanos , Terapia Molecular Dirigida/métodos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Análisis de SupervivenciaAsunto(s)
Neoplasias de la Mama , Síndrome Metabólico , Entrenamiento de Fuerza , Sarcopenia , Biomarcadores , Humanos , Obesidad , Sobrepeso , SobrevivientesRESUMEN
Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous-65% to 85% of heart rate maximum-aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, -4.4; 95% CI, -5.9 to -2.7; P < .001). Sarcopenic obesity (appendicular skeletal mass index, P = .001; body mass index, P = .001) and circulating biomarkers, including insulin ( P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001), were significantly improved postintervention compared with usual care. At 3-month follow-up, all metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P < .01). Conclusion Combined resistance and aerobic exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.