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BACKGROUND: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy. METHODS: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model. RESULTS: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03). CONCLUSION: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer. TRIAL NUMBERS: NCT02167932, NCT02328313, NCT03761706.
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Neoplasias de la Mama , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Persona de Mediana Edad , Ansiedad , Neoplasias de la Mama/tratamiento farmacológico , Ejercicio Físico , CaminataRESUMEN
PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.
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Neoplasias de la Mama , Antraciclinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). METHODS: Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. RESULTS: In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30 kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. CONCLUSION AND RELEVANCE: Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.
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Neoplasias de la Mama , Músculos Psoas , Neoplasias de la Mama/tratamiento farmacológico , Canadá , Quimioterapia Adyuvante/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Músculo Esquelético , Estudios RetrospectivosRESUMEN
BACKGROUND: Advances in breast cancer research are making treatment options increasingly effective and reducing mortality. Body composition is an example of a prognostic tool that can help personalize breast cancer treatments and further increase their effectiveness. In this study, we examine the association of several body composition measures with comorbidities, physical function, and quality of life. METHODS: This study is a cross-sectional analysis of 99 women with early breast cancer scheduled for chemotherapy. Univariate regression models were used to identify significant associations of body composition metrics with patient demographics, clinical characteristics, measures of physical function, and patient-reported outcomes (PRO)s. Multivariable modeling was used to evaluate associations adjusted for age. RESULTS: Median age was 58 (range 24-83), 27% were non-white, and, 47% were obese (≥ 30 kg/m2). Increasing age was associated with lower Skeletal Muscle Density (SMD) (p = 0.0001), lower Skeletal Muscle Gauge (SMG) (p = 0.0005), and higher Visceral Adipose Tissue (VAT) (p < 0.0001). In patients with a prolonged Timed Up and Go tests (> 14 s), mean VAT was 57.87 higher (p = 0.004), SMD 5.70 lower (p = 0.04), and SMG 325.4 lower (p = 0.02). For each point of higher performance on the Short Physical Performance Battery (SPPB), VAT decreased 12.24 (p = 0.002) and SMD rose 1.22 (p = 0.02). In multivariable analysis adjusting for age, the association of TUG > 14 with higher VAT remained significant (p = 0.02). CONCLUSIONS: Suboptimal body composition prior to treatment is associated poor physical function and may be an indicator of clinical importance.
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Composición Corporal , Índice de Masa Corporal , Neoplasias de la Mama/fisiopatología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Body composition metrics as predictors of adverse events are a growing area of interest in oncology research. One barrier to the use of these metrics in clinical practice is the lack of standardized cut points for identifying patients with at-risk body composition profiles. We examined the association of chemotherapy adverse events with several body composition measures, using alternative cut points from published studies. METHODS: This is a retrospective study of women diagnosed with early breast cancer (EBC). Axial computerized tomography (CT) images from lumbar L3 segments were analyzed for the following body composition measures: myosteatosis (low Skeletal Muscle Density/SMD), sarcopenia (low Skeletal Muscle Index/SMI), and high Visceral Adipose Tissue (VAT). Adverse events during chemotherapy were dose reduction, early treatment discontinuation, and hospitalization. Log-binomial modeling was used to evaluate associations between body composition measures at different cut points with adverse events, adjusting for age, race, Body Mass Index/BMI, and comorbidities. Relative risks were reported as the measure of association. RESULTS: In a sample of 338 women, mean age was 51, 14% were age 65 or older, 32% were non-white, 40% had obesity (/BMI ≥ 30 kg/m2), and mean number of comorbidities was 1.56. In multivariable analysis (MV), all three SMD cut points for myosteatosis had significant associations with total number of adverse events, as well as different cut points having significant associations with either dose reduction, early treatment discontinuation or hospitalization. SMI and VAT were not significant in the MV analysis; however, in some models, age and total comorbidities were significant for adverse events. CONCLUSIONS: Among CT-derived measures of body composition, myosteatosis determined at any of three SMD cut points was associated with total and individual adverse events during chemotherapy for early breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Composición Corporal , Neoplasias de la Mama/tratamiento farmacológico , Músculo Esquelético/patología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Obesidad/diagnóstico por imagen , Obesidad/patología , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Sarcopenia/patología , Adulto JovenRESUMEN
PURPOSE: Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcomes for overall survival (OS), time to tumor progression (TTP), and chemotherapy toxicity in a meta-analysis. METHODS: A systematic search of the literature for randomized controlled trials and observational studies was conducted on MEDLINE, Cochrane CENTRAL, and EMBASE through May 1, 2019. Two reviewers independently searched and selected. Meta-analysis was conducted using a random-effects model. The risk of bias was evaluated using the Newcastle-Ottawa quality assessment for cohorts and GRADE summary of findings tool from Cochrane. RESULTS: A total of 754 articles were screened from which 6 articles and one abstract were selected. Using skeletal muscle index (SMI), patients classified as sarcopenic had a 68% greater mortality risk compared to non-sarcopenic patients (HR 1.68 95% CI 1.09-2.59, 5 studies) (p = .02) (i2 = 70%). Low muscle density was not predictive of OS (HR 1.44 95% CI 0.77-2.68, 2 studies) (p = .25) (i2 = 87%). Patients with sarcopenia (56%) had more grade 3-5 toxicity compared to non-sarcopenic (25%) (RR 2.17 95% CI 1.4-3.34, 3 studies) (p = .0005) (i2 = 0%). TTP was nearly 71 days longer in advanced/metastatic patients classified as non-sarcopenic compared to patients with sarcopenia (MD - 70.75 95% CI - 122.32 to - 19.18) (p = .007) (i2 = 0%). CONCLUSION: Our synthesis of the literature shows that patients with sarcopenia have more severe chemotherapy toxicity as well as shorter OS and TTP, and that low muscle density is prognostic of OS for women with metastatic breast cancer. Our findings suggest that in clinical practice, body composition assessment is valuable as a prognostic parameter in breast cancer.
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Composición Corporal , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Músculo Esquelético/patología , Sarcopenia/etiología , Sarcopenia/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Progresión de la Enfermedad , Femenino , Humanos , Evaluación del Resultado de la Atención al Paciente , PronósticoRESUMEN
In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.
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PURPOSE: Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a FitbitTM throughout their waking hours, and Fitbit steps were uploaded directly into study computers. METHODS: Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week. RESULTS: Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with fewer Fitbit steps were: non-white race (p = 0.012), high school education or less (p = 0.0005), higher body mass index (p = 0.0024), and never/almost never drinking alcohol (p = 0.0048). Physical activity variables associated with greater Fitbit steps were: pre-chemotherapy history of vigorous physical activity (p = 0.0091) and higher self-reported walking minutes/week (p < 0.001), and higher outcome expectations from exercise (p = 0.014). Higher baseline anxiety (p = 0.03) and higher number of chemotherapy-related symptoms rates "severe/very severe" (p = 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (p = 0.004), as was self-reported walking minutes prior to start of chemotherapy (p < 0.0001). CONCLUSIONS: Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.
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Antineoplásicos/efectos adversos , Neoplasias de la Mama/rehabilitación , Terapia por Ejercicio/estadística & datos numéricos , Monitoreo Fisiológico/instrumentación , Cooperación del Paciente/estadística & datos numéricos , Caminata/estadística & datos numéricos , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Terapia por Ejercicio/métodos , Femenino , Monitores de Ejercicio , Humanos , Mastectomía , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/estadística & datos numéricos , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Medición de Resultados Informados por el Paciente , Estudios ProspectivosRESUMEN
PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. METHODS: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.
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Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/etiología , Neoplasias Primarias Secundarias , Factores de Edad , Anciano , Anciano de 80 o más Años , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Riesgo , Factores de TiempoRESUMEN
Most breast cancer (BC) tumors are early stage and hormone receptor positive, where treatment generally includes adjuvant endocrine treatment (ET). Oncology providers and women about to start ET want to know about side effects, including potential weight gain. The aim of this study was a literature review to identify the independent effect of ET on post-diagnosis weight gain. Weight gain is of concern with regard to potential associations with BC recurrence, mortality, and quality of life in survivorship. We conducted a targeted review of the literature. Thirty-eight studies met our inclusion criteria. Patient-reported weight gain ranged widely from 18 to 52 % of patients in Year 1 and from 7 to 55 % in Year 5. Some studies reported categories of weight change: lost weight (9-17 %), stable weight (47-64 %), and gained weight (27-36 %). Most studies comparing ET with placebo or tamoxifen with AI reported no significant difference between the two groups. Wide-ranging and inconsistent results point to the need for further research to clarify annual weight change (loss, gain, stability) from BC diagnosis through 5 years of ET and beyond. There is also a need to explore weight change by type of ET and to explore risk factors for weight gain in women on ET, including tumor type, sociodemographic characteristics, and health behaviors. More specific information is needed to identify high-risk BC patients who could be targeted for weight management interventions.
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Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Aumento de Peso , Antineoplásicos Hormonales/uso terapéutico , Ensayos Clínicos como Asunto , Femenino , Humanos , Estudios Observacionales como Asunto , Calidad de Vida , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The aim of this study was to explore the effect of one bout of aerobic exercise on epinephrine, norepinephrine, cortisol, glucose, lactate, and free fatty acid (FFA) responses in breast cancer survivors and healthy controls. 9 female breast cancer survivors and 9 women without a history of cancer completed 30 min of cycle ergometry exercise at 60% of VO2peak. Blood samples were taken pre-exercise, immediately post-exercise, and 2 h post-exercise from which plasma concentrations of study variables were measured. Immediately and 2 h post-exercise, increases were observed in epinephrine (control group only) norepinephrine (both groups), lactate (both groups), and FFA (both groups immediately post-exercise; breast cancer survivor group only at 2 h post-exercise) (p<0.05). Cortisol decreased immediately and 2 h post-exercise in the control group while glucose decreased immediately post-exercise in the breast cancer survivor group (p<0.05). In conclusion, breast cancer survivors appeared to display attenuated epinephrine, cortisol, and lactate responses while displaying larger magnitude changes in glucose and FFA responses compared to controls. These preliminary findings may have implications for the regulation of metabolism during exercise in breast cancer survivors.
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Ciclismo/fisiología , Neoplasias de la Mama/terapia , Ejercicio Físico/fisiología , Sobrevivientes , Adulto , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Estudios de Casos y Controles , Epinefrina/sangre , Prueba de Esfuerzo , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Hidrocortisona/sangre , Ácido Láctico/sangre , Persona de Mediana Edad , Consumo de Oxígeno/fisiologíaRESUMEN
BACKGROUND: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. PATIENTS AND METHODS: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. RESULTS: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). CONCLUSIONS: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Nitrilos/uso terapéutico , Premenopausia , Triazoles/uso terapéutico , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/diagnóstico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Nitrilos/efectos adversos , Placebos , Posmenopausia , Calidad de Vida , Sobrevida , Tamoxifeno/uso terapéutico , Resultado del Tratamiento , Triazoles/efectos adversosRESUMEN
BACKGROUND: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer. PATIENTS AND METHODS: CALGB 9840 evaluated weekly paclitaxel (80 mg/m(2)) versus paclitaxel every 3 weeks (175 mg/m(2)); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m(2) each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55-64 years (29%), and (iii) ≥65 years (26%). RESULTS: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity. CONCLUSIONS: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.
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Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/efectos adversos , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Metástasis de la Neoplasia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios RetrospectivosRESUMEN
BACKGROUND: Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects. PATIENTS AND METHODS: CALGB 49907 was a randomized trial comparing standard chemotherapy (CMF or AC, provider/patient choice) with capecitabine in patients aged ≥65 with stage I-IIIB breast cancer. Those randomized to standard therapy and choosing CMF were prescribed oral cyclophosphamide 100 mg/m(2) for 14 consecutive days in six 28-day cycles. Persistence was defined as being prescribed six cycles of at least one of the three CMF drugs. Adherence was the number of cyclophosphamide doses that women reported they had taken divided by the number prescribed. Persistence and adherence were based on case report forms and medication calendars. RESULTS: Of 317 randomized to standard chemotherapy, 133 received CMF. Median age was 73 (range 65-88). Seventy-one percent submitted at least one medication calendar; 65% persisted with CMF. Non-persistence was associated with node negativity (P = 0.019), febrile neutropenia (P = 0.002), and fatigue (P = 0.044). Average adherence was 97% during prescribed cycles. CONCLUSIONS: Self-reported adherence to cyclophosphamide was high, but persistence was lower, which may be attributable to toxic effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cumplimiento de la Medicación , Cooperación del Paciente , Factores de Edad , Anciano , Anciano de 80 o más Años , Capecitabina , Quimioterapia Adyuvante/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Metotrexato/efectos adversos , Metotrexato/uso terapéuticoRESUMEN
BACKGROUND: The evidence that body composition parameters influence multiple cancer outcomes is rapidly expanding. Excess adiposity deposits in muscle tissue, termed myosteatosis, can be detected in CT scans through variations in the density of muscle tissues (Hounsfield Units). Patients with similar muscle mass but different amounts of intramuscular adipose infiltration have increased chemotherapy toxicity, time to tumor progression and other adverse outcomes among different cancer types. Our review examines the impact of myosteatosis on overall survival (OS) in patients with cancer. METHODS: A systematic search of the literature was conducted on PubMed/ MEDLINE, Cochrane CENTRAL, and EMBASE. Meta-analysis was conducted using a random-effects model. Risk of bias was evaluated using the Newcastle-Ottawa Quality assessment for cohort studies, funnel plot (publication bias), and GRADE summary of findings tool from Cochrane. RESULTS: A total of 4880 articles were screened from which 40 articles selected, including 21,222 patients. The overall mean proportion of patients with myosteatosis was 48 % (range 11-85 %). Using skeletal muscle density (SMD), patients classified as having myosteatosis had 75 % greater mortality risk compared to non-myosteatosis patients (HR 1.75 95 % CI 1.60-1.92, 40 studies) (p < .00001) (i2 = 62 %). Specifically, myosteatosis was prognostic for worse OS in patients with gynecological, renal, periampullary/pancreatic, hepatocellular, gastroesophageal, and colorectal carcinoma, and lymphomas. CONCLUSION: Our analysis of the literature shows that cancer patients with myosteatosis have shorter survival. Our findings suggest that in oncological practice, muscle density assessment is valuable as a prognostic parameter.
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Músculo Esquelético , Enfermedades Musculares , Neoplasias , Composición Corporal , Estudios de Cohortes , Humanos , Músculo Esquelético/patología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/patología , Neoplasias/complicaciones , Neoplasias/patología , Obesidad/patología , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
Cancer is the second leading cause of death in the USA and will probably surpass heart disease, the current leader, over the next few years. As in other affluent nations, cancer in the USA is a disease of ageing, with a median age at diagnosis of 67 years. Moreover, men and women in average health who reach age 65 years will probably live an average of 20 more years and it is estimated that by 2025 20% of Americans will be 65 years and older compared with 12% of the present population. This will place an increasing burden on providers of cancer care and complicate the medical management of many elders. There is now great interest in educating primary care physicians about the management of cancer care of the elderly. Professional groups, such as the American Society of Clinical Oncology, the American Association of Cancer Research, National Cancer Institute-sponsored co-operative groups and the National Institutes on Aging, continue to support programmes to improve geriatric training of physicians and provide research money for those interested in geriatric oncology. Access to cancer care varies in the USA and older patients have not had the same standard of care as younger patients. This has probably resulted in poor outcomes for many. Also, clinical trial participation by elders has been poor. Several more recent trials focusing on older patients have been more successful, but accrual remains a major issue. Financial constraints have limited trial opportunities for elders and hopefully will improve in the future. A major challenge for those in North America will be to provide the health care for elders with cancer and other diseases in the coming years. To meet this challenge we must expand and train the number of health care providers at all levels.
Asunto(s)
Accesibilidad a los Servicios de Salud , Neoplasias/epidemiología , Neoplasias/terapia , Anciano , Anciano de 80 o más Años , Ensayos Clínicos como Asunto , Comorbilidad , Femenino , Geriatría , Humanos , Masculino , Neoplasias/diagnóstico , Prevalencia , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. PATIENTS AND METHODS: An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. RESULTS: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033). CONCLUSIONS: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.
Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Estrógenos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Nitrilos/uso terapéutico , Progesterona , Triazoles/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/administración & dosificación , Supervivencia sin Enfermedad , Método Doble Ciego , Humanos , Estimación de Kaplan-Meier , Letrozol , Metástasis Linfática , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/epidemiología , Nitrilos/administración & dosificación , Aceptación de la Atención de Salud , Placebos , Posmenopausia , Modelos de Riesgos Proporcionales , Recurrencia , Tamoxifeno/uso terapéutico , Triazoles/administración & dosificaciónRESUMEN
Increasing age is the major risk factor for breast cancer. About half of all new breast cancers and more than half of breast cancer deaths in affluent nations occur in women 65 years and older. Endocrine therapy with aromatase inhibitors or tamoxifen is appropriate adjuvant therapy for older women with life expectancies of greater than 5 years and hormone receptor positive tumors. The greatest benefit of adjuvant chemotherapy is in elders with hormone receptor negative, node positive, or high-risk node negative tumors. The effect of co-morbidity on survival must be factored into all adjuvant therapy decisions and newer validated tools can accurately estimate non-breast cancer related survival. Age bias still exists and results in frequent undertreatment of older women and compromised survival. Elders remain under-represented in clinical trials and should be encouraged to participate. Health care providers as well as government leaders and patients need to be educated on cancer in elders.
Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Factores de Edad , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Factores de Riesgo , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences. PURPOSE: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care access factors to cancer staging at diagnosis in Black and White breast cancer patients. METHODS: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables. RESULTS: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P < .02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV cancer versus stage I-IIN0 cancer among Blacks compared with Whites (odds ratio reduction from 2.19 to 1.68). CONCLUSION: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients.
Asunto(s)
Negro o Afroamericano , Neoplasias de la Mama/etnología , Población Blanca , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Conductas Relacionadas con la Salud , Accesibilidad a los Servicios de Salud , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Análisis de Regresión , Factores de Riesgo , Factores Socioeconómicos , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.