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1.
Breast Cancer Res Treat ; 206(2): 369-376, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38584192

RESUMO

BACKGROUND: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. METHODS: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival. RESULTS: Sarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. CONCLUSION: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.


Assuntos
Composição Corporal , Neoplasias da Mama , Sarcopenia , Humanos , Feminino , Pessoa de Meia-Idade , Composição Corporal/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Idoso , Estudos Retrospectivos , Sarcopenia/induzido quimicamente , Sarcopenia/patologia , Adulto , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/diagnóstico por imagem , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Prognóstico , Tiazóis
2.
Cancer Treat Rev ; 122: 102666, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064877

RESUMO

BACKGROUND: As the treatment for metastatic breast cancer (MBC) often includes sequential lines of therapy, data on post-protocol treatment in clinical trials are valuable in the assessment of long-term outcomes. The objective of this study was to assess the reported data on post-protocol therapy in clinical trials supporting US Food and Drug Administration (FDA) approval of drugs for MBC. METHODS: All initial and subsequent publications related to FDA approved indications for MBC between January 2000 and February 2023 were identified. Collected data included study design, patients' characteristics and whether reporting on post-protocol therapy was available. Differences in study design and population between studies with and without data on post-protocol therapy were evaluated. FINDINGS: Forty-one indications for MBC were identified. Data were evaluated from 249 publications or abstracts, comprising 20,152 patients. Reporting of post-protocol therapy was available for 22 (53.7 %) indications. Reported data were often incomplete. Reporting has not improved over time with reported data in 50 % and 55.2 % studies between 2000 and 2010 and 2011-2023 (p value for the difference = 1.0), respectively. Studies with OS as their primary endpoints were associated with significantly higher reporting of post-protocol therapy, (p = 0.02). Other characteristics of study design and population were comparable between studies with and without data on post-protocol therapy. CONCLUSIONS: Data on post-protocol therapy in trials supporting FDA approval of drugs for MBC are available for only half of the indications. As subsequent lines of therapy may have a crucial role in patients' outcome, post-protocol reporting should be included in the regulatory submission and be made available publicly.


Assuntos
Neoplasias da Mama , Humanos , Estados Unidos , Feminino , Neoplasias da Mama/tratamento farmacológico , Projetos de Pesquisa , Aprovação de Drogas , United States Food and Drug Administration , Revisões Sistemáticas como Assunto
3.
BMC Cancer ; 23(1): 1031, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875892

RESUMO

PURPOSE: One-half of hormone receptor-positive (HR +) breast cancer (BC) patients have low expression of HER2 (HER2-low) and may benefit from trastuzumab deruxtecan (TDXd). This study aimed to identify parameters associated with HER2-low levels in primary and metastatic tumors. We specifically sought to determine whether OncotypeDX and HER2 mRNA levels could identify patients who would otherwise be considered HER2-negative by immunohistochemistry (IHC). METHODS: This retrospective analysis of all consecutive HR + patients who underwent OncotypeDX from January 2004 to December 2020 was conducted in a single medical center (n = 1429). We divided HER2-negative cases into HER2-low (IHC = 1 + or 2 + and non-amplified fluorescent situ hybridization) and HER2-0 (IHC = 0). HER2 RT-PCR was evaluated from the OncotypeDX results. RESULTS: HER2-low cases exhibited significantly higher HER2 RT-PCR scores (p = 2.1e-9), elevated estrogen receptor (ER) levels (p = 0.0114), and larger tumor sizes compared to HER2-0 cases (> 2 cm; 36.6% vs. 22.1%, respectively, p < 0.00001). Primary tumors > 2 cm were more likely to be HER2-low (OR = 2.07, 95% CI: 1.6317 to 2.6475, p < 0.0001). Metastatic BCs expressed higher HER2 IHC scores compared with primary BCs (Wilcoxon signed-rank, p = 0.046). HER2 IHC scores were higher for low-risk vs. medium-risk OncotypeDX (p = 0.0067). No other clinical or pathological parameters were associated with the increase in HER2 levels in the metastatic samples. CONCLUSION: It might be beneficial to use clinical data from the primary tumor, including the HER2 RT-PCR score, to determine a HER2-low status.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Humanos , Feminino , Receptor ErbB-2/metabolismo , RNA , Estudos Retrospectivos , Imuno-Histoquímica , Neoplasias da Mama/patologia , Reação em Cadeia da Polimerase
4.
Oncologist ; 28(1): 84-e70, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36398879

RESUMO

BACKGROUND: In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC). METHODS: In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up. RESULTS: Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01). CONCLUSION: Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health. CLINICALTRIALS.GOV IDENTIFIER: NCT02682836.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Exercício Físico , Projetos Piloto , Qualidade de Vida , Caminhada
5.
Support Care Cancer ; 26(10): 3527-3532, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29696427

RESUMO

BACKGROUND: Hypersplenism-related thrombocytopenia (HST) may delay or preclude chemotherapy. Partial splenic embolization (PSE) has been used at our center to overcome prolonged HST. PATIENTS AND METHODS: Between November 2012 and April 2015, 11 PSE procedures were performed in 10 patients; 9 had metastatic colorectal cancer and 1 had widespread pancreatic cancer. PSE was performed by selective catheterization of the splenic artery followed by injection of embolic particles, ranging from 300-700 um, until a 50% reduction in the splenic parenchyma blush was achieved. RESULTS: Splenomegaly was evaluated by splenic index, mean value 970 cm3 (range, 358-2277 cm3), normal mean 120-480 cm3. Mean platelet count immediately prior to PSE was 64.5 K/UL (range, 17-104 K/UL); within 10-14 days following the procedure, it increased to 224 K/UL (range, 83-669 K/UL). Only one patient's count remained less than 100 K/UL 2 weeks after embolization. After the procedure, all patients complained of mild abdominal pain that lasted for a few days; one patient developed post-embolization syndrome. No other significant complications were observed. Mean hospital stay was 2.5 days (range, 2-5 days). Chemotherapy was resumed 7-53 days (mean, 18 days) after the procedure in nine patients. One patient did not receive chemotherapy; he underwent local treatment of liver metastasis. Prolonged thrombocytopenia recurred in four patients, one of whom was successfully retreated by PSE. CONCLUSIONS: PSE can be considered as a treatment option for HST.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Embolização Terapêutica/métodos , Hiperesplenismo/terapia , Trombocitopenia/terapia , Idoso , Neoplasias Colorretais/complicações , Feminino , Humanos , Hiperesplenismo/complicações , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
6.
Oncology (Williston Park) ; 32(2): 58-63, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29492945

RESUMO

Triple-negative breast cancer, which affects about 10% of older women with breast cancer, represents a major treatment challenge in this population. Treatment decisions for these patients can best be made based on geriatric assessment, estimated life expectancy, whether the treatment goal is prolonged survival or palliation, the potential benefits and toxicities of a specific treatment, and the patient's personal goals for treatment. Treatment outcomes for healthy older and younger women are similar, but great challenges exist in managing the vulnerable and frail patient. The cornerstone of therapy for early-stage triple-negative breast cancer is local therapy (surgery and radiation) and, for most patients, adjuvant chemotherapy. In the management of metastatic triple-negative breast cancer, all therapy is palliative and chemotherapy is the treatment of choice. Since all treatment modalities in older patients-especially chemotherapy-can affect physical and mental function, a geriatric assessment is key in selecting the most appropriate treatment strategy. Many older patients (older than 70 years) are poor candidates for state-of-the-art therapy, and some who have substantial comorbidities not related to breast cancer may opt for palliative and hospice care. In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.


Assuntos
Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Idoso , Feminino , Avaliação Geriátrica , Humanos , Expectativa de Vida , Metástase Neoplásica , Neoplasias de Mama Triplo Negativas/patologia
7.
J Geriatr Oncol ; 9(1): 68-73, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28844849

RESUMO

OBJECTIVE: Computerized tomography (CT) imaging is routine in oncologic care and can be used to measure muscle quantity and composition that may improve prognostic assessment of older patients. This study examines the association of single-slice CT-assessed muscle measurements with a frailty index in older adults with cancer. MATERIALS AND METHODS: Using the Carolina Senior Registry, we identified patients with CT imaging within 60days ± of geriatric assessment (GA). A 36-item Carolina Frailty Index was calculated. Cross-sectional skeletal muscle area (SMA) and Skeletal Muscle Density (SMD) were analyzed from CT scan L3 lumbar segments. SMA and patient height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was calculated by multiplying SMI×SMD. RESULTS: Of the 162 patients, mean age 73, 53% were robust, 27% pre-frail, and 21% frail. Significant differences were found between robust and frail patients for SMD (29.4 vs 24.1 HU, p<0.001) and SMG (1188 vs 922AU, p=0.003), but not SMI (41.9 vs 39.5cm2/m2, p=0.29). After controlling for age and gender, for every 5 unit decrease in SMD, the prevalence ratio of frailty increased by 20% (PR=1.20 [1.09, 1.32]) while the prevalence of frailty did not differ based on SMI. CONCLUSIONS: Muscle mass (measured as SMI) was poorly associated with a GA-based frailty index. Muscle density, which reflects muscle lipid content, was more associated with frailty. Although frailty and loss of muscle mass are both age-related conditions that are predictive of adverse outcomes, our results suggest they are separate entities.


Assuntos
Fragilidade/diagnóstico , Músculo Esquelético/diagnóstico por imagem , Neoplasias/epidemiologia , Sarcopenia/diagnóstico , Idoso , Estudos Transversais , Feminino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Sarcopenia/epidemiologia
8.
Cancer Chemother Pharmacol ; 81(2): 413-417, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29159476

RESUMO

PURPOSE: Great heterogeneity exists in the ability of adults with cancer to tolerate chemotherapy. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The objective of this exploratory study was to examine the association of low skeletal muscle, commonly known as sarcopenia, on the pharmacokinetics (PKs) of 5-fluorouracil (5FU) in patients receiving FOLFOX for colorectal cancer. METHODS: We performed a secondary analysis of a completed multicenter trial that investigated PK-guided 5FU dosing in patients receiving mFOLFOX6 +/- bevacizumab for colorectal cancer. Cycle 1 PK samples were obtained 2-44 h after the start of the 5FU infusion (steady state). RESULTS: No significant differences in first cycle 5FU area-under-the-concentration-time-curve (AUC) were found between sarcopenic and non-sarcopenic patients (17.3 vs. 19.3 AUC, p = 0.43). Patients with grade 3/4 toxicity had a higher dose of 5FU per kg lean body mass (LBM) (105 vs. 93 mg/kg, p = 0.06), most notably for hematological toxicities (110 vs. 94 mg/kg, p = 0.002); however, no correlation between the dose/LBM and 5FU AUC was found. CONCLUSIONS: Although our results did not confirm the impact of low skeletal muscle on PKs of 5FU, further research exploring the impact of body composition on chemotherapy PKs and related toxicities is warranted with the potential for alternative dosing strategies in sarcopenic patients to reduce unnecessary toxicities while maintaining efficacy.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacocinética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Músculo Esquelético/patologia , Sarcopenia/complicações , Sarcopenia/patologia , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Compostos Organoplatínicos/uso terapêutico , Tomografia Computadorizada por Raios X
9.
Oncologist ; 23(4): 433-439, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29242282

RESUMO

BACKGROUND: Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient because most clinical trials lack systematic measurement. The primary purpose of this study was to evaluate the association between patient-reported comorbidity and all-cause mortality using various comorbidity scoring algorithms. MATERIALS AND METHODS: The Carolina Senior Registry was linked with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using the patient-reported Older Americans Resources and Services Questionnaire subscale that assesses 13 specific conditions and the degree to which each impairs activities. Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all-cause mortality. RESULTS: The study sample included 539 patients; the median age was 72 years, 72% were female, and 47% had breast cancer. Overall, 92% reported ≥1 comorbid condition, with a mean of 2.7 conditions (range 0-10), with arthritis and hypertension the most common (52% and 50%, respectively). Approximately 60% reported a functional limitation related to comorbidity. After adjusting for time from diagnosis to geriatric assessment, age, cancer type, and stage, the risk of death increased by 5% for each unit increase in comorbidity burden score (adjusted hazard ratio [HR] = 1.05, 95% confidence interval [CI]: 1.01-1.10) and 12% for each comorbid condition impacting function (HR = 1.12, 95% CI: 1.02-1.23). CONCLUSION: Comorbid conditions in older adults with cancer are highly prevalent and associated with all-cause mortality, particularly those conditions that impair function. Routine comorbidity assessment should be included in clinical trials and can be measured via a simple one-page patient-reported questionnaire. IMPLICATIONS FOR PRACTICE: In order to optimize and personalize the care of older adults with cancer, systematic measurement of comorbidities is necessary in both clinical trials and routine practice. Patient-reported comorbid conditions in older adults with cancer are highly prevalent and are associated with increased risk of all-cause mortality, particularly for those conditions that impair function. Comorbidity can be systematically measured via a one-page patient-reported questionnaire and should be incorporated into future clinical trials and considered for use in oncology clinics to aid in assessing older adults with cancer.


Assuntos
Comorbidade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Medidas de Resultados Relatados pelo Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica , Humanos , Masculino , Neoplasias/patologia , North Carolina/epidemiologia , Prevalência , Sistema de Registros , Risco , Inquéritos e Questionários , Análise de Sobrevida
12.
Oncotarget ; 8(20): 33658-33665, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28431396

RESUMO

BACKGROUND: Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent in older adults and linked with adverse outcomes in cancer, yet the definition and role of sarcopenia remains uncertain. The aim of this study was to examine the association of Computerized Tomography (CT) assessed skeletal muscle measures with physical function in older adults with cancer. RESULTS: CTs for 185 patients were available. Median age 73 (IQR 68-76) and 56.5% female. After controlling for sex and BMI, we found no evidence that SMI was associated with physical function impairments. Both SMD and SMG were associated physical function impairments and higher values were associated with decreased limitations in instrumental activities of daily living (RR 0.84 [CI 0.73-0.96] and 0.94 [CI 0.89-0.99], respectively), climbing stairs (RR 0.84 [CI 0.76-0.94] and 0.91 [CI 0.87-0.96]), walking 1 block (RR 0.77 [CI 0.67-0.90] and 0.91 [CI 0.85-0.97]), and prolonged Timed Up and Go (RR 0.83 [CI 0.75-0.92] and 0.92 [CI 0.88-0.96]). MATERIALS AND METHODS: Using the Carolina Senior Registry, we identified patients with CT imaging performed within 60 days +/- of baseline geriatric assessment (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar segments. Muscle area and height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. CONCLUSIONS: Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments. Skeletal muscle radiodensity was more associated with physical function and may aid in identifying older adults at risk for functional impairments.


Assuntos
Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Neoplasias/patologia , Neoplasias/fisiopatologia , Fatores Etários , Idoso , Composição Corporal , Feminino , Avaliação Geriátrica , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , Aptidão Física , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Sarcopenia/patologia , Sarcopenia/fisiopatologia , Tomografia Computadorizada por Raios X
13.
Clin Cancer Res ; 23(14): 3537-3543, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28143874

RESUMO

Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane-based chemotherapy.Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23-75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (<1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05).Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537-43. ©2017 AACR.


Assuntos
Antraciclinas/administração & dosagem , Composição Corporal/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Antraciclinas/efeitos adversos , Índice de Massa Corporal , Neoplasias da Mama/fisiopatologia , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxoides/efeitos adversos
14.
Oncologist ; 22(3): 324-334, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28232597

RESUMO

BACKGROUND: Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16-49 years), management decisions are challenging to both the patient and the multidisciplinary team. MATERIALS AND METHODS: Experts in breast cancer at the University of North Carolina conducted a targeted literature search regarding the multidisciplinary treatment approaches to BCDP: medical, surgical, and radiation oncology. Supportive care, including antiemetic agents, and imaging approaches were also reviewed. RESULTS: Review of the literature revealed key points in the management of BCDP. Surgical management is similar to that in nonpregnant patients; pregnant patients may safely undergo breast-conserving surgery. Recommendations should be tailored to the individual according to the clinical stage, tumor biology, genetic status, gestational age, and personal preferences. Anthracycline-based chemotherapy can be safely initiated only in the second and third trimesters. The rate of congenital abnormalities in children exposed to chemotherapy is similar to the national average (approximately 3%). Dosing of chemotherapy should be similar to that in the nonpregnant patient (i.e., actual body surface area). Antihuman epidermal growth factor receptor 2 therapy, radiation, and endocrine treatment are contraindicated in pregnancy and lactation. Care should include partnership with obstetricians. The literature regarding prognosis of BCDP is mixed. CONCLUSION: To maximize benefit and minimize risk to the mother and fetus, an informed discussion with the patient and her medical team should result in an individualized treatment plan, taking into account the timing of the pregnancy and the stage and subtype of the breast cancer. Because BCDP is rare, it is essential to collect patient data in international registries. The Oncologist 2017;22:324-334 IMPLICATIONS FOR PRACTICE: Breast cancer during pregnancy is a major ethical and professional challenge for both the patient and the multidisciplinary treatment team. Although the oncologic care is based on that of the non-pregnant breast cancer patient, there are many challenges from regarding the medical, surgical and radiation oncology and obstetrical aspects of care that need to be considered to deliver the safest and best treatment plan to both the mother and developing fetus.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/cirurgia , Neoplasias da Mama/patologia , Gerenciamento Clínico , Feminino , Humanos , Mastectomia Segmentar , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Prognóstico
15.
BMC Cancer ; 17(1): 7, 2017 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28052766

RESUMO

BACKGROUND: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. METHODS: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. RESULTS: Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010-2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). CONCLUSIONS: Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality.


Assuntos
Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida
16.
Clin Cancer Res ; 23(3): 658-665, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27489287

RESUMO

PURPOSE: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes. EXPERIMENTAL DESIGN: Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan-Meier method, and Cox regression modeling were used. RESULTS: MBC patients (N = 40), median age 55 (range, 34-80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3-4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events-defined as any grade 3-4 toxicities, hospitalizations, dose reductions, or dose delay-(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3-4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07). CONCLUSIONS: SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658-65. ©2016 AACR.


Assuntos
Adenocarcinoma/secundário , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Composição Corporal , Neoplasias da Mama/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Músculo Esquelético/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Taxoides/efeitos adversos , Tomografia Computadorizada por Raios X , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Índice de Massa Corporal , Superfície Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/induzido quimicamente , Sarcopenia/etiologia , Gravidade Específica , Taxoides/administração & dosagem
17.
Lancet Oncol ; 17(6): e220, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27299272

Assuntos
Caquexia , Neoplasias , Humanos
18.
Eur J Cancer ; 57: 58-67, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26882087

RESUMO

BACKGROUND: Body composition plays an important role in predicting treatment outcomes in adults with cancer. Using existing computed tomographic (CT) cross-sectional imaging and readily available software, the assessment of skeletal muscle mass to evaluate sarcopenia has become simplified. We performed a systematic review and meta-analysis to quantify the prognostic value of skeletal muscle index (SMI) obtained from cross-sectional CT imaging on clinical outcomes in non-haematologic solid tumours. METHODS: We searched PubMed and the American Society Clinical Oncology online database of meeting abstracts up to October 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment SMI on clinical outcomes in patients with non-haematologic solid tumours. The primary outcome was overall survival (OS) and the secondary outcomes included cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 7843 patients from 38 studies were included. SMI lower than the cut-off was associated with poor OS (HR = 1.44, 95% CI = 1.32-1.56, p < 0.001). The effect of SMI on OS was observed among various tumour types and across disease stages. Worse CSS was also associated with low SMI (HR = 1.93, 95% CI = 1.38-2.70, p < 0.001) as well as DFS (HR = 1.16, 95% CI = 1.00-1.30, p = 0.014), but not PFS (HR = 1.54, 95% CI = 0.90-2.64, p = 0.117). CONCLUSIONS: This meta-analysis demonstrates that low SMI at cancer diagnosis is associated with worse survival in patients with solid tumours. Further research into understanding and mitigating the negative effects of sarcopenia in adults with cancer is needed.


Assuntos
Neoplasias/mortalidade , Sarcopenia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcopenia/etiologia , Adulto Jovem
19.
J Oncol Pract ; 12(2): 123-32, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26869650

RESUMO

Breast cancer is the most common cancer in women, with an incidence that rises dramatically with age. The average age at diagnosis of breast cancer is 61 years, and the majority of woman who die of breast cancer are age 65 years and older. Major improvements in public health and medical care have resulted in dramatic increases in longevity. The oldest old (those age 80 years and older) are a rapidly expanding group and now comprise 9 million members of the US population. The treatment of individuals who are age 80 years and older is complex and involves clearly defining the goals and value of treatment while also weighing risks, such as the potential effects of treatment on functional loss and quality of life. Limited evidence-based treatment guidelines exist for the caring of this older cohort of patients with breast cancer. Data from clinical trials that enroll primarily younger patients lack the information needed to estimate the likelihood of toxicities that can be life changing in older adults. Clinicians who make treatment recommendations should place the available evidence in the context of the patient's life expectancy and geriatric assessment results that include an evaluation of a patient's functional status, comorbidities, cognition, social support, nutritional status, and psychological state. Furthermore, these decisions should be placed in the context of the patient's goals for treatment, preferences, and values. This review summarizes the current literature and focuses on the role of geriatric assessment in treatment recommendations for patients age 80 years and older with early and metastatic breast cancer.


Assuntos
Neoplasias da Mama/terapia , Fatores Etários , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etiologia , Terapia Combinada , Comorbidade , Gerenciamento Clínico , Feminino , Avaliação Geriátrica , Humanos , Expectativa de Vida , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Cuidados Paliativos
20.
Clin Breast Cancer ; 16(3): e43-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26642811

RESUMO

BACKGROUND: A strong recommendation has been made to perform repeat biopsy for recurrent metastatic breast cancer (RMBC), to reconfirm the histologic features, and to assess for possible changes in hormone receptors (HRs) or human epidermal growth factor receptor 2 (HER2) status. The present study was undertaken to assess the documented and nondocumented factors affecting physicians' decisions to perform a repeat biopsy in patients with RMBC. PATIENTS AND METHODS: We reviewed the medical records of 410 patients with RMBC for whom recurrence had developed between January 2000 and August 2014. The demographic data and characteristics regarding early and metastatic disease were recorded. The written follow-up records were examined, seeking considerations for or against repeat biopsy. Multivariate analysis was performed using logistic regression to determine the nondocumented reasons for repeat biopsy. RESULTS: A new biopsy was performed in 295 of 410 patients (72%). However, only 88 of the 295 patients (30%) had a documented reason for rebiopsy. The reason for not performing repeat biopsy was documented for only 1 of the 115 patients. The main documented consideration for rebiopsy was to obtain a new receptor status (recorded in 47 of 88 patients; 53%). The other recorded reasons were suspicion of a second primary, differential diagnosis of metastasis from a second primary, the time from early diagnosis, and patient desire. Significant, but undocumented, considerations for repeat biopsy were low stage at early diagnosis, year of recurrence, interval to recurrence, and site of recurrence. Only for 165 of 295 patients (56%) was the full HR and HER2 status from the new biopsy specimen obtained. CONCLUSION: Nondocumented factors influence physicians' decisions for referring patients for rebiopsy. This might reflect a low rate of patient involvement in their disease management and decision making.


Assuntos
Neoplasias da Mama/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Padrões de Prática Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade , Reoperação
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