Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
Oncologist ; 29(3): e345-e350, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37897406

RESUMEN

INTRODUCTION: Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. METHODS: This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. RESULTS: 239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment. CONCLUSION: Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.


Asunto(s)
Neoplasias de la Mama , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Masculino , Rwanda/epidemiología , Estudios Transversales , Estudios Prospectivos , Neoplasias de la Mama/patología
2.
Breast Cancer Res Treat ; 198(1): 31-41, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36592233

RESUMEN

PURPOSE: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed. METHODS: Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. RESULTS: We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028). CONCLUSION: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Estudios Retrospectivos , Riesgo , Genómica , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/tratamiento farmacológico , Quimioterapia Adyuvante
3.
Breast Cancer Res Treat ; 190(3): 477-489, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34542773

RESUMEN

PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20+ B-cell frequencies (CD20+), and PD-L1 expression on tumor (PD-L1+carcinoma cells) and immune (PD-L1+TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20+, and combined CD20+ and PD-L1+TILs (CD20+PD-L1+TILs), while LABC contained more PD-L1+TILs and PD-L1+ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1+ carcinoma cells, and combined CD20+ and PD-L1+ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1+TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20+ and CD20+PD-L1+TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20+PD-L1+TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20+PD-L1+TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.


Asunto(s)
Neoplasias de la Mama , Neoplasias Inflamatorias de la Mama , Antígenos CD20 , Linfocitos B , Antígeno B7-H1/genética , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Linfocitos Infiltrantes de Tumor , Pronóstico
4.
J Cancer Educ ; 36(6): 1325-1332, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-32504362

RESUMEN

Effective communication between providers and patients with serious illness is critical to ensure that treatment is aligned with patient goals. We developed and tested an implementation strategy for incorporating the previously developed Serious Illness Conversation Guide (SICG), a clinician script, into hematology-oncology fellowship training at a single US academic medical center. Between December 2017 and April 2018, we trained 8 oncology fellows to use and document the SICG. The training included associated communication skills-such as handling emotion and headlining-over 7 didactic sessions. Implementation strategies included training 4 oncology faculty as coaches to re-enforce fellows' skills and an electronic medical record template to document the SICG. We assessed effectiveness using 4 approaches: (1) SICG template use among fellows in the 12 months following training, (2) fellow confidence pre- and post-intervention via survey, (3) performance in 2 simulated patient encounters, and (4) semi-structured interviews after 12 months. Fellows successfully implemented the SICG in simulated patient encounters, though only 2 of 6 fellows documented any SICG in the clinical practice. Most fellows reported greater confidence in their communication after training. Thematic analysis of interviews revealed the following: (1) positive training experience, (2) improved patient preference elicitation, (3) selected SICG components used in a single encounter, (4) prioritize other clinical duties, (5) importance of emotion handling skills, (6) no faculty coaching receive outside training. Despite acquisition of communication skills, promoting new clinical behaviors remains challenging. More work is needed to identify which implementation strategies are required in this learner population.


Asunto(s)
Hematología , Comunicación , Becas , Humanos , Oncología Médica , Encuestas y Cuestionarios
5.
Breast Cancer Res Treat ; 182(3): 665-677, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32562118

RESUMEN

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).


Asunto(s)
Neoplasias de la Mama/genética , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Mutación , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Biopsia Líquida/métodos , Metástasis de la Neoplasia , Pronóstico
6.
Am J Occup Ther ; 73(5): 7305205070p1-7305205070p11, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31484031

RESUMEN

OBJECTIVE: The objective of this study was to assess the feasibility of conducting a future full-scale trial to test the efficacy of an in-home occupational therapy intervention designed to reduce disability in older adult cancer survivors. METHOD: Participants reporting activity limitations during or after cancer treatment were enrolled in a Phase 1 pilot randomized controlled trial comparing the 6-wk intervention (n = 30) to usual care (n = 29). Descriptive data on retention rates were collected to assess feasibility of intervention and study procedures. Potential efficacy was explored through participants' self-reported disability, quality of life, activity level, and behavioral activation at 0, 8, and 16 wk after enrollment. RESULTS: Retention rates were high regarding completion of the intervention (90%) and outcome assessments (90% of usual-care participants and 80% of intervention participants). Outcomes consistently favored the intervention group, although group differences were small. CONCLUSION: The procedures were feasible to implement and acceptable to participants.


Asunto(s)
Terapia Ocupacional , Calidad de Vida , Anciano , Supervivientes de Cáncer/estadística & datos numéricos , Humanos , Terapia Ocupacional/métodos , Evaluación de Resultado en la Atención de Salud
7.
Am J Occup Ther ; 72(2): 7202205110p1-7202205110p8, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29426388

RESUMEN

OBJECTIVE: In this pilot study of a home-based occupational therapy intervention intended to reduce disability and improve quality of life, our objective was to identify rates of goal attainment and patterns of goal adjustment of participants. METHOD: Thirty older adults with cancer were randomized to the intervention arm, and 24 participants identified goals and completed the six-session intervention. An exploratory content analysis of qualitative and quantitative session data was performed. RESULTS: Participants set 63 6-wk goals and attained 62% of them. Most of the goals addressed walking (28%), sedentary leisure (24%), exercising (16%), or instrumental activities of daily living (14%). When 6-wk goals were not attained (n = 24), there were 10 instances of goal disengagement and 14 instances of goal reengagement. CONCLUSION: Although most participants were able to meet their goals, many also changed their goals and priorities after reflection and attempts to resume or initiate meaningful activities.

8.
J Cell Biochem ; 117(11): 2454-63, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27146558

RESUMEN

The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Terapia Molecular Dirigida , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Mutación/genética
9.
Exp Mol Pathol ; 100(3): 421-5, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27095739

RESUMEN

BACKGROUND: Metastatic breast cancer is a genetically heterogeneous disease and effective therapies for advanced stage disease are limited. METHODS: In this study, distant metastases of 22 formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were sequenced using the Ion Torrent PGM and the 50 gene AmpliSeq Cancer Hotspot Panel v2 from 10ng of extracted DNA using 318 chips. Data analysis was performed with the Ion Torrent Variant Caller Plugin (hg19) and Golden Helix's SVS software for annotation and prediction of the significance of the variants. RESULTS: All patients were female with a median age of 61years (range 37-85years). Metastatic sites included liver (n=6, 27%), skin (n=5, 23%), brain (n=4, 18%), lymph node (n=3, 14%), lung (n=2, 9%), retroperitoneum (n=1, 4.5%), and colon (n=1, 4.5%). Overall, 28 variants in 11 genes were observed. Five (23%) samples showed no alterations and 17 (77%) showed at least one potentially biologically significant variant (BSV) defined as having FDA-approved drugs or clinical trials evaluating their significance. BSVs included mutations in the following genes: TP53 (n=8), APC (n=4), PIK3CA (n=5), MET (n=2), ERBB2 (n=2), AKT1 (n=1), CDKN2A (n=1), KRAS (n=1), and FGFR3 (n=1). CONCLUSIONS: Potentially actionable mutations were identified in the majority of breast cancer metastases. Evaluating metastatic breast tumors using a NGS approach provides a better understanding of the mechanisms behind tumor progression and evolution and also identifies additional potentially beneficial therapeutic targets for patient management or eligibility for clinical trials.


Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Proteína de la Poliposis Adenomatosa del Colon/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasa Clase I , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-met/genética , Receptor ErbB-2/genética , Proteína p53 Supresora de Tumor/genética
10.
Oncologist ; 20(9): 1011-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26205736

RESUMEN

BACKGROUND: Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients' tumor genetic profiles and provide treatment recommendations. PATIENTS AND METHODS: DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors. RESULTS: During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months. CONCLUSION: For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes. IMPLICATIONS FOR PRACTICE: Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment.


Asunto(s)
Técnicas de Apoyo para la Decisión , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Medicina de Precisión/métodos , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/patología , Patología Molecular/métodos
11.
Hematol Oncol Clin North Am ; 38(1): 171-184, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37369612

RESUMEN

This review explores the effect of common everyday factors, such as alcohol, tea and coffee consumption, on the risk for lung cancer. We performed an umbrella review of current systematic reviews. The risk for lung cancer was increased with alcohol or coffee intake and decreased with tea intake. While evidence for alcohol is of low quality, the effect of coffee may be confounded by the smoking effect. The protective effect of tea intake is present, but the evidence is also of low quality.


Asunto(s)
Café , Neoplasias Pulmonares , Humanos , , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/prevención & control , Fumar/efectos adversos , Fumar/epidemiología , Estilo de Vida
12.
Hematol Oncol Clin North Am ; 38(1): 199-207, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37442675

RESUMEN

Due to the current limited capacity to provide digital mammography-based screening to all women, and the lack of modern surgical oncology methods, mastectomy is still the predominant form of surgical treatment in many parts of the world. As such there is little incentive to detect breast cancer earlier and significant fear of treatment and outcomes continues to contribute to late presentations. Neoadjuvant chemotherapy, pre-operative breast MRI and surgical mapping techniques can combine forces to allow for more women to be treated with breast conservation, decrease fear of treatment and improve outcomes.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Mastectomía/métodos , Kosovo , Mamografía , Terapia Neoadyuvante
13.
Hematol Oncol Clin North Am ; 38(1): 77-85, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37429789

RESUMEN

The resilience of the system in most specialized oncological institutions in Ukraine should be acknowledged, as well as the level of provision of high-quality special care quickly recovered in the center and areas close to a war zone. This situation has undoubtedly impacted global cancer research progress, as Ukraine is an important venue for many cancer trials.


Asunto(s)
Neoplasias , Humanos , Ucrania/epidemiología , Neoplasias/epidemiología , Neoplasias/terapia , Oncología Médica
14.
Hematol Oncol Clin North Am ; 38(1): 229-238, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37516631

RESUMEN

Although current value frameworks and economic models have allowed us to better quantify the net benefit associated with cancer therapy, holistic cancer care must consider patient time, family and social values, and overall life expectancy. Training programs must include training in health services research, difficult conversations, and shared decision-making strategies that are developed in social and cultural frameworks for their settings.


Asunto(s)
Países en Desarrollo , Neoplasias , Humanos , Neoplasias/terapia
15.
Hematol Oncol Clin North Am ; 38(1): 137-170, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37635047

RESUMEN

Lifestyle factors play a major role in the risk of breast cancer. This review aimed to examine the size of the effect of select lifestyle factors on risk for breast cancer and assess the quality of existing evidence. The authors performed an umbrella review of systematic reviews. The authors found an increased risk for breast cancer associated with obesity, alcohol intake, and smoking and a decreased risk due to physical activity. The evidence for sleep disruption and duration indicates risk for breast cancer, but it is limited in size, statistical significance, and quality of evidence.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Índice de Masa Corporal , Revisiones Sistemáticas como Asunto , Obesidad/epidemiología , Obesidad/complicaciones , Estilo de Vida , Factores de Riesgo
16.
Hematol Oncol Clin North Am ; 38(1): 185-197, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37635048

RESUMEN

Our international partnerships have fostered longstanding collaborative relationships leading to the development of unique, locally-designed, and sustainable training programs that serve as models for global health education and cooperation.


Asunto(s)
Educación a Distancia , Modelos Educacionales
17.
NPJ Breast Cancer ; 10(1): 93, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39426965

RESUMEN

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2- breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87-0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78-0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

18.
bioRxiv ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39386444

RESUMEN

Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease. Using CRISPR-Cas9 genome-wide knockout screening in ER+ breast cancer cells, we identified a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration in endocrine-tolerant persister cells. Quantitative proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters where oxidative phosphorylation was required to generate ATP. A phase II clinical trial was conducted to evaluate changes in mitochondrial markers in primary ER+/HER2-breast tumors induced by neoadjuvant endocrine therapy ( NCT04568616 ). In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content. Genetic profiling and barcode lineage tracing showed that endocrine-tolerant persistence occurred stochastically without genetic predisposition. Mice bearing cell line- and patient-derived xenografts were used to measure the anti-tumor effects of mitochondrial complex I inhibition in the context of endocrine therapy. Pharmacological inhibition of complex I suppressed the tumor-forming potential of persisters and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts. These findings indicate that mitochondrial metabolism is essential in endocrine-tolerant persister ER+ breast cancer cells and warrant the development of treatment strategies to leverage this vulnerability in the context of endocrine-sensitive disease. Statement of Significance: Endocrine-tolerant persister cancer cells that survive endocrine therapy can cause recurrent disease. Persister cells exhibit increased energetic dependence upon mitochondria for survival and tumor re-growth potential.

19.
JAMA Netw Open ; 7(3): e242478, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38517442

RESUMEN

Importance: Following treatment, breast cancer survivors face challenges participating in valued activities. Objective: To determine whether a telephone-based coaching rehabilitation intervention enhances activity participation in the year following breast cancer treatment. Design, Setting, and Participants: In this multisite, single-blind randomized clinical trial (Optimizing Functional Recovery of Breast Cancer Survivors), recruitment occurred between August 28, 2019, and April 30, 2022. Data collection was completed by April 1, 2023. Participants were recruited from 2 cancer centers (Dartmouth College and the University of Alabama at Birmingham) and via social media advertisements. Women aged 18 years or older who had completed primary treatment for stage I to III breast cancer within 1 year and reported participation restrictions were eligible to participate. Randomization was stratified by site, treatment, and time since treatment. Interventions: The intervention, delivered via telephone over 9 sessions, used behavioral activation and problem-solving principles to promote activity participation. The education-based attention control condition was delivered via telephone at matched intervals. Main Outcomes and Measures: The primary outcome was participation, assessed using 5 measures, including Patient-Reported Outcomes Measurement Information System (PROMIS) social participation-satisfaction measure. One individualized outcome allowed participants to specify activities for which they wanted to foster recovery. Outcomes were collected by telephone by blinded coordinators at baseline and at 8, 20, and 44 weeks. The individualized outcome was assessed at the first and last intervention and control session. Results: Among 1996 patients identified, 303 were eligible and enrolled. Of these, 284 women (94%; mean [SD] age, 56.1 [10.2] years) completed baseline assessments and were randomized, and 81% or more of each group completed the final assessment with no adverse events. Of those who completed the final assessment, 118 of 114 (82%) were in the intervention group, and 113 of 140 (81%) were attention control participants. Between-group differences were not statistically significant for the main measures of PROMIS satisfaction (week 20: Cohen d, 0.1 [95% CI, -0.09 to 0.29] and week 44: Cohen d, -0.08 [95% CI, -0.27 to 0.11]) and ability (week 20: Cohen d, 0.15 [95% CI, -0.06 to 0.37] and week 44: Cohen d, -0.08 [95% CI, -0.27 to 0.11]). On the individualized outcome, intervention participants reported significantly greater improvements in activity satisfaction (Cohen d, 0.76 [95% CI, 0.48-1.02]) and performance (Cohen d, 0.60 [95% CI, 0.32-0.87]). Conclusions and Relevance: In this randomized clinical trial, the intervention catalyzed greater improvements in self-selected activity participation and goal disengagement but did not otherwise accelerate recovery compared with the control condition. Future research should determine what intervention features may lead to the greatest reductions in participation restrictions and other measures that may detect functional recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT03915548.


Asunto(s)
Neoplasias de la Mama , Medicina , Femenino , Humanos , Persona de Mediana Edad , Recuperación de la Función , Método Simple Ciego , Teléfono , Adolescente , Adulto Joven , Adulto , Anciano
20.
Ecancermedicalscience ; 17: 1631, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38414961

RESUMEN

Introduction: Cancer is a growing public health concern in Africa, especially in low- and middle-income countries (LMICs) like Rwanda. Increased cancer incidences translate into increased utilisation of cancer medicine. Access to affordable cancer medicines in Rwanda is a pressing issue as the National Health Insurance plan does not provide coverage for cancer medicines. In this study, we investigated the utilisation patterns of cancer medicines in Rwanda. Methods: This retrospective cross-sectional study was conducted at all referral hospitals (n = 3) capable of delivering chemotherapy in Rwanda. The data collection was over a period of 6 months, during which a team of trained research assistants reviewed a convenience sample of selected patient charts. Both paper charts and electronic medical records were used to collect patients' data, including cancer type, stage, treatment setting, type of drugs or regimen used and completed cycles. Data were analysed using descriptive statistics. Results: A total of 630 patients received chemotherapy during the study period and were included. Seventy-seven percent (n = 486) were female and mean age was 51 (SD ± 13). Among all patients receiving chemotherapy, 43% (n = 270) had breast cancer, 22% (n = 140) had cervical cancer and 19% (n = 121) had colorectal cancer. The majority of patients (71%) had a community-based insurance. Butaro Cancer Centre treated the most patients (48%, n = 303). Thirty-six percent (221/630) had stage III cancer. The most common regimens within the cohort were adriamycin, cyclophosphamide and taxane, capecitabine and oxaliplatin (CAPOX), paclitaxel + carboplatin and a single agent cisplatin given concurrently with radiotherapy. The proportion of chemotherapy that was given in the curative and palliative setting was 72% and 28% respectively. Conclusion: Access to affordable cancer medicines remains a challenge in Rwanda. The study's findings provide valuable information on the utilisation patterns of cancer medicines in Rwanda, which can be used to guide policy decisions and improve cancer care in the country.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA