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1.
J Am Acad Dermatol ; 90(2): 288-298, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37797836

RESUMEN

BACKGROUND: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. OBJECTIVE: To develop time-to-event risk prediction models for melanoma metastatic recurrence. METHODS: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. RESULTS: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. LIMITATIONS: Retrospective nature and cohort from one geography. CONCLUSIONS: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología
2.
J Am Acad Dermatol ; 88(6): 1308-1316, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36828138

RESUMEN

BACKGROUND: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes. OBJECTIVE: Examine the impact of melanoma subtypes on cirAE onset and survival among ICI recipients. METHODS: Retrospective multi-institutional cohort study. Multivariate time-series regressions were utilized to assess relationships between melanoma subtype, cirAE development, and survival. RESULTS: Among 747 ICI recipients, 236 (31.6%) patients developed a cirAE. Patients with acral melanoma were less likely to develop a cirAE (hazard ratio [HR] = 0.41, P = .016) compared to patients with nonacral cutaneous melanoma. Across all melanoma subtypes, cirAEs were associated with reduced mortality (HR = 0.76, P = .042). Patients with acral (HR = 2.04, P = .005), mucosal (HR = 2.30, P < .001), and uveal (HR = 4.09, P < .001) primaries exhibited the worst survival. LIMITATIONS: Retrospective cohort study. CONCLUSION: This is the first study to demonstrate differences in cirAE development among melanoma subtypes. The presence of cirAEs was associated with better survival. Further, the lower incidence of cirAEs may be a marker of immunotherapy response, which is reflected in the association between acral melanoma and mortality.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/epidemiología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/epidemiología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Estudios de Cohortes , Incidencia , Melanoma Cutáneo Maligno
3.
Breast Cancer Res Treat ; 174(2): 505-514, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30560462

RESUMEN

PURPOSE: Distant relapse metastatic breast cancer (rMBC) incidence and survival are vital measures of breast cancer diagnosis and treatment progress over time. METHODS: We conducted a retrospective cohort study of stage I-III invasive breast cancer, 1990-2011, follow-up through 2016 [N = 8292, rMBC = 964 (12%)] at a community-based institution. Patient and tumor characteristics (treatment, distant recurrence, vital status) from BC registry data were evaluated. Survival analysis and Cox proportional hazards (HzR) with 95% confidence intervals (95% CI) were calculated using distant recurrence and distant disease-specific survival (DDSS) endpoints. RESULTS: Both 5- and 10-year distant relapse (rMBC) declined over time from 1990-1998 to 2005-2011 [11% to 5%, 16% to 8% (p < 0.001)]. Proportionately, HER2 + BC distant relapse decreased 9% and triple negative (HR-/HER2-) increased 8% (p = 0.011). In the Cox model, lower stage [stage I: HzR = 0.08 (0.07, 0.10), stage II: 0.29 (0.25, 0.33)], more recent diagnosis years [1999-2004: HzR = 0.60 (0.51, 0.70), 2005-2011: HzR = 0.44 (0.38, 0.52)], HR+ [HzR = 0.62 (0.53, 0.72)], and age 40+ [HzR = 0.81 (0.67, 0.98)] had decreased rMBC risk. Compared to HR+/HER2- BC, triple-negative BC had increased rMBC risk [HzR = 2.02 (1.61, 2.53)] but HER2+ subtypes did not. HR-, age 70+, > 1, or visceral metastases and stage III disease were associated with worse DDSS. DDSS did not improve over time. CONCLUSION: rMBC incidence declined over time with decreased HER2-positive distant recurrence, a shift to more triple-negative BC and consistently poor distant disease survival.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/metabolismo , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
4.
Cancer Causes Control ; 30(2): 149-164, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30656540

RESUMEN

PURPOSE: We employed a city-level ecologic analysis to assess predictors of race-specific (black and white) breast cancer mortality rates. METHODS: We used data from the National Center for Health Statistics and the US Census Bureau to calculate 2010-2014 race-specific breast cancer mortality rates (BCMR) for 47 of the largest US cities. Data on potential city-level predictors (e.g., socioeconomic factors, health care resources) of race-specific BCMR were obtained from various publicly available datasets. We constructed race-specific multivariable negative binomial regression models to estimate rate ratios (RR) and 95% confidence intervals (CIs). RESULTS: Predictors of the white BCMR included white/black differences in education (RR 0.95; CI 0.91-0.99), number of religious congregations (RR 0.87; CI 0.77-0.97), and number of Medicare primary care physicians (RR 1.15; CI 1.04-1.28). Predictors of the black rate included white/black differences in household income (RR 1.03; CI 1.01-1.05), number of mammography facilities (RR 1.07; CI 1.03-1.12), and mammogram use (RR 0.93; CI 0.89-0.97). CONCLUSIONS: Our ecologic analysis found that predictors of breast cancer mortality differ for the black and white rate. The results of this analysis could help inform interventions at the local level.


Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Población Blanca/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Ciudades/epidemiología , Ciudades/etnología , Femenino , Humanos , Mamografía/estadística & datos numéricos , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Factores Socioeconómicos , Estados Unidos/epidemiología , Estados Unidos/etnología
5.
Breast Cancer Res Treat ; 149(1): 255-61, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25504083

RESUMEN

Breast cancer (BC) has been associated with pregnancy if diagnosed within 5-10 years after delivery (pregnancy-associated BC, PABC). PABC carries a poor prognosis compared to sporadic BC in Western populations. Data are limited regarding PABC in Asian populations, where longer periods of breastfeeding, higher birth rates and a lower median age of BC at diagnosis have been noted, all of which are known to influence prognosis. We used two datasets of women treated for early BC in Shanghai 1990-2012 (n = 10,161 and n = 7,411). For the analysis of BC risk after pregnancy we compared the distribution of pregnancy in our dataset to that in Shanghai using age-specific fertility rates. For disease-free survival (DFS) evaluation, we restricted our data to women ≤45 years. Women <30 years had a significantly elevated BC risk within 5 years of completing a pregnancy compared to women who had not been pregnant in the previous 5 years. In women aged 20-24 the relative risk (RR) was 3.33 (P = 0.012), and for women aged 25-29 the RR was 1.76 (P = 0.0074). For women >30, the RR was decreased. Patients with PABC had a higher risk of recurrence or death (hazard ratio (HR) for DFS 1.72, P = 0.019) compared to women with non-PABC by univariable analysis. Age was eliminated from the multivariable model by backward selection, resulting in tumor stage (3 versus 1, HR 3.08, P < .001) and recent pregnancy (HR 1.62, P < 0.05) as significant independent prognosticators. Having had a full-term pregnancy in the previous 5 years was associated with a 62 % increased risk of recurrence. We show that recent full-term pregnancy significantly elevates BC risk in women <30 in Shanghai, and that women diagnosed with PABC have a particularly adverse prognosis. Health care providers and women in Asian populations should be made aware of these results.


Asunto(s)
Neoplasias de la Mama/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Neoplásicas del Embarazo/epidemiología , Adulto , Factores de Edad , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , China , Supervivencia sin Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/patología , Periodo Posparto , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Pronóstico
6.
Lancet Oncol ; 15(5): 489-538, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24731404

RESUMEN

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.


Asunto(s)
Neoplasias/terapia , Anciano , Anciano de 80 o más Años , Alcoholismo/epidemiología , Neoplasias de la Mama/diagnóstico , China , Neoplasias Colorrectales/diagnóstico , Características Culturales , Detección Precoz del Cáncer/tendencias , Desarrollo Económico/tendencias , Contaminación Ambiental/efectos adversos , Etnicidad , Femenino , Servicios de Salud/economía , Accesibilidad a los Servicios de Salud/tendencias , Fuerza Laboral en Salud/tendencias , Disparidades en Atención de Salud/tendencias , Humanos , India , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Neoplasias/prevención & control , Servicios de Salud Rural/tendencias , Federación de Rusia/epidemiología , Sexismo , Fumar , Estigma Social , Servicios Urbanos de Salud/tendencias
7.
Cancer Causes Control ; 25(7): 859-68, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24801045

RESUMEN

PURPOSE: Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype. METHODS: The Marin Women's Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry. RESULTS: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants. CONCLUSION: These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.


Asunto(s)
Neoplasias de la Mama/epidemiología , Mama/patología , Hipertensión Inducida en el Embarazo , Glándulas Mamarias Humanas/anomalías , Receptor IGF Tipo 1/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Factores de Edad , Anciano , Densidad de la Mama , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/genética , Estudios Transversales , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Embarazo
8.
Crit Rev Oncol Hematol ; 196: 104289, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38341119

RESUMEN

New treatments have increased survival of patients with melanoma, and methods to monitor patients throughout the disease process are needed. Circulating tumor DNA (ctDNA) is a predictive and prognostic biomarker that may allow routine, real-time monitoring of disease status. We surveyed 44 US physicians to understand their preferences and practice patterns for biomarker and ctDNA testing in their patients with melanoma. Tumor biomarker testing was often ordered in stage IIIA-IV patients. Barriers to biomarker testing include insufficient tissue (60%) and lack of insurance coverage (54%). ctDNA testing was ordered by 16-18% of physicians for stages II-IV. Reasons for not using ctDNA testing included lack of prospective data (41%), ctDNA testing used for research only (18%), and others. Physicians (≥74%) believed that ctDNA assays could help with monitoring and treatment selection throughout the disease process. Physicians consider ctDNA testing potentially valuable for clinical decision-making but cited concerns that should be addressed.


Asunto(s)
ADN Tumoral Circulante , Melanoma , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , ADN Tumoral Circulante/genética , Biomarcadores de Tumor/genética , Proteínas Proto-Oncogénicas B-raf/genética , Mutación
9.
BMC Public Health ; 13: 1169, 2013 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-24330527

RESUMEN

BACKGROUND: The 2009 U.S. Preventive Services Task Force (USPSTF) changed mammography guidelines to recommend routine biennial screening starting at age 50. This study describes women's awareness of, attitudes toward, and intention to comply with these new guidelines. METHODS: Women ages 40-50 years old were recruited from the Boston area to participate in focus groups (k = 8; n = 77). Groups were segmented by race/ethnicity (Caucasian = 39%; African American = 35%; Latina = 26%), audio-taped, and transcribed. Thematic content analysis was used. RESULTS: Participants were largely unaware of the revised guidelines and suspicious that it was a cost-savings measure by insurers and/or providers. Most did not intend to comply with the change, viewing screening as obligatory. Few felt prepared to participate in shared decision-making or advocate for their preferences with respect to screening. CONCLUSIONS: Communication about the rationale for mammography guideline changes has left many women unconvinced about potential disadvantages or limitations of screening. Since further guideline changes are likely to occur with advances in technology and science, it is important to help women become informed consumers of health information and active participants in shared decision-making with providers. Additional research is needed to determine the impact of the USPSTF change on women's screening behaviors and on breast cancer outcomes.


Asunto(s)
Mamografía/normas , Adulto , Actitud Frente a la Salud , Etnicidad , Femenino , Grupos Focales , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Humanos , Mamografía/psicología , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Grupos Raciales , Estados Unidos
10.
J Public Health Manag Pract ; 19(5): 461-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23266756

RESUMEN

CONTEXT: Avon Foundation for Women grantees provide breast cancer services through patient navigation (PN) in an effort to alleviate barriers to care among underserved women. OBJECTIVE: To gain a better understanding of how PN programs function, this study explores variations in the use of navigators, types of services offered, description of clients they serve, tracking of treatment completion, and evaluation mechanisms. PARTICIPANTS: Fifty-six Avon PN programs funded since 2008 throughout the United States were contacted. DESIGN: An online survey was distributed to the grantees of which 44 (81%) complete responses were collected and analyzed. RESULTS: Clients were racially and ethnically diverse, mostly in the 40- to 64-year old age range (64%) and 91.6% with an average income of less than $30 000. Women were either uninsured (50.7%) or receiving Medicaid (32.4%). PN programs were both community and hospital-based (22.5%); many hospitals (35.2%) were described as safety nets (eg, provide a significant level of care to low-income, uninsured, vulnerable populations). On-site services included breast screening (eg, mammography and breast ultrasound) and treatment (eg, breast surgery and radiation therapy). Some barriers to care identified by the programs included transportation, access to appointments, language, and financial issues (eg, cost of screening and treatment specifically for those uninsured). More than 39% of programs provided care across the cancer continuum. CONCLUSIONS: Many Avon PN programs incorporated navigation services that span the cancer care continuum. They addressed disparities by offering navigation and on-site medical services to reduce multiple systems barriers and social issues related to breast care.


Asunto(s)
Neoplasias de la Mama , Fundaciones , Accesibilidad a los Servicios de Salud , Navegación de Pacientes/organización & administración , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Barreras de Comunicación , Femenino , Humanos , Persona de Mediana Edad , Navegación de Pacientes/métodos , Evaluación de Programas y Proyectos de Salud , Proveedores de Redes de Seguridad , Estados Unidos , Poblaciones Vulnerables
11.
J Immunother Cancer ; 11(5)2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37137552

RESUMEN

With multiple PD-(L)1 inhibitors approved across dozens of indications by the US Food and Drug Administration, the number of patients exposed to these agents in adjuvant, first-line metastatic, second-line metastatic, and refractory treatment settings is increasing rapidly. Although some patients will experience durable benefit, many have either no clinical response or see their disease progress following an initial response to therapy. There is a significant need to identify therapeutic approaches to overcome resistance and confer clinical benefits for these patients. PD-1 pathway blockade has the longest history of use in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Therefore, these settings also have the most extensive clinical experience with resistance. In 2021, six non-profit organizations representing patients with these diseases undertook a year-long effort, culminating in a 2-day workshop (including academic, industry, and regulatory participants) to understand the challenges associated with developing effective therapies for patients previously exposed to anti-PD-(L)1 agents and outline recommendations for designing clinical trials in this setting. This manuscript presents key discussion themes and positions reached through this effort, with a specific focus on the topics of eligibility criteria, comparators, and endpoints, as well as tumor-specific trial design options for combination therapies designed to treat patients with melanoma, NSCLC, or RCC after prior PD-(L)1 pathway blockade.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pulmonares , Melanoma , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Ensayos Clínicos como Asunto , Melanoma/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico
12.
JCO Glob Oncol ; 7: 602-610, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33909474

RESUMEN

The International Cancer Research Partnership (ICRP) is an active network of cancer research funding organizations, sharing information about funded research projects in a common database. Data are publicly available to enable the cancer research community to find potential collaborators and avoid duplication. This study presents an aggregated analysis of projects funded by 120 partner organizations and institutes in 2006-2018, to highlight trends in cancer research funding. Overall, the partners' funding for cancer research increased from $5.562 billion (bn) US dollars (USD) in 2006 to $8.511bn USD in 2018, an above-inflation increase in funding. Analysis by the main research focus of projects using Common Scientific Outline categories showed that Treatment was the largest investment category in 2018, followed by Early Detection, Diagnosis, and Prognosis; Cancer Biology; Etiology; Control, Survivorship, and Outcomes; and Prevention. Over the 13 years covered by this analysis, research funding into Treatment and Early Detection, Diagnosis, and Prognosis had increased in terms of absolute investment and as a proportion of the portfolio. Research funding in Cancer Biology and Etiology declined as a percentage of the portfolio, and funding for Prevention and Control, Survivorship and Outcomes remained static. In terms of cancer site-specific research, funding for breast cancer and colorectal cancer had increased in absolute terms but declined as a percentage of the portfolio. By contrast, investment for brain cancer, lung cancer, leukemia, melanoma, and pancreatic cancer increased both in absolute terms and as a percentage of the portfolio.


Asunto(s)
Investigación Biomédica , Neoplasias Pancreáticas , Bases de Datos Factuales , Humanos , Inversiones en Salud
13.
Clin Cancer Res ; 27(2): 394-401, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33188142

RESUMEN

Tremendous progress has been made in treating patients with metastatic melanoma over the past decade. In that timeframe, the FDA has approved 12 novel treatments for patients with advanced unresectable melanoma, comprising both kinase-targeted therapies and immune checkpoint inhibitors (ICI), and five treatments for adjuvant (postoperative) use in patients with high-risk resectable stage III melanoma. It is not known whether outcomes can be further improved by administering kinase inhibitors or ICI in the neoadjuvant (presurgical) setting in patients with high-risk resectable melanomas. Noting research community interest in exploring the neoadjuvant approach for treating melanoma and recognizing that early harmonization of methodologies may expedite the development of therapeutics in this space, the FDA and Melanoma Research Alliance convened a public workshop on November 6, 2019, in National Harbor, Maryland, to discuss key issues. The workshop consisted of 23 faculty and included more than 250 live participants. Topics discussed included opportunities for advancing novel endpoints for regulatory purposes as well as translational research, clinical trial design considerations, and strategies for optimizing patient selection while mitigating risk.


Asunto(s)
Investigación Biomédica/métodos , Congresos como Asunto , Melanoma/terapia , Terapia Neoadyuvante/métodos , Neoplasias Cutáneas/terapia , Investigación Biomédica/organización & administración , Quimioterapia Adyuvante/métodos , Humanos , Inmunoterapia/métodos , Melanoma/inmunología , Melanoma/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Estados Unidos , United States Food and Drug Administration
14.
Cancer Cell ; 39(5): 610-631, 2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-33545064

RESUMEN

There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.


Asunto(s)
Modelos Animales de Enfermedad , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Microambiente Tumoral/inmunología , Animales , Humanos , Inmunidad/inmunología , Inmunoterapia/métodos , Melanoma/patología , Neoplasias Cutáneas/patología
15.
Cancer Epidemiol Biomarkers Prev ; 26(6): 809-815, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28522448

RESUMEN

Background: Distant metastatic breast cancer (MBC), including metastases found at diagnosis (de novo) and those occurring later (recurrence), represents the most severe form of the disease, when resource utilization is most intensive. Yet, the number of women living with MBC in the United States is unknown. The objective of this article is to use population-based data to estimate the prevalence of MBC.Methods: We used a back-calculation method to estimate MBC prevalence from U.S. breast cancer mortality and survival from the Surveillance, Epidemiology and End Results (SEER) registries. On the basis of the illness-death process, this method assumes that each observed breast cancer death is the result of MBC, either de novo or a recurrence with metastatic disease.Results: We estimate that by January 1, 2017, there will be 154,794 women living with MBC in the United States, three in four initially diagnosed with stage I-III breast cancer who later progressed to MBC.Median survival and 5-year relative survival for de novo MBC increased over the years, especially in younger women. We estimate a two-fold increase in 5-year relative survival rate from 18% to 36%, for women diagnosed with de novo MBC at age 15-49 between 1992-1994 and 2005-2012, respectively.Conclusions: This study demonstrates an increasing number of women in the United States living with MBC, likely the result of improvements in treatment and aging of the U.S. POPULATION: Impact: The increasing burden of MBC highlights the importance of documenting recurrence to foster more research into the specific needs of this understudied population. Cancer Epidemiol Biomarkers Prev; 26(6); 809-15. ©2017 AACR.


Asunto(s)
Neoplasias de la Mama/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estados Unidos , Adulto Joven
16.
NPJ Breast Cancer ; 3: 7, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28649647

RESUMEN

Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an "atypical response" will increase understanding of the mechanisms involved in cancer progression and treatment resistance, accelerate biomarker identification, and improve precision medicine by allowing clinicians to prospectively select optimal treatments. Based on our review, we suggest two ways to move this field forward. First, we suggest that clear categorization of "atypical responders" is needed. This encompasses three sub-categories of patients: "exceptional responders" (those with an unusually favorable treatment response), "rapid progressors" (patients demonstrating an unusually poor or no therapeutic response), and "exceptional survivors" (patients who have far outlived their initial prognosis). Such categorization may depend upon the clinical context and disease subtype. Second, we suggest that atypical responses may be due not only to somatic mutations in tumors, but also to inherited polymorphisms in non-tumor tissue, host and tumor environments, lifestyle factors, co-morbidities, use of complementary and integrative medicine, and the interaction among these components. Here, we summarize new research initiatives exploring atypical responses, the potential reasons for atypical responses, and a strategic call to action. Rigorous studies of normal and atypical responses to treatment will be needed to strengthen understanding of the role of non-tumor factors. Clinical trial design for targeted and other types of therapies should be enhanced to collect data in a standardized manner beyond tumor genetics, resulting in more thorough study of the whole patient.

17.
Cancer Res ; 62(22): 6385-9, 2002 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-12438220

RESUMEN

The Sonic hedgehog (Shh) signaling pathway plays a critical role in normal cerebellar development and has been implicated in medulloblastomas, common malignant childhood tumors of the cerebellum. To test whether Shh mis-expression is sufficient for medulloblastoma formation, we used ultrasound biomicroscopy-guided in utero injection of a Shh-expressing retrovirus into the cerebellum of 13.5-day mouse embryos to show that direct activation of the Shh pathway can lead to tumor formation. Significantly, medulloblastomas were observed in 76% of the mice infected with Shh-expressing retrovirus. Furthermore, contrary to recent suggestions that the Shh transcriptional target Gli1 plays a critical role in Shh-induced tumorigenesis, we found that medulloblastomas form in Gli1 null mutant mice. We have developed an efficient mouse model of medulloblastoma and shown that Gli1 is not required for tumorigenesis when Shh signaling is activated upstream in the pathway.


Asunto(s)
Neoplasias Cerebelosas/etiología , Meduloblastoma/etiología , Proteínas Oncogénicas/genética , Transactivadores/fisiología , Factores de Transcripción/genética , Animales , Neoplasias Cerebelosas/genética , Cerebelo/embriología , Cerebelo/metabolismo , Femenino , Proteínas Hedgehog , Masculino , Meduloblastoma/genética , Ratones , Ratones Mutantes , Embarazo , Retroviridae/genética , Transducción de Señal/fisiología , Transactivadores/biosíntesis , Transactivadores/genética , Proteína con Dedos de Zinc GLI1
18.
Cancer Epidemiol ; 45: 169-173, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27720130

RESUMEN

INTRODUCTION: This paper presents race-specific breast cancer mortality rates and the corresponding rate ratios for the 50 largest U.S. cities for each of the 5-year intervals between 2005 and 2014. METHODS: The 50 largest cities in the U.S. were the units of analysis. Numerator data were abstracted from national death files where the cause was malignant neoplasm of the breast (ICD-10=C50) for women. Population-based denominators were obtained from the U.S. Census Bureau for 2010-2014. To measure the racial disparity, we calculated Black:White rate ratios (RRs) and confidence intervals for each 5-year period. To determine whether changes over time in the disparity were statistically significant, we calculated a 2-sided z score for the change in the relative percent difference between the Black and White rates for 2005-2009 and 2010-2014. RESULTS: At the most recent time point (2010-2014), the RR was significantly greater than 1.00 in the US and 24 cities. The change in the Black:White disparity was statistically significant in five cities and the US. The percent difference increased significantly in Atlanta, GA (from 4.1 to 117.4, p<0.001); San Antonio, TX (from 24.4 to 79.3, p=0.034); and the US (from 39.7 to 43.1, p=0.007). The percent difference decreased significantly in Memphis, TN (from 111.0 to 68.9, p=0.043); Philadelphia, PA (from 43.1 to 23.5, p=0.049); and Boston, MA (from 48.9 to 0.7, p=0.022). CONCLUSION: This analysis provides updated city-level breast cancer mortality data for Black and White women through 2014, and reveals that in the US and 24 of the 43 largest US cities, Black women continue to die from breast cancer at a higher rate than their White counterparts. Importantly, however, a few cities, Memphis, Boston and Philadelphia, showed a decrease in the Black:White breast cancer mortality disparity between 2005-2009 and 2010-2014.


Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Etnicidad/estadística & datos numéricos , Disparidades en el Estado de Salud , Población Blanca/estadística & datos numéricos , Femenino , Humanos , Tasa de Supervivencia , Factores de Tiempo , Estados Unidos/epidemiología
19.
Cancer Epidemiol ; 38(2): 118-23, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24602836

RESUMEN

INTRODUCTION: This paper presents race-specific breast cancer mortality rates and the corresponding rate ratios for the 50 largest U.S. cities for each of the 5-year intervals between 1990 and 2009. METHODS: The 50 largest cities in the U.S. were the units of analysis. Numerator data were abstracted from national death files where the cause was malignant neoplasm of the breast (ICD-9=174 and ICD-10=C50) for women. Population-based denominators were obtained from the U.S. Census Bureau for 1990, 2000, and 2010. To measure the racial disparity, we calculated non-Hispanic Black:non-Hispanic White rate ratios (RRs) and confidence intervals for each 5-year period. RESULTS: At the final time point (2005-2009), two RRs were less than 1, but neither significantly so, while 39 RRs were >1, 23 of them significantly so. Of the 41 cities included in the analysis, 35 saw an increase in the Black:White RR between 1990-1994 and 2005-2009. In many of the cities, the increase in the disparity occurred because White rates improved substantially over the 20-year study period, while Black rates did not. There were 1710 excess Black deaths annually due to this disparity in breast cancer mortality, for an average of about 5 each day. CONCLUSION: This analysis revealed large and growing disparities in Black:White breast cancer mortality in the U.S. and many of its largest cities during the period 1990-2009. Much work remains to achieve equality in breast cancer mortality outcomes.


Asunto(s)
Población Negra/estadística & datos numéricos , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Disparidades en el Estado de Salud , Población Blanca/estadística & datos numéricos , Ciudades/epidemiología , Femenino , Humanos , Estados Unidos/epidemiología
20.
J Healthc Qual ; 36(6): 47-53, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24033402

RESUMEN

This study compares rates of completion of client intake forms (CIFs) collected via three interview modes: audio computer-assisted self-interview (ACASI), face-to-face interview (FFI), and self-administered paper-based interview (SAPI). A total of 303 clients served through the Avon Breast Health Outreach Program (BHOP) were sampled from three U.S. sites. Clients were randomly assigned to complete a standard CIF via one of the three interview modes. Logistic regression analyses demonstrated that clients were significantly more likely to complete the entire CIF via ACASI than either FFI or SAPI. The greatest observed differences were between ACASI and SAPI; clients were almost six times more likely to complete the CIF via ACASI as opposed to SAPI (AOR = 5.8, p < .001). We recommend that where feasible, ACASI be utilized as an effective means of collecting client-level data in healthcare settings. Adoption of ACASI in health centers may translate into higher completion rates of intake forms by clients, as well as reduced burden on clinic staff to enter data and review intake forms for completion.


Asunto(s)
Computadores/estadística & datos numéricos , Recolección de Datos/métodos , Entrevistas como Asunto/métodos , Encuestas y Cuestionarios/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estados Unidos , Adulto Joven
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