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1.
Blood Rev ; 65: 101169, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38220565

RESUMO

In the recent few decades, outcomes in patients diagnosed with hematological malignancies have been steadily improving. However, the improved prognosis does not distribute equally among patients from different backgrounds. Besides cancer biology, demographic and geographic disparities have been found to impact overall survival significantly. Specifically, patients from underrepresented minorities including Black and Hispanics, and those with uninsured status, having low socioeconomic status, or from rural areas have had worse outcomes historically, which is uniformly true across all major subtypes of hematological malignancies. Similar discrepancy is also seen in the health care professional field, where a gender gap and a disproportionally low representation of health care providers from underrepresented minorities have been long existing. Thus, a comprehensive strategy to mitigate disparity in the health care system is needed to achieve equity in health care.


Assuntos
Neoplasias Hematológicas , Hispânico ou Latino , Humanos , Pessoal de Saúde , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Prognóstico , Estados Unidos , Brancos , Negro ou Afro-Americano
2.
Cancer ; 130(9): 1600-1608, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100492

RESUMO

BACKGROUND: Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations. METHODS: This was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu-positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were analyzed by BRCA mutation status. Univariate and multivariable Cox proportional hazards regression models were used to analyze the association between clinical variables and outcomes. RESULTS: Of 1099 patients with HER2/neu-positive BC, 73 (6.6%) tested positive for BRCA1/2 mutations. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. At a median follow-up of 78.6 months, the 5-year recurrence-free survival rate was 85% in BRCA carriers and 87% in noncarriers (p = .79), and the 5-year overall survival rate was 94% in BRCA carriers and 94% in noncarriers (p = .78). In a multivariable model, BRCA was not associated with recurrence-free survival (hazard ratio, 0.99; 95% confidence interval, 0.51-1.90; p = .96) or overall survival (hazard ratio, 0.83; 95% confidence interval, 0.33-2.07; p = .69). CONCLUSIONS: BRCA1/2 mutations occurred in 6.6% of patients with HER2/neu-positive BC and did not affect survival outcomes. Assessing the potential benefits of new treatment strategies, such as combining anti-HER2/neu therapies with poly(ADP-ribose) polymerase inhibitors, may lead to enhanced outcomes for these patients.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Células Germinativas , Mutação em Linhagem Germinativa , Mutação , Inibidores de Poli(ADP-Ribose) Polimerases , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Análise de Sobrevida
3.
Acta Haematol ; 146(6): 431-457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37459852

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a disease of the hematopoietic system that remains a therapeutic challenge despite advances in our understanding of the underlying cancer biology in the past decade. It is also an affliction of the elderly that predominantly affects patients over 60 years of age. Standard therapy involves intensive chemotherapy that is often difficult to tolerate in older populations. Fortunately, recent developments in molecular targeting have shown promising results in treating leukemia, paving the way for novel treatment strategies that are easier to tolerate. SUMMARY: Venetoclax, a BCL-2 inhibitor, when combined with a hypomethylating agent, has proven to be a highly effective and well-tolerated drug and established itself as a new standard for treating AML in patients who are unfit for standard intensive therapy. Other targeted therapies include clinically proven and FDA-approved agents, such as IDH1/2 inhibitors, FLT3 inhibitors, and Gemtuzumab, as well as newer and more experimental drugs such as magrolimab, PI-kinase inhibitors, and T-cell engaging therapy. Some of the novel agents such as magrolimab and menin inhibitors are particularly promising, providing therapeutic options to a wider population of patients than ever before. Determining who will benefit from intense or novel low-intense therapy remains a challenge, and it requires careful assessment of individual patient's fitness and disease characteristics. KEY MESSAGES: This article reviews past and current treatment strategies that harness various mechanisms of leukemia-targeting agents and introduces novel therapies on the horizon aimed at exploring therapeutic options for the elderly and unfit patient population. It also provides a strategy to select the best available therapy for elderly patients with both newly diagnosed and relapsed/refractory AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Idoso , Pessoa de Meia-Idade , Antineoplásicos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Clin Breast Cancer ; 19(2): e343-e351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30527350

RESUMO

BACKGROUND: Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer. MATERIALS AND METHODS: The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan-Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival. RESULTS: The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching. CONCLUSION: Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Adulto , Idoso , Encéfalo/patologia , Encéfalo/efeitos da radiação , Irradiação Craniana , Bases de Dados Factuais , Feminino , Disparidades em Assistência à Saúde , Humanos , Pessoa de Meia-Idade , Pontuação de Propensão , Radiocirurgia , Fatores Socioeconômicos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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