RESUMO
Breast cancer (BCa) has long been a health burden to women across the globe. However, the burden is not equally carried across races. Though the manifestation and behavior of BCa differs among racial groups, the racial representation of models used in preclinical trials and clinical trial participants lacks this heterogeneity. Women of African Ancestry (WAA) are disproportionately afflicted by having an increased risk of developing BCas that are more aggressive in nature, and consequently suffer from poorer outcomes relative to women of European ancestry (WEA). Notwithstanding this, one of the most commonly used tools in studying BCa, cell lines, exhibit a sizeable gap in cell line derivatives of WEA relative to WAA. In this review, we summarize the available BCa cell lines grouped by race by major suppliers, American Type Culture Collection (ATCC) and the European Collection of Authenticated Cell Cultures (ECACC). Next, examined the enrollment of WAA in clinical trials for BCa. Of the cell lines found provided by ATCC and ECACC, those derived from WEA constituted approximately 80% and 94%, respectively. The disparity is mirrored in clinical trial enrollment where, on average, WEA made up more than 70% of participants in trials found where ancestry information was provided. As both experimental models and clinical trial participants primarily consist of WEA, results may have poorer translatability toward other races. This highlights the need for greater racial diversity at the preclinical and clinical levels to more accurately represent the population and strengthen the translatability of results.
Assuntos
Neoplasias da Mama , População Branca , População Negra , Feminino , HumanosRESUMO
BACKGROUND: Breast cancer is the leading cause of cancer and cancer related deaths in Jamaican women. In Jamaica, women often present with advanced stages of breast cancer, despite the availability of screening mammography for early detection. The utilization of screening mammography for early breast cancer diagnosis seems to be limited, and this study investigated the national patterns of mammographic screening and the impact of mammography on the diagnosis of breast cancer in Jamaica. METHODS: A retrospective analysis of the records of the largest mammography clinic in Jamaica was done for the period January 2011 to December 2016. Descriptive statistics was performed on relevant patient characteristics with calculation of rates and proportions; cross-tabulations were utilized to assess relationship of covariates being studied on the outcomes of interest. Results are reported in aggregate form with no identifiable patient data. RESULTS: 48,203 mammograms were performed during the study period. 574 women (1.2%) had mammograms suspicious for breast cancer with median age of 57 years (range 30-95 years); 35% were under the age of 50. 4 women with suspicious findings had undergone 'screening mammography', with the remaining having 'diagnostic mammography'. 38% reported previous mammograms, with a mean interval of 8 years between previous normal mammogram and mammogram suspicious for breast cancer. Median age at first screening mammogram was 51 years (range 41-77). CONCLUSION: Breast cancer screening mammography is underutilized in Jamaica. An organized national breast cancer screening programme is recommended to improve adherence to international breast cancer screening guidelines.
Assuntos
Neoplasias da Mama , Mamografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Renal cell carcinoma (RCC) accounts for 2% of all adult malignancies and is associated with a case fatality rate as high as 40%. RCC has been on the rise for the last 6 decades at a steady increase of 2% per annum. Much work has been done to uncover the pathogenesis of the disease and the role of angiogenesis has been a recurrent denominator connected to vascular endothelial growth factor (VEGF) and its downstream effectors along with the mammalian target of rapamycin (mTOR) mediated signal transduction pathway. OBJECTIVE: This review will discuss relevant inhibitors of key biomarkers to the disease in hopes of paving the way for novel treatments geared towards improving RCC morbidity and mortality rates. RESULTS AND CONCLUSION: Currently, treatment of advanced RCC includes one or more of the following: partial or radical nephrectomy, systemic therapy, immunotherapy and targeted therapy. Still drug resistance continues to be a challenge to many of the approved drugs and those undergoing clinical trials. However, the inclusion of targeted therapies has improved advanced RCC treatment success rates over that of surgery alone, and over that of the use of traditional chemotherapy for this relatively chemo-resistant disease. In an era of personalized medicine, research utilizing a polypharmacology approach could enhance efficacy of drug leads to treating RCC.
Assuntos
Inibidores da Angiogênese/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/metabolismo , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/metabolismo , Terapia de Alvo Molecular , Medicina de Precisão , Transdução de Sinais/efeitos dos fármacosRESUMO
We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer.
RESUMO
BACKGROUND: We investigated the prevalence of Lynch syndrome as a hereditary cause of colon cancer in the young Jamaican colorectal cancer (CRC) population. METHODS: We identified patients aged 40 years or younger in whom primary CRC was diagnosed at the University Hospital of the West Indies from January 2004 to December 2008. We reviewed the medical records and hematoxylin and eosin (H&E)-stained histopathology slides. Tumour blocks were tested for microsatellite instability (MSI). Patients with MSI-high phenotype (MSI-H) tumours had genetic counselling, after which genomic DNA was extracted from peripheral blood to test for MLH1 and MSH2 germline mutations. Patients also had pedigree mapping. RESULTS: There were 25 patients with CRC aged 40 years or younger with no history of hereditary colon cancer syndrome. The patients' mean age was 33 (range 21-40) years. Histopathologic review confirmed CRC in all patients; 8 of 25 (32%) showed morphologic features suggestive of MSI. We detected MSI-H in 5 of 23 (22%) tumour blocks tested. Review with H&E staining correctly identified 80% of cases positive for MSI-H. The false-positive rate and positive predictive value on H&E review was 50%. The negative predictive value of histomorphologic H&E review was 94%. Three patients were available for and had mutational analysis of DNA mismatch repair genes; 2 were positive for mutations in keeping with Lynch syndrome and 1 had MLH1 alterations of uncertain significance. All 3 met the Amsterdam criteria for hereditary nonpolyposis CRC. CONCLUSION: Thirteen percent of the population had mutations in keeping with Lynch syndrome. This prevalence is similar to that reported for white populations.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , População Negra/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Mutação em Linhagem Germinativa , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Fatores de Confusão Epidemiológicos , Análise Mutacional de DNA , Feminino , Humanos , Jamaica/epidemiologia , Masculino , Proteína 1 Homóloga a MutL , Linhagem , Valor Preditivo dos Testes , Projetos de Pesquisa , Estudos RetrospectivosRESUMO
BACKGROUND: A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. METHODS: Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. CONCLUSIONS: The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.