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Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer
No full textBackground: In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.
Methods: Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.
Results: In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.
Conclusions: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.)
Herbal Medicine Practices of Patients With Liver Cancer in Peru: A Comprehensive Study Toward Integrative Cancer Management
No full textRationale: The highest burden of liver cancer occurs in developing countries, where the use of herbal medicine (HM) is still widespread. Despite this trend, few studies have been conducted to report HM practices of patients with a hepatic tumor in the developing world. Hence, this study aimed to document the use of HM among patients with liver cancer in Peru.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: TRR was a recipient of a doctoral fellowship from Innóvate Perú (069-FINCyT-BDE-2014)||JPC was a recipient of a doctoral fellowship from the Peruvian National Council for Science and Technology (212-2015-FONDECYT)||ER and FD were supported by the Young Research Teams Associated with IRD Program (JEAI-INCAncer)||and GB, PP, JG, ED, and SB were supported by the Third Cancer Plan of the French National Alliance for Life Sciences and Health (ENV201408)
Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden
No full textIn Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1-6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas' indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.This study was funded by the French National League against Cancer (team label LNCC) and Odyssey-RE; E.D., S.B., and P.P. were supported by the Third Cancer Plan, ITMO Cancer of the French National Alliance for Life Sciences and Health (ENV201408); J.P.C. was a recipient of a doctoral fellowship from the Peruvian National Council for Science and Technology (212-2015-FONDECYT); L.C. was a recipient of a doctoral fellowship from French National Research Institute for Sustainable Development (IRD) (EMHE-ARTS-2016-878573B); and L.C., E.R., and S.C. were supported by the Young Research Teams Associated with IRD Program (INCAncer). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors wish to acknowledge all patients whose participation was essential to the achievement of this study. The authors are grateful to Karina Cancino, Dany Cordova, Franco Doimi, Macarena Farías, and Maricarmen Valera from the Cancer Research Biobank of the Department of Pathology of INEN for their leadership in aggregating the medical records and collecting the biomedical specimens. We thank Damien Mornico for his considerable help in viral sequence submissions and Lucas Robinson for his valuable editorial assistance
Phase I/II study on kilovoltage surface brachytherapy in conjunctival cancer: preliminary results
No full textIntroduction: In ocular conjunctival carcinoma after surgery, adjuvant treatment has a role and kilovoltage surface brachytherapy opens a new door for the range of therapeutic options. Materials and methods: Between October 2014 and June 2017, at the National Institute of Neoplastic Diseases (INEN) from Peru, 39 patients with squamous cell carcinoma of ocular conjunctiva, T1-T3, resected, were selected to receive adjuvant treatment. The portable accelerator of 50-kV INTRABEAM (Carl Zeiss Meditec) was used, after local anaesthesia and blocking of ocular muscles movement. The doses used were 18 Gy for patients with free margins and 22 Gy for positive edges, according to calculation of equivalent dose of 2Gy per fraction of 46 and 66 Gy, respectively, assuming a tumoural α/β ratio of 8 Gy. The prescription was done to 2 mm depth. Results: The median age was 69 years, distributed evenly between both genders, with a median follow-up of 12 months. The surgical margins were 59% free and 41% committed, with no difference between the institutions where the surgery was performed (P = 0.069). The median tumour size was 7 mm with 2 mm of invasion, 61.5% was T2 and 35.9% T1. The mean time between surgery and irradiation was 1.5 months, 23.1% of patients developed grade I toxicity of spontaneous resolution, without evidence of greater degree in any case. The dose had no statistical relationship with toxicity (P = 0.533). One-year disease-free survival was 96.7%. Conclusions: Kilovoltage surface brachytherapy is an applicable and reproducible tool in the treatment of squamous cell carcinoma of ocular conjunctiva. The administered doses are well tolerated by patients with low levels of acute toxicity. Longer follow-up is needed to establish disease control rates and late toxicities
MGMT promoter methylation in Peruvian patients with glioblastoma
No full textPurpose: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation predicts the outcome and response to alkylating chemotherapy in glioblastoma. The aim of this study is to evaluate the prevalence of MGMT methylation in Peruvian glioblastoma cases. Patients and methods: We evaluated retrospectively 50 cases of resected glioblastoma during the period 2008-2013 at Instituto Nacional de Enfermedades Neoplasicas in Peru. Samples consisted of paraffin embedded and frozen tumour tissue. MGMT-promoter methylation status and the expression level of MGMT gene were evaluated by methylation-specific PCR and real-time PCR, respectively. Results: Unmethylated, methylated and partially methylated statuses were found in 54%, 20% and 26% of paraffin-embedded samples, respectively. Methylation status was confirmed in the Virgen de la Salud Hospital and frozen samples. There was an association between the status of MGMT-promoter methylation and the level of gene expression (p = 0.001). Methylation was associated with increased progression-free survival (p = 0.002) and overall survival (OS) (p < 0.001). Conclusion: MGMT-promoter methylation frequency in Peruvian glioblastoma is similar to that reported in other populations and the detection test has been standardised
Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer
No full textTriple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150-0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets
Breast cancer subtype and survival among Indigenous American women in Peru
No full textLatina women in the U.S. have relatively low breast cancer incidence compared to Non-Latina White (NLW) or African American women but are more likely to be diagnosed with the more aggressive "triple negative" breast cancer (TNBC). Latinos in the U.S. are a heterogeneous group originating from different countries with different cultural and ancestral backgrounds. Little is known about the distribution of tumor subtypes in Latin American regions. Clinical records of 303 female Peruvian patients, from the Peruvian National Cancer Institute, were analyzed. Participants were diagnosed with invasive breast cancer between 2010 and 2015 and were identified as residing in either the Selva or Sierra region. We used Fisher's exact test for proportions and multivariable Cox Proportional Hazards Models to compare overall survival between regions. Women from the Selva region were more likely to be diagnosed with TNBC than women from the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the hazard of mortality was 1.7 times higher in women from the Selva than the Sierra (p = 0.025); this survival difference appeared to be largely explained by differences in the prevalence of TNBC. Our results suggest that the distribution of breast cancer subtypes differs between highly Indigenous American women from two regions of Peru. Disentangling the factors that contribute to this difference will add valuable information to better target prevention and treatment efforts in Peru and improve our understanding of TNBC among all women. This study demonstrates the need for larger datasets of Latin American patients to address differences between Latino subpopulations and optimize targeted prevention and treatment
Emergence and spread of carbapenem-resistant Acinetobacter baumannii international clones II and III in Lima, Peru
No full textCarbapenem-resistant Acinetobacter baumannii is the top-ranked pathogen in the World Health Organization priority list of antibiotic-resistant bacteria. It emerged as a global pathogen due to the successful expansion of a few epidemic lineages, or international clones (ICs), producing acquired class D carbapenemases (OXA-type). During the past decade, however, reports regarding IC-I isolates in Latin America are scarce and are non-existent for IC-II and IC-III isolates. This study evaluates the molecular mechanisms of carbapenem resistance and the epidemiology of 80 non-duplicate clinical samples of A. baumannii collected from February 2014 through April 2016 at two tertiary care hospitals in Lima. Almost all isolates were carbapenem-resistant (97.5%), and susceptibility only remained high for colistin (95%). Pulsed-field gel electrophoresis showed two main clusters spread between both hospitals: cluster D containing 51 isolates (63.8%) associated with sequence type 2 (ST2) and carrying OXA-72, and cluster F containing 13 isolates (16.3%) associated with ST79 and also carrying OXA-72. ST2 and ST79 were endemic in at least one of the hospitals. ST1 and ST3 OXA-23-producing isolates were also identified. They accounted for sporadic hospital isolates. Interestingly, two isolates carried the novel OXA-253 variant of OXA-143 together with an upstream novel insertion sequence (ISAba47). While the predominant A. baumannii lineages in Latin America are linked to ST79, ST25, ST15, and ST1 producing OXA-23 enzymes, we report the emergence of highly resistant ST2 (IC-II) isolates in Peru producing OXA-72 and the first identification of ST3 isolates (IC-III) in Latin America, both considered a serious threat to public health worldwide.This study was supported by Cienciactiva of CONCYTEC, contract no. 164-2016-FONDECYT||Planes Nacionales de I+D+i 2008-2011/2013-2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0013 and REIPI RD16/0016/ 0010)||the 2017 call for Strategic Action on Health (PI17/01932), co-financed by European Development Regional Fund “A way to achieve Europe” and operative program Intelligent Growth 2014-2020||and grant 2014 SGR 0653 from the Departament d’Universitats, Recerca i Societat de la Informació, of the Generalitat de Catalunya. I.R. was supported by the Department of Health, Generalitat de Catalunya, grant SLT002/16/00349. Part of these data have been presented as a poster communication at the 18th International Congress on Infectious Diseases, 3–4 March, 2018, Buenos Aires, Argentina, and at the XXVIII-European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Madrid (Spain), 21–24 April, 2018
[Anemia as a prognostic factor in cancer patients]
No full textObjective.: To determine the frequency and prognostic value of anemia in cancer patients receiving care at the National Institute of Neoplastic Diseases (Instituto Nacional de Enfermedades Neoplásicas - INEN) between January and April of 2010. Materials and methods.: Anemia was considered for men with hemoglobin levels at <13 g/dL; and for women, at <12 g/dL. Associations between qualitative features were assessed with a Chi-square test. Kaplan-Meier estimator was used for the analysis of the survival curves, and differences between the curves were performed with the log-rank test. Results.: 772 patients were included; 584 (75.7%) had solid tumors and 188 (24.3%) had hematologic malignancies. Anemia was diagnosed in 359 patients (46.5%); hematologic malignancies in 127 patients (67.6%); and solid neoplasms in 235 (40.2%). Hematologic malignancies with the highest frequency of anemia were chronic myeloid leukemia, acute leukemias, and multiple myeloma (100%, 92.5% and 60%, respectively); and were cancer of gastrointestinal, gynecological, and urological origin were in the group of solid neoplasms (62%, 52.1% and 45%, respectively). Two hundred and four (204) patients (26.4%) were transfused. In 762 patients, a significant difference in overall survival was found between groups with and without anemia, estimated at 5 years in 62% and 47% respectively (p <0.001). In the solid tumor subgroup (p = 0.002), and the hematological malignancies subgroup (p = 0.007), such association was also found. Conclusions.: Anemia is common in cancer patients, and its presence determines an independent prognostic factor in overall survival
Detection of the human papillomavirus in samples obtained by self-collection technique in a group of peruvian college students
No full textCross-sectional study that determined the frequency and the genotypes of the (HR-HPV) high-risk human papillomavirus through the self-collection technique in a group of college students of Lima. Two hundred twenty-one (221) students participated and the DNA of the HR-HPV was detected with polymerase chain reaction (PCR). The frequency of HR-HPV in participants was 43.4%; of this group, genotype HPV 16 was present in 15.6%, HPV 18 in 4.2%, and another HR-HPV in 80.2%. We can conclude that the frequency of HR-HPV is greater in the group of college students of this study in comparison with previous national investigations