Browsing by Author "Pinto, JA"

Now showing 1 - 8 of 8

Barriers in Latin America for the management of locally advanced breast cancer
(Cancer Intellilgence, 2019) Pinto, JA; Pinillos, L; Villarreal-Garza, C; Morante, Z; Villarán, MV; Mejía, G; Caglevic, C; Aguilar, A; Fajardo, W; Usuga, F; Carrasco, M; Rebaza, P; Posada, AM; Tirado-Hurtado, I; Flores, C; Vallejos-Sologuren, CS
Breast cancer (BC) is a highly prevalent malignancy in Latin American women, most cases being diagnosed at locally advanced or metastatic stages when options for cancer care are limited. Despite its label as a public health problem in the region, Latin American BC patients face several barriers in accessing standard of care treatment when compared with patients from developed countries. In this review, we analyse the landscape of the four main identified barriers in the region: i) high burden of locally advanced/advanced BC; ii) inadequate access to medical resources; iii) deficient access to specialised cancer care and iv) insufficient BC research in Latin America. Unfortunately, these barriers represent the main factors associated with the BC poor outcomes seen in the region. Targeted actions should be conducted independently by each country and as a region to overcome these limitations and create an enhanced model of BC care.
Chip-based digital Polymerase Chain Reaction as quantitative technique for the detection of PIK3CA mutations in breast cancer patients
(Elsevier Ltd, 2022) Giannoni-Luza, S; Acosta, O; Murillo Carrasco, AG; Danos, P; Cotrina Concha, JM; Guerra Miller, H; Pinto, JA; Aguilar, A; Araujo, JM; Fujita, R; Buleje, J
Background: PIK3CA is a gene frequently mutated in breast cancer. With the FDA approval of alpelisib, the evaluation of PIK3CA for activating mutations is becoming routinely. Novel platforms for gene analysis as digital PCR (dPCR) are emerging as a potential replacement for the traditional Sanger sequencing. However, there are still few studies on chip-based dPCR to detect mutations in tumor samples. Thus, this cross-sectional study aimed to assess the sensibility of a chip-based dPCR to detect and quantify PIK3CA mutations and compare its performance with Sanger sequencing. Materials and Methods: Tumor samples from 57 breast cancer patients (22 pre-treatment samples, 32 tumors after neoadjuvant chemotherapy, and three lymph nodes) were collected and analyzed by Sanger sequencing and dPCR for the three PIK3CA most relevant mutations (p.E545K, p. H1047R, and p. H1047L). Digital PCR sensitivity, specificity, and overall performance were estimated by contingency tables, receptor operator characteristic (ROC), and area under the curve (AUC). Association of PIK3CA mutations with clinicopathological variables was conducted. Results: Sanger sequencing identified PIK3CA mutations in six patients (10.5%), two with p. H1047R, and four with p. E545K. Digital PCR confirmed those mutations and identified 19 additional patients with at least one mutation. Comparison between dPCR and Sanger sequencing showed a sensitivity of 100% (95% CI 53–100%), and a specificity of 84.2% (95% CI 83–84.2%). Besides, p. H1047R mutation detected by dPCR showed a significant association with breast cancer phenotype (p = 0.019) and lymphatic nodes infiltration (p = 0.046). Conclusions: Digital PCR showed a high sensitivity to detect mutations in tumor samples and it might be capable to detect low-rate mutations and tumor subpopulations not detected by Sanger sequencing. © 2022 The Author(s)
Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer
(Nature Publishing Group, 2018) Araujo, JM; Gomez, AC; Aguilar, A; Salgado, R; Balko, JM; Bravo, L; Doimi, F; Bretel, D; Morante, Z; Flores, C; Gomez, HL; Pinto, JA
Triple 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.
Genomic landscape of lung cancer in the young
(Frontiers Media S.A., 2022) Ruiz-Mendoza, R; Galvez-Nino, M; Roque, K; Montes-gila, J; Nuñez, Mará; Raez, Luis; Sánchez-Gambetta, Sergio; Jaúregui, Sandra; Viale, Sandra; Smith, Edward S; Pinto, JA; Mas López, L
Background: Lung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients. Methods: Comparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment. Results: Overall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0% EGFR, 46.9% (n=15) vs 43.3% (n=13) ERBB2, 12.5% (n=4) vs 16.7% (n=5) KRAS, 15.6% (n=5) vs 16.7% (n=5) ALK, 6.3% (n=2) vs 3.3% (n=1) RET, 0.0% vs 3.3% (n=1) RET, 0.0% vs 3.3% (n=1) ROS1, 3.1% (n=1) vs 3.3% (n=1) NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability. Conclusion: NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.
PUM1 and RNase P genes as potential cell-free DNA markers in breast cancer
(Wiley-Liss Inc., 2021) Murillo Carrasco, A; Acosta, O; Ponce, J; Cotrina, J; Aguilar, A; Araujo, J; Rebaza, P; Pinto, JA; Fujita, R; Buleje, J
Background: Cell-free DNA (cfDNA) is used in clinical research to identify biomarkers for diagnosis of and follow-up on cancer. Here, we propose a fast and innovative approach using traditional housekeeping genes as cfDNA targets in a copy number analysis. We focus on the application of highly sensitive technology such as digital PCR (dPCR) to differentiate breast cancer (BC) patients and controls by quantifying regions of PUM1 and RPPH1 (RNase P) in plasma samples. Methods: We conducted a case-control study with 82 BC patients and 82 healthy women. cfDNA was isolated from plasma using magnetic beads and quantified by spectrophotometry to estimate total cfDNA. Then, both PUM1 and RPPH1 genes were specifically quantified by dPCR. Data analysis was calibrated using a reference genomic DNA in different concentrations.Results: We found RNase P and PUM1 values were correlated in the patient group (intraclass correlation coefficient [ICC] = 0.842), but they did not have any correlation in healthy women (ICC = 0.519). In dPCR quantification, PUM1 showed the capacity to distinguish early-stage patients and controls with good specificity (98.67%) and sensitivity (100%). Conversely, RNase P had lower cfDNA levels in triple-negative BC patients than luminal subtypes (p < 0.025 for both), confirming their utility for patient classification.Conclusion: We propose the PUM1 gene as a cfDNA marker for early diagnosis of BC and RNase P as a cfDNA marker related to hormonal status and subtype classification in BC. Further studies with larger sample sizes are warranted.
Sex, immunity, and cancer
(Elsevier B.V., 2022) Pinto, JA; Araujo, JM; Gómez, HL
The composition of the tumor microenvironment is the complex result of the interaction between tumoral and host factors. Since there are several differences in the regulation of gene circuits between sexes, mainly influenced by sex hormones, the tumor-host interaction presents some differences, leading tumors to evolve under different conditions. Nowadays, it is well known the existence of sexual dimorphism in the regulation of the immune system, where women present an improved immunity to various infectious agents and, on the other hand, a higher incidence of autoimmune diseases than men. In oncology, differences in cancer susceptibility, response to treatment, and clinical outcomes between men and women patients are well known. Recently, sex-specific differences have also been reported in mutations in driver genes and the prognostic value of several biomarkers. Sex has been a widely forgotten biomarker in cancer therapy, but it has recently acquired great relevance due to the different results seen in immunotherapy treatment. © 2021 Elsevier B.V.
Status of breast cancer in Latin American: Results of the breast cancer revealed initiative
(Elsevier Ireland Ltd, 2023) Ayala, N; Barchuk, S; Inurrigarro, G; Celano, C; Soriano-García, JL; Bolaños, P; Mohs-Alfaro, M; Tapia-González, H; Perez-Martinez, R; Samtani, S; Alvarado-Cabrero, I; Villarreal-Garza, C; Tamez-Salazar, J; Magallanes-Garza, GI; Vazquez, D; Castro, J; Gómez-Macías, GS; Ferrigno, A; Morante, Z; Vilchez, S; Cotrina, JM; Doimi, F; Santander, G; Acevedo, C; Ortega, V; Lavista, F; Richter, L; Gianella, M; Paredes ,M; Flores-Balcázar, CH; Pinto, JA; Gomez, HL
The Breast Cancer Revealed initiative was designed and conducted to know the status of breast cancer at each point of breast cancer care, through i) prevention, ii) detection, iii) diagnosis, iv) treatment, and iv) the capacity of our health systems. The expert panel from 11 Latin American countries identified several strategies and proposed high impact priorities, including implementation of prevention policies, improve primary healthcare capacity for breast cancer screening, have adequate infrastructure to make effective and timely diagnoses, have a multidisciplinary team in the treatment process, access to a variety of treatments for all types of patients, have a coordinated and articulated system from primary care to specialized hospital. In a region with limited resources, prioritization in high-impact strategies for breast cancer control could lead to improved clinical outcomes and quality of life for our patients.
Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer
(Frontiers Media SA, 2023) Morante, Z; Ferreyra, Y; Pinto, JA; Valdivieso, N; Castañeda, C; Vidaurre, T; Valencia, G; Rioja, P; Fuentes, H; Cotrina, JM; Neciosup, S; Gomez, HL
Introduction: Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups. Materials and methods: We analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days). Results: In univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0–31), intermediate (score:32–64), and high-risk (score: 65–100) cohorts; meanwhile, Model N°02: low (score: 0–26), intermediate (score: 27–55), and high (score: 56–100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set. Conclusions: We developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups.