Characterization of triple negative breast cancer gene expression profiles in Mexican patients.

Triple negative breast cancer (TNBC) is an aggressive type of cancer that accounts for ~23% of breast tumors in Mexico. In an attempt to understand in an improved way the behavior of TNBC, throughout the years, gene expression in these tumors has been studied. Lehman et al identified 6 subtypes of gene expression in TNBC with distinct characteristics. In the present study, it was aimed to assess clinical, pathological and prognostic characteristics of TNBC in a Mexican-based cohort. A total of 55 patients diagnosed with TNBC at Mexico's National Institute of Cancer (INCan) were included. Tumor needle biopsy samples were obtained and subjected to microarray analysis. Patients were thus classified into one of the 6 TNBC molecular subtypes. The prognostic, clinical and pathological information of patients was obtained, and differences across molecular subtypes were sought. Out of the 55 included patients, the following subtypes were identified: 9 basal-like-1, 11 basal-like-2 (BSL2), 16 immunomodulatory (IM), 12 mesenchymal, 6 androgen receptor-like and 1 mesenchymal stem-like. Mean follow-up time was 47.1 months. The IM molecular subtype had the best overall survival (OS) (median OS was not reached). BSL2 had the worst OS (15 months). A complete pathologic response to neoadjuvant chemotherapy was obtained more often in the IM subtype (P=0.032). No significant associations were found between any of the clinical or pathological characteristics and the TNBC molecular subtypes. The results obtained from the present study should be considered when seeking to implement a clinical-molecular model for TNBC patient care, particularly in Hispanic-based populations, as they have been frequently underrepresented in clinical studies assessing TNBC molecular subtypes.

Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapyinduced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial / Efecto de la suplementación con ácidos grasos omega-3 sobre la toxicidad secundaria a quimioterapia neoadyuvante en pacientes con cáncer de mama localmente avanzado: ensayo clínico aleatorizado

Background: antineoplastic treatment for locally advanced breast cancer (LABC) includes neodjuvant chemotherapy (NeoCT). However, side effects occur frequently, affecting the functional capacity and quality of life of patients as a result of the proinflammatory state of this therapy. In this work, omega-3 polyunsaturated fatty acids (PUFA Ω-3) were administered as they have been reported to modulate some molecular pathways such as nuclear factor-kappa B (NF-κB), which is associated with toxicity secondary to the administration of anthracyclines. Objective: to evaluate the effects of PUFA Ω-3 on the toxicity, side effects, body composition, cardiometabolic profile and quality of life in women with LABC after NeoCT. Methods: fifty-three women with LABC were included in a double-blinded, placebo-controlled clinical trial. Patients randomly received 2.4 g/day of PUFA Ω-3 (EPA 1.6 g and DHA 0.8 g) or placebo during NeoCT with adriamycin/cyclophosphamide followed by paclitaxel+/-trastuzumab. Adverse effects related to chemotherapy were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) and the Subjective Global Scale of the Edmonton Symptom Assessment System (ESAS). Body composition and cardiometabolic blood profile were also evaluated. Results: no significant differences were found between groups in the hematological and anthropometric toxicity parameters. Within the Edmonton scale, xerostomia presented a significant improvement (p = 0.032) in patients supplemented with PUFA Ω-3. Conclusion: supplementation with PUFA Ω-3 showed no change in body composition, cardiometabolic profile or toxicity due to NeoCT. It only showed significant improvement in xerostomia

Introducción: uno de los tratamientos para el cáncer de mama localmente avanzado (CMLA), es la quimioterapia neoadyuvante (QTNeo). Sin embargo, los efectos secundarios afectan el estado funcional y la calidad de vida de los pacientes, especialmente por el estado inflamatorio que originan. En este trabajo se administraron los ácidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vías moleculares como las que inducen la activación del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administración de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composición corporal, el perfil cardiometabólico y la calidad de vida en mujeres con CMLA durante la QTNeo. Métodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clínico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/día de AGPI Ω-3 (EPA 1,6 g y DHA 0,8 g) o placebo durante la quimioterapia neoadyuvante con adriamicina/ciclofosfamida seguido de paclitaxel +/- trastuzumab. Se evaluaron los eventos adversos relacionados con la quimioterapia mediante los Criterios de terminología común para eventos adversos (CTCAE, versión 4.03) y la escala Global subjetiva del Sistema de Evaluación de los Síntomas de Edmonton (ESAS), la composición corporal y la toxicidad cardiometabólica. Resultados: no hubo diferencias significativas entre los grupos en los parámetros de toxicidad hematológica y antropométricos. La xerostomía de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusión: la suplementación con AGPI Ω-3 no mostró cambios en la composición corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontró una mejoría significativa en la xerostomía

Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapy-induced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial.

INTRODUCTION: Background: antineoplastic treatment for locally advanced breast cancer (LABC) includes neodjuvant chemotherapy (NeoCT). However, side effects occur frequently, affecting the functional capacity and quality of life of patients as a result of the proinflammatory state of this therapy. In this work, omega-3 polyunsaturated fatty acids (PUFA Ω-3) were administered as they have been reported to modulate some molecular pathways such as nuclear factor-kappa B (NF-κB), which is associated with toxicity secondary to the administration of anthracyclines. Objective: to evaluate the effects of PUFA Ω-3 on the toxicity, side effects, body composition, cardiometabolic profile and quality of life in women with LABC after NeoCT. Methods: fifty-three women with LABC were included in a double-blinded, placebo-controlled clinical trial. Patients randomly received 2.4 g/day of PUFA Ω-3 (EPA 1.6 g and DHA 0.8 g) or placebo during NeoCT with adriamycin/cyclophosphamide followed by paclitaxel+/-trastuzumab. Adverse effects related to chemotherapy were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) and the Subjective Global Scale of the Edmonton Symptom Assessment System (ESAS). Body composition and cardiometabolic blood profile were also evaluated. Results: no significant differences were found between groups in the hematological and anthropometric toxicity parameters. Within the Edmonton scale, xerostomia presented a significant improvement (p = 0.032) in patients supplemented with PUFA Ω-3. Conclusion: supplementation with PUFA Ω-3 showed no change in body composition, cardiometabolic profile or toxicity due to NeoCT. It only showed significant improvement in xerostomia.

INTRODUCCIÓN: Introducción: uno de los tratamientos para el cáncer de mama localmente avanzado (CMLA), es la quimioterapia neoadyuvante (QTNeo). Sin embargo, los efectos secundarios afectan el estado funcional y la calidad de vida de los pacientes, especialmente por el estado inflamatorio que originan. En este trabajo se administraron los ácidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vías moleculares como las que inducen la activación del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administración de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composición corporal, el perfil cardiometabólico y la calidad de vida en mujeres con CMLA durante la QTNeo. Métodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clínico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/día de AGPI Ω-3 (EPA 1,6 g y DHA 0,8 g) o placebo durante la quimioterapia neoadyuvante con adriamicina/ciclofosfamida seguido de paclitaxel +/- trastuzumab. Se evaluaron los eventos adversos relacionados con la quimioterapia mediante los Criterios de terminología común para eventos adversos (CTCAE, versión 4.03) y la escala Global subjetiva del Sistema de Evaluación de los Síntomas de Edmonton (ESAS), la composición corporal y la toxicidad cardiometabólica. Resultados: no hubo diferencias significativas entre los grupos en los parámetros de toxicidad hematológica y antropométricos. La xerostomía de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusión: la suplementación con AGPI Ω-3 no mostró cambios en la composición corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontró una mejoría significativa en la xerostomía.

Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma.

PURPOSE: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. METHODS: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. RESULTS: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. CONCLUSION: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

Clinical characteristics and outcomes of older women with breast cancer in Mexico.

INTRODUCTION: Although the epidemiology of breast cancer in older women has been widely described before, little is known about the clinical characteristics and prognosis of older patients living in developing countries. Here, we studied older women with breast cancer treated at a public cancer center in Mexico City, and compared their outcomes with their younger counterparts. MATERIALS AND METHODS: We retrospectively analyzed a database of 5488 women treated for breast cancer at a single institution. We compared clinical characteristics, treatment and survival between women aged <65 and ≥65 years of age. Survival analyses were performed for each molecular subtype. RESULTS: 851 women (15.5%) were ≥65 years of age, of which 45% presented with Stages III-IV disease. Compared with their younger counterparts, older women had lower grade disease, a larger proportion of hormone receptor positive tumors, and were less likely to receive both chemotherapy and radiotherapy. At 5 years, no differences in both disease free and overall survival were found between younger and older women in a multivariate model including stage, grade, tumor subtype and treatment received. CONCLUSIONS: In contrast with reports from high-income countries, older women with breast cancer in developing nations present with more advanced disease requiring more aggressive treatment. Strategies aimed at earlier detection, improved access to care, and downstaging among older adults are greatly needed in Mexico and in the rest of the developing world.

Clinical and Epidemiological Profile of Breast Cancer in Mexico: Results of the Seguro Popular.

Purpose One half of the Mexican population lacks comprehensive health care coverage. In 2003, a reform to the General Health Law was approved that led to the creation of the System of Social Protection in Health and made universal health coverage mandatory. The main innovation of this reform was Seguro Popular, which provided coverage for breast cancer. Here we report the outcomes of women with breast cancer treated at a cancer center in Mexico under Seguro Popular. Materials and Methods This was a retrospective cohort study that included all patients with breast cancer treated in the Instituto Nacional de Cancerología in Mexico City between January 2007 and December 2013 with Seguro Popular coverage. Demographic and clinical information were collected and survival outcomes were analyzed. Results A total of 4,300 women with breast cancer were included in this analysis. Most patients had locally advanced disease at diagnosis (53%, n = 2,293), and 13% (n = 558) presented with stage IV disease. Neoadjuvant chemotherapy was administered to 1,834 patients (52%), with a pathologic complete response in 25.1% (n = 460). Median follow-up was 40.5 months. Five-year survival for the entire cohort was 82% (95% CI, 81% to 84%). Five-year survival was 97% for early-stage disease (95% CI, 95% to 98%), 82% for locally advanced disease (95% CI, 80% to 84%), and 36% for metastatic disease (95% CI, 30% to 42%). Conclusion This represents the first description of a cohort of patients with breast cancer treated in Mexico under Seguro Popular. Seguro Popular has allowed our institution, and other Mexican centers, to establish efficient standardized mechanisms to treat patients with breast cancer.

Molecular Subtypes and Prognosis in Young Mexican Women With Breast Cancer.

INTRODUCTION: Young age represents an adverse prognostic factor in breast cancer (BC), and young women present with more advanced and aggressive disease. In Latin America, BC is increasing in young women, and there is a lack of information regarding the characteristics and outcomes of this patient population. PATIENTS AND METHODS: We retrospectively analyzed a database of 4315 women treated for BC at a single institution. We compared clinical characteristics, treatment, and survival between women ≤ 40 and > 40 years of age. Survival analyses were performed for each molecular subtype. RESULTS: A total of 662 women (15.3%) were ≤ 40 years old. Younger women had more advanced disease, higher grade, and a larger proportion of luminal B and triple-negative tumors (P < .001). At 5 years, both disease-free and overall survival (OS) were lower in younger women, although there were no differences after adjusting for stage. Five-year OS was worse for young women with hormone receptor-positive, human epidermal growth factor receptor 2-negative subtype (82% vs. 87.1%; P = .03), but not for those with human epidermal growth factor receptor 2-positive or triple-negative disease. This difference can be attributed to luminal B tumors, which showed a worse 5-year OS in younger women (79.1% vs. 85.2%; P = .03). CONCLUSION: Although young Mexican patients with BC have more aggressive disease at presentation than older women, only those with luminal B tumors have a worse survival after adjusting for stage. Strategies aimed at downstaging the disease and at improving the treatment of luminal B tumors in this population are needed.

Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer.

Locally advanced breast cancer (LABC) cases have a varying five-year survival rate, mainly influenced by the tumor response to chemotherapy. Paclitaxel activity (response rate) varies across populations from 21.5% to 84%. There are some reports on genetic traits and paclitaxel; however, there is still considerable residual unexplained variability. In this study, we aimed to test the association between eleven novel markers and tumor response to paclitaxel and to explore if any of them influenced tumor protein expression. We studied a cohort of 140 women with LABC. At baseline, we collected a blood sample (for genotyping), fine needle aspirates (for Western blot), and tumor measurements by imaging. After follow-up, we ascertained the response to paclitaxel monotherapy by comparing the percent change in the pre-, post- tumor measurements after treatment. To allocate exposure, we genotyped eleven SNPs with TaqMan probes on RT-PCR and regressed them to tumor response using linear modeling. In addition, we compared protein expression, between breast tumors and healthy controls, of those genes whose genetic markers were significantly associated with tumor response. After adjusting for multiple clinical covariates, SNPs on the LPHN2, ROBO1, SNTG1, and GRIK1 genes were significant independent predictors of poor tumor response (tumor growth) despite paclitaxel treatment. Moreover, proteins encoded by those genes are significantly downregulated in breast tumor samples.

68Ga-DTPA Anti-HER2 positron emission tomography/CT successfully predicts the overexpression of human epidermal growth factor receptor in lung metastases from breast cancer.

Molecular identification of a metastatic tumour without the inconvenience of a biopsy and the time required for pathological characterization is possible using molecular imaging. Here, we present the case of a patient with breast cancer in whom 68Ga-diethylenetriamine pentaacetic acid anti-human epidermal growth factor receptor 2 positron emission tomography-CT was successfully employed to characterize the expression of human epidermal growth factor receptor 2 in metastatic sites.

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas.

OBJECTIVE: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. METHODS: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T1 weighted, T2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards. RESULTS: During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ2 (3) = 9.098, p = 0.028. CONCLUSION: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy.

Breast cancer in young women has been shown to have an aggressive behavior and worse prognosis. Studies evaluating young women enrolled in clinical trials of neoadjuvant chemotherapy have shown that age is a determinant factor in the achievement of a pathological complete response (pCR). In this study, we sought to analyze the outcomes of young patients treated with neoadjuvant chemotherapy at a single institution. 1639 patients treated with neoadjuvant chemotherapy were included. 316 patients ≤40 years were compared with 1323 patients aged >40 years regarding the achievement of a pCR (defined as no invasive residual tumor in the breast or lymph nodes). Disease-free survival (DFS) and overall survival were compared between groups according to pCR status and subtype, defined by hormone receptor (HR) and HER2 status. Young women were more likely to have a pCR than their older counterparts (37.4 vs. 26.3 %, P < 0.001). This difference was significant both for HR+/HER2- and triple-negative (TN) tumors. Young age and achieving less than pCR were associated with a greater chance of recurrence for the entire population. Age was not an independent factor for recurrence in TN and HER2+ disease. However, being younger than 40 increased recurrence risk in HR+/HER2- tumors. The achievement of a pCR was not associated with improved DFS in young women with HR+/HER2- tumors. Although young women have a high rate of pCR, they also have a worse prognosis. In a real-world clinical setting, the achievement of a pCR was an independently significant protective factor for recurrence across all subtypes and ages, except for HR+, HER2- disease in young women.

[Review of pharmacokinetic monitoring of 5-Fluorouracil as a tool to increase efficacy and safety]. / Revisión del monitoreo farmacocinético del 5-fluorouracilo como herramienta para incrementar eficacia y seguridad.

Recent progress in medical knowledge has indicated that both clinical and biological markers will determine the response to different medical treatments: age, gender and genetics will determine the success of treatment. Genetic variability in this respect is fundamental and determines efficiency and safety of drugs, as well as susceptibility and illness' development. Fortunately, personalized medicine now offers individually tailored treatment strategies for each patient's needs. This is of outmost importance in oncology, since treatment is per se toxic and the commonly found low serum drug concentrations result in low treatment efficacy. Personalized medicine will allow a better approach to this, until now, a poorly managed disease. In this review we intent to raise awareness of personalized medicine and of clinical pharmacologic monitoring, with the aim to achieve adequate levels of efficacy and safety in the use of the cytotoxic drug 5-Fluorouracil (5-FU). Additionally, the importance of pharmacogenomics for the use of 5-FU is discussed. We designed this discussion towards medical practitioners challenged with treatment decisions every day, together with their patients.

Los pacientes bajo tratamiento con alopurinol pueden presentar reacciones adversas potencialmente mortales, particularmente al inicio del tratamiento. Las reacciones cutáneas adversas por alopurinol tienen una prevalencia aproximada del 2 %. Presentamos dos casos de síndrome de hipersensibilidad por alopurinol en pacientes mexicanos en quienes la hiperuricemia asintomática fue la indicación para su uso. El médico general y el especialista deben estar alerta ante este síndrome que ocasiona alta morbilidad y mortalidad.