Brain metastasis risk prediction model in females with hormone receptor-positive breast cancer.

BACKGROUND: Breast cancer is a leading cause of cancer-related deaths in females, and the hormone receptor-positive subtype is the most frequent. Breast cancer is a common source of brain metastases; therefore, we aimed to generate a brain metastases prediction model in females with hormone receptor-positive breast cancer. METHODS: The primary cohort included 3,682 females with hormone receptor-positive breast cancer treated at a single center from May 2009 to May 2020. Patients were randomly divided into a training dataset (n = 2,455) and a validation dataset (n = 1,227). In the training dataset, simple logistic regression analyses were used to measure associations between variables and the diagnosis of brain metastases and to build multivariable models. The model with better calibration and discrimination capacity was tested in the validation dataset to measure its predictive performance. RESULTS: The variables incorporated in the model included age, tumor size, axillary lymph node status, clinical stage at diagnosis, HER2 expression, Ki-67 proliferation index, and the modified Scarff-Bloom-Richardson grade. The area under the curve was 0.81 (95 % CI 0.75-0.86), p < 0.001 in the validation dataset. The study presents a guide for the clinical use of the model. CONCLUSION: A brain metastases prediction model in females with hormone receptor-positive breast cancer helps assess the individual risk of brain metastases.

Análisis de la mortalidad por cáncer en México utilizando los resultados del Global Burden of Disease 2021 / Analysis of cancer mortality in Mexico using the results of the Global Burden of Disease 2021 study

Resumen Antecedentes: En México, las tasas de mortalidad por cáncer han experimentado cambios a lo largo de las últimas décadas. Objetivo: Analizar la evolución de las tasas de mortalidad por cáncer en México entre 1990 y 2021. Materiales y métodos: Del Global Burden of Disease (GBD) se obtuvieron las tasas de mortalidad de los 10 tipos de cáncer más predominantes en México, en el ámbito nacional y por estados, considerando distintos grupos etarios y el sexo. En el GBD se reasignan las causas mal clasificadas y se distribuyen entre los distintos cánceres; posteriormente se modelan y ajustan las causas al total de fallecimientos con un modelo de conjunto de causas de muerte y un corrector de causas, con lo cual se corrigen registros de mortalidad del INEGI. Resultados: La tasa de mortalidad por cáncer pasó de 117.87 en 1990 a 84.18 en 2021. En las mujeres, los cánceres de mama, cervicouterino, estómago y pulmón fueron los más frecuentes; en los hombres, de próstata, estómago, pulmón, colon y recto. Destacó la disminución de la mortalidad por cáncer en hombres y mujeres, en particular por cáncer de pulmón y cérvix uterino. Conclusiones: Los resultados ofrecen información para desarrollar políticas de salud y estrategias de prevención y control específicas para enfrentar el impacto del cáncer en México.

Abstract Background: In Mexico, cancer mortality rates have undergone changes over the past decades. Objective: To analyze the evolution of cancer mortality rates in Mexico between 1990 and 2021. Materials and methods: Based on the Global Burden of Disease study, the mortality rates for the 10 most prevalent types of cancer in Mexico were obtained, at the national and regional level and by states, considering different age groups and gender. Global Burden of Disease reassigns misclassified causes and distributes them among different types of cancer; subsequently, it models and adjusts the causes to the total number of deaths with a model of a set of causes of death and a cause corrector, which corrects INEGI’s mortality records. Results: The cancer mortality rate went from 117.87 in 1990 to 84.18 in 2021. In women, breast, cervical, stomach and lung cancers were the most frequent. In men, the most common were prostate, stomach, lung, and colon and rectum cancer. The decrease in cancer mortality for men and women stood out, particularly from lung and cervical cancer. Conclusions: The results provide information for the development of health policies and specific prevention and control strategies to address the impact of cancer in Mexico.

Understanding Sociodemographic Factors among Hispanics Through a Population-Based Study on Testicular Cancer in Mexico.

Testicular cancer (TCa) is a rare malignancy affecting young men worldwide. Sociodemographic factors, especially socioeconomic level (SEL) and healthcare access, seem to impact TCa incidence and outcomes, particularly among Hispanic populations. However, limited research has explored these variables in Hispanic groups. This study aimed to investigate sociodemographic and clinical factors in Mexico and their role in health disparities among Hispanic TCa patients. We retrospectively analyzed 244 Mexican TCa cases between 2007 and 2020 of a representative cohort with diverse social backgrounds from a national reference cancer center. Logistic regression identified risk factors for fatality: non-seminoma histology, advanced stage, and lower education levels. Age showed a significant trend as a risk factor. Patient delay and healthcare distance lacked significant associations. Inadequate treatment response and chemotherapy resistance were more likely in advanced stages, while higher education positively impacted treatment response. Cox regression highlighted non-seminoma histology, below-median SEL, higher education, and advanced-stage survival rates. Survival disparities emerged based on tumor histology and patient SEL. This research underscores the importance of comprehensive approaches that integrate sociodemographic, biological, and environmental factors to address health disparities improving outcomes through personalized interventions in Hispanic individuals with TCa.

A brain metastasis prediction model in women with breast cancer.

BACKGROUND: Breast cancer (BC) is a leading cause of mortality and the most frequent malignancy in women, and most deaths are due to metastatic disease, particularly brain metastases (BM). Currently, no biomarker or prediction model is used to predict BM accurately. The objective was to generate a BM prediction model from variables obtained at BC diagnosis. METHODS: A retrospective cohort of women with BC diagnosed from 2009 to 2020 at a single center was divided into a training dataset (TD) and a validation dataset (VD). The prediction model was generated in the TD, and its performance was measured in the VD using the area under the curve (AUC) and C-statistic. RESULTS: The cohort (n = 5009) was divided into a TD (n = 3339) and a VD (n = 1670). In the TD, the model with the best performance (lowest AIC) was built with the following variables: age, estrogen receptor status, tumor size, axillary adenopathy, anatomic clinical stage, Ki-67 expression, and Scarff-Bloom-Richardson score. This model had an AUC of 0.79 (95%CI, 0.76-0.82; p < 0.0001) in the TD. The 10-fold cross-validation showed the good stability of the model. The model displayed an AUC of 0.81 (95%CI, 0.77-0.85; P < 0.0001) in the VD. Four groups, according to the risk of BM, were generated. In the low-risk group, 1.2% were diagnosed with BM (reference); in the medium-risk group, 5.0% [HR 4.01 (95%CI, 1.8 - 8.8); P < 0.0001); in the high-risk group, 8.5% [HR 8.33 (95%CI, 4.1-17.1); P < 0.0001]; and in the very high-risk group, 23.7% [HR 29.72 (95%CI, 14.9 - 59.1); P < 0.0001]. CONCLUSION: This prediction model built with clinical and pathological variables at BC diagnosis demonstrated robust performance in determining the individual risk of BM among patients with BC, but external validation in different cohorts is needed.

Mortality Prognosis Factors in Patients with Active Cancer Under Treatment, and Severe COVID-19.

BACKGROUND: COVID-19 is associated with systemic inflammation. This inflammatory response is further deregulated by oncological treatments increasing mortality in this population. However, there is conflicting information regarding the clinical factors that increase mortality in patients with severe COVID-19. OBJECTIVE: The aim of this study was to identify prognostic factors associated with mortality during severe COVID-19 in patients with active cancer. In addition, the correlation between oncologic codes and mortality related to severe COVID-19 was evaluated. PATIENTS AND METHODS: We analyzed a cohort of Mexican patients with active cancer and severe COVID-19 between March 2020 and February 2021. We collected information on patient demographic characteristics, COVID-19 symptoms, clinical and laboratory data, and treatments. Patients were classified according to oncologic code. We defined the oncological code based on clinical stage, treatment intention, performance status before COVID-19, and median overall survival with palliative treatment. A log-rank test was performed to determine survival. A multivariate logistic regression model was used to adjust for potential confounders. RESULTS: One hundred fifty-two patients with severe COVID-19 were analyzed. The red oncologic code was associated with an increased risk of mortality OR 22.8 (CI 95% 5.0-105.1, p <0.001), low oxygen saturation OR 5.4 (CI 95% 1.7-17.4, p = 0.005), chronic corticosteriod use OR 4.3 (CI 95% 1.0-18.1, p = 0.050) and high D-dimer level OR 3.2 (CI 95% 1.2-8.2, p = 0.019). CONCLUSIONS: The survival of patients with active cancer and severe COVID-19 was possible to identify, at the time of admission, specific oncological characteristics. Based on this code, decreased oxygen saturation, increased D-dimer levels, and chronic corticosteroid use were the main predictive factors related to mortality.

Insurance status and access to cervical cancer treatment in a specialized cancer center in Mexico.

To describe access to complete treatment in women with cervical cancer and state-sponsored insurance versus no insurance. We conducted a retrospective observational study. The source population consisted of women treated for cervical cancer from January 2000 to December 2015 in a tertiary care hospital. We included 411 women with state-sponsored insurance and 400 without insurance. We defined access to cervical cancer treatment as complete treatment (according NCCN/ESMO (National Comprehensive Cancer Network/European Society for Medical Oncology) standards) and timely initiation of treatment (less than 4 weeks). Clinical and sociodemographic characteristics were described and analyzed with logistic regression using complete treatment as the main outcome. A total of 811 subjects were included, the median age was 46 (IQR (Interquartile range) 42-50) years. Most of them were married (36.1%), unemployed (50.4%), and had completed primary school (44.0%). The most common clinical stages at diagnosis were II (38.2%) and III (24.7%). In the adjusted regression model, being married (OR (odds ratio): 4.3, 95% CI (confidence interval): 1.74-10.61) and having paid employment (OR: 2.79, 95% CI: 1.59-4.90) or state-sponsored insurance (OR: 1.54, 95% CI: 1.04-2.26) were positively associated with the possibility of having a complete treatment. Women with insurance were likely to be younger and receive timely treatment compared with uninsured women. Complete treatment was associated to insurance status and advanced stages of cervical cancer. State-sponsored insurance improves access to complete treatment. Government policies are needed to avoid social and economic inequity and provide better management of cervical cancer in our country.

Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker.

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Analysis of cancer mortality in Mexico using the results of the Global Burden of Disease 2021 study.

BACKGROUND: In Mexico, cancer mortality rates have undergone changes over the past decades. OBJECTIVE: To analyze the evolution of cancer mortality rates in Mexico between 1990 and 2021. MATERIALS AND METHODS: Based on the Global Burden of Disease study, the mortality rates for the 10 most prevalent types of cancer in Mexico were obtained, at the national and regional level and by states, considering different age groups and gender. Global Burden of Disease reassigns misclassified causes and distributes them among different types of cancer; subsequently, it models and adjusts the causes to the total number of deaths with a model of a set of causes of death and a cause corrector, which corrects INEGI's mortality records. RESULTS: The cancer mortality rate went from 117.87 in 1990 to 84.18 in 2021. In women, breast, cervical, stomach and lung cancers were the most frequent. In men, the most common were prostate, stomach, lung, and colon and rectum cancer. The decrease in cancer mortality for men and women stood out, particularly from lung and cervical cancer. CONCLUSIONS: The results provide information for the development of health policies and specific prevention and control strategies to address the impact of cancer in Mexico.

ANTECEDENTES: En México, las tasas de mortalidad por cáncer han experimentado cambios a lo largo de las últimas décadas. OBJETIVO: Analizar la evolución de las tasas de mortalidad por cáncer en México entre 1990 y 2021. MATERIALES Y MÉTODOS: Del Global Burden of Disease (GBD) se obtuvieron las tasas de mortalidad de los 10 tipos de cáncer más predominantes en México, en el ámbito nacional y por estados, considerando distintos grupos etarios y el sexo. En el GBD se reasignan las causas mal clasificadas y se distribuyen entre los distintos cánceres; posteriormente se modelan y ajustan las causas al total de fallecimientos con un modelo de conjunto de causas de muerte y un corrector de causas, con lo cual se corrigen registros de mortalidad del INEGI. RESULTADOS: La tasa de mortalidad por cáncer pasó de 117.87 en 1990 a 84.18 en 2021. En las mujeres, los cánceres de mama, cervicouterino, estómago y pulmón fueron los más frecuentes; en los hombres, de próstata, estómago, pulmón, colon y recto. Destacó la disminución de la mortalidad por cáncer en hombres y mujeres, en particular por cáncer de pulmón y cérvix uterino. CONCLUSIONES: Los resultados ofrecen información para desarrollar políticas de salud y estrategias de prevención y control específicas para enfrentar el impacto del cáncer en México.

Cancer Prevention Behaviors in Workers of a Referral Cancer Center in Mexico City: A Pilot Study on Early Detection Awareness for Cancer.

BACKGROUND: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City. METHODS: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated with prevention behaviors were identified by logistic regression. RESULTS: We recruited 301 workers; 77% were women. The median self-reported BMI was 26.4 kg/m2, 9.97% smoked, 78% drank alcohol, and 89% did not get at least 150 min/week of physical activity. In women, age (OR = 1.3 95%CI 1.01-1.06) and physical activity of 150 min/week (OR = 2.52 95% CI 1.28-4.96) were associated with cancer prevention behaviors. No risk factors were associated with healthy behaviors among men. CONCLUSION: Health workers may have unhealthy lifestyles and behaviors, is essential to create supportive environments to promote cancer prevention counseling and programs effectively.

Supracricoid Partial Laryngectomy With and Without Neoadjuvant Chemotherapy in Glottic Cancer.

OBJECTIVES/HYPOTHESIS: To demonstrate that a group of patients who are not considered candidates for organ preservation can achieve organ preservation through neoadjuvant chemotherapy + surgery and to determine if there are differences regarding organ preservation, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) after comparing such group with another one undergoing standard treatment. METHODS: Patients with laryngeal cancer were retrospectively analyzed and divided into two groups. Group A included patients who were initially treated with supracricoid laryngectomy. Group B included patients with T3N0 glottic squamous cell carcinoma with arytenoid fixation. Patients were offered neoadjuvant chemotherapy. Both groups underwent bilateral selective neck dissection of lymph nodes (II-V) and intentional search of the Delphian lymph nodes. RESULTS: Thirty-four patients were assigned to group A of surgery alone, and 16 patients were included in group B of induction chemotherapy. No statistical differences were found regarding sex, tumor localization, histological diagnosis, TNM staging, recurrence, or organ preservation. DFS, OS, and CSS at 60 months were the same in both groups. No statistical differences were found when comparing induction versus noninduction groups according to the T-stage in DFS, OS, and CSS. CONCLUSIONS: Neoadjuvant chemotherapy allows to perform conservative surgery in patients with poor functional prognosis or who are not good candidates for organ preservation at first. We could perform safe surgery, and there was no more recurrence. Hence DFS is not modified (i.e., there was no more recurrence); consequently, OS and CSS are not affected. Neoadjuvant chemotherapy plus supracricoid partial laryngectomy-cricohyoidoepiglottopexy is an oncologically safe procedure that preserves basic functions such as breathing, phonation, and swallowing. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:156-162, 2022.

Clinicopathological and immunohistochemical behavior of ductal carcinoma of the salivary and lacrimal gland in a Mexican Mestizo population.

PURPOSE: Salivary gland tumors are rare and include benign and malignant entities with different behavior and prognosis. Salivary gland carcinoma accounts for 0.2% of all cancers and 5-9% of head and neck carcinomas. We aim to describe the clinicopathological characteristics and discuss the immunohistochemical findings of salivary ductal carcinoma. METHODS: We obtained 17 cases (2.3%) of salivary ductal carcinoma (SDC) from 727 patients with parotid tumors at our cancer center from a database covering a 22-year period (1996-2018). Two pathologists confirmed the diagnosis and excluded 6 cases. Eleven cases were assessed by immunohistochemistry (IHC) for HER2, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), mammaglobin, P53, GATA3, S100, cytokeratins (7,8,14,18, and 20), P63, PAX8, calponin, and SOX10. RESULTS: Eleven SDC cases were in advanced stage, and 80% had metastasis. All cases were surgically treated, and 40% received different adjuvant chemotherapy regimens. we found that most patients were dead of disease. The histological and immunohistochemical analysis showed that 70% of cases were high-grade, 40% were positive for HER2, and 50% for AR. Moreover, a high Ki-67 proliferative index was detected in all cases. We observed luminal differentiation in 50% of cases. CONCLUSION: SDC is a rare entity and survival is very poor. It is histologically similar to ductal carcinoma of the breast. However, important differences exist that help to distinguish them in case of synchronous cancers. The clinical behavior of SDC seems to be more aggressive and IHC analysis is useful for designing therapies.

Role of Neck Dissection in Organ-Preservation for Glottic Squamous Cell Carcinoma.

The surgical approach to the neck in laryngeal cancer depends on the tumor site and stage. Clinical practice guidelines recommend elective neck dissection in ≥ T2 N0 and all supraglottic cancers; however, there is no evidence supporting these recommendations. The objective is to evaluate the results of bilateral elective neck dissection in patients with glottic cancer who underwent supracricoid partial laryngectomy (SCPL) with cricohyoidoepiglottopexy (CHEP). Thirty-five patients diagnosed with ≥ T2 N0 laryngeal squamous cell carcinoma (LSCC) in a single-center retrospective study. Right-sided neck dissections yielded 900 lymph nodes, none of which were positive for metastatic disease. Left-sided neck dissections yielded 949 lymph nodes, one of which was positive for malignancy. Prelaryngeal (Delphian) neck dissection was performed in all patients. Out of 50 lymph nodes removed; one was positive for malignancy. Median overall survival was 172 months, and the 60-month overall survival was 87.3%. The 60-month disease-specific survival was 97.1%. Bilateral neck dissection and Delphian node dissection showed a low rate of metastasis (2.8%). Radical neck dissection may thus represent overtreatment; however, this surgical procedure could be justified to prevent regional recurrences.

Genotoxicity of Marijuana in Mono-Users.

Marijuana (Cannabis sp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.

Identification of a high-risk group for brain metastases in non-small cell lung cancer patients.

PURPOSE: Identification of a high-risk group of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) could lead to early interventions and probably better prognosis. The objective of the study was to identify this group by generating a multivariable model with recognized and accessible risk factors. METHODS: A retrospective cohort from patients seen at a single center during 2010-2020, was divided into a training (TD) and validation (VD) datasets, associations with BM were measured in the TD with logit, variables significantly associated were used to generate a multivariate model. Model´s performance was measured with the AUC/C-statistic, Akaike information criterion, and Brier score. RESULTS: From 570 patients with NSCLC who met the strict eligibility criteria a TD and VD were randomly assembled, no significant differences were found amid both datasets. Variables associated with BM in the multivariate logit analyses were age [P 0.001, OR 0.96 (95% CI 0.93-0.98)]; mutational status positive [P 0.027, OR 1.96 (95% CI 1.07-3.56); and carcinoembryonic antigen levels [P 0.016, OR 1.001 (95% CI 1.000-1.003). BM were diagnosed in 24% of the whole cohort. Stratification into a high-risk group after simplification of the model, displayed a frequency of BM of 63% (P < 0.001). CONCLUSION: A multivariate model comprising age, carcinoembryonic antigen levels, and mutation status allowed the identification of a truly high-risk group of BM in NSCLC patients.

Prostate Cancer Risk Calculators for Healthy Populations: Systematic Review.

BACKGROUND: Screening for prostate cancer has long been a debated, complex topic. The use of risk calculators for prostate cancer is recommended for determining patients' individual risk of cancer and the subsequent need for a prostate biopsy. These tools could lead to better discrimination of patients in need of invasive diagnostic procedures and optimized allocation of health care resources. OBJECTIVE: The goal of the research was to systematically review available literature on the performance of current prostate cancer risk calculators in healthy populations by comparing the relative impact of individual items on different cohorts and on the models' overall performance. METHODS: We performed a systematic review of available prostate cancer risk calculators targeted at healthy populations. We included studies published from January 2000 to March 2021 in English, Spanish, French, Portuguese, or German. Two reviewers independently decided for or against inclusion based on abstracts. A third reviewer intervened in case of disagreements. From the selected titles, we extracted information regarding the purpose of the manuscript, analyzed calculators, population for which it was calibrated, included risk factors, and the model's overall accuracy. RESULTS: We included a total of 18 calculators from 53 different manuscripts. The most commonly analyzed ones were the Prostate Cancer Prevention Trial (PCPT) and European Randomized Study on Prostate Cancer (ERSPC) risk calculators developed from North American and European cohorts, respectively. Both calculators provided high diagnostic ability of aggressive prostate cancer (AUC as high as 0.798 for PCPT and 0.91 for ERSPC). We found 9 calculators developed from scratch for specific populations that reached a diagnostic ability as high as 0.938. The most commonly included risk factors in the calculators were age, prostate specific antigen levels, and digital rectal examination findings. Additional calculators included race and detailed personal and family history. CONCLUSIONS: Both the PCPR and ERSPC risk calculators have been successfully adapted for cohorts other than the ones they were originally created for with no loss of diagnostic ability. Furthermore, designing calculators from scratch considering each population's sociocultural differences has resulted in risk tools that can be well adapted to be valid in more patients. The best risk calculator for prostate cancer will be that which has been calibrated for its intended population and can be easily reproduced and implemented. TRIAL REGISTRATION: PROSPERO CRD42021242110; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242110.

Association of the neutrophil-to-lymphocyte ratio with brain metastases in Hispanic breast cancer patients.

BACKGROUND: Breast cancer (BC) is one of the most common cancers and leading cause of cancer-related deaths in women. Metastatic disease, particularly brain metastases (BM), is associated with death in BC patients. The neutrophil-to-lymphocyte ratio (NLR) has been associated with BC prognosis, but it is not usually used in clinical practice and has not been associated with BM. We aimed to determine if there is an association between NLR and BM and if NLR is associated with survival in a Hispanic population. METHODS: A retrospective cohort with a total of 2,104 patients with a confirmed diagnosis of BC at a single referral center were randomly divided into training and validation datasets. Univariable and multivariable analyses were performed to study the association of NLR with BM and/or survival. RESULTS: No significant differences between datasets were identified. A high NLR (> 2.2) was associated with a higher frequency of BM after multivariable adjustment in both datasets. Overall survival was shorter in patients with a high NLR; however, the most important factor associated with outcome was the presence of BM. The interaction NLR/BM was not statistically significant. CONCLUSION: A high NLR at BC diagnosis was associated with a higher frequency of BM, and the presence of BM was associated with worse overall survival in Hispanic BC patients.

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied. Herein, lncRNA expression was profiled using RNA sequencing in biopsies from patients who subsequently showed either response or no response to treatment. GATA3-AS1 was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1 was experimentally validated by quantitative RT-PCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1 is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9% and a specificity of 75.0%. The statistical model was based on luminal B-like patients and adjusted by menopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; P = 0.001); GATA3-AS1 was established as an independent predictor of response. Thus, lncRNA GATA3-AS1 is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.

Trends in breast-conserving surgery in Mexico after the implementation of a public health insurance system.

Although breast conserving surgery is the standard of care for patients with localized breast cancer in high-income countries, little is known about its use in developing countries, where disparities in access to treatment may lead to an increased use of mastectomy. We examined the use of breast conserving surgery at a Mexican cancer center after the implementation of a public insurance program aimed at providing coverage for previously uninsured patients. Between 2006 and 2016, 4519 women received surgical treatment for breast cancer, of which 39% had early-stage disease. The proportion of patients treated with breast conserving surgery increased from 10% in the 2006-2009 period to 33% in the 2013-2016 period, with most of this increase occurring among women with early-stage disease (17-52%). Improving access to care and reducing the financial burden of breast cancer in developing countries may lead to an increased use of breast conserving surgery.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Cervical Cancer in Young Women: Do They Have a Worse Prognosis? A Retrospective Cohort Analysis in a Population of Mexico.

BACKGROUND: Cervical cancer (CC) is a global problem; it is among the five leading causes of cancer death in women. Several studies have examined the association between age and disease prognosis; however, controversy still exists. The objective of the present study is to determine if age at diagnosis has an impact on overall survival (OS) and disease-free survival (DFS). MATERIALS AND METHODS: Retrospective cohort of 2,982 patients with CC treated at the National Cancer Institute of Mexico from 2005 to 2015. We collected demographic, clinical, and treatment data, as well as current status, of 2 groups: women under and over 40 years of age. We calculated OS and DFS rates with Kaplan-Meier estimates. Cox proportional hazards modeling was used to determine risks. RESULTS: The median follow-up time was 26.5 months (percentile [P]25 -P75 , 11-60.23). When comparing DFS, OS, stage, and histologic subtype between young patients <40 and adult patients >40, we did not observe any difference. We found that in both groups, locally advanced and advanced stage, neuroendocrine subtype, hydronephrosis, and positive inguinal lymph nodes increased the risks of death and recurrence. Having been pregnant was identified as protective factor in DFS (hazard ratio, 0.54; 95% confidence interval, 0.04-0.71). CONCLUSION: We corroborated that age at diagnosis is not a prognostic factor for decreased or increased OS or DFS, and in both groups, the stage, histologic subtype, hydronephrosis, and node involvement were identified as factors adverse to OS and DFS, and pregnancy history was a protective factor in DFS. IMPLICATIONS FOR PRACTICE: The present study directly affects everyday clinical practice because it allows us to focus on the most relevant prognostic factors in patients with cervical cancer. When planning treatment and follow-up, clinicians should focus on stage at diagnosis, histologic subtype, hydronephrosis, and distant metastasis instead of patients' age. They should also be aware of any previous pregnancies and poor response, or nonresponse, to treatment, which results in disease progression and persistence. Paying attention to these factors affecting overall survival and disease-free survival will help treat patients better and increase their chances of survival and improve their quality of life.