Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico.

INTRODUCTION: Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. METHODS: The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. RESULTS: A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. CONCLUSIONS: This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.

This study examined the effects of advanced lung cancer (stage IV non-small cell lung cancer [NSCLC]) on patients in Mexico, focusing on the health, financial, and caregiver burdens. Researchers studied adults over 18 years of age undergoing cancer treatment at four medical centers across Mexico, analyzing treatment costs and time lost due to illness. All costs were updated to 2022 Mexican pesos (MXN) values. Treating one patient for 1 year can cost up to MXN 1 million in public hospitals and more than MXN 2 million in private hospitals. Patients might lose about 84­335 days of work annually, with caregivers losing 13­30 days. These lost workdays significantly impact finances, costing approximately MXN50,000­178,000 per patient per year in public hospitals and MXN438,000 in private hospitals. The study concludes that understanding these costs can help create better treatment plans, improving patient care and reducing financial burdens. By aligning treatment strategies across public and private healthcare settings, patients could benefit from more consistent and effective care, potentially leading to better health outcomes and reducing the overall impact of the disease on their lives and the broader healthcare system.

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study.

OBJECTIVES: Stereotactic Ablative Radiotherapy (SABR) has shown high rates of local control and prolonged survival in early-stage non-small cell lung cancer (NSCLC), though its role in oligometastatic disease is undefined. This study aimed to evaluate SABR as a local consolidative therapy (LCT) in oligometastatic NSCLC patients. METHODS: In this prospective, single-arm phase 2 trial, we sought to evaluate SABR in patients with stage IV NSCLC, with ≤ five lesions, including the primary tumor. Patients received initial systemic therapy according to international guidelines. Patients without progression after front-line therapy (two months of targeted therapy and ≥ four cycles of chemotherapy) were evaluated by an 18F-FDG-PET/CT to receive consolidative SABR (45-60 Gy in 3-5 fractions) to the primary and all intrapulmonary metastatic sites. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. RESULTS: A total of 47 patients were included. Mean age was 58.9 years, 59.6 % were female, 87.2 % had adenocarcinoma histology, and the contralateral lung was the main site of metastases in 42.6 %. All patients received systemic front-line therapy, chemotherapy in 61.7 %, and a tyrosine kinase inhibitor (TKI) in 38.3 %. Disease control rate (DCR) and complete metabolic response (CMR) to SABR were 93.6 % and 70.2 %. Median PFS was 34.3 months (95 %CI; 31.1-38.8) for the total cohort; patients with a CMR had a median PFS of 53.9 monthsvs.31.9 months in those without CMR (p = 0.011). Median OS was not reached.Grade 1, 2, and 3 pneumonitis were observed in 79.5 % (31/39), 12.8 % (5/39) and 7.7 % (3/39), respectively. No grade ≥4 toxicities were observed. CONCLUSION: The use of SABR as LCT in oligometastatic NSCLC patients was well tolerated and showed favorable results regarding PFS and OS compared with historical data. The benefit was significantly higher in patients who reached a CMR as assessed by 18F-FDG-PET/CT.

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy, associated with poor outcomes in patients with metastatic disease (mMCC). Management has been dramatically altered as a result of incorporating immune checkpoint blockade agents. MCC data from Latin America (LATAM) come from case-series or individual records. Regional registries are lacking. A need for better registries to improve current knowledge about MCC is highlighted. Our objectives were to describe a real-world experience with avelumab as a second-line (or first-line in unfit patients) treatment in a subset of LATAM participants enrolled in a global Expanded Access Program (EAP) for patients with mMCC, and to evaluate its contribution to the resolution of the concerns described in a recent regional experts review. MATERIALS AND METHODS: We reviewed data of LATAM participants in an avelumab EAP for mMCC treatment (NCT03089658). EAP patient had unresectable or mMCC with progressive disease after one line of chemotherapy, and were ineligible for clinical trials or unfit for chemotherapy. RESULTS: 46 patients (median age: 71.6 years; 60.9% males; median treatment duration: 7.9 months) were included in the LATAM EAP. Physician-assessed objective responses were available for 19 patients. Complete response rate was 15.8% and partial response rate reached 42.1%, summarizing an objective response rate of 57.9%. Stable disease rate was 10.5%, with a disease control response of 68.4%. CONCLUSION: Avelumab showed robust efficacy and a safety profile consistent with global EAP data. Results are aimed to improve current knowledge about mMCC treatment and access to immunooncologic strategies for treating LATAM patients.

Efficacy and Safety of Pembrolizumab Plus Docetaxel vs Docetaxel Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: The PROLUNG Phase 2 Randomized Clinical Trial.

Importance: Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy. Objective: To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. Design, Setting, and Participants: The Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. Interventions: The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. Main Outcomes and Measures: The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. Results: Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified. Conclusions and Relevance: In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02574598.

Access to lung cancer therapy in the Mexican population: opportunities for reducing inequity within the health system.

Lung cancer is a major global public health problem, yet the disease is highly stigmatized, which impairs the opportunities to get optimal treatment for these patients. Globally, as well as locally in Mexico, lung cancer is the main cause of cancer-related deaths. Despite this, it is the only one among the five deadliest cancers in Mexico which is not covered by Popular Health Insurance. Lung cancer treatment is a complex algorithm, which requires fully trained personnel to assess each patient in order to determine standard-of-care therapy based on several factors associated with the molecular profile of the tumor, as well as patient characteristics and their financial capabilities. Coupled to this, in the recent decade, several breakthrough therapies have been launched, shifting the outlook for certain patient subgroups. However, none of these novel therapies are currently available to patients who have public-based health insurance. In this paper, we review the inequities present in the Mexican health system and highlight the importance of addressing these opportunities.

El cáncer de pulmón es un problema de salud pública a nivel global. Sin embargo, la enfermedad conlleva un gran nivel de estigma que disminuye las posibilidades de obtener un tratamiento óptimo para estos pacientes. El cáncer de pulmón es la causa principal de muertes relacionadas con cáncer, tanto en el mundo como localmente en México. A pesar de esto, en la lista de las cinco neoplasias con mayor mortalidad en México, el cáncer de pulmón es la única que no se encuentra cubierta por parte del Seguro Popular. El tratamiento del cáncer de pulmón es un algoritmo complejo, el cual requiere personal altamente calificado para la valoración de cada paciente y la determinación del estándar-de-cuidado, dependiendo de varios factores relacionados tanto con el perfil molecular del tumor como con las características del paciente y sus posibilidades económicas. Aunado a esto, en la década en curso ha surgido una gran cantidad de nuevas posibilidades terapéuticas que cambian el pronóstico de ciertos subgrupos de pacientes. Sin embargo, estas terapias no están disponibles para pacientes que se encuentran asegurados por parte del sistema público de salud en México. En este trabajo se revisaron las inequidades que se presentan en el sistema de salud en México y se recalcó la importancia de actuar sobre estas áreas de oportunidad.

Access to lung cancer therapy in the Mexican population: opportunities for reducing inequity within the health system / Acceso a la terapia para cáncer de pulmón en la población mexicana: oportunidades para reducir la inequidad en el sistema de salud

Abstract: Lung cancer is a major global public health problem, yet the disease is highly stigmatized, which impairs the opportunities to get optimal treatment for these patients. Globally, as well as locally in Mexico, lung cancer is the main cause of cancer-related deaths. Despite this, it is the only one among the five deadliest cancers in Mexico which is not covered by Popular Health Insurance. Lung cancer treatment is a complex algorithm, which requires fully trained personnel to assess each patient in order to determine standard-of-care therapy based on several factors associated with the molecular profile of the tumor, as well as patient characteristics and their financial capabilities. Coupled to this, in the recent decade, several breakthrough therapies have been launched, shifting the outlook for certain patient subgroups. However, none of these novel therapies are currently available to patients who have public-based health insurance. In this paper, we review the inequities present in the Mexican health system and highlight the importance of addressing these opportunities.

Resumen: El cáncer de pulmón es un problema de salud pública a nivel global. Sin embargo, la enfermedad conlleva un gran nivel de estigma que disminuye las posibilidades de obtener un tratamiento óptimo para estos pacientes. El cáncer de pulmón es la causa principal de muertes relacionadas con cáncer, tanto en el mundo como localmente en México. A pesar de esto, en la lista de las cinco neoplasias con mayor mortalidad en México, el cáncer de pulmón es la única que no se encuentra cubierta por parte del Seguro Popular. El tratamiento del cáncer de pulmón es un algoritmo complejo, el cual requiere personal altamente calificado para la valoración de cada paciente y la determinación del estándar-de-cuidado, dependiendo de varios factores relacionados tanto con el perfil molecular del tumor como con las características del paciente y sus posibilidades económicas. Aunado a esto, en la década en curso ha surgido una gran cantidad de nuevas posibilidades terapéuticas que cambian el pronóstico de ciertos subgrupos de pacientes. Sin embargo, estas terapias no están disponibles para pacientes que se encuentran asegurados por parte del sistema público de salud en México. En este trabajo se revisaron las inequidades que se presentan en el sistema de salud en México y se recalcó la importancia de actuar sobre estas áreas de oportunidad.

[Age associated survival rate in non small cell lung cancer]. / Supervivencia en relación con la edad en cáncer pulmonar de células no pequeñas.

BACKGROUND: Worldwide, lung cancer is the leading cause of death due to cancer. Non small cell lung cancer (NSCLC) constitutes 70% of cases. Clinical course and survival differ depending of age at diagnosis OBJECTIVE: Determine the epidemiology and survival rate of NSCLC associated with age of onset of the disease. PATIENTS AND METHODS: We carried out a retrospective study between January 1993-January 2007 and included patients with confirmed NSCLC. Three groups were included: group 1: < 49 yrs, group 2: 50-69 yrs, group 3: > 70 yrs. Age, ECOG, comorbidity, family background, smoking, clinical stage, histology, metastatic sites, treatment and overall survival were analyzed. Statistical analysis was done using descriptive methods, Kruskall-Wallis, ANOVA, chi-2, Student's T-test and Kaplan-Meier tests. RESULTS: 183 patients, 23 (12.6%) < 49 years, 108 (59%) from group 2 and 52 cases (28.4%) > 70 yrs. Median age was: 43.2, 61.2 and 75.6 yrs (p < 0.05), respectively. The majority were women (56.4%) in group 1, p= 0.036. Comorbidity: 17.4%, 55.5% and 76.9%, p= 0.000. 52.5% smokers, 87% and 62.9%, p= 0.009. Symptoms included: cough (38.9%, 25%, 43.6%), thoracic pain (33.3%, 41.3%, 30.8%) and dyspnea (33.3%, 16.3%, 38.5%), p > 0.05. Adenocarcinoma was the most frequent type (78.2%, 63.9% and 54.5%). Stage IIIB was observed among 17.4% of patients studied, 23.1%, 23.1% and stage IV 52.2%, 44.4%, 50%, respectively. Median overall survival in stages I and II was 21 months, 18 months in stage IIIA (p > 0.05). Stages IIIB-IV the median overall survival was 11, 8.5 and 4 months respectively (p= 0.034). CONCLUSIONS: Younger patients displayed a more aggressive disease course yet also displayed a higher survival rate. Patients over 70 years have a higher incidence of comorbidity and ECOG 2.

Supervivencia en relación con la edad en cáncer pulmonar de células no pequeñas / Age associated survival rate in non small cell lung cancer

Antecedentes: El cáncer pulmonar es la principal causa de muerte por cáncer en el mundo; el de células no pequeñas (NSCLC por sus siglas en inglés) representa 70% de los casos. El comportamiento clínico y la supervivencia pueden variar en función de la edad. Objetivo: Determinar el comportamiento epidemiológico y supervivencia global en NSCLC en relación con la edad. Métodos: Estudio retrospectivo del periodo de enero de 1993 a diciembre de 2007, en pacientes con NSCLC confirmado. Se designaron tres grupos: 1, edad menor o igual a 49 años; 2, 50 a 69 años de edad; 3, 70 años o más. Analizamos edad, ECOG (escala para medir calidad de vida del Eastern Cooperative Oncologic Group), comorbilidad, historia familiar, tabaquismo, etapa clínica, sitios metastásicos, tipo histológico, tratamiento, supervivencia global. Para el análisis se emplearon métodos descriptivos y las pruebas de Kruskal-Wallis, ANOVA, χ2, t de Student y Kaplan-Meier. Resultados: Se estudiaron 183 pacientes, 23 (12.6%) del grupo 1, 108 (59%) del grupo 2 y 52 (28.4%) del grupo 3. Mediana de edad: 43.2, 61.2 y 75.6 años, respectivamente (p<0.05). Las mujeres predominaron en el grupo 1 (p=0.036). Comorbilidad: 17.4, 55.5 y 76.9% (p=0.000). Tabaquismo positivo: 52.5, 87 y 69.2% (p=0.009). Síntomas: tos (38.9, 25 y 43.6%), dolor torácico (33.3, 41.3, 30.8%) y disnea (33.3, 16.3, 38.5%), p>0.05. El adenocarcinoma fue el tipo más frecuente (78.2, 63.9 y 54.5%). Etapa IIIB (17.4, 23.1, 23.1%) y etapa IV (52.2, 44.4, 50%). Supervivencia global en etapas I y II: 21 meses versus 18 meses en la etapa IIIA (p>0.05); en las etapas IIIB a IV fue 11, 8.5 y 4 meses, respectivamente (p=0.034). Conclusiones: Los jóvenes cursan con enfermedad más agresiva y los mayores de 70 años tienen mayor frecuencia de comorbilidad y ECOG 2. La supervivencia es mayor entre los jóvenes.

BACKGROUND: Worldwide, lung cancer is the leading cause of death due to cancer. Non small cell lung cancer (NSCLC) constitutes 70% of cases. Clinical course and survival differ depending of age at diagnosis OBJECTIVE: Determine the epidemiology and survival rate of NSCLC associated with age of onset of the disease. PATIENTS AND METHODS: We carried out a retrospective study between January 1993-January 2007 and included patients with confirmed NSCLC. Three groups were included: group 1: < 49 yrs, group 2: 50-69 yrs, group 3: > 70 yrs. Age, ECOG, comorbidity, family background, smoking, clinical stage, histology, metastatic sites, treatment and overall survival were analyzed. Statistical analysis was done using descriptive methods, Kruskall-Wallis, ANOVA, chi-2, Student's T-test and Kaplan-Meier tests. RESULTS: 183 patients, 23 (12.6%) < 49 years, 108 (59%) from group 2 and 52 cases (28.4%) > 70 yrs. Median age was: 43.2, 61.2 and 75.6 yrs (p < 0.05), respectively. The majority were women (56.4%) in group 1, p= 0.036. Comorbidity: 17.4%, 55.5% and 76.9%, p= 0.000. 52.5% smokers, 87% and 62.9%, p= 0.009. Symptoms included: cough (38.9%, 25%, 43.6%), thoracic pain (33.3%, 41.3%, 30.8%) and dyspnea (33.3%, 16.3%, 38.5%), p > 0.05. Adenocarcinoma was the most frequent type (78.2%, 63.9% and 54.5%). Stage IIIB was observed among 17.4% of patients studied, 23.1%, 23.1% and stage IV 52.2%, 44.4%, 50%, respectively. Median overall survival in stages I and II was 21 months, 18 months in stage IIIA (p > 0.05). Stages IIIB-IV the median overall survival was 11, 8.5 and 4 months respectively (p= 0.034). CONCLUSIONS: Younger patients displayed a more aggressive disease course yet also displayed a higher survival rate. Patients over 70 years have a higher incidence of comorbidity and ECOG 2.

[Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype]. / Recurrencia y supervivencia en cáncer mamario temprano con inmunofenotipo triple-negativo.

BACKGROUND: Axillary lymph node status, hormonal receptors (HR) and HER2 expression are significant prognostic factors for early breast cancer. Triple negative immunophenotype (HER2 and HR negative) is associated with a high frequency of recurrence and lower overall survival. The objective was assess clinical behavior, recurrence and survival of patients with triple negative early breast cancer and patients with other immunophenotypes. MATERIAL AND METHODS: We carried out a retrospective study among women with stages I-IIB over 18 years with determination of HR and HER2 expression by immunohistochemical assay. We identified 5 groups: triple negative, triple positive, HER2 negative & HR positive, HER2 positive & HR negative, HER2 negative & 1 HR positive. We recorded age, date of diagnosis, clinical stage, tumor size, axillary lymph node status, ER, PR, HER2, p53, angiogenesis, Ki67, type of surgery, adjuvant treatment, time to recurrence, number and recurrence site and overall survival. RESULTS: 17 patients (15.4%) had triple negative phenotype, 14 (12.7%) triple positive, 52 (47.3%) were localized in group 3, 11 (10%) in 4 and 16 (14.5%) in group 5. Triple negative phenotype was associated with increased cellular proliferation (p < 0.000); being young (median 43 years), large tumor size (median size 2.5 cm) lower proportion of patients in stage I and high frequency of p53 positive (78.5%). We observed a high frequency of recurrence and death among the triple negative group and among the HER2 positive and HR negative cases. CONCLUSIONS: Triple negative breast cancer is more common among young women and is associated with a high frequency of recurrence and mortality. Clinical behavior among triple negative breast cancer cases is aggressive and displays a similar clinical profile that observed among HER2 positive and HR negative patients.

Recurrencia y supervivencia en cáncer mamario temprano con inmunofenotipo triple-negativo / Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype

Antecedentes: El estado ganglionar axilar, la expresión de los receptores hormonales y del HER2 son importantes factores pronóstico en cáncer de mama temprano. El inmunofenotipo triple negativo (HER2 y receptores hormonales negativos) se ha asociado con mayor frecuencia de recurrencia y menor tiempo de supervivencia. El objetivo de esta investigación fue evaluar el comportamiento clínico, recurrencia y supervivencia en mujeres con cáncer de mama temprano-triple negativo y otros inmunofenotipos. Material y métodos: Estudio retrospectivo de mujeres en etapas IIIB, mayores de 18 años, en quienes se determinó la expresión de la proteína HER2, receptores de estrógeno y de progesterona a través de inmunohistoquímica. Se identificaron cinco grupos: triple negativo, triple positivo, HER2 negativo y receptores hormonales positivos, HER2 positivo y receptores hormonales negativos, HER2 negativo y un receptor hormonal positivo. En cada caso se analizó la edad, fecha del diagnóstico, etapa clínica, tamaño tumoral, estado ganglionar axilar, receptores de estrógenos, progesterona, HER2, p53, angiogénesis, Ki67, tipo de cirugía realizada, tratamiento adyuvante, tiempo a la recurrencia, número y sitios de la recurrencia, así como el tiempo de sobrevida global. Resultados: 17 pacientes (15.4%) manifestaron el fenotipo triple negativo; 14 (12.7%), triple positivo; 52 (47.3%) en el grupo 3, 11 (10%) en el 4 y 16 (14.5%) en el grupo 5. El fenotipo triple negativo se asoció con proliferación celular aumentada (p<0.000), menor edad (mediana 43 años), mayor tamaño tumoral (mediana 2.5 cm) y menor proporción de pacientes en etapa I, así como mayor frecuencia de expresión positiva de la proteína p53 (78.5%). Observamos mayor frecuencia de recurrencia y de muerte en el grupo triple negativo y en HER2 positivo con receptores hormonales negativos. Conclusiones: El cáncer de mama triple negativo se presenta en mujeres jóvenes y se asocia con proliferación celular aumentada, induce mayor incidencia de recurrencia y de mortalidad. El comportamiento biológico del cáncer de mama con fenotipo triple negativo es agresivo y similar al observado en pacientes con HER2 positivo y receptores hormonales negativos.

BACKGROUND: Axillary lymph node status, hormonal receptors (HR) and HER2 expression are significant prognostic factors for early breast cancer. Triple negative immunophenotype (HER2 and HR negative) is associated with a high frequency of recurrence and lower overall survival. The objective was assess clinical behavior, recurrence and survival of patients with triple negative early breast cancer and patients with other immunophenotypes. MATERIAL AND METHODS: We carried out a retrospective study among women with stages I-IIB over 18 years with determination of HR and HER2 expression by immunohistochemical assay. We identified 5 groups: triple negative, triple positive, HER2 negative & HR positive, HER2 positive & HR negative, HER2 negative & 1 HR positive. We recorded age, date of diagnosis, clinical stage, tumor size, axillary lymph node status, ER, PR, HER2, p53, angiogenesis, Ki67, type of surgery, adjuvant treatment, time to recurrence, number and recurrence site and overall survival. RESULTS: 17 patients (15.4%) had triple negative phenotype, 14 (12.7%) triple positive, 52 (47.3%) were localized in group 3, 11 (10%) in 4 and 16 (14.5%) in group 5. Triple negative phenotype was associated with increased cellular proliferation (p < 0.000); being young (median 43 years), large tumor size (median size 2.5 cm) lower proportion of patients in stage I and high frequency of p53 positive (78.5%). We observed a high frequency of recurrence and death among the triple negative group and among the HER2 positive and HR negative cases. CONCLUSIONS: Triple negative breast cancer is more common among young women and is associated with a high frequency of recurrence and mortality. Clinical behavior among triple negative breast cancer cases is aggressive and displays a similar clinical profile that observed among HER2 positive and HR negative patients.

[Biomarkers in the prognosis and treatment response of breast cancer]. / Biomarcadores en el pronóstico y respuesta al tratamiento en cáncer mamario.

PURPOSE: To determine the prognostic value of c-erbB-2, p53, hormone receptors and angiogenesis, on recurrence free time and its relationship to treatment in breast cancer patients. METHODS: Women with histologic diagnosis of breast cancer and immunohistochemical determination of biologic factors. Clinic, histologic, molecular factors and recurrence free time were registered. RESULTS: 101 patients, ages 51.98 +/- 11.5 years. Follow-up 32.52 +/- 24.3 months. Tumor recurred in 31, (30.69%); 15 (48.33%) had tumor size above 2.1 cm, 19 (61.29%) showed positive estrogen receptors and 18 (58.07%) for progesterone; 20 (64.51%) to c-erbB-2 expression (64.51%); 18 to p53; average microvessels 24.48 +/- 17.27. Tumor size related to recurrence, p = 0.008. Kruskal-Wallis test did not show a difference when correlating survival free time and biologic factors. 24 pts. (77.41%) received hormones; 20 (64.5%) chemotherapy (61.29%); 19 (61.29%) radiotherapy. Response prediction to hormones with estrogen receptor positive, p = 0.059; to chemotherapy in angiogenesis under 40 vessels/field-0.024. CONCLUSIONS: Tumor size has prognostic implications. A clear positive tendency was observed with p53 and higher microvessel density. Estrogen receptors offer predictive response value to hormone treatment and lower vascular density to chemotherapy, treatment indicators of possible therapeutic association.

Biomarcadores en el pronóstico y respuesta al tratamiento en cáncer mamario / Biomarkers in the prognosis and treatment response of breast cancer

PURPOSE: To determine the prognostic value of c-erbB-2, p53, hormone receptors and angiogenesis, on recurrence free time and its relationship to treatment in breast cancer patients. METHODS: Women with histologic diagnosis of breast cancer and immunohistochemical determination of biologic factors. Clinic, histologic, molecular factors and recurrence free time were registered. RESULTS: 101 patients, ages 51.98 +/- 11.5 years. Follow-up 32.52 +/- 24.3 months. Tumor recurred in 31, (30.69); 15 (48.33) had tumor size above 2.1 cm, 19 (61.29) showed positive estrogen receptors and 18 (58.07) for progesterone; 20 (64.51) to c-erbB-2 expression (64.51); 18 to p53; average microvessels 24.48 +/- 17.27. Tumor size related to recurrence, p = 0.008. Kruskal-Wallis test did not show a difference when correlating survival free time and biologic factors. 24 pts. (77.41) received hormones; 20 (64.5) chemotherapy (61.29); 19 (61.29) radiotherapy. Response prediction to hormones with estrogen receptor positive, p = 0.059; to chemotherapy in angiogenesis under 40 vessels/field-0.024. CONCLUSIONS: Tumor size has prognostic implications. A clear positive tendency was observed with p53 and higher microvessel density. Estrogen receptors offer predictive response value to hormone treatment and lower vascular density to chemotherapy, treatment indicators of possible therapeutic association.

Dermatomiositis asociada con cáncer gástrico como síndrome paraneoplásico / Dermatomyositis and gastric cancer as paraneoplastic syndrome

La dermatomiositis es un trastorno en el que el músculo esquelético resulta afectado por un proceso inflamatorio no supurativo, manifestado por debilidad proximal y erupción cutánea. La dermatomiositis puede relacionarse con infección viral, enfermedades del tejido conectivo como lupus eritematoso sistémico, enfermedad mixta del tejido conectivo y en menor proporción con neoplasias. Se reporta un caso de dermatomiositis asociado con adenocarcinoma gástrico en un hombre joven, lo cual constituye un caso poco común. La incidencia varía de 6 a 43 por ciento de los casos; cuando la dermatomiositis se presenta junto con neoplasia, ésta puede aparecer hasta dos años después del cuadro de miositis, constituyendo un síndrome paraneoplásico. Las neoplasias frecuentemente relacionadas son cánceres de ovario, de mama, pulmonar y neoplasias digestivas como cánceres de colon y gástrico.

Colesterol total en cáncer de mama y tamoxifen / Total cholesterol in breast cancer and tamoxifen

Antecedentes: En México, el cáncer de mama representó en el año de 1997 la segunda causa de muerte por neoplasia en la población general, induciendo 9,050 fallecimientos. El tamoxifen es un fármaco antiestrogénico utilizado en la terapia adyuvante del tratamiento de enfermedad metastásica y en la quimioprevención del cáncer mamario. Existe relación entre los estrógenos y los niveles de lípidos en sangre. Objetivo: Evaluar el comportamiento de los niveles séricos de colesterol en pacientes con cáncer de mama tratadas con tamoxifen. Pacientes y métodos: Mujeres con cáncer mamario, sin distinción de edad, con estado positivo o desconocido de receptores estrogénicos, en tratamiento con tamoxifen al menos por seis meses, en quienes se realizó control de colesterol sérico al menos en tres ocasiones. Se excluyen aquéllas con historia de diabetes mellitus, dislipidemia previamente conocida, hipertensión arterial, con terapia a base de corticosteroides, metástasis hepáticas y quienes recibieron quimioterapia simultánea. Se valoraron: edad, estadío clínico, tiempo de uso del tamoxifen, síntomas asociados al empleo del fármaco, presencia de eventos cardiovasculares, nivel de receptores hormonales, colesterol al inicio de la terapia, a los seis meses y al año, así como las causas de defunción. Resultados: Veintinueve mujeres, edad promedio 56.2 + 10.9 años; 18 mayores y 11 menores de 50 años. Etapa I con ocho casos, 27.6 por ciento; IIa, 27.6 por ciento; IIb 10, 34.5 por ciento; dos se consideraron en etapa IIIb y una no fue etapificable. Determinación de receptores estrogénicos: 14 positivos y uno negativo; receptores de progesterona positivos en 10 y negativos en dos. Tamoxifen se empleó en promedio 41.9 + 18.3 meses. Se asoció con bochornos; dolor óseo difuso; nausea; dispepsia; disminución de la agudeza visual; vértigo y distensión abdominal. Colesterol inicial 198 mg/dL, a los seis meses 211.46 y al final 199.83, p = 0.644; entre las mayores de 50 años se observaron cifras de 208.2 + 18.9, 217.6 + 52.3 y 202 + 45.6, respectivamente; mientras que entre las menores de 50 años se determinaron cifras de 183 + 26.9, 194.1 + 19.3 y 186.7 + 36.1, respectivamente; no se evidenció diferencia significativa. Se observaron tres eventos vasculares, isquemia cerebral transitoria, cardiopatía isquémica e insuficiencia cardíaca. Conclusión: La terapia antiestrogénica con tamoxifen, del cáncer mamario, no modifica significativamente los niveles séricos de colesterol total

Quimioterapia en cáncer germinal y epitelial de ovario / Chemotherapy in germinal and epithelial ovarian cancer

Genéricamente, el cáncer de ovario representa enfermedades con comportamientos clínicos distintos. Así, los tumores poco frecuentes de células germinales son tratados con éxito en la gran mayoría de las pacientes, mediante regímenes convencionales de quimioterapia. En contraste, en el cáncer epitelial, que representa el 90 por ciento de los casos, a pesar de que muestra sensibilidad a la quimioterapia, no se ha logrado alcanzar resultados satisfactorios. En la búsqueda de mejores respuestas para el tratamiento de la neoplasia epitelial de ovario, recientemente se han investigado nuevos fármacos como paclitaxel, doxorrubicina liposomal, docetaxel, topotecan, gemcitabina y combinaciones de diferentes drogas, así como tratamientos con base en anticuerpos monoclonales que ofrecen una nueva esperanza. El objetivo de este trabajo es revisar y difundir las tácticas de tratamiento citotóxico disponibles para esta neoplasia.

Trombosis venosa profunda del miembro superior / Deep venous thrombosis of upper extremity

Aunque los fenómenos trombóticos venosos profundos de los miembros superiores ocupan menos del 5 por ciento de todas las trombosis venosas profundas, recientemente en nuestra práctica clínica hemos observado un incremento de estos casos, principalmente asociados al empleo de catéteres venosos centrales, razón por la cual decidimos hacer una revisión del tema y de la casuística de los autores.

Quimioterapia en cáncer germinal y epitelio de ovario / Chemotherapy in germinal and epithelial ovarian cancer

Genéricamente el cáncer de ovario representa enfermedades con comportamientos clínicos distintos. Así, los tumores poco frecuentes de células germinales son tratados con éxito en la gran mayoría de las pacientes, mediante regímenes convencionales de quimioterapia. En contraste, en el cáncer epitelial, que representa 90 por ciento de los casos, a pesar de que muestra sensibilidad a la quimioterapia aún no se ha logrado alcanzar resultados satisfactorios. En la búsqueda de mejores respuestas para el tratamiento de la neoplasia epitelial de ovario, recientemente se han investigado nuevos fármacos como docetaxel, topotecan, gemcitabina y combinaciones de diferentes drogas así como tratamientos con base en anticuerpos monoclonales que ofrecen una nueva esperanza.

Pamidronato en el tratamiento de metástasis óseas / Pamidronate in the treatment of bone metatases

Antecedentes: Mecanismos humorales y no humorales están involucrados en la génesis de las metástasis óseas. La manifestación más común es el dolor. Objetivo: Valorar los efectos terapéuticos y adversos relacionados con la administración de pamidronato en enfermos con metástasis óseas. Pacientes y métodos: Fueron incluidos sujetos con neoplasia metastásica a hueso que recibieron pamidronato al menos en una ocasión. Pacientes con uso simultáneo de otros fijadores de calcio fueron excluidos de este estudio. El pamidronato fue administrado en dosis de 90 mg por vía intravenosa en 120 minutos cada 30 días. Se evaluó: edad, sexo, neoplasia, sitios metastásicos, indicación para la terapia, número de aplicaciones, síntomas asociados. Se determinó el nivel sérico de calcio y de fosfatasa alcalina. El dolor se calificó con una escala de 0 a 10. Resultados: El estudio incluyó diez hombres y 24 mujeres con edad promedio 58.38 + 15.84 años (rango 16 a 84). Recibieron 3.24 + 1.6 aplicaciones (rango 1 a 6). Veinte de los pacientes eran mujeres con cáncer de mama. Mieloma múltiple cinco, próstata cuatro, pulmón tres, paraganglioma y enfermedad de Paget uno. El 28.57 por ciento de los casos tuvieron dos o más sitios metastásicos. Las indicaciones para usar pamidronato fueron: Dolor óseo en 27 sujetos y riesgo de fractura en siete. Además del fármaco se aplicó radioterapia simultáneamente en 17 pacientes; en 12 de éstos por dolor severo y en cinco por metástasis cerebrales. Cinco enfermos refirieron dolor óseo moderado a severo; otros dos (5.88 por ciento) señalaron fatiga muscular y uno presentó "flu-like", náusea e insomnio. Antes de la infusión, la intensidad del dolor, fue de 8.71 + 1.57 (rango 4 a 10) y después del primer ciclo fue de 3.77 + 2.58 (rango 0 a 10), p < 0.0001. La cifra inicial promedio de calcio sérico fue de 8.96 + 0.68 mg/dL (rango 7.8 a 10.1) y la mediana de fosfatasa alcalina fue de 121 mg/dL (rango 36 a 903). Posterior a la segunda aplicación los niveles fueron de 8.93 + 0.36 mg/dL (rango 8.94 a 9.6) para el calcio sérico y de 121.5 mg/dL (rango 50 a 920) para la fosfatasa alcalina, p > 0.05. Antes del tratamiento se registró fractura transtrocantérica en tres (8.82 por ciento) pacientes. Conclusión: El pamidronato produce pocos efectos secundarios que no suelen ser frecuentes; no modificó significativamente las cifras séricas de calcio ni de fosfatasa alcalina y redujo la intensidad del dolor. Puede ser administrado simultáneamente con radioterapia

Fertilidad y cáncer / Cancer and fertility

En los tratamientos contra el cáncer se ha logrado obtener los mejores resultados en niños, adolescentes y adultos jóvenes, pero cobrando un costo en la capacidad reproductiva. A mediano y largo plazos, los órganos y tejidos sanos, particularmente las gónadas, pueden ser afectados, con consecuencias negativas para la fertilidad. Cirugía, radioterapia y tratamiento sistémico pueden interferir con la capacidad reproductiva. La magnitud del daño por citotóxicos varía según agente, dosis y edad del paciente al momento del tratamiento. En la gónada masculina los esquemas de quimioterapia deterioran las células tallo germinales, mientras que las células de Leydig rara vez son afectadas por lo que se conserva la función androgénica; la espermatogénesis puede recuperarse en forma tardía. Con ciertos tumores las cuentas espermáticas se encuentran bajas aun antes del inicio del tratamiento. La interrupción de la función ovárica se registra en mujeres adultas y guarda relación con la dosis acumulada. En productos de embarazo de sobrevivientes de cáncer, no se ha documentado aumento en teratogénesis o mutagénesis. El embarazo después del cáncer mamario no presenta efectos adversos sobre la supervivencia. Hombres y mujeres jóvenes que deben ser tratados contra el cáncer, deberán ser alertados sobre la fertilidad y recibir apoyo para restaurar una vida sana. Desde su inicio, el plan terapéutico deberá intentar proteger las gónadas, preservar células germinales e incluir una consulta sobre programas de fertilidad asistida.