Survival rates of advanced estrogen-receptor positive breast cancer. Analysis of 211 cases

ABSTRACT Background: About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical pre-sentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates. Material and Methods: We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017. Results: The median overall survival (OS) was 37 months. Median OS for the period 1997/2006 and 2007/2017 were 33 and 42 months, respectively (p = 0.47). Luminal A, ABC stage IV disease at diagnosis displayed better OS rates than Luminal B stage IV tumors (100 and 32 months respectively, p < 0.01). Conclusions: Clinical presentation (stage IV vs. systemic recurrence) and tumor subtype are key determinants of OS in ABC.

Antecedentes: Casi el 80% de los casos de cáncer de mama (CM) son positivos para receptores de estrógenos (RE+). Éstos se caracterizan por una mejor sobrevida y respuesta a terapia endocrina. Objetivo: Caracterizar a pacientes con CM avanzado (CMA), RE+, y determinar sobrevida según presentación clínica y subtipos. Material y Métodos: Analizamos en nuestra base de datos los antecedentes de 211 pacientes con CMA RE+, tratados en nuestra institución en el período 1997-2017. Se evaluó el impacto de la presentación clínica (estadio IV al diagnóstico, enfermedad de novo, versus recurrencia sistémica) y subtipo de CM, en los niveles de sobrevida. Resultados: La mediana de sobrevida global (SG) fue de 37 meses. La mediana de SG para el período 1997/2006 y 2007/2017 fue de 33 y 42 meses; respectivamente (p = 0,47). Pacientes con CMA, estadio IV, Luminal A al momento del diagnóstico mostraron mejores tasas de SG frente al estadio IV del Luminal B (100 y 32 meses respectivamente (p < 0,01). Conclusiones: La presentación clínica (estadio IV, de novo, versus recurrencia sistémica) y subtipo son determinantes clave de la SG en CMA.

Características clínicas y pronóstico de pacientes con cáncer de mama HER2 positivo avanzado, en la era antes y después de terapias anti-HER2 / Survival of patients with advanced HER2+ breast cancer. Analysis of a cancer center database

Background: HER2+ breast cancer (BC) subtype overexpresses the Human Epidermal growth factor Receptor type-2 (HER2) and is characterized by its aggressiveness and its high sensitivity to monoclonal antibody-based HER2-targeted therapies. Aim: To assess the prognosis and evaluate the impact of novel anti-HER2 therapies on advanced HER2+ BC patients treated at our institution over the last decades. Material and Methods: Analysis of the patient database at a cancer center of a university hospital. Information about the subtype of cancer was obtained in 2,149 of 2,724 patients in the database. Eighteen percent of the latter were HER2+. We analyzed data of 83 of these patients with advanced disease. Results: Median overall survival (OS) was 24 months. For patients treated between 1997-2006 median OS was 17 months and for those treated in the period 2007-2017 median OS was 32 months (p = 0.09). Conclusions: A non-significant trend towards better survival in the last decade was observed. HER2+ BC overall survival has improved in our center. This can be probably attributed to the use of novel more effective anti-HER2 therapies.

Actividad física y cáncer de mama: un tratamiento dirigido / Physical activity and breast cancer

In Chile breast cancer (BC) is the first cause of death in women. While the most important risk factor for its development is estrogenic stimulation, environmental factors and lifestyles also contribute to its pathogenesis. Epidemiological studies show a direct relationship between physical activity (PA), incidence and recurrence of BC. Supervised PA practice is recommended in most cancer patients to improve their quality of life, to reduce adverse effects from treatment and eventually to improve the prognosis of the disease. We review the epidemiological evidence linking PA and BC and the biological basis of this relationship. We also review the relevant interventional studies and we explore some practical indications of PA in patients with BC, as a model for other tumors of epidemiological importance.

Entendiendo las terapias actuales en melanoma metastásico / Understanding current therapies in metastatic melanoma

Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.

Evaluación del valor pronóstico de la relación neutrófilos/linfocitos en cáncer de mama de subtipos agresivos / Neutrophil/lymphocyte ratio in complete blood count as a mortality predictor in breast cancer

The white blood cell count is one of the most sensitive markers associated with inflammation. The neutrophil/lymphocyte count ratio may be an independent factor for breast cancer mortality. Aim: To assess the predictive value of the neutrophil/lymphocyte ratio for mortality in breast cancer. Material and Methods: Review of the database of a cancer center of a University hospital. Patients with infiltrating breast cancer treated between 1997 and 2012 were selected. The pathology type and lymph node involvement were obtained from the pathology report. The expression of estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) was determined by immunohistochemistry or in situ fluorescent hybridization (FISH). The absolute peripheral neutrophil and lymphocyte counts were obtained from a complete blood count obtained at least three months before treatment. Patients were followed for a median of 61 months (range 1-171). Results: From 323 eligible patients, after excluding those in stage IV and those without an available complete blood count, 131 patients were analyzed (81 with negative receptors and 117 HER2 enriched). The neutrophil/lymphocyte ratio was similar in both types of tumors (2.1 and 1.91 respectively). Twenty two patients died during follow-up. Surviving patients with HER2 enriched tumors had a lower neutrophil/lymphocyte ratio than those who died (1.79 and 3.21 respectively, p < 0.01). In a multivariate analysis, including age, tumor stage and lymph node involvement as confounding factors, the neutrophil/lymphocyte ratio was still significantly associated with a risk of death with a hazard ratio of 2.56. Conclusions: A high neutrophil/lymphocyte ratio in the complete blood count can be a predictor of death in breast cancer.

Inmunohistoquímica convencional como predictor de respuesta y sobrevida en pacientes con cáncer de mama tratadas con quimioterapia preoperatoria: Experiencia de un centro / Predictive value of conventional immuno-histochemical biomarkers in breast cancer

Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) in breast cancer (BC) identifies patients with good prognosis. Aim: To assess if the clinico-pathological subtype, determined by classic immunohistochemical (IHC) markers, is able to predict pCR and prognosis in BC patients treated with NCT. Material and Methods: One hundred thirty three BC patients aged 24-80 years, were treated with NCT. Clinico-pathological subtype was defined based on classic IHC markers. pCR was defined as the absence of invasive neoplastic cells in the breast and lymph nodes, on final breast surgery. Results: pCR was achieved in 8.2% of patients, 3.5 and 19.5% in luminal and hormonal receptor (HR) negative tumors respectively (p < 0.01). Median follow-up was 72.6 months (3.5-190). Patients who achieved pCR had higher overall survival (OS) (p = 0.04). A univariate analysis revealed that size of the tumor, ratio of metastatic to examined lymph nodes and absence of HR were significant predictors of pCR. These findings were not replicated in the multivariate analyses. Conclusions: Clinico-pathological subtypes were independent prognostic factors for pCR and OS in BC patients in our cohort. These findings support using classic and cheap biomarkers as a predictive tool for NCT in BC.

Terapia endocrina neoadyuvante en cáncer de mama, una alternativa de tratamiento e investigación / Neoadyuvant endocrine therapy in breast cancer

Neoadjuvant chemotherapy is an accepted strategyforpatients with locally advanced breast cáncer. This approach increases the possibilities ofconservative treatment and improves the resectability rates ofinitially unresectable tumors. In addition, preoperative systemic therapy allows the evaluation of prognostic and predictive factors, dynamically and in vivo. Since over 80% ofthese tumors express estrogen receptors (ER), endocrine therapy seems a logical treatment to employ in the neoadjuvant setting. The advent ofnew drugs that regúlate the ERfunction, along with the results of severa! clinical studies with the use of neoadjuvant endocrine therapy, support the feasibility and safety of utilizing this strategy before surgery. We herein analyze the available clinical evidence about the use of neoadjuvant therapy aiming to regúlate the activity ofthe ER. We also discuss the valué of predictive factors that could help the oncologist to select those patients most likely to benefit from this approach and the role of endocrine therapy as a research instrument.

Dengue in Nicaragua, 1994: reintroduction of serotype 3 in the Americas / Dengue en Nicaragua, 1994: reintroducción del serotipo 3 en las Américas

El objetivo principal de este informe fue describir la reaparición del serotipo 3 del dengue en las Américas después de 17 años de ausencia, tal como se observó recientemente en Nicaragua. Se examinaron en total 356 muestras de suero obtenidas por medio del sistema nicaragüense de vigilancia del dengue durante una epidemia en octubre de 1994. En 43% de las muestras se detectaron anticuerpos IgM contra el dengue y los sueros de 12 de las 18 áreas atendidas por los sistemas locales integrales de salud dieron resultados positivos. Además, se aislaron virus de dengue en 5 de 24 sueros de pacientes con síntomas hemorrágicos: en 3 se aisló el serotipo 3 y en 2, el serotipo 1. Mediante pruebas de laboratorio, en 26 de 39 pacientes hospitalizados en León y Managua se consideró probable o se confirmó el diagnóstico de dengue con manifestaciones hemorrágicas o dengue hemorrágico. En 18 pacientes diagnosticados de dengue con manifestaciones hemorrágicas, los síntomas más comunes fueron fiebre, cefalea, vómito, mialgia, artralgia y epistaxis. Los ocho pacientes restantes, en los que se diagnosticó dengue hemorrágico probable, tuvieron fiebre, malestar general, hemorragias, trombocitopenia y hemoconcentración, y los títulos de anticuerpos a la prueba de inhibición de la hemaglutinación oscilaron de 640 a 20 480. Se confirmó así la reintroducción del serotipo 3 del dengue en la Región y su capacidad para producir casos de dengue hemorrágico. En Nicaragua, por lo menos, es evidente que la reintroducción del serotipo 3 del dengue ha producido un aumento de los casos de dengue clásico y dengue hemorrágico. Si no se presta atención urgente al control del mosquito vector de la enfermedad, la experiencia descrita podría constituir el preludio lúgubre de futuros acontecimientos similares en las Américas

The principal aim of the report presented here is to describe the reappearance of dengue serotype 3 in the Americas, following a 17-year absence, through the recent experience of Nicaragua. In all, 356 serum samples obtained through Nicaragua's dengue monitoring system in October 1994 during an epidemic were examined. Anti-dengue IgM antibodies were detected in 43% of these, with sera from 12 of the 18 areas covered by Nicaragua's local integrated health care systems yielding positive results. In addition, dengue virus was isolated from 5 of 24 sera obtained from patients with hemorrhagic symptoms, dengue 3 being isolated from 3 of these samples and dengue 1 from the other 2. A diagnosis of dengue with hemorrhagic manifestations or of hemorrhagic dengue was supported or confirmed by laboratory findings obtained from 26 of 39 patients hospitalized in León or Managua. The most frequent symptoms of 18 patients diagnosed as having dengue with hemorrhagic manifestations were fever, headache, vomiting, myalgia, arthralgia, and epistaxis. The remaining eight patients, diagnosed as having probable hemorrhagic dengue, exhibited fever, general malaise, hemorrhaging, thrombocytopenia, hemoconcentration, and hemagglutination-inhibition antibody titers ranging from 640 to 20 480. Overall, the reappearance of dengue serotype 3 in the Region was confirmed, together with its ability to produce cases of hemorrhagic dengue. At least in Nicaragua, it is apparent that the introduction of dengue serotype 3 has prompted an increase in the number of classical dengue and hemorrhagic dengue cases, a scenario that might constitute the grim prelude to future developments in the Americas if urgent attention is not given to controlling the disease's mosquito vector