The role of modern parameters and their relationship with recurrence risk as assessed by Oncotype DX: real-world evidence.

Genomic analysis through various platforms is an essential tool for determining prognosis and treatment in a significant subgroup of early-stage breast cancer patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative status. Additionally, combined clinical and pathological characteristics can accurately predict the recurrence score (RS), as demonstrated by the University of Tennessee risk nomogram. In this study, we aimed to identify classical clinical-pathological factors associated with high RS in a local population, including modern parameters such as current abemaciclib treatment recommendations, HER2-low status, different Ki-67 cutoff values, and samples obtained from secondary primary tumours. This is a retrospective single-institution study that analysed a total of 215 tumour samples. Among lymph node-negative patients (n = 179), age, Ki67 values, and progesterone receptor status predicted RS after multivariate analysis. HER2-low status was not associated with RS differences (p = 0.41). Among lymph node-positive patients (n = 36), MonarchE inclusion criteria (15) were not associated with a higher RS (p = 0.61), and HER2-low did not reach statistical significance. However, tumours classified as secondary primaries numerically exhibited a higher RS. Based on these findings from our real-world sample, the mere application of clinical and pathological parameters is insufficient to predict RS outcomes. Modern parameters such as HER2-low status or adjuvant abemaciclib recommendations were not associated with RS differences. Regarding the observation of secondary tumours, more evidence is needed to understand whether prior hormone therapy exposure impacts the biological risk of secondary primary tumours.

The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).

Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients.

PURPOSE: The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant and trastuzumab, improves progression-free survival (PFS) in hormone receptor-positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared with standard-of-care (SOC) chemotherapy combined with trastuzumab. We report the final overall survival (OS) analysis, updated safety and efficacy data, and exploratory biomarker results from monarcHER. PATIENTS AND METHODS: monarcHER (NCT02675231), a randomized, multicenter, open-label, phase II trial, enrolled 237 patients across Arm A (abemaciclib, trastuzumab, fulvestrant), Arm B (abemaciclib, trastuzumab), and Arm C (SOC chemotherapy, trastuzumab). Following the statistical plan, OS and PFS were estimated in all arms. RNA sequencing (RNA-seq) was performed on archival tissue. RESULTS: Median OS was 31.1 months in Arm A, 29.2 months in Arm B, and 20.7 months in Arm C [A vs. C: HR, 0.71; 95% confidence interval (CI), 0.48-1.05; nominal two-sided P value 0.086; B vs. C: HR 0.83 (95% CI, 0.57-1.23); nominal two-sided P value 0.365]. Updated PFS and safety findings were consistent with previous results. The most frequently reported treatment-emergent adverse events included diarrhea, fatigue, nausea, neutrophil count decrease, and anemia. In exploratory RNA-seq analyses, Luminal subtypes were associated with longer PFS [8.6 vs. 5.4 months (HR, 0.54; 95% CI, 0.38-0.79)] and OS [31.7 vs. 19.7 months (HR, 0.68; 95% CI, 0.46-1.00)] compared with non-Luminal. CONCLUSIONS: In this phase II trial, abemaciclib + trastuzumab ± fulvestrant numerically improved median OS in women with HR+, HER2+ ABC compared with SOC chemotherapy + trastuzumab.

Cyclin-Dependent Kinase 4/6 Inhibitor Outcomes in Patients With Advanced Breast Cancer Carrying Germline Pathogenic Variants in DNA Repair-Related Genes.

PURPOSE: In recent years, unprecedented benefits have been observed with the development of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. However, there is scarce evidence of their value in specific populations, such as patients carrying germline pathogenic variants in DNA repair-related genes. PATIENTS AND METHODS: We retrospectively studied the efficacy of CDK 4/6 inhibitors plus endocrine therapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Three cohorts were compared, including patients harboring germline pathogenic variants in DNA repair-related genes (gBRCA1/2-ATM-CHEK2 mutated), those tested without these mutations (wild type [WT]), and the nontested subgroup. Relevant prognostic factors including age, metastatic site (visceral v nonvisceral), Eastern Cooperative Oncology Group, and prior treatment with CDK 4/6 inhibitors were stratified by univariate and multivariate Cox regression models. RESULTS: Among the total population (n = 217), 15 (6.9%) patients carried gBRCA1/2 (n = 10)-ATM (n = 4)-CHEK2 (n = 1) pathogenic variants, 45 (20.7%) were WT, and 157 (72.4%) were nontested. Gene pathogenic variant carriers were younger (P < .001). Most patients (164, 75.6%) had not received prior endocrine therapy in the advanced setting. Median progression-free survival was shorter in patients with evaluated germline pathogenic variants (10.2 months [95% CI, 5.7 to 14.7]), compared with WT and nontested patients (15.6 months [95% CI, 7.8 to 23.4], and (17.6 months [95% CI, 12.9 to 22.2]; P = .002). Consistently, a worse median overall survival was observed in the subgroup with germline pathogenic variants than in the WT group (P = .006). Multivariable analysis showed that mutation status was an independent prognostic factor of progression-free survival (P = .020) and overall survival (P = .012). CONCLUSION: In this retrospective real-world study, gBRCA1/2-ATM-CHEK2 pathogenic variants were independently associated with poor outcomes in patients with advanced breast cancer treated with CDK4/6 inhibitors.

Valor de la ruptura capsular y extensión extranodal en el ganglio centinela como predictores del estado axilar en pacientes con cáncer de mama T1-T2 / Significance of extracapsular extension in sentinel lymph nodes as a predictor of axillary lymph node status in T1-T2 breast cancer patients

Introducción: Identificar aquellas pacientes con cáncer de mama en estadíos iniciales que no se benefician de la linfadenectomía (LA), a pesar de contar con ganglios centinela positivos, constituye un desafío. El ensayo ACOSOG-Z0011 modificó el paradigma de la cirugía axilar, pero aún no está claro qué efecto tiene la ruptura capsular (RC) y su extensión (EEC) en el compromiso axilar. Material y método: Se incluyeron 214 pacientes intervenidas quirúrgicamente entre 2009-2019 en el Centro mamario del Instituto Alexander Fleming, con cáncer de mama en T1-2, en las que la biopsia de ganglio centinela (BGC) resultó positiva, y se realizó LA. Se realizaron comparaciones entre aquellas pacientes con y sin RC. Las pacientes con RC fueron divididas en dos grupos, según la EEC fuera mayor o igual a 2 mm, o menor a 2 mm. Para los distintos grupos de pacientes, se analizaron variables clínicas y anatomo-patológicas, incluyendo edad, estado menopáusico, subtipo biológico, grado nuclear, tamaño tumoral, invasión linfovascular (ILV) y multicentricidad. Resultados: La RC se asoció a una mayor probabilidad de presentar ganglios no centinela positivos, y en particular a la presencia de 4 o más ganglios positivos. Este grupo de pacientes presentó con más frecuencia ILV. En cuanto a la EEC, no hallamos diferencias significativas de acuerdo a la extensión de la ruptura (EEC<2 mm y EEC≥2 mm), aunque en el análisis uni y multivariado evidenció un mayor riesgo de presentar ≥4 ganglios positivos en el grupo de pacientes con EEC≥2 mm. Discusión: En línea con la bibliografía actual, encontramos que la RC es un hallazgo frecuente y que se asocia a una mayor probabilidad de presentar metástasis ganglionar, en especial 4 o más ganglios positivos. Al separar a las pacientes de acuerdo a la EEC, no hallamos diferencias en cuanto a la proporción de pacientes con ganglios positivos en la LA. Estos resultados difieren de los obtenidos por otros centros, en donde se ha demostrado una mayor probabilidad de contar con ganglios no centinela positivos en el grupo de pacientes con EEC>2mm. Conclusiones: En la bibliografía actual existe consenso en relación al rol de la RC como factor de riesgo, y nuestros resultados apoyan esta hipótesis. Sin embargo, resulta menos claro el papel que juega la magnitud de la EEC. Esto podría deberse, por un lado, a la falta que bibliografía disponible, y por otro, a la falta de consenso para determinar la medición de la EEC En línea con publicaciones recientes que no hallan diferencias significativas en la recurrencia de la enfermedad a largo plazo según la magnitud de la EEC, será fundamental continuar con un futuro análisis que contemple estos aspectos en nuestra población. Al día de hoy, no contamos con evidencia que nos permita afirmar que las pacientes con EEC<2 mm puedan beneficiarse de la omisión de LA

Introduction: The identification of those early breast cancer patients with no clear benefit from axillary lymph node dissection (ALND) in spite of the presence of positive sentinel lymph nodes (SLNs), remains controversial. Although the ACOSOG-Z001 trial has significantly altered management of the axilla, the role played by the extracapsular extension (ECE) is still a subject of debate. Materials and method: In the present study, we analysed 214 early breast cancer patients with positive SLN biopsy, who underwent ALND at Instituto Alexander Fleming between 2009 and 2019. Patients were divided into two categories based on the presence or absence of ECE; those patients with ECE were further divided based on the extent of ECE (ECE<2 mm and ECE≥2 mm). Analysis of clinical-pathological parameters was performed, including age, menopausal status, tumor subtype, nuclear grade, tumor size, lymphovascular invasion (LVI) and multicentricity. Results: ECE was associated with an increased probability of additional positive nodes in the ALND, and these patients were also more likely to have 24 positive nodes. LVI was increased in patients with ECE. Additionally, we found no significant differences regarding the number of positive nodes when comparing patients according to the extent of ECE (ECE<2 mm and ECE≥2 mm). Univariate and multivariate analyses of factors associated with involvement of ≥4 nodes at completion ALND resulted in an increased odds ratio for patients with ECE ≥2 mm. Discussion: In line with recent literature, we found ECE is frequently observed in breast cancer patients and is associated with an increased probability of lymph node metastases, and these patients are also more likely to have 24 positive nodes. We found no significant differences in terms of the proportion of patients with positive lymph nodes in ALND when comparing patients with and without ECE. Our results differ from other studies that showed a higher risk of non-sentinel lymph nodes metastases in patients with ECE>2mm. Conclussions: There is cumulative evidence on the role of ECE as a risk factor in breast cancer patients, and our findings further support this hypothesis. However, the extent of ECE is still a topic of heated debate, and its role in disease progression is less clear, given there are relatively few studies addressing this matter and there are discrepancies in the way the extent of ECE is measured. Considering recent publications where no significant differences were found in terms of longterm disease recurrence when stratifying patients according to the extent of ECE, our future endeavours should focus on the assessment of the course of the disease. To date, we have no evidence supporting the idea that patients with ECE<2mm could actually benefit from omis- sion of ALND.

Breast Cancer in Young Women Presents With More Aggressive Pathologic Characteristics: Retrospective Analysis From an Argentine National Database.

PURPOSE: Multiple studies have reported that breast cancer in young patients is associated with aggressive characteristics, and it is suggested that prognosis is worse independently of pathologic variables. PATIENTS AND METHODS: We performed a retrospective analysis of the Breast Cancer Registry of the Argentinian Society of Mastology, including public and private centers. Patients ≤ 40 years of age at diagnosis were classified as "young," and patients ≤ 35 years of age at diagnosis were classified as "very young." Univariate and multivariate analyses were performed to detect differences between groups. RESULTS: Patients ≤ 40 years of age comprised 10.40% (739/7,105) of the participants, with an average age of 35.61 ± 4.04 years. Multivariate analysis showed that human epidermal growth factor receptor 2 (HER2)-positive tumor phenotype (odds ratio [OR], 1.82), nodal involvement (OR, 1.69), histologic grade (grade 3 OR, 1.41), and tumor size (T2 OR, 1.37; T3-T4, 1.47) were independently associated with younger age at diagnosis. Patients ≤ 35 years of age (n = 286), compared with patients 36 to 40 years of age, had a higher proportion of HER2 tumors (24.58% v 16.94%; P = .021), absence of progesterone receptor expression (29.85% v 22.95%; P = .043), and stage 3 cancer (29.34% v 18.52%; P < .001). Fewer breast-conserving surgeries (75.37% v 62.89%; P < .001) and more adjuvant chemotherapy (59.04% v 36.66%; P < 0.001) were reported in patients ≤ 40 years of age. CONCLUSION: In the population studied, breast cancer in young women was associated with aggressive pathologic features and locally advanced disease at the time of diagnosis. Moreover, tumor characteristics in very young patients with breast cancer nested in the population ≤ 40 years of age showed differences in important prognostic factors. More high-quality evidence is needed to improve treatment strategies in these patients.

Quimioterapia neoadyuvante: indicaciones y resultados. Experiencia de 15 años en el Instituto Alexander Fleming / Neoadjuvant chemotherapy: indications and results. Fifteen years of experience at Instituto Alexander Fleming

Introducción Existe consenso sobre los subgrupos de pacientes con más probabilidades de beneficiarse del tratamiento neoadyuvante, pero su utilización en la práctica clínica es variable. Las pacientes con cáncer de mama en etapa temprana susceptibles de requerir quimioterapia adyuvante podrían considerarse para realizar quimioterapia neoadyuvante (qtna). Objetivos Evaluar las tasas de cirugía conservadora en pacientes con cáncer de mama que reciben qtna y describir las tendencias de respuestas clínica, imagenológica y patológica en la mama y la axila. Material y método Se realizó una evaluación retrospectiva de 125 pacientes con cáncer de mama invasor (Estadios IB-IIA/B-IIIA), operadas en el Instituto Alexander Fleming en el período 2002-2018. Resultados Las tasas más altas de respuesta patológica completa (pcr) se obtuvieron en los tumores her2, tn y Luminal B-her2, representando el 56%, 55% y 40% respectivamente. En la respuesta patológica completa ganglionar, las tasas más altas se obtuvieron en los Luminal B-her2 82%, los tn 80% y los her2 70%. Las tasas de cirugía conservadora fueron: para Luminal A 44%, para Luminal B 58%, para Luminal B-her2 54%, para her2 76% y para tn 59%. Conclusiones Concordante con trabajos publicados, se describen altas tasas de cirugía conservadora y altas tasas de pcr en tumores her2 y tn

Introduction Even though there is evidence about better outcomes after neoadjuvant chemotherapy (nac) for breast cancer (bc), it is unclear who are the indicated patients and what are the correct indications for using it. Our hypothesis is that early stage bc patients, who are identified as susceptible for adjuvant chemotherapy, could be the most benefited of receiving nac. Objectives We aimed to study the number of patients who received nac and breast conserving surgery (bcs) assessing clinical, pathological and radiological response in both, breast and axilla. Materials and method We carried out a retrospective study of 125 patients newly diagnosed of bc (Stage IB-IIA-B and IIIA) who received nat and bcs in our institution, "Instituto Alexander Fleming", during the 2002-2018 period Results We obtained the higher rates of pathological complete response (pcr) in her2 being 56%; for tn was 55% and 40% for Luminal B-her2. The highest rates of complete pathological lymph node response were obtained in Luminal B-her2 82%, tn 80% and her2 70%. The rates for bcs where 44%, 58%, 54% and 76% for Luminal A, Luminal B, Luminal B-her2 and her2 respectively. Conclusions There is current data available supporting our findings, having similar results for bcs and pcr performing bcs after nat

Alertas de cardiotoxicidad en el tratamiento con trastuzumab en cáncer de mama, 4 años de seguimiento / Cardiotoxicity Alerts during Treatment with Trastuzumab in Breast Cancer at Four-year Follow-up

RESUMEN Introducción: El tratamiento adyuvante de cáncer de mama Her2+ incluye adriamicina y trastuzumab, un anticuerpo monoclonal con efecto cardiotóxico del que no se conoce el verdadero impacto epidemiológico de toxicidad cardíaca en poblaciones no seleccionadas en la Argentina. Objetivos: Conocer el impacto cardiotóxico del tratamiento con trastuzumab en adyuvancia en cáncer de mama en una población no seleccionada a más de 12 meses después de finalizado su tratamiento. Material y métodos: Sobre 888 pacientes prospectivos con cáncer de mama, 231 pacientes (38%) presentaban cáncer de mama Her2+, en tratamiento adyuvante con adriamicina + trastuzumab. Las pacientes fueron evaluadas mediante fracción de eyección ventricular izquierda, en pretratamiento, fin de adriamicina y cada 3 meses en el seguimiento. Se definió cardiotoxicidad a la caída de la fracción de eyección ventricular izquierda > 10% según el American College of Cardiology, se subanalizó con algoritmos del estudio B-31 y MD ANDERSON. Resultados: Presentaron caída de la fracción de eyección ventricular izquierda > 10%: 150/231 pacientes (65%) respecto del basal con un seguimiento medio de 48 ± 12 meses. En el análisis por grupo, las pacientes incluidas en el B-31 vs. MD Anderson vs. el American College of Cardiology presentaron mayor pérdida porcentual de la fracción de eyección ventricular izquierda durante el tratamiento: 20% vs. 20% vs. 16% con p < 0,04, finalizaron el seguimiento con fracción de eyección ventricular izquierda < 50%: 42% vs.41% vs. 33% con p = 0,01, respectivamente. Conclusiones: En la población con trastuzumab bajo control cardioncológico, se observó luego de un seguimiento medio de 48 ± 12 meses: 1 - Caída significativa de la fracción de eyección ventricular izquierda en más del 60% de la población. 2 - Las distintas guías muestran diferentes riesgos cardiotóxicos lo que requiere un monitoreo continuo cardioncológico.

ABSTRACT Background: Adjuvant treatment of HER2+ breast cancer includes adriamycin and trastuzumab, a monoclonal antibody that produces cardiotoxicity. The actual epidemiologic impact of trastuzumab-related cardiotoxicity in unselected populations in Argentina remains unknown. Objectives: The aim of this study was to evaluate the impact of trastuzumab-related cardiotoxicity during adjuvant treatment for breast cancer in an unselected population after >12 months of completing therapy. Methods: Among 888 patients prospectively evaluated for breast cancer, 231 (38%) were HER2+ and received adjuvant therapy with adriamycin and trastuzumab. Left ventricular ejection fraction was evaluated before treatment, after completing adriamycin and then every 3 months during follow-up. Cardiotoxicity was defined as a decline in left ventricular ejection fraction >10%, according to the definition of the American College of Cardiology and was compared with the definitions of the B-31 trial and the MD Anderson Cancer Center. Results: A decline in left ventricular ejection fraction >10% from baseline values occurred in 65% (n=150) of the patients during a mean follow-up of 48±12 months. In the per group analysis, patients included in the B-31and MD Anderson Cancer Center vs. the American College of Cardiology definitions presented greater percent fall in left ventricular ejection fraction during treatment: 20% vs. 20% vs. 16%, respectively (p<0.04) and ended treatment with left ventricular ejection fraction <50% in 42% vs. 41% vs. 33% of cases, respectively (p=0.01). Conclusions: In the population treated with trastuzumab under cardio-oncology surveillance during 48±12 months: 1 - Left ventricular ejection fraction was significantly decreased in more than 60% of patients. 2 - Different guidelines show different cardiotoxicity risks which demands continuous cardio-oncological monitoring.

High neutrophil to lymphocyte ratio and decreased CD69+NK cells represent a phenotype of high risk in early-stage breast cancer patients.

PURPOSE: Breast cancer (BC) is a highly heterogeneous disease presenting a broad range of clinical and molecular characteristics. In the past years, a growing body of evidence demonstrated that immune response plays a significant role in cancer outcome. However, immune prognostic markers are not completely validated in clinical practice in BC patients. MATERIALS AND METHODS: With the aim to characterize immune features, several parameters were analyzed in peripheral blood at diagnosis of 85 nonmetastatic BC patients between April 2011 and July 2014. RESULTS: With a median follow-up of 38.6 months, peripheral blood analysis of BC patients (stages I, II, and III) showed that total lymphocyte and T lymphocyte counts were augmented in nonrelapsed patients. Also, a higher neutrophil-to-lymphocytes ratio was associated with prolonged disease-free survival. Natural killer cell receptor analysis revealed that early activation receptor CD69 was associated with a better outcome. CONCLUSION: This preliminary evidence is in accordance with the concept of immune surveillance. We suggest an "immune phenotype" that provides relevant prognostic information in early-stage BC patients and which could be useful in the decision-making process.

Los linfocitos estromales intratumorales (tils) como factor pronóstico en tumores primarios de mama Triple Negativos / Tumor infiltrating lymphocytes (tils) in Triple Negative breast cancer as a prognostic factor

Introducción Los tumores de mama se encuentran frecuentemente rodeados por células inflamatorias como signo de interacción entre el tumor y el huésped, siendo esta crítica para el desarrollo y progresión del cáncer. Algunas observaciones sugieren el valor pronóstico de los linfocitos estromales intratumorales (tils). Sin embargo, su evaluación no es rutinaria ya que su relevancia clínica aún no se encuentra consolidada. Objetivos Los objetivos de este trabajo son: • la evaluación de la concordancia interobservador de los linfocitos intratumorales (tils); • su relación con la sobrevida libre de enfermedad (sle); • su valoración como factor pronóstico en cáncer de mama Triple Negativo. Material y método Se seleccionaron retrospectivamente pacientes con tumores de mama Triple Negativos operados en el Instituto Alexander Fleming entre 2010-2016 sin tratamiento neoadyuvante, alcanzando una muestra de 65 pacientes. Resultados El porcentaje mediano de tils fue de 30% (12,5-50), y se consideraron como "Tumores ricos en linfocitos" (Lymphocyte Predominant Breast Cancerlpbc) a los de 19 pacientes (29,2%). Tanto la presencia de tils (p>0,01) como la definición del subtipo de lpbc (p=0,03) presentaron asociación estadísticamente significativa con la recurrencia de enfermedad. En el análisis multivariado, presentaron asociación la histología ductal y el valor de tils. Por cada 10% de aumento, disminuye 31% el riesgo de recaída. El valor de tils estratificado en 3 subgrupos (≤20; 30-40; ≥50%) presentó asociación estadísticamente significativa con la Sobrevida Libre de Enfermedad (Log Rank <0,01). Conclusiones En este trabajo se logró describir una característica tumoral y del huésped reproducible, cuya instrumentación podría generalizarle por el potencial valor pronóstico.

Introduction Breast tumors are frequently surrounded by inflammatory cells as a sign of interaction between the tumor and host, being this relationship critical for cancer development and progression. Present evidence suggests that tumor infiltrating lymphocytes (tils) may provide prognostic information. Nevertheless, tils description is not generalized as its clinical relevance is not consolidated. Objectives • evaluation of interobserver concordance of intratumoral lymphocytes (tils); • its relationship with Disease Free Survival; • its assessment as a prognostic factor in Triple Negative breast cancer. Materials end method Triple Negative breast cancer patients with surgery in Instituto Alexander Fleming, between 2010-2016, without neoadyuvant treatment, were selected retrospectively. 65 patients were selected. Results In the 65 patients selected, tils median percentage was 30% (12.5-50), and 19 (29.2%) were considered Lymphocyte Predominant Breast Cancer (lpbc). tils percentage (p>0.01) and lpbc subtype (p=0.03) presented significant association with disease recurrence. Multivariate analysis showed that ductal histology and tils percentage are associated with disease recurrence. For every 10% increment in tils, there was a 31% reduction of risk of recurrence. High tils value stratified in 3 subgroups (≤20; 30-40; ≥50%) was associated with better Disease Free Survival (Log Rank 0.01). Conclusions Due to its potential prognostic value and its technical reproducibility, we believe that this tumoral and host characteristic must be generalized.

Predictive Factors for Non-Sentinel Lymph Node Metastasis in Patients with ACOSOG Z0011 Criteria.

BACKGROUND: Nodal staging constitutes an element of great importance in the treatment planning for early breast cancer. The ACOSOG Z0011 trial demonstrated that sentinel lymph node (SLN) biopsy alone results in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection. The purpose of this study was to determine the rate of patients that fulfill the ACOSOG Z0011 inclusion criteria and to define predictive factors for non-SLN positivity. METHODS: A retrospective analysis of the breast surgery database of the Argentinian Society of Mastology was carried out. Patients were selected if they fulfilled the ACOSOG Z0011 inclusion criteria. The association of clinical and pathological factors with non-SLN positivity was evaluated in univariate and multivariate analysis. RESULTS: Among 8,262 patients, 973 had positive SLN, and 348 satisfied the inclusion criteria. Histological grade (G3 vs. G1-2, odds ratio (OR) 1.81; p = 0.024), tumor size (T2 vs. T1, OR 2.39; p = 0.001), and age (>50 vs. <50 years, OR 1.95; p = 0.007) were associated with non-SLN positivity in multivariate analysis. CONCLUSION: Although the clinical relevance of our data is not established, older women with tumors bigger than 2 cm and/or high histological grade are at greater risk of having metastatic disease in the lymph nodes if axillary lymph node dissection is avoided. This subgroup of patients represents only 30% of the trial population.

High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in Node Metastasis in Primary Breast Cancers.

PURPOSE: Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER2) expression may vary during tumoral progression. We aimed to describe and compare ER, PR, and HER2 expressions in primary breast tumors and synchronic axillary nodal metastases, and evaluate phenotypic correlations between them. METHODS: Patients were identified prospectively through surgical procedures between September 2013 and July 2016. The status of ER, PR, HER2, and Ki-67 were pathologically analyzed in breast cancers and axillary nodal metastases; these patients were classified based on the breast cancer phenotypes into five subgroups. RESULTS: Synchronic axillary nodal metastases were observed in 127 patients. In breast cancers and nodal metastases, correlation analyses of ER, PR, and Ki-67 expression showed a statistical dependence and concordance between these samples was unambiguously demonstrated through Bland-Altman plots for each determination. Primary breast tumors were classified as follows: luminal A, 41.6%; luminal B, 40.0%; luminal B/HER2, 9.6%; HER2, 2.4%; triple negative, 6.4%. Alterations in phenotype were observed in 28% of patients. The most frequent phenotypic alteration was from luminal B to A (36.4%). Ten cases (30.3%) showed alterations with therapeutic implications; six gained HER2 overexpression, and four, hormonal receptor (HR) expression. A moderate strength of agreement (Cohen's κ coefficient, 0.59; 95% confidence interval, 0.48-0.71) was observed. In multivariate analyses, high histologic grade (odds ratio [OR], 2.79; p<0.047) and high Ki-67 expression (OR, 1.05; p<0.037) were independent factors predictive of phenotypic alterations. CONCLUSION: Strong correlations were observed in HR and Ki-67 expressions between primary breast tumors and axillary nodal metastases, and a moderate concordance was observed in their phenotypical characteristics. Nevertheless, alterations did exist, and one-third of these changes may have therapeutic implications. The nodal metastases of tumors with high grade and high Ki-67 expression may need to be analyzed, to obtain complete therapeutic information.

TDM-1 en cáncer de mama metastásico HER2 positivo. Experiencia institucional / TDM-1 in HER2 positive metastatic breast cancer. Institutional experience

El cáncer de mama es una de las enfermedades más frecuentes en todo el mundo. La amplificación del proto-oncogén HER2 se presenta en 20-25% de los tumores de mama. TDM-1 es un conjugado anticuerpo-quimioterápico. Se realizó en forma retrospectiva, observacional y descriptiva un análisis de los datos de pacientes con diagnóstico de cáncer de mama metastásico HER2 positivo, que realizaban y/o habían realizado tratamiento con dicho fármaco. Se evaluaron 27 mujeres. La indicación de TDM-1 fue en 7.4% (2) en primera línea, 37% (10) en segunda línea, y 55.5% (15) en líneas posteriores, con un tiempo a la progresión de 7.44 meses (IC: 4.33-NC) para el global de pacientes, tasa de respuesta objetiva de 44% y se constataron 7 (26%) toxicidades G3-4 (AU)

Breast cancer is one of the most common diseases worldwide. HER2 proto-oncogene amplification occurs in 20-25% of breast tumors. TDM-1 is an antibody-chemotherapeutic conjugate. We performed a retrospective, observational and descriptive analysis of data from patients diagnosed with metastatic HER2 positive breast cancer who were and / or had been treated with this drug. Twenty-seven women were evaluated. The indication for TDM-1 was 7.4% (2) in the 1st line, 37% (10) in the 2nd line, and 55.5% (15) in later lines, with a time to progression of 7.44 months (CI:4.33-NC) for the global patient, objective response rate was 44% and 7 (26%) G3-4 toxicities were found (AU)