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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.
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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).
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Generalized lymphatic anomaly (GLA) is an infrequent multiorgan disease characterized by the presence of abnormal proliferation of lymphatic vessels. The diagnosis requires histological confirmation, and the treatment is controversial. We are presenting a case of a 28-year-old male patient who was diagnosed with an extragonadal mediastinal nonseminomatous germ cell tumor. He underwent chemotherapy, and during this treatment, radiologic findings evidenced lytic lesions. Multiple biopsies were performed, which revealed the presence of abnormal lymphatic vessels, characteristic of GLA. There are different etiologies of osteolytic lesions, and on some occasions, they mimic a tumoral entity. The clinical suspicion of GLA is the first step in approaching the diagnosis, particularly in young adult patients.
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Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clinical complete response (cCR) could receive nonoperative management (NOM). However, different patterns of response have challenged management strategies. Case Description: A 34-year-old woman diagnosed with dMMR LARC started treatment with capecitabine 2,000 mg/m2 on day 1 to 14 and oxaliplatin 130 mg/m2 on day 1 and every 21 days. Magnetic resonance imaging (MRI), performed three cycles later, showed local progression of the primary rectal lesion, which at that time had new peritoneal reflex involvement. A new hepatic lesion in segment V was observed. Due to disease progression, she was administered pembrolizumab 200 mg every 21 days. After three cycles, a discordant radiological response was observed on a new MRI scan that showed a complete response of the liver lesion and magnetic resonance tumor regression grade (mrTRG) 1 in the rectum. However, new involvement of the mesentery and enlargement of the regional lymph nodes (LNs) were also evident. A new colonoscopic biopsy was performed, showing no cancerous cells. She underwent surgery on the rectum and liver lesion. Pathology showed a complete response of the rectal wall and liver lesion, but 1 of 22 LNs was positive for adenocarcinoma (ypT0 N1 M0). The patient continued on pembrolizumab, and 14 months after surgery, she had not relapsed. Conclusions: Neoadjuvant immunotherapy for rectal cancer requires new recommendations for the assessment of clinical response. Pseudoprogression should be ruled out as an atypical response before deciding on surgical treatment. We propose an algorithm to address pseudoprogression in this setting.
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Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.
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Carcinoma , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Vacuna BCG/uso terapéutico , Antígeno B7-H1 , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Vejiga Urinaria , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , BiomarcadoresRESUMEN
Given the increasing complexity of cancer care, multidisciplinary tumor boards have become essential in daily clinical oncology practice. The Project Extension for Community Healthcare Outcomes (ECHO) initiative developed an innovative telementoring model using a "hub and spoke" design consisting of a team of experts (hub) that offers a full service to multiple participants (the spokes) during regularly scheduled sessions discussing patients' clinical cases. The Alexander Fleming Cancer Institute in Buenos Aires was the first hub in Latin America to implement Project ECHO for gastrointestinal tumors. In our 3-year experience, 80 patients from 37 centers were evaluated within Project ECHO and a range of three to five cases were discussed in each meeting. From our perspective, the impact of this novel approach was a remarkable strategy to reduce care disparities by equalizing access to high-quality medical knowledge in a multidisciplinary environment for medical discussions. Additionally, it was shown to have a cost-effective impact directly on the patients and the local health system, since relevant costs were saved after unnecessary treatments, studies and travel expenses were avoided.
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A 68-year-old man, without a family history of cancer, was treated for primary cutaneous melanoma of the scalp. Two years later, a right lateral cervical lymph recurrence was observed and he was treated with lymphadenectomy and adjuvant nivolumab for 1 year. Four years from the initial melanoma diagnosis, a computer tomography scan showed a solid nodular lesion of 26 × 40 × 75 mm inside the previously known inguinoscrotal hernia. A new recurrence of melanoma was the most probable diagnosis and a right inguinal hernioplasty was performed. Notably, the histopathological examination revealed a mesenteric fibromatosis with the typical immunohistochemical pattern (strong nuclear staining of ß-catenin). Interestingly, this represents the first case of a patient with a mesenteric desmoid tumour presenting as an inguinal hernia masking a cutaneous melanoma recurrence.
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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.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/genética , Reparación del ADN/genética , Femenino , Células Germinativas/metabolismo , Humanos , Estudios RetrospectivosRESUMEN
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.
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Femenino , Ganglio Linfático Centinela , Axila , Neoplasias de la Mama , Ganglios Linfáticos , Metástasis Linfática , Metástasis de la NeoplasiaRESUMEN
Objetivo: Revisar la correlación radiopatológica de las lesiones de potencial maligno incierto (B3) de nuestra institución, evaluar la conducta y establecer el porcentaje de subestimación en relación a las lesiones tratadas quirúrgicamente. Material y método: Estudio retrospectivo de la base de datos de procedimientos intervencionistas efectuados en el servicio de diagnóstico por imágenes del Instituto Alexander Fleming entre mayo de 2016 y diciembre de 2019 inclusive. Se incluyeron las pacientes con resultado histológico en la biopsia percutánea de uno o más de los siguientes diagnósticos: atipia epitelial plana (AEP), cicatriz radiada/lesión esclerosante compleja (CR), hiperplasia ductal atípica (HDA), neoplasia lobular clásica (NL), lesión papilar (LP) o tumor phyllodes (TP). Resultados: De 67 pacientes analizadas, el 43.3% se manifestaron en los estudios por imágenes con nódulos y en un 37.3% con microcalcificaciones agrupadas. La LP fue la lesión B3 más frecuente en un 44.8% seguido por la AEP en un 16.4%. El 98.5% de las pacientes presentó adecuada concordancia radiopatológica. Fueron sometidas a cirugía 48 pacientes, las 19 pacientes restantes continuaron con seguimiento clínico radiológico. La anatomía patológica de la pieza quirúrgica reflejó que en un 33.3% hubo subestimación en relación a la biopsia; en más de la mitad de los casos correspondieron a CDIS. Conclusiones: El porcentaje de subestimación con resultado final de CDIS o CDI de bajo grado se encontró dentro de los parámetros hallados en la literatura. Si bien logramos reducir la tasa de cirugías al 71% de pacientes con lesiones B3, una adecuada selección para efectuar exéresis con aguja por sistema de vacío podría reducir aún más el número de cirugías innecesarias y probablemente la tasa de subestimación.
Objective: To review the radiopathological correlation of lesions of uncertain malignant potential (B3) diagnosed in our institution, as well as to evaluate the therapeutic conduct and to establish the percentage of underestimation of the excised lesions. Material and method: This work consists of a retrospective study of the database which in- cludes the interventional procedures performed in the Imaging Department of the Alexander Fleming Institute between May 2016 and December 2019. Patients with a histological outcome in the percutaneous biopsy of one or more of the following diagnosis were included: flat epithelial atypia (FEA), radial scar (RS) /complex sclerosing lesion (CSL), atypical ductal hyperplasia (ADH), classic lobular neo- plasia (LN), papillary lesión (PL) or phyllodes tumor (PT). Results: Out of the 67 analyzed patients, 43.3% were perceived as nodules at imaging examinations and 37.3% as grouped microcalcifications. Papillary lesion was the most frequently diagnosed B3 lesion (44.8%), followed by flat epithelial atypia (16.4%). 98.5% of patients presented an accurate imaging-pathology concordance. 48 patients underwent surgery and the remaining 19 patients continued with clinical and radiological follow-up. The histopathology of the surgical specimen reflected that in 33.3% of the cases there was an underestimation in relation to the percutaneous biopsy; in over half of these cases they corresponded with DCIS. Conclusions: The percentage of underestimation with final diagnosis of DCIS or low grade IDC coincided with the parameters found in current literature. Even though we were able to reduce the surgical rate to 71% of patients with B3 lesions, a proper selection of cases which could be candidates for vacuum assisted excisional biopsy could further reduce the number of unnecessary surgeries and probably the un- derestimation rate as well.
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Femenino , Neoplasias , Biopsia , Diagnóstico por ImagenRESUMEN
Objetivo: Determinar la tasa de identificación intra operatoria por el médico cirujano de los ganglios marcados con suspensión de carbón activado previo a la neoadyuvancia. El objetivo secundario es determinar la concordancia entre los ganglios linfáticos marcados con carbón y aquellos considerados ganglios centinelas. Material y método: Es un estudio retrospectivo desde el año 2016 hasta el año 2020. Se incluyeron 27 pacientes con cáncer de mama en estadios T1 - T3 que realizaron quimioterapia neoadyuvante y con axila con estadio N1 y N2. Los ganglios axilares biopsiados con resultado positivo fueron marcados con suspensión de carbón activado, posteriormente las pacientes realizaron quimioterapia neoadyuvante. Se evaluó la tasa de detección y concordancia del ganglio marcado con el ganglio centinela durante el procedimiento quirúrgico. Resultados: Del total de pacientes en 20 casos se realizó efectivamente la identificación por inspección visual de la suspensión de carbón activado en la cavidad axilar durante la cirugía. La tasa de detección fue del 74%. Del total de 20 pacientes en los cuales se identificó carbón visualmente en el acto quirúrgico, 16 se sometieron a biopsia de ganglio centinela. En 81% de los casos hubo una coincidencia entre el ganglio marcado con carbón y el ganglio centinela. Conclusión: En nuestro trabajo la tasa de detección intraoperatoria de los ganglios marcados con carbón está en concordancia con lo publicado en la literatura. Esto catapulta a este método de marcación como una alternativa factible para realizar una disección axilar dirigida asegurándole al médico cirujano la resección de una ganglio positivo de inicio para su análisis anatomopatológico de respuesta. Hemos comprobado que la marcación con carbón no interfiere con la técnica estándar utilizada para la biopsia de ganglio centinela sino que su uso en conjunto mejora la técnica dignóstica.
Objetive: The aim of this study was to determine the rate of identification of activated charcoal suspension during surgery in positive lymph nodes before neadjuvant chemotherapy. The secondary objetive is to determine the rate of concordance between the marked lymph nodes and the sentinel lymph nodes. Material and method: A retrospective study that goes from the year 2016 - 2020. It includes 27 patients with breast cancer (T1 - T3) and positive lymph nodes (N1 - N2). Patients with biopsy - confirmed nodal metatases were marked with activated charcoal suspension in the sampled node. After this procedure patients underwent neoadjuvant chemotherapy and axillary surgery. The rate of detection and the concordance of the marked lymph node with the sentinel lymph nodes was calculated. Results: Of the 27 patients enrolled in this study in 20, the marked node was detected during surgery. The detection rate was of 74%. Of these 20 patientes, 16 had sentinel node biopsy. There was an 81% rate of concordance between the sentinel lymph node and the tattooed lymph node. Conclusions: In our study, the detection rate of marked lymph node is concordant with the numbers publised by other studies. This shows that axillary lymph node tattooing with activated charcoal suspension is a viable, low cost and precise method when performing targeted axillary dissection. We identified that the tattooing procedure does not affect the standard sentinel node biopsy, in fact, when used together it improves its diagnostic performance.
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Humanos , Femenino , Carbón Orgánico , Axila , Tatuaje , Biopsia , Neoplasias de la Mama , Disección , Ganglio Linfático CentinelaRESUMEN
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.
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Neoplasias de la Mama , Adulto , Neoplasias de la Mama/epidemiología , Quimioterapia Adyuvante , Femenino , Humanos , Mastectomía Segmentaria , Pronóstico , Estudios RetrospectivosRESUMEN
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
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Cirugía General , Neoplasias de la Mama , Quimioterapia Adyuvante , Terapia NeoadyuvanteRESUMEN
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.
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Humanos , Femenino , Neoplasias de la Mama , Linfocitos , Linfocitos Infiltrantes de Tumor , Neoplasias de la Mama Triple NegativasRESUMEN
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.
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Determinar la incidencia de ganglio centinela (GC) positivo en pacientes con Carcinoma ductal in situ (CDIS) y microinvasor (T1mic); y describir las características clinicopatológicas de los mismos en relación con el compromiso axilar. Material y método: Se realizó un estudio retrospectivo en 46 pacientes con diagnóstico de CDIS y en 88 pacientes con T1mic a las cuales se les realizó la biopsia del ganglio centinela (BGC), en el período comprendido entre marzo de 1999 y octubre de 2013. Para el análisis estadístico, se utilizó el programa SPSS 17.0. Resultados: Una paciente de 46 (2,1%) con CDIS presentó una micrometástasis en el estudio diferido. No se completó la linfadenectomía axilar (LA). En 4 de las 88 pacientes (4,5%) con T1mic, el GC fue positivo (2 micrometástasis y 2 macrometástasis). A este grupo se le efectuó linfadenetomía axilar (LA); A este grupo se le efectuó linfadenetomía axilar (LA); una paciente presentó un ganglio positivo (micrometástasis) en los ganglios no centinela (GNC). Cuatro pacientes (4,5%) con T1mic presentaron recidiva en la mama y una (1,1%) a distancia. No hubo recurrencias en la paciente con CDIS. En todos estos casos, el GC había sido negativo. Conclusiones: Nuestros resultados son coincidentes con los de la literatura mundial. Actualmente, en el CDIS, no indicamos la BGC, excepto en CDIS extensos, sospecha de invasión en biopsias con aguja gruesa o cuando la paciente debe ser sometida a una mastectomía. A pacientes con T1mic les realizamos la BGC...
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Humanos , Carcinoma Intraductal no Infiltrante , Biopsia del Ganglio Linfático CentinelaRESUMEN
Clinical studies suggest that triple negative breast cancer (TNBC) patients with epidermal growth factor receptor (EGFR)-expressing tumors could benefit from therapy with Cetuximab, which targets EGFR. NK cells are the primary effectors of antibody (Ab)-dependent cell-mediated cytotoxicity (ADCC) and thus play a role in Ab-based therapies. We have previously described diminished levels of Cetuximab-mediated ADCC in vitro in patients with advanced breast cancer. Here, we investigated the potential causes of this NK-cell functional deficiency. We characterized NK-cell activating/inhibitory receptors in the peripheral blood of breast cancer patients and found CD85j inhibitory receptor overexpression. The capacity of NK cells to perform Cetuximab-triggered ADCC against TNBC cells correlated inversely with CD85j expression, even in the presence of the stimulatory cytokines IL-2 or IL-15. Hence, patients expressing high levels of CD85j had an impaired ability to lyse TNBC cells in the presence of Cetuximab. We also found that CD85j overexpression was associated with HLA-I and soluble HLA-G expression by tumors. A CD85j functional blockade with a CD85j antagonist Ab restored ADCC levels in breast cancer patients and reverted this negative effect. Our data suggest that strategies that overcome the hurdles of immune activation could improve Cetuximab clinical efficacy.
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Anticuerpos Monoclonales Humanizados/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos , Antígenos CD/metabolismo , Células Asesinas Naturales/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/metabolismo , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/terapia , Adulto , Antineoplásicos/farmacología , Estudios de Casos y Controles , Cetuximab , Receptores ErbB/antagonistas & inhibidores , Femenino , Antígenos HLA/metabolismo , Antígenos HLA-G/metabolismo , Humanos , Células K562 , Receptor Leucocitario Tipo Inmunoglobulina B1 , Persona de Mediana Edad , Adulto JovenRESUMEN
Despite NK cells being originally identified because of their ability to kill tumor cells in vitro, only limited information is available on NK cells infiltration of malignant tumors, especially in humans. NK cells infiltrating human colorectal carcinomas (CRCs) were analyzed to identify their potential protective role in an antitumor immune response. The expression and function of relevant molecules were analyzed from different sources, comparing tumor-associated NK cells (TANKs) with autologous peripheral blood NK cells (PB-NKs) from CRC patients-the latter in comparison with PB-NKs from normal donors. TANKs displayed a profound alteration of their phenotype with a drastic reduction of NK cell receptor expression. Co-culture experiments showed that CRC cells produce modulation in NK phenotype and functionality. Moreover, PB-NKs from CRC patients also exhibited an altered phenotype and profound defects in the ability to activate degranulation and IFN-γ production. For the first time, TANK and PB-NK cells from CRC patients have been characterized. It is shown that they are not capable of producing relevant cytokines and degranulate. Taken together, our results suggest that NK cells from CRC patients present alterations of phenotype and function therefore supporting the progression of cancer.
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Células Sanguíneas/inmunología , Neoplasias Colorrectales/inmunología , Células Asesinas Naturales/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Receptores de Células Asesinas Naturales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Degranulación de la Célula , Transformación Celular Neoplásica , Células Cultivadas , Femenino , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Células Asesinas Naturales/genéticaRESUMEN
Triple-negative breast cancer (TNBC) patients do not benefit from target-specific treatments and is associated with a high relapse rate. Epidermal growth factor receptor is frequently expressed in TNBC and is a candidate for new therapies. In this work, we studied Cetuximab-mediated immune activity by NK cells. Thirteen activating/inhibitory receptors were examined on peripheral blood and tumor infiltrating NK cells. NK-cell functionality was evaluated using as effectors tumor-modulated NK cells and NK cells from patients. We evaluated the treatment with Cetuximab plus IL-2 or IL-15 in vivo in TNBC xenografts. Tumor NK-cells receptor profile showed upregulation of inhibitory receptors and downregulation of activating ones. Tumor-modulated NK cells were less cytotoxic. They could perform antibody-dependent cellular cytotoxicity (ADCC) triggered by Cetuximab, although impaired, it could still be restored by stimulation with IL-2 or IL-15. Patients with advanced disease displayed diminished levels of ADCC compared to healthy volunteers. ADCC was restored and potentiated with both cytokines, which were also effective in enhancing the therapeutic activity of Cetuximab in vivo. The combination of Cetuximab with IL-15 and IL-2 may be considered an attractive therapeutic approach to enhance the clinical efficacy of Cetuximab in TNBC.
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Anticuerpos Monoclonales Humanizados/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Interleucina-15/farmacología , Interleucina-2/farmacología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Adulto , Animales , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cetuximab , Femenino , Humanos , Ratones , Ratones Desnudos , Persona de Mediana Edad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Metallothioneins are a family of small, cysteine-rich proteins with many functions. Immunohistochemical evaluation of all metallothionein 1 + 2 isoforms in colorectal tumors has demonstrated an important down-regulation compared with normal tissue, although its prognostic significance is unclear. Moreover, the contribution of individual isoforms to overall metallothionein down-regulation is not known. To address these important issues, we analyzed the messenger RNA expression levels of all functional metallothionein 1 + 2 isoforms by quantitative reverse transcription polymerase chain reaction in 22 pairs of normal and tumor-microdissected epithelia and correlated these to the overall immunohistochemical protein expression. Our results showed that 5 isoforms (MT1G, 1E, 1F, 1H, and 1M) were lost during the transition from normal mucosa to tumor, whereas MT1X and MT2A were less down-regulated, and their expression was correlated with overall protein positivity. Second, we showed that MT1G hypermethylation occurred in cell lines and in 29% of tumor samples, whereas histone deacetylase inhibitors are able to induce most isoforms. Furthermore, we analyzed by immunohistochemistry 107 normal mucosae, 25 adenomas, 81 carcinomas, and 19 lymph node metastases to evaluate metallothionein expression during different stages of cancer development and to assess its relationship to patient survival. A lower immunohistochemical expression was associated with poorer survival, although it was not an independent predictor. Overall, this study identifies for the first time the relevant metallothionein isoforms for colorectal cancer progression, supports the concept that their loss is associated with worse prognosis, and suggests 2 mechanisms for epigenetic repression of metallothionein expression in colorectal tumors.