ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations.

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

A Review on Manufacturing Processes of Biocomposites Based on Poly(α-Esters) and Bioactive Glass Fillers for Bone Regeneration.

The incorporation of bioactive and biocompatible fillers improve the bone cell adhesion, proliferation and differentiation, thus facilitating new bone tissue formation upon implantation. During these last 20 years, those biocomposites have been explored for making complex geometry devices likes screws or 3D porous scaffolds for the repair of bone defects. This review provides an overview of the current development of manufacturing process with synthetic biodegradable poly(α-ester)s reinforced with bioactive fillers for bone tissue engineering applications. Firstly, the properties of poly(α-ester), bioactive fillers, as well as their composites will be defined. Then, the different works based on these biocomposites will be classified according to their manufacturing process. New processing techniques, particularly additive manufacturing processes, open up a new range of possibilities. These techniques have shown the possibility to customize bone implants for each patient and even create scaffolds with a complex structure similar to bone. At the end of this manuscript, a contextualization exercise will be performed to identify the main issues of process/resorbable biocomposites combination identified in the literature and especially for resorbable load-bearing applications.

Adenoid cystic carcinoma and basaloid carcinoma of the breast: A clinicopathological study.

Adenoid cystic carcinoma of the breast (ACCB) is a rare triple negative tumor (TNT) with an excellent prognosis in most cases. Three different histologic types are recognized: classic ACCB, solid basaloid ACCB (SB-ACCB), and ACCB with high-grade transformation. A majority of these tumors show characteristic molecular and immunohistochemical (IHC) features, with fusion of MYB and NFIB genes and overexpression of MYB, respectively. Basaloid carcinomas of the breast (BCB) are infrequently described. They resemble SB-ACCB and TNT of no special type (TNT-NST). We have studied the clinicopathological features of 17 ACCB and 9 BCB, investigating the expression of MYB by IHC and the rearrangements of MYB by fluorescence in situ hybridization (FISH). MYB was expressed by IHC in 15 ACCB and in 3 BCB. MYB FISH detected rearrangements in 11 ACCB and in 2 BCB. After a mean follow-up of 90 months, with a range of 12-204 months, 2 patients with ACCB with high-grade transformation and 1 patient with BCB developed metastases and died of disease. In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.

Model Composites Based on Poly(lactic acid) and Bioactive Glass Fillers for Bone Regeneration.

Poly(l-lactide-co-d,l-lactide) PDLA/45S5 Bioglass® (BG) composites for medical devices were developed using an original approach based on a thermal treatment of BG prior to processing. The aim of the present work is to gain a fundamental understanding of the relationships between the morphology, processing conditions and final properties of these biomaterials. A rheological study was performed to evaluate and model the PDLA/BG degradation during processing. The filler contents, as well as their thermal treatments, were investigated. The degradation of PDLA was also investigated by Fourier transform infrared (FTIR) spectroscopy, size-exclusion chromatography (SEC) and mechanical characterization. The results highlight the value of thermally treating the BG in order to control the degradation of the polymer during the process. The present work provides a guideline for obtaining composites with a well-controlled particle dispersion, optimized mechanical properties and limited degradation of the PDLA matrix.

Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer.

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539-0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727-0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561-0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546-0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.

Risk of Exclusion in People with Disabilities in Spain: Determinants of Health and Poverty.

In this paper, we analyze data from the 2012 Encuesta de Integración Social y Salud (Social Integration and Health Survey) of the Instituto Nacional de Estadística (Spanish National Institute of Statistics) to obtain profiles created by combining disability, poverty and social exclusion. We hypothesize that the probability that people will experience social exclusion increases if they have a disability, chronic illness or limitation in conducting everyday activities, and that this probability is greater for women than for men. To conduct our analysis, we constructed a social exclusion model based on a series of social determinants that acts as a dependent variable. In this context, social exclusion is understood to go beyond the concept of financial poverty. We performed bivariate analyses, in which we calculated the Odds Ratios (OR) for certain variables considered to be predictors of social exclusion. We also performed a means comparison test and an ANOVA test to observe differences between individuals with recognized disability and those without. Finally, we conducted logistic regression analysis to determine which vulnerability profiles are most likely to experience a situation of social exclusion. We also discuss the limitations of our study, and suggest areas in, which the relationships between health, social exclusion and disability can be further investigated.

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study.

BACKGROUND: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. METHODOLOGY: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. RESULTS: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. CONCLUSION: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.

Is Regression after Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer Different in Sentinel and Non-sentinel Nodes?

Tumor draining sentinel lymph nodes (SLNs) are the sites of selective changes as compared to non-SLNs. They show features of tumor-reactive lymphadenopathy, including increased total number of functional blood vessels, but a relative immunosuppressed status has also been described in them. We explored the hypothesis of a selective regression or non-regression in SLNs versus non-SLNs in 142 patients with 110 estrogen receptor-positive and 32 estrogen receptor-negative tumors undergoing both SLN biopsy and axillary lymph node dissection after neoadjuvant therapy by assessing the tumoral (metastatic) and regression statuses of SLNs and non-SLNs separately. Of the 89 cases with signs of nodal regression, 22 cases (25%) were in favor of a selective non-regression in SLNs, 18 cases (20%) were supportive of a selective and more pronounced regression in the SLNs and the remaining showed equal degrees of regression or non-regression in SLNs and non-SLNs. The results indicate that there is no obvious difference in the degree of regressive histological changes shown by SLNs and NSLNs. Therefore, this phenomenon may not be a major contributor to the higher false negative rate of SLN biopsy after neoadjuvant treatment.

Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients: FN14 and GRP94 from Diagnosis to Prophylaxis.

FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.

Proteinuria de tipo nefrótico en la nefroangioesclerosis hipertensiva: características clínicas y evolutivas / Nephrotic proteinuria in hypertensive nephrosclerosis: Clinical and evolution characteristics

Fundamento y objetivo: Coincidiendo con otros autores, hemos observado que algunos pacientes afectados de nefroangioesclerosis hipertensiva (NH) pueden presentar proteinuria de rango nefrótico. Comparamos las características clínicas y evolutivas diferenciales de estos pacientes con los de otras enfermedades glomerulares. Material y método: Se comparan pacientes biopsiados por proteinuria nefrótica con diagnóstico de NH (casos) frente a otro tipo de enfermedad glomerular (controles). Resultados: Un 5,1% de las biopsias correspondían a diagnóstico de NH. Las características de los casos y controles fueron, respectivamente: proteinuria de 4,7 (extremos 3-11,4) frente a 5,5 (3-28,1) g/24 h/1,73 m2 (p = NS); albúmina plasmática media (DE) de 39,5 (6,4) frente a 29,4 (10) g/dl (p = 0,001); edema grave en 10 frente a 63% de los casos; y edad de 58,8 (12,6) frente a 45,5 (19,6) años. Asimismo, los casos presentaron mayor tiempo de evolución de la hipertensión, mayor porcentaje de episodios cardiovasculares previos (39 frente a 16%), con cifras de presión arterial más elevadas (166/90 frente a 133/75 mmHg; p = 0,01) y peor pronóstico renal. Conclusiones: La NH debería incluirse en el diagnóstico diferencial de la proteinuria de rango nefrótico. La ausencia de edemas y la albúmina normal son indicadores clínicos diferenciales que pueden ayudar a la toma de decisiones (AU)

Background and objective: Nephrotic range proteinuria can occur in patients with biopsy proven hypertensive nephrosclerosis (HN). We analysed the differential clinical and evolution characteristics of these patients compared with other glomerular diseases. Material and method: This is a case-control descriptive analysis obtained from the renal pathology registry of our hospital. Clinical features, treatment and evolution of these patients (cases) were compared with nephrotic patients with other glomerular diseases (controls). Results: Five point one percent of biopsies with HN diagnosis. Case/control characteristics were: proteinuria 4.7 [3-11.4] versus 5.5 [3-28.1] g/24 h/1.73 m2 (P = NS). Normal albumin compared with controls (39.5 [6.4] versus 29.4 [10] g/dL; P = .001), significant oedemas only in 10 versus 63% of controls. HN were older (58.8 [12.6] versus 45.5 [19.6] years), had longer hypertension duration before renal biopsy and more previous cardiovascular events (39 versus 16%). Mean blood pressure was higher (166/ 90 versus 133/75 mmHg; P = .01) and had worse renal outcome. Conclusions: HN must be included in the differential diagnosis of nephrotic range proteinuria in hypertensive patients. The absence of oedema and normal serum albumin are distinctive clinical characteristics that can help in decision-making before performing a renal biopsy (AU)

[Nephrotic proteinuria in hypertensive nephrosclerosis: clinical and evolution characteristics]. / Proteinuria de tipo nefrótico en la nefroangioesclerosis hipertensiva: características clínicas y evolutivas.

BACKGROUND AND OBJECTIVE: Nephrotic range proteinuria can occur in patients with biopsy proven hypertensive nephrosclerosis (HN). We analysed the differential clinical and evolution characteristics of these patients compared with other glomerular diseases. MATERIAL AND METHOD: This is a case-control descriptive analysis obtained from the renal pathology registry of our hospital. Clinical features, treatment and evolution of these patients (cases) were compared with nephrotic patients with other glomerular diseases (controls). RESULTS: Five point one percent of biopsies with HN diagnosis. Case/control characteristics were: proteinuria 4.7 [3-11.4] versus 5.5 [3-28.1] g/24h/1.73m(2) (P=NS). Normal albumin compared with controls (39.5 [6.4] versus 29.4 [10] g/dL; P=.001), significant oedemas only in 10 versus 63% of controls. HN were older (58.8 [12.6] versus 45.5 [19.6] years), had longer hypertension duration before renal biopsy and more previous cardiovascular events (39 versus 16%). Mean blood pressure was higher (166/90 versus 133/75mmHg; P=.01) and had worse renal outcome. CONCLUSIONS: HN must be included in the differential diagnosis of nephrotic range proteinuria in hypertensive patients. The absence of oedema and normal serum albumin are distinctive clinical characteristics that can help in decision-making before performing a renal biopsy.

HER2 blockade in metastatic collecting duct carcinoma (CDC) of the kidney: a case report.

BACKGROUND: Collecting duct carcinoma of the kidney (CDC) is a rare cancer associated with bad prognosis and, at present, with no specific effective therapies. CASE REPORT: We report a clinical case with disseminated highgrade CDC presenting with widespread metastasis to both lungs, pelvic bones, axial skeleton, and the central nervous system (posterior fossa, both hemispheres and pituitary-hypothalamic). The primary tumor in the kidney was demonstrated (by fluorescence in situ hybridization and immunohistochemistry with Herceptest (3+ score)) to significantly overexpress HER2. Critically ill at presentation, the patient received oral capecitabine together with double HER2 blockade with both intravenous trastuzumab and oral lapatinib. His clinical response was a dramatic improvement and a progressive decline in the radiological size of all of his multiple cancer lesions. CONCLUSION: Double HER2 blockade is an effective therapy in disseminated CDC even in the presence of brain metastases.

Guidelines for HER2 testing in breast cancer: a national consensus of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM).

Identifying breast cancers with HER2 overexpression or amplification is critical as these usually imply the use of HER2-targeted therapies. DNA (amplification) and protein (overexpression) HER2 abnormalities usually occur simultaneously and both in situ hybridisation and immunohistochemistry may be accurate methods for the evaluation of these abnormalities. However, recent studies, including those conducted by the Association for Quality Assurance of the Spanish Society of Pathology, as well as the experience of a number of HER2 testing National Reference Centres have suggested the existence of serious reproducibility issues with both techniques. To address this issue, a joint committee from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) was established to review the HER2 testing guidelines. Consensus recommendations are based not only on the panellists' experience, but also on previous consensus guidelines from several countries, including the USA, the UK and Canada. These guidelines include the minimal requirements that pathology departments should fulfil in order to guarantee proper HER2 testing in breast cancer. Pathology laboratories not fulfilling these standards should make an effort to meet them and, until then, are highly encouraged to submit to reference laboratories breast cancer samples for which HER2 determination has clinical implications for the patients.

The great mimicker: fat necrosis of the breast--magnetic resonance mammography approach.

Fat necrosis of the breast is a common benign inflammatory process resulting from injury to breast fat. The pathogenesis of fat necrosis helps to explain its imaging features, which range from benign to malignant-appearing findings. This article reviews the role of magnetic resonance mammography and other conventional imaging techniques in the differential diagnosis of fat necrosis.

Recomendación para la determinación de HER2 en cáncer de mama. Consenso nacional de la Sociedad Españolade Anatomía Patológica (SEAP) y de la SociedadEspañola de Oncología Médica (SEOM) / Guidelines for HER2 testing in breast cancer. A national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

La identificación de los carcinomas de mama con amplificación/sobreexpresión de HER2 es crítica en la práctica clínicadiaria ya que estas neoplasias requieren un tratamientoespecífico que incluye el uso de terapias dirigidas. Tanto lastécnicas de hibridación in situ como las técnicas inmunohistoquímicasson métodos apropiados para la identificación decánceres de mama HER2 positivos. Sin embargo, numerososestudios, incluidos los desarrollados por la Asociación para laGarantía de Calidad en Patología de la SEAP (AGCP) y laexperiencia de centros de referencia nacionales en la determinaciónde HER2 han puesto de manifiesto importantesproblemas de reproducibilidad entre laboratorios. Por estosmotivos, patólogos expertos en la determinación de HER2 deestos centros de referencia, así como oncólogos médicos conuna contrastada actividad en cáncer de mama, en representaciónde las sociedades respectivas (SEAP y SEOM), han trabajadopara debatir y consensuar las recomendaciones nacionalesde determinación de HER2. Estas recomendaciones sebasan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicadaen recientes guías de distintos países, tales como EstadosUnidos, Reino Unido y Canadá.En este consenso, se recomiendan los requisitos mínimosque un laboratorio de Anatomía Patológica debe cumplirpara garantizar la adecuada determinación de HER2 enla práctica diaria. Aquellos laboratorios que carezcan de losestándares mínimos expuestos en esta guía deberían trabajaren alcanzarlos y durante este proceso remitir a laboratoriosde referencia las muestras en las que la determinaciónde HER2 tenga implicaciones clínicas para las pacientes (AU)

Breast cancers with HER2 alterations are critical toidentify because such tumors require unique treatment,including the use of targeted therapies. HER2 alterationsat the DNA (amplification) and protein (overexpression)level usually occur in concert, and both in situ hybridizationand immunohistochemistry can be accurate methodsto assess these alterations. However, recent studies includingthose conducted by the Association for QualityAssessment of the Spanish Society of Pathology and theexperience of several national reference centres for HER2testing have suggested that serious reproducibility issuesexist with both techniques. To address this, a joint committeeof both the Spanish Society of Pathology and theSpanish Society of Medical Oncology has met to reviewguidelines for HER2 testing. Consensus recommendationare based not only on panellist’s experience but also inthose consensus guidelines previously reported in severalcountries, such as United Stated, United Kingdom andCanada . These guidelines include minimal requirements thatPathology Department must meet in order to guaranteeappropriate HER2 testing in breast cancer. Pathology laboratoriesthat do not meet these standards must put effort toreach them and, in the meantime, send clinical cases to referencecentres (AU)

Interval breast cancers in a community screening programme: frequency, radiological classification and prognostic factors.

The frequency of interval cancers (IC) can be an indicator inversely related to the quality of a breast screening programme. The objectives were to estimate the frequency of IC, to classify IC by posterior radiological review, and to describe the prognostic factors of these IC. The setting was the Sabadell-Cerdanyola Breast Cancer Screening Programme, in Northeast Spain. We developed a population-based study of the IC occurring in the first three rounds (1995-2001). The indicators used were the incidence rate of invasive IC per 10 000 women screened and the proportional incidence, stratified by age group, type of screening and the round, and the time elapsed since the last screening mammogram. A radiological informed consensus review was used to classify the IC. No specific pattern of incidence rates was evident with respect to age, type of screening, or round, although screening was generally more sensitive in women aged 60-69 years. The proportional incidence for the period 0-11 months was always under 30%. Twenty-one percent of 38 IC evaluated (95% CI: 8.0-34.0) were attributed to errors in the screening process (false negatives). No major differences in the prognostic factors of the 57 IC were identified on examining the radiological type or the time since the last screening mammogram. We observed a high frequency of IC from 12 months after screening. It is necessary to reach a consensus regarding the definition and the analysis of IC and to establish mechanisms that would allow all the malignant tumours diagnosed in the target population to be identified.

Carcinoma microinvasivo de mama: estudio clinicopatológico de 18 casos / Microinvasive breast carcinoma: a clinicopathological profile of 18 cases

Introducción: La definición exacta del carcinoma microinvasivo de mama sigue siendo problemática, y su comportamiento clínico incierto. Hemos estudiado de forma retrospectiva 38 casos con el diagnostico de carcinoma microinvasivo realizado en diversas instituciones, según los criterios de Silver y Tavassoli. Material y métodos: Describimos las características clinicopatológicas y la reproducibilidad del diagnostico de microinvasion, siguiendo los criterios predeterminados. También estudiamos el valor de la p63 y de la calponina, para establecer la integridad de la capa mioepitelial. Resultados: Los casos fueron revisados por dos de los autores (FG, VM) y reclasificados como carcinoma microinvasivo en 18 casos (47%), microinvasión dudosa, 1 caso, carcinoma ductal in situ (DCIS) con el pseudoinvasión, 11 casos (28,9%), y carcinoma ductal invasor pT1a y pT1b en 8 casos (21,6%). El tamaño del DCIS asociado varió entre 7 y 80 mm. En once casos solo había un foco de microinvasión, los otros casos demostraron dos o tres focos de microinvasión. Dos casos mostraron invasión vascular como la única evidencia del microinvasión. El estudio immunohistoquímico con la calponina y la p63 fue útil en la diagnosis en el 50% de los casos. La axila se extirpó en 15 casos, con un solo ganglio positivo (6,6%). El seguimiento ha oscilado entre 3-120 meses (promedio de 42 meses) con sólo una recidiva local sobre la cicatriz por CDIS a los 9 meses. Conclusiones: El sobrediagnóstico histológico es uno de los problemas de esta entidad. Unos criterios morfológicos estrictos y el uso de la inmunohistoquímica es útil en el diagnóstico diferencial con el CDIS y el carcinoma ductal infiltrante. La incidencia de las recurrencias locales y la metástasis ganglionar son bajas y usualmente se asocian a CDIS de alto grado con necrosis. La extirpación del ganglio centinela puede estar indicada en casos de CDIS con microinvasión

Introduction: The exact definition of microinvasive breast carcinoma remains problematic, and its clinical behavior is uncertain. We have studied retrospectively 38 cases with the diagnosis of microinvasive carcinoma made in different institutions, according to the criteria of Silver and Tavassoli. Material and Methods: We describe the clinico-pathologic characteristics and the reproducibility of the diagnosis of microinvasion, following predetermined criteria. We also study the value of immunohistochemical stains with p63 and calponin, to establish the integrity of the myoepithelial layer. Results: The cases were reviewed by two of the authors (FG, VM) and reclassified as microinvasive carcinoma, 18 cases (47%), doubtful microinvasion, 1 case, ductal carcinoma in situ (DCIS) with pseudoinvasion, 11 cases (28.9%), and invasive ductal carcinoma pT1a and pT1b, 8 cases (21.6%).The size of the associated DCIS varied between 7 and 80 mms. In eleven cases one single focus of microinvasion was found, the other cases showed two or three foci of microinvasion. Two cases showed angiolymphatic invasion, as the only evidence of microinvasion. Immunohistochemistry with calponin and p63 was helpful in the diagnosis of microinvasion in 50% of the cases. Axillary lymph nodes were obtained in 15 cases, and a single positive lymph node was found. One patient recurred as DCIS in the surgical scar nine months after surgery. The other patients were disease free after a variable follow-up, between 3 and 120 months (average 42 months). Conclusions: Microinvasive breast carcinoma is often overdiagnosed histologically. The implementation of strict morphological criteria and the use of immunohistochemistry may be helpful in the differential diagnosis with DCIS and invasive ductal carcinoma. The incidence of local recurrence and lymph node metastases is low, and it is usually associated with the presence of high grade DCIS with necrosis. Sentinel lymph node biopsy may be indicated in cases of DCIS with microinvasion (AU)

Analysis of the pathologic response to primary chemotherapy in patients with locally advanced breast cancer grouped according to estrogen receptor, progesterone receptor, and HER2 status.

PURPOSE: In clinical practice, it is possible to classify breast tumors according to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression: ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative, and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR positive, and HER2 overexpressing; and the less frequent remaining 4 combinations. The aim of this study was to determine the percentage of pathologic complete response (pCR) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes grouped according to ER, PgR, and HER2 status. PATIENTS AND METHODS: Patients with LABC treated with primary chemotherapy including anthracyclines and taxanes were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using the chi(2) test; and correlations with a P value of < or = 0.05 were considered statistically significant. RESULTS: A total of 103 patients were treated. Only 100 patients were included for the analysis of pCR. Eighteen patients exhibited pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER-negative, PgR-negative, and HER2-negative disease (P < 0.01); 35.7% (5 of 14) had ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER-positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had ER-positive, PgR-positive, and HER2-negative disease (P < 0.01). CONCLUSION: In patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status can help predict pCR to primary chemotherapy.

Relationship between the method of detection and prognostic factors for breast cancer in a community with a screening programme.

OBJECTIVES: To analyse and compare the prognostic factors of breast cancer in the target population of our community-screening programme as a function of the method of detection and to analyse the differences in the prognostic factors as a function of the patient's age and the screening episode. SETTING: A Breast Cancer-Screening Programme (BCSP) in Northeast Spain. METHODS: Observational study of all primary malignant breast lesions diagnosed in a woman between 50 and 69 years of age between 18 October 1995 and 31 December 2002. The 16 centres that women from the target population might have attended were contacted. RESULTS: A total of 225 (37.2%) of the lesions included were diagnosed through the BCSP, 59 (9.7%) interval cancers were detected, and 321 (53.1%) were detected through other circuits. Node involvement was significantly lower in the lesions detected at screening (32%) in comparison to the interval cancers (41.8%) and those detected through other circuits (47.5%). A significantly larger percentage of the interval tumours (28.6%) and the lesions diagnosed outside the BCSP (22.1%) scored >5.4 on the Nottingham Prognostic Index (NPI) than those diagnosed within the programme (10.9%). The relation between the NPI and the detection method was only statistically significant in the 65-69-year-old age group. The NPI score of the tumours detected by the BCSP showed a statistically significant association with age. CONCLUSION: This analysis has shown notable differences in some prognostic factors for breast cancer according to the method of detection. Association between age and the a priori prognosis of the malignant lesions arises.