Agreement between incisional and excisional biopsies for hormone receptors and her2 in breast cancer.

INTRODUCTION: Breast cancer is the leading cause of cancer mortality in Mexican women. OBJECTIVE: The objective of the study was to identify concordances among core needle biopsy (CNB) and excisional biopsies (EB) regarding diagnosis, hormonal receptors (HR), and human epidermal growth factor receptor 2 (Her2). MATERIALS AND METHODS: Core number, demographic data, histological type, and treatment were documented for each sample. Reported HR and Her2 score from both samples were compiled. RESULTS: 70 women with both CNB/EB were included. Median age was 58 (36-87) years; initial diagnosis in CNB were invasive ductal 56 (80%), lobular 10 (14%), and mixed 4 (6%) carcinomas. Diagnostic agreement among CNB and EB was of 97%, k = 0.65. A concordance of 92% (k = 0.75), 75% (k = 0.26), and 67% (k = 0.46) was observed for estrogen receptors, progesterone receptors, and Her2 determinations, and positive predictive values in CNB were 0.96, 0.89, and 0.44, respectively. CONCLUSION: HR and Her2 concordances using manual-immunohistochemistry (IHC) were found within the range of values obtained using automatized-IHC. When compared to tumor heterogeneity, technical/reading errors contribute more to discordances.

INTRODUCTION: El cáncer de mama es la principal causa de mortalidad por cáncer en mujeres mexicanas. OBJETIVO: Identificar la concordancia entre la biopsia con aguja de corte (BAC) y la biopsia escisional (BE) con respecto al diagnóstico, receptores hormonales (RH) y Her2. MATERIAL Y MÉTODOS: Se registró el número de fragmentos cilíndricos, datos demográficos, tipo histológico y tratamiento. Se recopilaron resultados de RH y Her2. RESULTADOS: Se incluyeron 70 mujeres con mediana de edad de 58 años. El diagnóstico inicial en BAC fue carcinoma ductal invasivo 56 (80%), lobular 10 (14%) y mixtos 4 (6%). El acuerdo de diagnóstico entre BAC y BE fue del 97%, k = 0.65. Se observó una concordancia de 92% (k = 0.75), 75% (k = 0.26) y 67% (k = 0.46) para las determinaciones de receptor de estrógenos (RE), receptor de progesterona (RP) y Her2, y los valores predictivos positivos en BAC fueron 0.96, 0.89 y 0.44, respectivamente. CONCLUSIÓN: Los RH y la concordancia de Her2 mediante inmunohistoquímica (IHC) manual se encuentran dentro del rango de valores obtenidos mediante el uso de IHC automatizada. Los errores técnicos/de lectura contribuyeron más a discordancia que la heterogeneidad tumoral.

Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence.

PURPOSE OF REVIEW: Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological results are not conclusive. Most studies have evaluated breast cancer (BC) as a single entity without considering the different molecular expressions, including estrogen receptor (ER), progesterone receptor (PR), and HER2, that could differ in their association with these contaminants. Hence, we assessed the association between biological concentration of OCP and BC, according to its molecular receptor expression, based on a systematic review and meta-analysis. RECENT FINDINGS: Of the 141 articles eligible for full-text review, nine met the inclusion criteria. The way in which molecular expression was reported was heterogeneous; therefore, the inclusion of studies in the meta-analysis was limited to eight articles. A negative association was identified for ß-hexachlorocyclohexane and trans-nonachlor with ER + tumors and between hexachlorobenzene and ER - tumors. No associations were observed for p,p'-dichlorodiphenyldichloroethylene, cis-nonachlor, and dieldrin, and it was not possible to evaluate the associations between OCP with HER2 expression or triple-negative tumors due to lack of data. The results suggest that some OCP might be associated with BC depending on the expression of ER. However, the evidence is not conclusive due to the scarce data. We identified several methodological aspects to fill the gaps in knowledge and increase the comparability among studies.

Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer.

Purpose: Sentinel lymph node (SLN) biopsy (SLNB) is the standard tool to stage the axilla of breast cancer patients. This study aimed to identify the predictors of positive SLNB in patients with clinically node-negative breast cancer. Patients and Methods: A retrospective, single-institution cohort of patients with early-stage breast cancer without clinically identifiable axillary lymphadenopathy was chosen from January 2010 to December 2018. Logistic regression was used to identify possible predictors of positive SLNB. Results: Four hundred and seventy patients were identified; their mean age was 50±11 years. Most patients had the following characteristics: invasive ductal carcinoma (n=382, 81.3%), unilateral tumor (n=461, 98.1%), unifocal disease (n=351, 74.7%), intermediate grade (n=276, 59.0%), and estrogen and progesterone receptor positivity with human epidermal growth factor receptor 2 negativity (n=305, 64.9%). The mean size of the breast mass was 2.3±1.5 cm. SLNB was positive in 128 (27.2%) cases. The mean number of SLNs was 2±1.2. Axillary lymph node dissection was performed in 109 patients. The mean number of lymph nodes removed was 15±6. In 66 (60.6%) of the 109 patients with metastatic axillary nodes, only the SLNs were found to be positive. The number of SLNs, tumor size, tumor grade, receptor status, prominent axillary lymph nodes, and lymphovascular invasion predicted positive SLNB (P = 0.01, 0.03, 0.03, and 0.04 and <0.001 and <0.001, respectively). Conclusion: Our results suggest that a number of histopathological and radiological characteristics of breast cancer can predict SLNB positivity in clinically node-negative breast cancer patients.

Assessment of Nerve Fiber Density and Expression of Hormonal Receptors Within Rectosigmoid Endometriosis Nodules.

STUDY OBJECTIVE: To assess nerve fiber density and expression of hormone receptors in bowel endometriosis. DESIGN: Cross-sectional study. SETTING: Private hospital. PATIENTS: Women with endometriosis undergoing laparoscopic segmental bowel resection (n = 54). INTERVENTIONS: Tissue samples were obtained from patients with surgically treated rectosigmoid endometriosis. MEASUREMENTS AND MAIN RESULTS: The rectosigmoid specimen containing the endometriosis nodule was manually sectioned and divided into 3 areas: core of the nodule, margin of the nodule, and healthy bowel tissue. The intensity of expression of estrogen and progesterone receptors was evaluated by immunohistochemistry and measured according to the Allred score. Nerve fibers were stained by immunohistochemistry using Protein Gene Product 9.5, and the density of nerve fillets was counted and expressed in number/mm². All glandular and stromal cells stained for estrogen; however, glandular cells stained more strongly than stromal cells (61.1% vs 35.2%; p = .01). Most of glandular and stromal cells stained strongly for progesterone receptors (90.7% vs 98.1%; p = .2). The density of nerve fibers was very high in the margin of the nodule (172.22±45.66/mm²), moderate in healthy bowel tissue (111.48±48.57/mm²), and very low in the core of the nodule (7.31±4.9/mm²); p = .01. CONCLUSION: Both glandular and stromal cells within the rectosigmoid endometriosis nodule express estrogen and progesterone receptors. Higher intensity of expression of estrogen receptors occurs in glandular cells. The density of nerve fibers is extremely high at the nodule margin and very low in the center of the nodule.

Prognostic value of androgen receptor expression in different molecular types of breast cancer in women.

BACKGROUND: Breast cancer is a common women's disease. Usually, oestrogen is blamed in the aetiology and correlated with the prognosis; however, androgens are recently raising concern about its role in the breast cancer treatment and prognosis. METHODS: In this study we retrieved archival paraffin blocks of breast cancer patients and stained it for androgen. Thereafter, we compared clinico-epidemiologic parameters, histopathology, neoadjuvant response and recurrence rate and pattern among patients with and without androgen receptor (AR) expression. RESULTS: In total, 119 patients fulfilled enrolment criteria; AR expression were present in 77.3% of the patients. AR expression was associated with less grade III (6.8% versus 36.4%), and less triple negative (6.2% versus 25%), but similar overall recurrence rate (25% versus 22.2%). However, distant recurrence was significantly higher in androgen positive patients (91.3% versus 33.3% of all recurrences). CONCLUSION: Androgen expression appears to be common among breast cancer, but with no clear implication in tumour aggressiveness or effect on the rate of recurrence. However, being commonly associated with distant spread may have an impact on survival of the patients.

Efficiency of microbial bio-agents as elicitors in plant defense mechanism under biotic stress: A review.

Numerous harmful microorganisms and insect pests have the ability to cause plant infections or damage, which is mostly controlled by toxic chemical agents. These chemical compounds and their derivatives exhibit hazardous effects on habitats and human life too. Hence, there's a need to develop novel, more effective and safe bio-control agents. A variety of microbes such as viruses, bacteria, and fungi possess a great potential to fight against phytopathogens and thus can be used as bio-control agents instead of harmful chemical compounds. These naturally occurring microorganisms are applied to the plants in order to control phytopathogens. Moreover, practicing them appropriately for agriculture management can be a way towards a sustainable approach. The MBCAs follow various modes of action and act as elicitors where they induce a signal to activate plant defense mechanisms against a variety of pathogens. MBCAs control phytopathogens and help in disease suppression through the production of enzymes, antimicrobial compounds, antagonist activity involving hyper-parasitism, induced resistance, competitive inhibition, etc. Efficient recognition of pathogens and prompt defensive response are key factors of induced resistance in plants. This resistance phenomenon is pertaining to a complex cascade that involves an increased amount of defensive proteins, salicylic acid (SA), or induction of signaling pathways dependent on plant hormones. Although, there's a dearth of information about the exact mechanism of plant-induced resistance, the studies conducted at the physiological, biochemical and genetic levels. These studies tried to explain a series of plant defensive responses triggered by bio-control agents that may enhance the defensive capacity of plants. Several natural and recombinant microorganisms are commercially available as bio-control agents that mainly include strains of Bacillus, Pseudomonads and Trichoderma. However, the complete understanding of microbial bio-control agents and their interactions at cellular and molecular levels will facilitate the screening of effective and eco-friendly bio-agents, thereby increasing the scope of MBCAs. This article is a comprehensive review that highlights the importance of microbial agents as elicitors in the activation and regulation of plant defense mechanisms in response to a variety of pathogens.

Analysis of Increased EGFR and IGF-1R Signaling and Its Correlation with Socio-Epidemiological Features and Biological Profile in Breast Cancer Patients: A Study in Northern Brazil.

INTRODUCTION: Breast cancer (BC) is the second most frequent cancer worldwide. It is known that a subset of BC has amplification, and overexpression of the epidermal growth factor receptor (EGFR) and high expression of the insulin-like growth factor receptor-1 (IGF-1R) are correlated with a favorable prognosis. This study aimed to evaluate the prognostic and predictive values of the EGFR and IGF-1R in tumor samples from patients with BC and their correlation with socio-epidemiological features. PATIENTS AND METHODS: We analyzed socio-epidemiological, clinical-pathological data and tumor tissues from 124 patients with BC undergoing treatment, to assess levels of EGFR and IGF-1R mRNA and protein. The predictive performance included the calculation of area-under-the-curve (AUC) to discriminate groups of patients with high and low mRNA expression associated with survival analysis within each molecular group of BC. RESULTS: We found a significant expression increase (p <0.001) in EGFR associated with body mass index, angiolymphatic invasion, compromised lymph nodes and follow-up in 58.1% of the triple-negative and HER overexpression tumors. The increase in IGF-IR was significant (p <0.001) in 41.9% of luminal tumors A and B. ROC analysis showed that EGFR had a higher predictive performance (AUC = 0.891) than IGF-1R (AUC = 0.60). The Kaplan-Meier analysis indicated that only the high expression of EGFR was associated with a decreased probability of survival for patients, what did not happen with IGF-1R. CONCLUSION: Our results suggest that EGFR and IGF-1R expression patterns associated with the clinical characteristics of patients and biological profile influenced the evolution of BC.

Impact of immunohistochemical profile changes following neoadjuvant therapy in the treatment of breast cancer.

INTRODUCTION: Currently, the indication for neoadjuvant chemotherapy is increasing in the treatment of breast cancer. Variability in the expression of biomarkers following neoadjuvant treatment has been observed, which could be accompanied by changes in the adjuvant treatment. OBJECTIVES: The primary objective was to evaluate the variability of biomarkers prior to and following neoadjuvant therapy. Secondary objectives were to determine which tumour subtype (as determined by immunohistochemical markers) most frequently achieved pathological complete response (pCR); whether the biomarker variation resulted in a change in immunophenotype and subsequently modification to the adjuvant treatment. MATERIALS AND METHODS: A retrospective observational analysis was carried out on patients with a diagnosis of breast cancer who had neoadjuvant therapy prior to surgery in the Breast Care Service of the Buenos Aires British Hospital between January 2009 and June 2020. RESULTS: One hundred and seventy-two patients were included. The pCR rate was 28.5%. The tumour immunophenotype that achieved pCR most frequently was the hormone receptor negative /HER2+ group with a value of 85.2%. The analysis was carried out on the 123 patients with residual disease. The observed variability for oestrogen receptors (ER) was 8.9%, for progesterone receptors (PR), 29.9% and for HER2, 13.8%. These changes were statistically significant. There were changes to the tumour immunophenotype in 26 cases (21.1%) with modifications to the adjuvant treatment in nine of these (34.6%; 7.3% of all tumours with residual disease). CONCLUSIONS: In this study, we observed statistically significant variability in the expression of ER, PR and HER2 prior to and following neoadjuvant treatment, which identified modifications in the tumour immunophenotype in 21.1%, and changes to the adjuvant treatment in 7.3% of all tumours with residual disease, justifying the re-assay of biomarkers in the surgical specimen.

Cambios en el perfil inmunohistoquímico pre y post neoadyuvancia en cáncer de mama. Experiencia del Hospital Británico de Buenos Aires / Changes in biomarkers in pre and post neoadjuvant breast carcinoma

Introducción: actualmente la quimioterapia neoadyuvante ha ampliado sus indicaciones en el tratamiento del cáncer de mama. Se observó variabilidad en la expresión de biomarcadores postneoadyuvancia que pueden acompañarse de cambios en el tratamiento adyuvane. Objetivos: el objetivo principal fue evaluar la variabilidad de biomarcadores pre y post neoadyuvancia. Los objetivos secundarios fueron determinar qué subtipo inmunohistoquímico tumoral alcanzó más frecuentemente la respuesta patológica completa (PCR), si la variación en los biomarcadores derivó en un cambio de inmunofenotipo y posteriormente en una modificación del tratamiento adyuvante. Material y método: se realizó un estudio retrospectivo observacional de las pacientes con diagnóstico de cáncer de mama que realizaron neoadyuvancia en el servicio de mastología del Hospital Británico de Buenos Aires entre enero 2009 y junio 2019. Resultados: se incluyeron 127 pacientes. La variabilidad observada para receptores de estrógeno (RE) fue de 7,6%, resultando no estadísticamente significativo. Para receptores de progesterona (RP) fue de 28,3% y para HER2 fue de 13,1%, estos cambios fueron estadísticamente significativos. El inmunofenotipo tumoral que alcanzó más frecuentemente la PCR fue el grup RH-/HER2+. Hubo cambios en el inmunofenotipo tumoral en 17 casos y modificaciones al tratamiento adyuvante en 5 de estos. Conclusiones: en este estudio observamos una variabilidad estadísticamente significativa en la expresión de RP y HER2 posteriormente al tratamiento neoadyuvante. En cambio la variabilidad de RE no es estadísticamente significativa. Estos cambios determinan modificaciones en el inmunofenotipo tumoral y en el tratamiento adyuvante en el 29,4% de estos casos (5,4% del total de la serie), justificando la reevaluación de biomarcadores en la pieza quirúrgica. La tasa de PCR fue del 27,6%. Se observó con mayor frecuencia en el grupo RH-/HER2+ alcanzando un valor de 83,3%.

Introduction: nowadays neoadjuvant chemotherapy has extended its indications in breast cáncer treatment. A variantion in tumoral biomark expression has been observed after neoadjuvant treatment, this can be accompanied by a modification in adjuvant treatment. Objetives: to evaluate the variability in biomarkers before and after neoajuvant chemotherapy. To observe which inmunehistochemical subtype reache most frequently pathologic complete response, to determine if changes in biomarkers derived in a change in adjuvant treatment. Material and method: this is an observational retrospective study on patients with breast cáncer diagnosis who underwent neoadjuvant chemotherapy in Buenos Aires British Hospital between 2009 and june 2019. Results: the variability observed for estrogen receptor was 7,6%, not statistically significant; for progesterone receptor was 28,3%, for HER2 13,1%, these modifications were statistically significant. Pathologic complete response was achieved most frequently by RH-/HER2+ carcinomas. We observed changes in subtype in 17 cases ant modifications to adjuvant treatment in 5 cases. Conclusions: in this study we observed modifications in progesterone receptors and HER2 expression before and after neoadjuvant treatment, these were statistically significan. The modifications in estrogen receptors expression were not statistically significant. They led to changes in tumoral subtype and in the adjuvant treatment in 29,4% of the cases. This justifies retesting tumoral biomarkers after the neadjuvant setting. The rate of pathologic complete response was of 27,6%, mainly given by RH-/HER2 + tumors.

Cáncer de mama triple negativo: otra enfermedad y nuevo reto / Triple negative breast cancer: another disease and a new challenge

El cáncer de mama Triple Negativo es un subtipo molecular que se caracteriza por ausencia de expresión de receptores de estrógeno, progesterona y proteína HER2. Representa el 10 % a 15 % de todos los subtipos de cáncer de mama con impacto en el pronóstico y en las líneas de tratamiento; siendo negativo para receptores hormonales y HER2, la terapéutica hormonal y anti-HER2 no cuentan para su manejo. Aún no se dispone de productos dirigidos a blancos específicos para esta categoría.(AU)

The Triple Negative breast cancer is a molecular subtype characterized by no expression of the estrogen, the progesterone and the HER2 protein receptors. They represents 10 % to 15 % of all the breast cancer subtypes with an impact on the prognosis and in the treatment lines; is negative for the hormone receptors and for the HER2, hormonal and the anti-HER2 therapeutics do not count for the management of them. The products targeting specific to this category are not yet available(AU)

MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines.

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15-20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.

Triple-Negative Breast Cancer Comparison With Canine Mammary Tumors From Light Microscopy to Molecular Pathology.

Many similar characteristics in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression, and response to standard therapies have promoted the approval of this comparative model as an alternative to mice. Breast cancer represents the second most frequent neoplasm in humans after lung cancer. Triple-negative breast cancers (TNBC) constitute around 15% of all cases of breast cancer and do not express estrogen receptor (ER), progesterone receptor (PR), and do not overexpress human epidermal growth factor receptor 2 (HER2). As a result, they do not benefit from hormonal or trastuzumab-based therapy. Patients with TNBC have worse overall survival than patients with non-TNBC. Lehmann and collaborators described six different molecular subtypes of TNBC which further demonstrated its transcriptional heterogeneity. This six TNBC subtype classification has therapeutic implications. Breast cancer is the second most frequent neoplasm in sexually intact female dogs after skin cancer. Canine mammary tumors are a naturally occurring heterogeneous group of cancers that have several features in common with human breast cancer (HBC). These similarities include etiology, signaling pathway activation, and histological classification. Molecularly CMTs are more like TNBCs, and therefore dogs are powerful spontaneous models of cancer to test new therapeutic approaches, particularly for human TNBCs. More malignant tumors of the breast are more often ER and PR negative in both humans and dogs. Promising breast cancer biomarkers in both humans and canines are cancer-associated stroma (CAS), circulating tumor cells and tumor DNA (ctDNA), exosomes and miRNAs, and metabolites.

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing in Women with Breast Cancer in Kampala, Uganda.

BACKGROUND: The expression of estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor-2 (HER2) has been reported to have an invaluable prognostic role. The aim of this study was to determine the expression of ER, PR and HER2 in women with breast cancer (BC) in Kampala, Uganda. METHODS: Expression of ER, PR and HER2 was determined immunohistochemically. Logistic regression was performed to determine the effect of the independent factors in predicting the risk of not expressing the breast markers. A two-tailed p<0.05 was regarded to be statistically significant. RESULTS: ER, PR and HER2 were expressed in 53.4%, 46.6% and 18.5%, respectively. ER and PR co-expression was present in 42.7% and 37.9% patients had triple negative breast cancer (TNBC). Age was an independent predictor of expression of ER (AOR = 0.18, 95% CI = 0.062-0.541, p = 0.002) and PR (AOR = 0.35, 95% CI = 0.129-0.968, p = 0.043). CONCLUSION: The majority of patients in this study had less than 50 years with high tumour grade. Interestingly, most of them had high expression of HER2 with TNBC which are molecular subtypes of BC with poor prognosis. Age was an independent predictor of expression of both ER and PR.

Assessment of breast cancer immunohistochemistry and tumor characteristics in Nigeria.

BACKGROUND: Female breast cancer is the leading type of cancer worldwide with an incidence of approximately 2.1 million in 2018. Hormone receptor status plays a vital role in its management. AIM: To determine the molecular expression pattern of biomarkers in breast cancer and their correlation with tumor variables. METHODS: This prospective study was designed to analyze expression patterns of estrogen receptor(ER), progesterone receptor (PR) and human epidermal growth factor receptor(HER2/neu) in breast cancer patients. The dataset has been taken from the Department of Radiotherapy and Oncology of Usmanu Danfodiyo University Teaching Hospital Sokoto, Nigeria from 1 January 2015 to 2 December 2019. The dataset had 259 records and 7 attributes. SPSS version 23.0 for statistical analysis was used. The data analyzed demographic and other clinicopathological characteristics as categorical variables. The mean and standard deviation were determined for the quantitative variable. RESULTS: A total of 259 breast cancer cases were included in the study. The mean age was 48.3 ± 11.0, with an age range of 26-80 years and a median age of 46 years. The morphological categories were invasive ductal carcinoma 258 (99.6%) and invasive lobular carcinoma 1 (0.4%). ER, positivity increased in 73 patients (50%) under the age of 50 years, as well as PR positivity increased in 34 patients (23.6%) under the age of 50 years. HER/2neupositivity decreased in 8 patients (5.6%) under the age of 50 years. Hormonal receptors were statistically significant with clinicopathological characteristics (P < 0.05). CONCLUSION: Our study showed that ER, PR and HER2/neuexpression had a strong correlation with age, tumor grade, tumor size and lymph node status. Hence, hormone receptor assessment is highly recommended because of its significance in clinical management and prognostication.

EO771, is it a well-characterized cell line for mouse mammary cancer model? Limit and uncertainty.

Among mouse mammary tumor models, syngeneic cell lines present an advantage for the study of immune response. However, few of these models are well characterized. The tumor line EO771 is derived from spontaneous breast cancer of C57BL/6 mice. These cells are widely used but are referenced under different names: EO771, EO 771, and E0771. The characteristics of the EO771 cells are well described but some data are contradictory. This cell line presents the great interest of developing an immunocompetent neoplastic model using an orthotopic implantation reflecting the mammary tumors encountered in breast cancer patients. This review presents the phenotype characteristics of EO771 and its sensitivity to nutrients and different therapies such as radiotherapy, chemotherapy, hormone therapy, and immunotherapy.

Recurrence/Regrowth in Grade I Meningioma: How to Predict?

The HLA-G and HLA-E molecules, Ki67, progesterone (PR), estrogen (ER) and androgen receptors (AR), p53, COX-2, and HER2 were studied to assess whether the biological behavior of grade I meningiomas is related to their expression. Tissue samples from 96 patients with grade I intracranial meningiomas were analyzed by immunohistochemistry on tissue microarray blocks (TMA) using antibodies specific for HLA-G, HLA-E, Ki67, PR, ER, AR, p53, COX-2, and HER2. Meningiomas were classified as small (≤2 cm, 1.0%), medium (>2 and ≤4 cm, 32.3%), and large (>4 cm, 66.7%). Tumor size was not related to recurrence/regrowth (p = 0.486), but was significantly correlated with peritumoral edema (p = 0.031) and intratumoral calcifications (p = 0.018). Recurrent meningiomas were observed in 14.6% of cases. Immunostaining for each marker was: HLA-G 100%; HLA-E 95.6%; PR 62%; ER 2.1%; AR 6.5%; p53 92.6%; COX-2 100%; HER2 0%; Ki67, mean 2.61 ± 2.29%, median 2.1%. Primary and recurrent meningiomas showed no significant relation with HLA-E and hormone receptors (p > 0.05), except for Ki67, where a higher median was observed in recurrent tumors than in primary (p = 0.014). The larger the tumor, the more severe the peritumoral edema, and the greater the presence of calcifications. Ki67 appears to be a good biomarker of recurrence/regrowth in grade I meningiomas.

Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor.

INTRODUCTION: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. AREAS COVERED: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. EXPERT OPINION: As shown in phase 2 and 3 clinical trials on efficacy and tolerability, abemaciclib is a potentially convenient, safe, and effective agent for the treatment of patients with advanced hormone receptor-positive patients. Orally administered abemaciclib in combination with aromatase inhibitors or fulvestrant has the potential to allow significant improvement in survival outcomes, quality of life, response rate, and duration of response even in poor prognosis subgroups. Adequate patients' information, clinical selection, and prompt, proactive management of side effects are mandatory.

A cumulative index of exposure to endogenous estrogens and breast cancer by molecular subtypes in northern Mexican women.

PURPOSE: To evaluate breast cancer (BC) molecular subtypes association with reproductive characteristics and an index of cumulative exposure to endogenous estrogens (EEI) in Mexican women. METHODS: We performed a study of incident cases and population controls in northern Mexico. We included BC cases with tumor molecular classification in their medical records (n = 509), and classified them as HR+/HER2- (ER+ and/or PR+ and HER2-) (n = 289), HER2+ (HR+ or HR-) (n = 117) or triple negative (TN) (n = 103). We matched controls (n = 1030) by age and place of residence with index cases. Women were interviewed about their reproductive history, from which the EEI was developed. We used logistic regression models to estimate BC molecular subtypes associations with reproductive characteristics and EEI. RESULTS: The EEI was higher in all subtypes compared to controls (Median HR+/HER2- 27.25, HER2+ 26.8, TN 24.2 vs. controls 22.8 years, p < 0.05), and was associated with HR+/HER2- (ORT3 vs. T1 = 2.58, 95% CI 1.77-3.55, p-trend < 0.001) and HER2+ (ORT3 vs. T1 = 4.17, 95% CI 2.15-8.08, p-trend < 0.001) BC. Additionally, HR+/HER2- tumors were positively associated with age at first pregnancy and age at menopause, and negatively with age at menarche, parity and breastfeeding. The HER2+ subtype was associated in the same direction as HR+/HER2- tumors with all the reproductive characteristics except for age at menarche. TN tumors were negatively associated with parity and breastfeeding. CONCLUSION: Endogenous estrogens exposure throughout Mexican women reproductive life may contribute to the development of all but TN BC, however, these findings should be confirmed in other Hispanic populations.

Hormone Receptors and Human Epidermal Growth Factor (HER2) Expression in Fine-Needle Aspirates from Metastatic Breast Carcinoma - Role in Patient Management.

INTRODUCTION: Estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor (HER2) are prognostic and predictive factors for breast carcinoma. We determined them by immunohistochemistry (IHC) on cell blocks from fine-needle aspirates (FNA) of metastatic breast carcinoma to axillary lymphnodes and compared them with that reported in the primary breast carcinoma (PBC) to document any change in their expression for future management. MATERIALS AND METHODS: ER, PR, and HER2 by IHC and HER2 oncogene by fluorescent in-situ hybridization (FISH) were studied on cell blocks of FNA of axillary lymphnodes in 53 of 94 PBC cases from 2012 to 2016. RESULTS: In 25 of 38 (65.8%) ER, PR negative PBC the metastasis on FNA was ER, PR+, whereas the 15 (28.3%) ER, PRPBC remained negative. In 10 of 11 (91%) of HER2-IHC+, PBC the metastatic tumor was HER2-IHC+. 7 of 32 (21.9%) HER2-IHC negative PBC were HER2-IHC+ in metastatic tumor. HER2-FISH was performed in 37 cases on FNA. Six of 37 were HER2 amplified/positive, whereas 9 and 19 remained equivocal and negative for HER2 copy number, and 3 were not interpretable. All the 6 HER2-FISH+ cases were positive by IHC. In our study, 34.2% of ER, PR+ cases of PBC became ER, PR- in the metastatic tumor and 21.9% of HER2-IHC negative PBC became HER2-IHC+ in the metastatic aspirate. CONCLUSION: ER, PR, and HER2 by IHC in cell blocks of metastatic lymphnodes are reliable. Change in receptor (34.2%) and HER2 status (21.9%) was documented, which is of clinical significance as these patients warrant a change of management.

Hormonal receptors in cutaneous vascular malformations: 51 cases.

Vascular malformations (VMs) are rare congenital anomalies that develop during embryogenesis in different types of vessels. Several triggering factors of cutaneous VMs include trauma, infections, or hormonal changes. We investigated the expression of hormonal receptors (androgen, estrogen, progesterone) in tissue samples of well-characterized VMs. A secondary objective was to identify self-reported triggering factors for these VMs, including hormonal changes, in the cohort of patients. We included patients with VM samples obtained in the tertiary center for vascular anomalies of the University Hospital Center of Tours, France, from January 1, 2007, to August 1, 2018. Immunohistochemistry was used to detect the expression of hormonal receptors (estrogen, progesterone, androgens). We obtained 51 samples from 51 patients: 13 cystic lymphatic malformations (CLMs), 16 venous malformations (VeMs), 11 arteriovenous malformations (AVMs), 4 combined VMs, 4 PIK3CA-related overgrowth spectrum, 1 Parkes-Weber syndrome, 1 Gorham syndrome, and 1 multiple lymphangioendotheliomatosis with thrombopenia. In total, 38 (74.5%) samples were positive for androgen receptor: 11 (84.6%) CLMs, 12 (75.0%) VeMs, 8 (72.2%) AVMs, and 7/11 (63.5%) other samples. All samples were negative for estrogen and progesterone receptors. Triggering factors were self-reported in 7 cases and were most frequently hormonal changes (n = 6, 18.2%). Hormonal triggers were frequent in AVMs (n = 4). Among patients with identified hormonal triggers, VM samples were positive for androgen receptor in 3 and negative in 3. Three-quarters of our VM samples expressed androgen receptor, and most CLM, VeM, and AVM samples were positive. Hormonal triggers were identified in 6/33 patients, mostly with AVMs.