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In female breast cancer (BC), elastosis is strongly related to estrogen receptor alpha (ERα) expression. Male breast cancers almost invariably express ERα; so, the aim of this study was to investigate elastosis frequency in invasive male BC as well as clinicopathological correlations, in comparison with females. A total of 177 male BC cases and 135 female BC cases were included, all ERα-positive and invasive carcinoma of no special type. Elastosis on H&E-stained slides was scored in a four-tiered system as elastosis grade (EG) 0 (no elastosis) to EG3 (high amount of elastosis). EG scores in male BC were correlated to histopathological characteristics and overall surviva and compared with female BC EG scores. Male BC showed some degree of elastosis in 26/117 cases (22.2%) with none showing EG3, while female BC cases showed elastosis in 89/135 cases (65.9%) with 21.5% showing EG3 (p < 0.001). This difference retained its significance in multivariate logistic regression. In male BC cases, no significant correlations were found between the amount of elastosis and age, grade, mitotic activity index, and PgR. In addition, no significant prognostic value of elastosis was seen. In conclusion, despite high ERα expression, male BC showed significantly less elastosis than female BC. Elastosis did not show clinicopathological correlations or prognostic value. Therefore, elastosis seems to be a less useful ERα tissue biomarker with less clinical significance in male BC compared with females, pointing towards important BC sex differences.

Objective To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment. .

Breast cancer is the most common female malignant neoplasm in Poland and around the world. Precise determination of tumor molecular profile allows application of appropriate anticancer therapy, increasing the chances of recovery. A 28-year-old woman detected a thickening in her left breast. Mammography showed a change measuring 60 mm (radiologically BIRADS 5). The biopsy revealed invasive ductal carcinoma, luminal subtype B, HER2 positive (cT3N1M0). Neoadjuvant chemotherapy was administered and then breast conserving surgery was performed. In postoperative histopathology cancer, biological subtype was evaluated: HER2 positive, nonluminal (ypT2ypN0cM0). Then, postoperative radiotherapy was performed. After 14 months, breast ultrasonography (US) and mammography (MGF) revealed the presence of suspicious changes (BIRADS 4). Tru-cut biopsy confirmed cancer recurrence (luminal subtype B, HER2 negative, ER negative, PgR: 10%, Ki-67: 70%). Despite implemented and modified chemotherapy regimens, local progression occurred. Genetic testing excluded BRCA gene mutation. The patient qualified for radical mastectomy modo Halsted (ypT4bN0cM0). Postoperative microscopic examination revealed triple negative breast invasive carcinoma of no special type. After 22 months, metastatic lesions in lungs and left retrosternal nodes appeared. Due to the limited possibilities of systemic treatment, the patient qualified for stereotactic radiotherapy of tumors in the lungs' and left retrosternal nodes. Advancement, histological type and molecular profile should be controlled at each stage of the disease, as they may change several times and require modification of therapy.

Introduction: Breast cancer is the most frequently diagnosed cancer among females worldwide. p53 tumor suppressor gene regulates the cell cycle and DNA repair and its over-expression in breast cancer is associated with a worse prognosis. Objective: This study was done to correlate p53 over-expression with histopathological parameters such as tumor size, tumor grade and lymph node metastasis in breast carcinoma. Materials and Methods: This retroprospective study was conducted in a tertiary care centre, western U.P. retroprospectively from July 2014 to June 2019. Immuno-histochemical evaluation of 50 histologically confirmed cases of breast carcinoma was done. Results: A total of 50 patients of breast carcinoma were analysed. Most common was Invasive carcinoma of no special type (NST). Most common age group involved was 40-49 years and majority were of age more than >45 years of age. Majority of breast carcinoma cases were of left breast and involving upper outer quadrant. In majority of cases, the tumor size was of more than 2 to 5cms. Majority of cases of breast carcinoma were of grade II according to Nottingham Modified Bloom Richardson System. More than half of patients with lymph nodes showed metastatic deposits. Majority of cases were in moderate prognostic index group. Out of 50 cases, 24(48%) cases showed p53 [removed]5%). High p53 [removed]>50%) was seen in 8(16%) cases of breast carcinoma. Conclusion: A statistically significant association was found between p53 expression, tumor size and lymph node metastasis. No statistically significant association was found between p53 overexpression and tumor grade. Overall, p53 overexpression was found to be poor prognostic factor and its detection may help in risk catergorization and designing future target therapies. Keywords: Breast cancer, Invasive carcinoma, Lymph node, p53 overexpression, Immuno-histochemistry.

The first genotype-phenotype relationship in breast pathology developed in 1994 with the discovery of the CDH1 gene. This finding eventually provided biological insight into the characteristic morphology of invasive lobular carcinoma. Subsequent investigative efforts have uncovered additional molecular alterations largely responsible for the histology of several breast neoplasms including secretory carcinoma, adenoid cystic carcinoma, tall cell carcinoma with reversed polarity, fibroepithelial lesions, and most recently, adenomyoepithelioma. Evaluation of the genomic landscape of other special types of breast cancer with distinctive growth patterns, such as invasive mucinous carcinoma, have yet to uncover recurring cytogenetic and/or molecular alterations. Despite the lack of a hallmark alteration in mucinous carcinoma, it is important to note the relative decrease in PIK3CA mutations compared with invasive carcinoma of no special type. In this review, we describe the clinical and pathologic features of breast tumors with recognized genotype-phenotype correlations and summarize the molecular alterations of mucinous carcinoma.

Background HER2 is the target of the therapeutic agents which are used to treat HER2-positive breast cancer. Reports have shown that the HER2 oncogene expression and its association with clinicopathological factors remain unclear in breast cancer (BC) patients. This study aimed to determine the correlation between HER2 expression and clinicalpathological characteristics of breast cancer in Vietnamese women. Methods Between June 2016 and August 2018, paraffin-embedded specimens from 237 patients with primary invasive breast carcinoma in Hue University Hospital and Hue Center Hospital, Hue city, Vietnam were examined for pathological features. The gene expression of HER2, ER, PR and Ki-67 were determined by immunohistochemistry (IHC). The gene amplification of Her2 was assessed by using Dual color in situ hybridization (DISH). Results The most frequent histological type was invasive carcinoma of no special type (NST) with 77.35%, the highest percentage of patients with Grade II was detected (59.36%), tumor size > 2 cm accounted for 71.31% of cases, Lymph node metastases were available in 57.86% cases. Most patients were diagnosed at stage II (59.18%). The majority of patients were classified as moderate Nottingham prognostic index (54.9%). Estrogen receptor and Progesterone receptor were positive in 53.16% and 50.63%, respectively. 76.37% of cases were in high expression group of Ki-67 (≥14%). HER2 IHC 2+, 3+ were accounted for 28.69% and HER2 gene amplification was detected in 31% cases. HER2 gene amplification and/or overexpression was significantly associated with cell proliferation index Ki67. Furthermore, HER2 gene expression tended to be more frequently found in tumors with large tumor size, high grade, high stage and high Nottingham prognostic index and confirmed their prognostic independent role. Conclusions Our data indicated that HER2 gene expression was significantly correlated with cell proliferation index Ki67, but not significantly associated with another clinicopathological factors in breast cancer of Vietnamese women. .

Introduction: Artificial intelligence systems are promising health care technologies, mainly in medical subareas such as pathology, and can be used as support methods for the histological diagnosis of mammary nodules. Objective: This study describes the method and results of the development of artificial intelligence software for the histopathological analysis of mammary nodules. Methods: The software was developed by using two neural networks - Inception and MobileNet. The database used for learning the conditions analyzed (histologically normal breast, fibroadenoma, fibrocystic changes, in situ ductal carcinoma, invasive carcinoma of no special type and invasive lobular carcinoma) was obtained after authorization of the Path Presenter site with 5,298 images. The 2,740 images used for the validation of the system were obtained from the Pathology Institute of Passo Fundo. Results: The present software had sensitivity of 80.5% [95% confidence interval (CI), 71.9%-89.1%] and specificity of 96.1% (95% CI, 94.3%-97.8%) for MobileNet and sensitivity of 73.8% (95% CI, 52.6%-115%) and specificity of 94.7% (CI 95%, 91.7%-97.7%) for Inception. For the differentiation of malignant conditions, it obtained a maximum sensitivity of 78.7% and specificity of 95.8%; for differentiation of benign conditions, the maximum sensitivity was 82.6% and the specificity was 97.4%. Conclusion: The present software presented promising results in the histopathological analysis of mammary nodules. It reinforced the idea that in the future the presence of diagnostic support systems in breast pathologies may play a crucial role in health care. RESUMEN Introducción: Los sistemas de inteligencia artificial son tecnologiasprometedoras en asistencia en salud, principalmente en áreas médicas como la patologia; pueden ser usados para el diagnóstico histopatológico de nódulos mamarios. Objetivo: Este estudio presenta el método y los resultados de la construcción de un software de inteligencia artificial para análisis histopatológico de nódulos mamarios. Métodos: El software fue desarrollado usando dos redes neurales. Se obtuvo la base de datos para el aprendizaje de las condicionas analizadas (mama histológicamente normal, fibroadenoma, cambios fibroquisticos de la mama, carcinoma ductal in situ, carcinoma invasivo de tipo no especial y carcinoma lobular invasivo) después de la aprobación de la página Path Presenter, con 5.298 imágenes. Las imágenes utilizadas para validación del sistema se obtuvieron del Instituto de Patologia de Passo Fundo, totalizando 2.740 imágenes. Resultados: El softwarepresentósensibilidaddel80,5% [intervalo de confianza (IC) 95%, 71,9%-89,1%] y especificidad de 96,1% (95% IC, 94,3%-97,8%) para MobileNet y sensibilidad de 73,8% (95% IC, 52,6%-115%) y especificidad de 94,7% (95% IC, 91,7%-97,7%) para Inception. Para diferenciación de condiciones malignas, obtuvo-se sensibilidad máxima de 78,7% y especificidad de 95,8%; para diferenciación de condiciones benignas, la sensibilidad máxima fue de 82,6% y la especificidad, de 97,4%. Conclusión: El software presentó resultados prometedores en el análisis histopatológico de nódulos mamarios, reforzando la idea de que, en el futuro, la presencia de sistemas de soporte diagnóstico de enfermedades mamarias puede desempenar un papel crucial en la rutina del sistema de salud. RESUMO Introdução: Sistemas de inteligência artificial são tecnologias promissoras de assistência em saúde, principalmente em subáreas médicas, como a patologia; podem ser utilizados como métodos de suporte para o diagnóstico) histopatológico de nódulos mamários. Objetivo: Este estudo apresenta a metodologia e os resultados da construção de um software de inteligência artificial para análise histopatológica de nódulos mamários. Métodos: O softwarefoi desenvolvido utilizando duas redes neuraispara a sua construção: Inception e MobileNet. O banco de dados utilizado para a aprendizagem das condições analisadas (mama histologicamente normal, fibroadenoma, alteração fibrocística, carcinoma ductal in situ, carcinoma invasivo do tipo não especial e carcinoma lobular invasivo) foi obtido após autorização do site Path Presenter, com 5.298 imagens. As imagens utilizadas para a validação do sistema foram obtidas do Instituto de Patologia de Passo Fundo, totalizando 2.740 imagens. Resultados: O software apresentou sensibilidade de 80,5% [intervalo de confiança (IC) 95%, 71,9%-89,1%] e especificidade de 96,1 % (95% IC, 94,3%-97,8%)para o MobileNet e sensibilidade de 73,8% (95% IC, 52,6%-115%) e especificidade de 94,7% (95% IC, 91,7%-97,7%) para o Inception. Para a diferenciação de condições malignas, obteve-se sensibilidade máxima de 78,7% e especificidade de 95,8%; para diferenciação de condições benignas, a sensibilidade máxima foi de 82,6% e a especificidade, de 97,4%. Conclusão: O software apresentou resultados promissores na análise histopatológica de nódulos mamários, reforçando que, no futuro, a presença de sistemas de suporte de diagnóstico das patologias mamárias pode se fazer presente na rotina do sistema saúde.

Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

BACKGROUND: To investigate the imaging findings and visibility of breast invasive lobular carcinoma (ILC) on diffusion-weighted imaging (DWI) and compare quantitative apparent diffusion coefficient (ADC) metrics of ILC and invasive carcinoma of no special type (NST) using a histogram analysis. METHODS: We performed an observational retrospective study of 629 consecutive women with pathologically proven ILC and invasive ductal carcinoma of NST, who underwent 3-T MRI including DWI, between January 2017 and August 2020. RESULTS: After propensity score matching, 71 women were allocated to each group. On DWI, 9 (12.7%) lesions of ILC and 4 (5.6%) invasive carcinomas of the NST were not visualized. For the tumor visibility on DWI, tumor size, tumor ADC value, and background diffusion grade were significantly associated with the visibility score in both groups (all P0.05). The mean ADC (1.226×10(−3) vs. 1.052×10(−3) mm(2)/s, P

Background: Breast carcinoma is a malignancy that occurs from breast cells that grow and continue to proliferate uncontrollably. Mucin 1 (MUC1) has become a topic of interest in cancer treatment due to its upregulation, which affects the invasion, proliferation, and survival of tumor cells, by reducing cell-cell adhesion and extracellular cell-matrix adhesion. Objective: To analyze the correlation between the immunohistochemical expression of Mucin 1 (MUC1) with histopathological grading and molecular subtypes in invasive breast carcinoma. Methods: Formalin-fixed tissue paraffin blocks from 42 patients with invasive breast carcinoma were used as research samples and Mucin 1 (MUC1) immunohistochemical staining was assessed. The correlation between Mucin 1 (MUC1) expression and histopathological grading and molecular subtypes was analyzed by statistical tests using the SPSS program. Results: Of the 42 samples studied, for the age group, the most found were in the age group 40-49 years and the age group 50-59 years (each with 35.7%), while the age group 20-29 years was the least (2.4%). The most histopathological subtypes were invasive carcinoma of no special type (85.7%), with grade 2 being the most common (42.8%). The most common molecular subtype was luminal B (40.5%). Mucin 1 (MUC1) was expressed in 73.8% of invasive breast carcinoma specimens. Conclusion: There is a significant unidirectional correlation between the immunohistochemical expression of Mucin 1 (MUC1), either with histopathological grading or with molecular subtypes in invasive breast carcinoma (p-value were 0.027 and 0.010, respectively).

Introduction Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. Methods We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where “mitogens” means “polyclonal activators” (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. Results The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower “stimulation index of polyclonal activators” (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Conclusion Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.

The material of patients with invasive carcinoma of no special type (ICNT) and nonmalignant diseases (ND) of the mammary gland was studied. When comparing the concentrations of histidine-rich glycoprotein (HRG) and E-cadherin (CDH1), statistically significant differences between ICNT and ND by HRG in the supernatant of blood cells and its spontaneous production by biopsies and by CDH1 at its induced production, as well as by influence indices of polyclonal activators on the production of CDH1 were found. When comparing the expression of immunohistochemical markers, no statistically significant differences between ICNT and ND were obtained.

Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.Rak molochnoĭ zhelezy v bol'shinstve sluchaev iavliaetsia primerom zlokachestvennogo novoobrazovaniia, sviazannogo s infil'tratsieĭ opukholi kletkami, obrazuiushchimi mikrookruzhenie opukholi i produtsiruiushchimi razlichnye tsitokiny. Tsel'iu issledovaniia byla otsenka tsitokinprodutsiruiushcheĭ funktsii opukholevykh kletok i ikh mikrookruzheniia v bioptatakh opukholi patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa (gruppa I) i u patsientov s nezlokachestvennymi zabolevaniiami molochnoĭ zhelezy (gruppa II). Bol'nye II gruppy byli razdeleny na gruppu IIa, v kotoruiu voshli patsienty tol'ko s fibroadenomoĭ, i gruppu IIb, v kotoruiu voshli ostal'nye patsienty s listovidnoĭ fibroadenomoĭ, fibroadenomatozom, fibrozno-kistoznoĭ mastopatieĭ, vnutriprotokovym papillomatozom, skleroziruiushchim adenozom i fibrozno-kistoznoĭ mastopatieĭ s mikrokal'tsinatami. Kontsentratsiiu IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF i MCP-1 opredeliali v supernatante bioptatov opukholeĭ. Dlia otsenki tsitokinprodutsiruiushcheĭ aktivnosti bioptatov opukholi i ee mikrookruzheniia opredeliali indeks vliianiia poliklonal'nykh aktivatorov na produktsiiu tsitokinov. Pri sravnenii I i II grupp byli polucheny vysokie indeksy vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-17, IL-18 i TNF-α u patsientov s nezlokachestvennymi zabolevaniiami. Bolee vysokie znacheniia indeksov vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-18, TNF-α, i IL-1β i sootnosheniia IL1β/IL1Ra byli u patsientov s fibroadenomoĭ po sravneniiu s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa. Statisticheski znachimykh razlichiĭ v gruppakh I i IIb po indeksam vliianiia poliklonal'nykh aktivatorov obnaruzheno ne bylo. Éto pozvoliaet predpolozhit' sushchestvovanie analogichnykh invazivnoĭ kartsinome nespetsificheskogo tipa izmeneniĭ v molochnoĭ zheleze u patsientov IIb gruppy. Pri sravnenii grupp IIa i IIb byli polucheny bolee vysokie znacheniia indeksa vliianiia poliklonal'nykh aktivatorov na produktsiiu IL-1β, a takzhe sootnosheniia IL1β/IL1Ra u patsientov s fibroadenomoĭ molochnoĭ zhelezy. Provedennoe issledovanie pozvolilo vyiavit' osobennosti tsitokinprodutsiruiushchego resursa bioptatov opukholeĭ u patsientov s invazivnoĭ kartsinomoĭ nespetsificheskogo tipa i s dobrokachestvennymi opukholiami molochnoĭ zhelezy.

Breast cancer (BC) remains the most prevalent female cancer in Egypt and worldwide. Microfibrillar-associated protein 5 (MFAP5) is a multifunctional glycoprotein. Although MFAP5 gene was among the genes that found globally expressed in human cancers, it had been only recently reported in few cancer research studies. This is a retrospective study that has been conducted on 66 Egyptian patients who had invasive carcinoma of no special type. Immunohistochemical staining for MFAP5 was applied on the archival formalin-fixed paraffin-embedded blocks. Staining was assessed semiquantitatively and correlated with the available clinicopathologic parameters and immunohistochemical subtypes of BC. MFAP5 epithelial cytoplasmic expression was observed in 89.4% (59/66) of cases. In contrast, nuclear expression was seen in non-neoplastic breast lobules and premalignant lesions adjacent to tumors that also exhibited constant staining in myoepithelial layer. Statistical analysis of epithelial cytoplasmic expression revealed association of MFAP5 expression with tumor size (P=0.046), high histologic grade (P=0.007), presence of lymph node metastasis (P=0.014), poor Nottingham Prognostic Index (NPI) (P=0.001), late stage (P=0.008), immunohistochemical subtypes of BC (P=0.018), and increased microvessel density using CD34 immunostianing (P=0.04). MFAP5 cytoplasmic expression was also observed in an adjacent duct carcinoma in situ component in 37/45 cases (82.2%). This study showed that MFAP5 is a novel myoepithelial cell marker that appears to be upregulated in duct epithelium in duct carcinoma in situ and invasive carcinoma of no special type during tumorogenesis and that its cytoplasmic expression in invasive tumors seems to have a poor prognostic role manifested by its association with poor prognostic parameters such as high grade, late stage, lymph node invasion, and increased microvessel density.

Breast cancer is the most commonly diagnosed cancer in female worldwide. BRCA 1 is located predominantly in nucleus. BRCA 1 is associated with breast cancer. Materials and Methods: This was retroprospective study, 50 known cases of breast carcinoma were analysed in Muzaffarnagar Medical College, Muzaffarnagar. Observation and Results: The age range of patients was from 28-70 years and mean age of patients was 50.24 years. Majority of breast carcinoma were above 45 years of age (64%) and of upper outer quadrant (52%) and of grade II (48%). Invasive carcinoma of no special type (NST) formed the majority of cases (82%) followed by Invasive lobular carcinoma (6%). Altered BRCA 1 expression was seen in ER, PR and HER 2 negative cases. Conclusions: Invasive Carcinoma of no special type was the commonest morphological type. Majority of cases of breast carcinoma were of grade II. Keywords: BRCA 1, Invasive Carcinoma NST, ER, PR, Her 2 neu, IHC.

Background: Breast cancer is the second most common cancer in Indian women. The incidence of Breast cancer in India is increasing slowly and has bad prognosis if detected in late stages. But, its incidence can be decreased if its detection is made at earliest stages, i.e. in the preinvasive stage. This present study was undertaken to assess clinico-pathological aspect of breast lesions in a tertiary care centre of Rohtas, Bihar. Material and Methods: A retrospective study was conducted in the department of Pathology, NMCH, Jamuhar, Sasaram. The data was collected form medical records department. The study period was of two years from January, 2017 to December, 2018 after approval from institutional ethics committee. Results: A total of 200 cases of breast lesions were analyzed. The ratio of benign to malignant lesions was 3.9:1. The overall mean age of patients with breast lesion was 34.5 years. Among 20.5% malignant cases, the age group affected most was 41-50 years. Only 6% of breast lesions were of inflammatory nature. This result is less as compared to past studies and all the lesions histologically were of chronic non-specific mastitis. The most common type of malignancy observed was invasive carcinoma of no special type (NST). Conclusion: The pattern of breast lesions provides valuable information regarding clinic-pathological profile of patients. The clinical diagnosis of breast lesions should be correlated with histopathological features for correct and adequate management of the case.

Background The EndoPredict (EP) test has been developed and validated for assessing recurrence risk in patients with estrogen receptor (ER)-positive HER2-negative breast cancer (BC). This test is based on the expression of 12 genes (molecular score), combined with clinicopathological criteria (i.e. tumor size and nodal status) (EPclin risk score). For node-positive patients, the weight given to the node status in the EPclin score is similar when considering pN1mi (]0.2-2mm]) or pN1 (>2mm, 1-3 positive lymph nodes). Our aim was to characterize the EPclin classification of the pN1mi subgroup in the French national registry for molecular signatures in ER+ BC. Methods Since April 2016, nine French laboratories using EP test in clinical practice prospectively implement a national registry for molecular prognostic signatures in ER+ BC. We analyzed the pN1mi subgroup with regards to their clinico-pathological characteristics, molecular EP score and EPclin risk score. Using the definition formula of the EPclin score [EPclin=0.35t + 0.64n + 0.28EP, with n=1 for pN0, 2 for pN1mi/pN1, 3 for pN2, 4 for pN3], we could calculate a hypothetical EPclin score if the pN1mi had been considered as pN0 [n factor=1]. Results By the end of 2017, the database included 1246 EP tests performed in routine practice, including 67 (5.4%) pN1mi. The pN1mi BC were ER+ HER2- (67/67, 100%), invasive carcinoma of no special type in 52/67 (78%), with a median tumor size of 18 mm (range 7-45; pT1c in 40/67). Among these, 22 were classified as EPclin low and 45 as EPclin high, with a median EP score of 6 (range 2-14), a median EPclin score of 3.70 (range 3-6), and a median relapse risk at 10-year of 15%(range 5-73). Most interestingly, 23/67 (34%; i.e. 1.8% of all EP tests performed) pN1mi BC displayed an EPclin score comprised between 3.4 and 4, just above the cut-off value of 3.3: these cases (and only these cases) would have been classified in a different risk category (i.e. EPclin low risk) if the node status would have been considered as negative. Conclusion With regards to EndoPredict test in pN1mi BC - and the persistent debate as to whether they should bear the same weight as node-positive (pN1) or negative (pN0) tumors - categorization in the EPclin class is not likely to be impacted by the node factor weight in the vast majority (>65%) of the pN1mi cases and >98% of all patients tested with EP. Only cases with an EPclin between 3.4 and 4 might be impacted. Citation Format: LaCroix-Triki M, Arnould L, MacGrogan G, Penault-Llorca F, Haudebourg J, Tas P, Garnier A, Vincent-Salomon A, Miquel C, Lehmann-Che J, Callens C, Quillien V, Cayre A, Lamy P-J, Rouleau E, De Cremoux P. EndoPredict prognostic signature in pN1mi, estrogen receptor-positive breast cancer: analysis of the French national registry for molecular signatures [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-23.

Background Several validated molecular subtyping tests for breast cancer based on gene expression profiling are now routinely used in clinical practice.The Prosigna® breast cancer (BC) prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The assay uses the 50-gene expression profile, weighted together with clinical variables, to generate a risk category and numerical score. The score is reported on a 0-100 scale, for hormone receptor positive BC. Prosigna test results classified tumors according to intrinsic subtypes (Lum A, Lum B, HER2-enriched, basal-like) and ROR risk groups (low risk, 0-40; intermediate risk, 41-60; and high risk, 61-100). For node-positive patients, the weight given to the node status is similar when considering pN1mi ([0.2-2mm]) or pN1 (>2mm, 1-3 positive lymph nodes). Our aim was to characterize the Prosigna test classification of the pN1mi subgroup in the French national registry for molecular signatures in ER+ BC. Methods Since 2018, four French laboratories using Prosigna test in clinical practice retrospectively implement a national registry for molecular prognostic signatures in ER+ BC. We analyzed the pN1mi subgroup with regards to their clinico-pathological characteristics, Prosigna test results and ROR risk score. Using the definition formula of the prosigna algorithm, we could calculate a hypothetical score if the pN1mi has been considered as pN0 and redefine risk categories for pN1mi breast cancers. Results The database included 886 tests performed in routine practice, including 91 (10.3%) pN1mi. The pN1mi BC were ER+ HER2- (88/91, 96.7%), invasive carcinoma of no special type in 81/91 (89%), with a median tumor size of 23 mm (range 12-60). Among these, the median ROR score was 44, and 51/91 tumors (56%) were classified as LumA tumors, 34/91 (41%) as LumB, two asHER2-enriched and one as basal-like. Interestingly, the probability of distant recurrence was 26% if pN1mi BC were considered as N+ but lowered to 10% if considered as pN0. Among the different molecular subtypes, the change from pN1 top N0 has different weight: in Lum A tumors, the switch in the probability of distant recurrences was 13 to 6% according to pN categorization of the pN1mi BC, and the median ROR score moved from 27 to 6 with 15/51(29%) of Lum A tumors considered as high risk if pN1 but only 1/51 if pN0; 31/51 (61%) versus 14/51 (27.5%) were in the intermediate risk group, and only 5/51 (10%) versus 34 (67%) in the low risk group. For LumB tumors, the switch in the probability of distant recurrences was 29% to 17% according to pN categorization and and the median ROR score moved from 60 to 15 with 36/37(97.3%) of Lum B tumors considered as high risk if pN1but only 13/37(35%) ifp N0; 1/37 versus 20/37 (54%) were in the intermediate risk group, and none of the 37 LumB versus 1 in the low risk group. Conclusion With regards to Prosigna test in pN1mi BC - and the persistent debate as to whether they should bear the same weight as pN1 pN0 tumors - categorization in ROR risk group is likely to be impacted by the node factor weight, and more importantly among Lum B tumors. Citation Format: Charafe-Jauffret E, Duprez-Paumier R, Berghian A, Penault-Llorca F, Dauplat MM, Boucraut A, Cohen M, Houvenaeghel G, Maroc C, Pradines A, Cayre A, Etancelin P, Lacroix-triki M. Prosigna prognostic signature in pN1mi, estrogen receptor-positive breast cancer:the pN categorization impacts the BC risk stratification [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-10.

Rafael da Silva Sá,1,2 Angela Flávia Logullo,3 Simone Elias,1 Gil Facina,1 Vanessa Monteiro Sanvido,1 Afonso Celso Pinto Nazário1 1Department of Gynaecology, Breast Surgery Team, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; 2Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, Brazil; 3Department of Pathology, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilCorrespondence: Rafael da Silva SáDepartment of Gynaecology, Breast Surgery Team, Universidade Federal de São Paulo (UNIFESP), Rua Marselhesa, 249, São Paulo, SP, CEP 04020-060, BrazilTel +55 11 55764848Email rafasamed@hotmail.comBackground: Mammography screening has become widely spread and provided a marked increase in ductal carcinoma in situ (DCIS) diagnosis. In DCIS, the ductal epithelium proliferates without invasion through the basal cell membrane. However, histologic underestimation can happen in some cases.Objective: To analyze the rate of histologic underestimation (histopathologic results upgraded to invasive carcinoma after surgery) and the rate of positive results of sentinel lymph node biopsy (SLNB) in patients diagnosed with DCIS in a Brazilian public hospital.Methods: We reviewed medical records of all consecutive patients admitted between 2009 and 2013 whose initial diagnosis was DCIS through core needle biopsy. DCIS cases with a high risk of invasion underwent SLNB. We excluded cases with invasion or micro-invasion components in the first biopsy.Results: A total of 86 women were included, most with microcalcifications as the primary radiological lesion (73.2%), and underwent preoperative biopsy, with an invasive component in 21 (24.4%) in the final pathology report. Most had invasive carcinoma of no special type (NST): 52.3% (n = 11) and microinvasive tumors (7 cases, 33.3%). The main factors associated with histologic underestimation were nodular lesion (61.9%, p< 0.001) and an ultra-sonography-guided biopsy (71.4%, p=0.0005). The positivity rate of SLNB was 4.3%. All these patients underwent mastectomy, and the initial histologic pattern was solid DCIS.Conclusion: The “histologic underestimation” rate among patients with DCIS was not low, and less than 5% of patients who underwent SLNB had axillary positivity. This result suggests that patients who have DCIS and a high risk of invasion and undergoing mastectomy should have SLNB. As to the patients who will undergo lumpectomy, SLNB could be omitted and could be performed if patients have upgraded to invasive breast cancer.Keywords: breast cancer, ductal carcinoma in situ, underestimation rates, positive sentinel lymph node

BackgroundMucinous breast cancer (MBC) is a rare histological type of breast cancer characterized primarily by the production and extracellular presence of mucin and it is usually associated with a better prognosis than other invasive breast neoplasms. Because of the low prevalence, MBC biology is not well understood. MethodsThe aim of the present study was to introduce the last 2-year experience regarding MBC pathological diagnostics in our clinical center and comparison of the obtained data with invasive breast carcinoma of no special type (NST) comprising the most common invasive breast cancer. ResultsWe identified 24 MBC cases representing 3.09% of all 766 invasive breast cancers, including 15 cases of pure type and 9 mixed MBCs. The median MBC patients’ age at presentation was 65.5 years. In comparison to NST, MBC presented a higher T stage with a statistically larger tumor median size, although lower regional lymph node involvement, tumor histological grade and TNM stage. ConclusionMBC is a rare type of breast cancer accounting for about 4% of all diagnosed breast cancers. Our findings are consistent with those published in recent years and show significant differences between MBC and NST cancer patients and also highlight differences between pure and mixed MBC emphasizing the essence of their differentiation. MBC is associated with a better long-term prognosis than NST and is characterized by the less aggressive biological behavior expressed through favorable clinicopathologic features in terms of tumor grade, regional lymph node involvement and hormone receptor status.

To date, there is indisputable evidence of significant CTC heterogeneity in carcinomas, in particular breast cancer. The heterogeneity of CTCs is manifested in the key characteristics of tumor cells related to metastatic progression – stemness and epithelial–mesenchymal (EMT) plasticity. It is still not clear what markers can characterize the phenomenon of EMT plasticity in the range from epithelial to mesenchymal phenotypes. In this article we examine the manifestations of EMT plasticity in the CTCs in breast cancer. The prospective study included 39 patients with invasive carcinoma of no special type. CTC phenotypes were determined by flow cytometry before any type of treatment. EMT features of CTC were assessed using antibodies against CD45, CD326 (EpCam), CD325 (N-cadherin), CK7, Snail, and Vimentin. Circulating tumor cells in breast cancer are characterized by pronounced heterogeneity of EMT manifestations. The results of the study indicate that the majority of heterogeneous CTC phenotypes (22 out of 24 detectable) exhibit epithelial–mesenchymal plasticity. The variability of EMT manifestations does not prevent intravasation. Co-expression of EpCAM and CK7, regardless of the variant of co-expression of Snail, N-cadherin, and Vimentin, are associated with a low number of CTCs. Intrapersonal heterogeneity is manifested by the detection of several CTC phenotypes in each patient. Interpersonal heterogeneity is manifested by various combinations of CTC phenotypes in patients (from 1 to 17 phenotypes).

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

Insulinoma-associated protein-1 (INSM1), a transcription factor encoded by the insulinoma associated-1 gene, is a second-generation biomarker of neuroendocrine differentiation. Its sensitivity and specificity in comparison with chromogranin-A and synaptophysin have been extensively validated in several organs, but evidence regarding its expression in mammary neoplasms is limited. In this study, INSM1 immunohistochemistry was validated in a cohort of 22 mammary neoplasms, enriched with special type breast carcinomas with known neuroendocrine differentiation as determined by immunohistochemistry for synaptophysin and chromogranin-A. Subsequently, INSM1 expression was evaluated in a consecutive series of 66 invasive breast cancer biopsies. In the validation cohort, 14 tumors were synaptophysin-positive, of which all but one showed INSM1 immunoreactivity. Eight tumors were synaptophysin-negative, of which 3 showed focal nuclear INSM1 expression. Six tumors were chromogranin-A-positive, of which one was INSM1-negative. When compared with synaptophysin, INSM1 seems more sensitive but less specific than chromogranin-A. In the biopsy cohort, only one invasive carcinoma of no special type showed substantial INSM1 immunoreactivity (ie, 25% of the tumor cells). Three more cases showed 1% nuclear INSM1 staining. We conclude that neuroendocrine differentiation in invasive breast carcinoma of no special type is a rare finding. Immunohistochemical biomarkers, comprising INSM1 as well as the first-generation biomarkers chromogranin-A and synaptophysin, are useful to distinguish neuroendocrine differentiation in breast neoplasms. The identification of neuroendocrine differentiation can be helpful to establish the diagnosis of special type breast carcinomas such as solid papillary carcinoma.

Introduction/Background The use of trastuzumab in the treatment of HER2-positive breast cancer has changed the natural history of this disease. Trastuzumab was approved as a component of neoadjuvant treatment as well as adjuvant and metastatic. Biosimilars demonstrate chemical similarity and clinical efficacy to a reference product and are an option to provide access to high-quality systemic therapy alternatives. Methodology This is a retrospective observational study revising patients treated with neoadjuvant therapy with trastuzumab (proposed biosimilar or trastuzumab) between january 2017 (period of introduction of the drug in our institution) - january 2020. All patients were treated with the same trastuzumab biosimilar drug. Results Twenty-two patients (n=22) were included, with mean age at diagnosis of 55 years (range 31–84). Fifteen (n=15) patients were treated with proposed biosimilar and 7 patients with trastuzumab. Regarding histologic type, 82% (n=18) of patients had invasive carcinoma of no special type (NST), 5% (n=1) apocrine, 5% (n=1) invasive lobular and 5% (n=1) mucinous carcinomas. Sixteen patients had HER2 positive, hormone receptor (HR) positive tumors and 6 patients a HER2 positive, HR negative tumors. Regarding treatment, 86% of patients were treated with anthracyclines and in 5% (n=1) pertuzumab was used. In the trastuzumab group, 2 patients presented grade 1 toxicity (heart failure); in the proposed biosimilar group, 2 patients presented grade 1 toxicities (heart failure and dyspnea). Infusion reactions were not documented, namely hyperthermia. Axillary pCR was achieved in 86% (n=6) and 53% (n=8) in trastuzumab and proposed biosimilar groups respectively. Breast pCR was achieved in 86% (n=6) and 33% (n=5) in trastuzumab and proposed biosimilar groups respectively. There was no statistically significant difference between the proposed biosimilar versus trastuzumab for toxicities, achievement of axillary and breast pCR. Conclusion The use of trastuzumab compared with the proposed biosimilar resulted in an equivalent axillary and breast pCR. Our results are concordant with the clinical trial results performed and support the evidence for their continued use. Disclosures No disclosure.

Purpose To evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands. Methods We selected all women from the Netherlands Cancer Registry diagnosed with invasive breast cancer (a) between 2011 and 2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was subdivided into an MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan–Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratios (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed. Results Of the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4004 (13%) with ILC. Of the 2464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. The distribution of breast MRI use was significantly lower over different age categories, from 49.0% aged 70. Multivariable Cox regression showed that breast MRI was not significantly associated with OS overall (HR 0.91, 95%-CI 0.74–1.11, p = 0.35), nor in the different histological subtypes. Multivariable Cox regression analysis showed that breast MRI was also not significantly associated with DFS (HR 1.16, 95%-CI 0.81–1.67), nor in the different histological subtypes. Conclusion Use of breast MRI was not significantly associated with an improved OS or DFS in patients treated with primary surgery.

Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an indicator for poor prognosis in patients with invasive breast carcinomas, but little is known about its clinical significance in node-negative breast cancer patients with hormone receptor (HR) + /HER2 − subtype, who are expected to have a favorable prognosis. Immunohistochemical analyses were performed on 169 resected specimens of node-negative invasive carcinoma of no special type with HR + /HER2 − subtype using antibodies for podoplanin. When more than 10% of CAFs showed immunoreactivity with podoplanin as strong as that of internal positive controls, the specimens were judged as podoplanin-positive. Podoplanin-positive status in CAFs was observed in 16.0% (27 of 169 cases) and it associated with high Ki67 labeling index (LI) (> 30%) (p = 0.03), higher stromal tumor-infiltrating lymphocytes (p

The research looks at concentrations of proteins and cytokines in blood cell supernatants as well as expression of histological markers of atypical cells in the breast diseases. Also, it examines the correlation between concentrations of proteins and cytokines and histological markers of atypical cells. It is found that concentration of histidine rich glycoprotein in blood cell supernatants in the invasive carcinoma of no special type is higher compared to benign breast diseases. Furthermore, the research observes the following statistical relationships: negative correlation between concentrations of estrogen receptor-α and expression of integrin β-1; positive correlation between concentrations of histidine rich glycoprotein and expression of type II collagen; positive correlation between concentrations of e-cadherin and expression of e-cadherin; and positive correlation between concentrations of plasminogen activator inhibitor-1 and expression of type II collagen. Cytokines production by blood cells is identified as Index of the influence of polyclonal activators (combination of mitogens). The research shows the difference in the Index of influence on IL-1RA and TNF-α production between benign breast diseases with high-risk and low-risk of malignant transformation, and between benign breast diseases with high-risk of malignant transformation and breast cancer with lymph node metastasis. The Index of the influence of polyclonal activators on IL-1RA production gets higher as disease prognosis worsens. As blood and tumor samples show, patients with benign breast diseases have negative correlation between index of the influence of polyclonal activators on IL-1RA production and expression of type II collagen. Additionally, patients with breast cancer, as well as breast cancer with lymph node metastasis have positive correlation between expression of e-cadherin and spontaneous and polyclonal activator-stimulated IL-1RA production. The results of the research showed that concentrations of histidine rich glycoprotein and IL-1RA in blood cells supernatant and expression of e-cadherin can be used as markers for early diagnosis of benign breast diseases with risk of malignant transformation.

Objective: Basal markers [cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR)] are used in identifying the basal-like breast carcinoma subtype, which is associated with a poor prognosis. However, the clinicopathological significance in early-stage invasive carcinoma of no special type (IC, NST) has not been well established. Material and Method: In a five-year period, 133 female patients with early-stage IC, NST with a median follow-up time of 89 months were included. The immunohistochemistry-based molecular subtypes were identified according to ASCO/CAP guidelines in 2013. The cutoff values for basal positivity were determined as 10% for each marker. Results: Basal positivity was recorded in 83.3% (5/6) of triple-negative breast cancers, 50% (2/4) of HER2-enriched, 18.6% (13/70) of luminal B, and 8.3% of luminal A (4/48) subtype. CK5/6 and EGFR positivity were significantly associated with ER negativity (p < 0.001). EGFR positive cases were significantly associated with PR negativity and HER2 positivity compared to negative cases. However, basal positivity was not associated with the patient outcome (p = 0.006 and p = 0.004, respectively). Conclusion: Basal positive IC, NSTs were associated with hormone receptor negativity and HER2 overexpression; these patients would therefore be less likely to respond to hormonotherapy and more likely to benefit from anti-HER2 treatment as well as dual-kinase inhibitors. The lack of standardization of the definition of basal marker positivity may contribute to the conflicting results of prognostic studies. Hence, further studies focusing on developing a standard protocol for determining basal marker positivity are needed not only for IC, NST but also for other histological types of breast cancer.

Objective: This study evaluated the histopathological features of ductal carcinoma in situ (DCIS), including cytological grade, architectural pattern and immunohistochemistry (IHC) in pure DCIS and DCIS associated with invasive carcinoma of no special type (ICNST). Methods: We evaluated a series of 232 cases of pure DCIS and DCIS associated with ICNST from a total of 399 breast carcinomas from a population consisting by women diagnosed with breast cancer and submitted to breast surgery from 2011 to 2015. Results: DCIS presented a mixed architectural pattern in most cases (56%); the solid subtype was the most common morphology (30%). High-grade DCIS was identified in 84/221 cases (38%), and comedonecrosis was present in 106/221 cases (48%). High-grade was more common in the solid subtype (61/155 cases, 39%, p < 0.001). Tumor size was greater in the presence of comedonecrosis than in the absence (mean 27 vs 20 mm, p = 0.009). Estrogen receptor (ER) was positive in 81% of cases with a cribriform pattern (p = 0.013). Greater locoregional recurrence was found in the comedonecrosis (15%) and micropapillary (19%) subtypes in DCIS associated with ICNST. Conclusion: We observed a greater relationship of ER with the low nuclear grade, while Ki-67 was related to the high-grade. DCIS presented a higher nuclear grade compared to ICNST. The less common pure pattern was the micropapillary, and the most common, the solid. Comedonecrosis was more frequent in the solid pattern. Our results showed that high-grade was more common in the solid and comedo subtype, and low-grade was more frequent in the cribriform.

Breast cancer is a heterogeneous disease with various histopathologic subtypes. Except for invasive carcinoma of no special type (NST), other subtypes are rare with limited data. The purpose of this study was to analyze the characteristics and prognosis of special histopathologic subtypes of breast cancer compared to NST. A total of 136,140 patients were analyzed using the Korean Breast Cancer Society Registry database between January 1996 and March 2019. The clinicopathologic features and survival outcomes of special type breast carcinoma were compared with those of NST. The prevalence of special subtypes other than NST was 13.7% (n = 18,633). Compared to NST, patients with lobular, medullary, metaplastic, and micropapillary carcinoma had larger tumors (p

CD34+ fibroblasts are constitutive stromal components of virtually all organs, including the mammary stroma, being involved in matrix synthesis, antigen presentation, and tumor-associated stromal remodeling. The most common subtype of invasive breast carcinoma, invasive carcinoma of no special type (IBC-NST), is known for its stromal loss of CD34+ fibroblasts while acquiring alpha smooth muscle actin-positive (α-SMA+) myofibroblasts, i.e., cancer-associated fibroblasts (CAF), whereas invasive lobular carcinoma (ILC) displays partial preservation of CD34+ fibroblasts. The aim of this study was to evaluate the prognostic relevance of stromal CD34+ fibroblasts and α-SMA+ myofibroblasts in an extended collection of ILC. A total of 133 cases of ILC, primarily resected between 1996 and 2004 at University Hospital Marburg, were examined semiquantitatively for stromal content of CD34+ fibroblasts and α-SMA+ myofibroblasts. Partial preservation of CD34+ fibroblasts in the tumor stroma of ILC was confirmed. Absence of CD34+ fibroblasts in the tumor stroma significantly correlated with the presence of α-SMA+ myofibroblasts (p = 0.010), positive lymph node status (p = 0.004), and pN stage (p = 0.006). Stromal loss of CD34+ fibroblasts was significantly associated with lower overall and disease-free survival rates (p = 0.012 and 0.013, respectively). Multivariate analysis adjusted for pT and pN stage revealed stromal loss of CD34+ fibroblasts as independent prognostic parameter (p = 0.05). To our knowledge, this is the first report defining prognostically relevant stromal subtypes of ILC with long-term follow-up. Future research targeting the potential diagnostic and therapeutic implications of CD34+ fibroblasts and CAF in breast cancer, especially ILC, is a promising field of interest.

Background Incidence of breast cancer in India is on raise and shows a 3–4 fold variation across the country. Materials and methods In this retrospective study, a total of n=181 histopathologically confirmed breast cancer cases who visited the tertiary Government hospitals during the period March 2016 to March 2017 were studied. Results Majority of the patients (n=108) are of the age group 40 to 59 years. Most of the women (n=112, 61.9%) belong to the Socio-economic class of Backward caste. Right breast is the common site of occurrence of breast cancer. Histological Grade II (n=95, 59.0%) is highly predominant. Invasive carcinoma of no special type (NST), is the most common histological type of breast tumor in 173 (95.6%) patients. Clinical stages of T2 (n=76, 42%), N1 (n=68, 37.6%) and M0 (n=163, 90.1%) were the most common stages. Triple negative breast cancer was noticed in (n=24, 28.9%) out of 83 patients analysed. Modified radical mastectomy (n=134, 74.0%) is the common surgical procedure followed in treating breast cancer. The total claim amount paid ranged from Rs. 10000 to 49999/- (US$ 154.98 -US $ 774.88) with the Mean cost incurred being Rs. 48,477/- (± Rs. 29,082 SD) which equals to US$ 748.97. Conclusion Majority of the patients are diagnosed at a later stage due to lack of awareness and access to preventive diagnostic services. Region specific research and planning evidence based preventive programs is the need of the hour.

Tumor deposits (TD) are irregular discrete tumor masses in adipose tissue, discontinuous from the primary tumor, that are described in various cancers. The incidence and/or prognostic value of TD in breast carcinomas have not been studied so far. We reevaluated 145 breast cancer patients, diagnosed and treated between 2001 and 2006 at our institution for the presence and incidence of TD. Histologic type, grade, size of the primary tumor, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 status of the tumor, and presence of peritumoral lymphovascular invasion were included in the data. TD were detected in 42 cases (29.0%). The mean age of the patients was 52.2 years (27-82). Most patients (79.3%) had either invasive carcinoma of no special type (NST) or invasive lobular carcinoma, and most tumors (86.9%) were either grade 2 or 3. After excluding TD from the number of metastatic lymph nodes, the pN status of 9 patients changed. Univariate analysis of 110 patients with follow-up information revealed that the new pN status (p = 0.036), presence of local recurrence (p = 0.016) and TD (p = 0.003) were significantly correlated with distant metastases. The median follow-up of the patients was 84 months (5-161), 10-year disease-free survival and overall survival were 67.2% and 73.7%, respectively. In multivariate analysis, presence of TD remained independently associated with distant metastasis (p = 0.002). The probability of distant metastasis was 3.3 times higher in patients with TD. These results emphasize that TD are present in breast cancer patients, and that their presence should warn the clinician in terms of possible distant metastasis. Therefore, presence of TD, the evaluation of which is neither time consuming nor require sophisticated methods, should be included in pathology reports.

The present study aimed to investigate the correlation between histologic grade and shear-wave elastography in evaluating invasive breast carcinoma of no special type (NST). A total of 84 breast lesions in 80 patients (age range, 32-64 years) were retrospectively evaluated. The patients underwent B-mode ultrasound and virtual touch tissue quantification diagnosis. A semi-quantitative method was then applied in order to determine the histologic grade of the invasive carcinoma of NST according to the grading system published by the World Health Organization. Among the 84 breast lesions, 14 (16.7%) were classified as Grade I, while 29 (34.5%) and 41 (48.8%) were determined to be of Grade II and Grade III, respectively. The size of the breast lesions increased with the increase in histological grade (P

Background CXCR4 is a chemokine receptor frequently overexpressed in invasive breast cancer that has been shown to play a major role in signaling pathways involved in metastasis. The aim of this retrospective analysis was to assess the diagnostic performance of CXCR4-directed PET imaging in patients with breast cancer using the recently introduced CXCR4-targeted PET probe 68Ga-Pentixafor. Results Thirteen patients with first diagnosis of breast cancer, four patients with recurrent disease after primary breast cancer, and one patient with axillary lymph node metastasis of unknown primary underwent CXCR4-targeted PET imaging using 68Ga-Pentixafor. Maximum standardized uptake values (SUVmax) and tumor-to-background (T/B) ratios of tumor lesions were measured and compared with pathological prognostic factors and molecular subtypes. 18F-FDG PET/CT images were available in 8/18 cases and were compared semi-quantitatively. Comparison with CXCR4 expression determined by immunohistochemistry was performed in 7/18 patients. Nine of 13 primary breast cancers were visually detectable on 68Ga-Pentixafor PET images (mean SUVmax of 3.0). The visually undetectable lesions included both cases of invasive lobular carcinoma (ILC) and two cases of invasive carcinoma of no special type (NST) without any hormone receptor and HER2 expression (triple negative). Metastases of recurrent breast cancer and unknown primary cancer were visually detectable in all five cases, exhibiting a mean SUVmax of 3.5. 18F-FDG PET demonstrated higher SUVmax in all patients compared to 68Ga-Pentixafor PET. A correlation between SUVmax obtained from 68Ga-Pentixafor PET and prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, proliferation index, tumor grade, or molecular subtypes was not observed. Conclusions CXCR4-directed PET imaging in patients with primary and recurrent breast cancer is feasible; however, tumor detectability is significantly lower compared to 18F-FDG PET. Moreover, we did not find any correlation between aforementioned prognostic factors of breast cancer and CXCR4-targeted tracer accumulation. Based on these results in a small patient cohort, CXCR4-targeted PET imaging does not seem to be suitable as a general diagnostic tool for imaging of breast cancer. Future CXCR4 imaging studies should investigate whether this modality might be useful in more specific applications, e.g., in therapeutic approaches especially under the view of current developments in targeted immune cell and immune checkpoint inhibitory therapy.

Objective To investigate the optimal acquisition time of contrast-enhanced cone-beam breast-CT (CBBCT) for best discrimination of breast lesion malignancy and whether contrast enhancement can aid in classification of tumor histology. Material and methods The study included patients with BI-RADS 4 or 5 lesions identified on mammography and/or ultrasound. All patients were examined by non-contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) at 2 and 3 min after contrast media (CM) injection. Lesion enhancement of suspicious breast lesions was evaluated in corresponding CBBCT slices. Results A total of 31 patients with 57 breast lesions, 30 malignant and 27 benign, were included. Malignant breast lesions demonstrated higher contrast enhancement than benign breast lesions at both 2 min and 3 min CE-CBBCT (2 min: 48.17 vs. 0.3 HU, p

The authors read with attention the case report by Vande Berg and coworkers, published on a previous issue of this journal, describing a rare diagnosis of rectal metastases of an incognito invasive lobular breast carcinoma (ILC), for which immunohistochemistry was decisive (1). Likewise, we share a similarly rare case of gastrointestinal metastases of breast carcinoma (BC), in which immunohistochemistry played a pivotal role.A 55-year-old woman was diagnosed in June 2015 with an Invasive Breast Carcinoma of no-special-type (IBCNST) grade III, human epidermal growth factor receptor 2 (HER2) positive, estrogen and progesterone receptors (ER/PR) negative. Biopsy revealed vascular permeation. Neoadjuvant chemotherapy and trastuzumab preceded surgery, performed in December 2015, followed by radiotherapy and trastuzumab. The patient remained free of disease until 2017, when a right cerebellar lesion was diagnosed as BC metastasis and was treated with stereotactic radiosurgery. In January 2020, the patient presented with a 1-month history of post-prandial vomiting, epigastric pain, anorexia, fatigue, and a 10 kg weight loss. Lab tests were unremarkable, except for small increase in CA-125 and CA-15.3.