Subtypes Of Invasive Ductal Carcinoma Research Articles

Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.

Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the -means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised -means algorithm. The unsupervised -means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within residual error margin. Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.

Comprehensive proteome, phosphoproteome and kinome characterization of luminal A breast cancer.

Breast cancer is one of the most frequently occurring malignant cancers worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histological subtypes of breast cancer. In this study, we aimed to deeply explore molecular characteristics and the relationship between IDC and ILC subtypes in luminal A subgroup of breast cancer using comprehensive proteomics and phosphoproteomics analysis. Cancer tissues and noncancerous adjacent tissues (NATs) with the luminal A subtype (ER- and PR-positive, HER2-negative) were obtained from paired IDC and ILC patients respectively. Label-free quantitative proteomics and phosphoproteomics methods were used to detect differential proteins and the phosphorylation status between 10 paired breast cancer and NATs. Then, the difference in protein expression and its phosphorylation between IDC and ILC subtypes were explored. Meanwhile, the activation of kinases and their substrates was also revealed by Kinase-Substrate Enrichment Analysis (KSEA). In the luminal A breast cancer, a total of 5,044 high-confidence proteins and 3,808 phosphoproteins were identified from 10 paired tissues. The protein phosphorylation level in ILC tissues was higher than that in IDC tissues. Histone H1.10 was significantly increased in IDC but decreased in ILC, Conversely, complement C4-B and Crk-like protein were significantly decreased in IDC but increased in ILC. Moreover, the increased protein expression of Septin-2, Septin-9, Heterogeneous nuclear ribonucleoprotein A1 and Kinectin but reduce of their phosphorylation could clearly distinguish IDC from ILC. In addition, IDC was primarily related to energy metabolism and MAPK pathway, while ILC was more closely involved in the AMPK and p53/p21 pathways. Furthermore, the kinomes in IDC were primarily significantly activated in the CMGC groups. Our research provides insights into the molecular characterization of IDC and ILC and contributes to discovering novel targets for further drug development and targeted treatment.

Abstract P2-23-11: Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases

Abstract Background: Invasive ductal carcinoma (IDC) accounts for ~80% of all invasive breast carcinomas (IBC) with several histologic subtypes comprising the remainder of cases. Some histologic subtypes of IDC (such as tubular carcinoma) have been associated with better prognosis, while other subtypes (such as metaplastic and micropapillary) have been associated with poorer prognosis. Prior studies have shown patients with early stage, hormone-receptor positive IBC that have low Recurrence Score® (RS), as measured by the 21-gene Oncotype DX® (ODX) assay, have little benefit from chemotherapy. Here, we report our experience with the histologic subtypes of IDC and associated patterns of observed gene expression using ODX. Methods: All US samples submitted for IBC ODX between 2005 to 2021 were reviewed. Ductal carcinoma NOS (DC), tubular carcinoma (TC), cribriform carcinoma (CC), mucinous carcinoma (MUC), lobular carcinoma classic, solid or alveolar type (ILC), pleomorphic lobular carcinoma (PL), medullary/medullary-like carcinoma (MED), metaplastic carcinoma (MET), micropapillary carcinoma (MP), papillary carcinoma (PC) and solid papillary carcinoma (SPC) were included. Quantitative expression of 16 cancer-related genes was measured on a scale from 2 to 15 (relative to reference genes) where 1 unit increment is associated with ~2-fold change in expression. RS was calculated as published. Descriptive statistics for the RS, individual genes (ER, PR, HER2), and gene groups [invasion gene group (IGG) and proliferation gene group (PGG)] were obtained. Results: A total of 957,624 samples were included in this analysis with 85.4% DC, 9.7% ILC, 2.8% MUC, 0.5% TC, 0.4% PL, 0.4% PC, 0.3% MP, 0.2% CC, 0.2% MED, 0.1% SPC, and 0.02% MET. For all types, a wide continuous range of RS was noted. MET had the highest median RS, followed in decreasing order by MED, PL, DC & ILC, TC, MUC, MP, CC, SPC, and PC. ER and PR were highest among PC and SPC. ER and PR were lowest among MED and MET. HER2 was highest among PC and TC and lowest among MED and MET. IGG was highest in MET and lowest in SPC. PGG was lowest for TC and highest for MED and MET. ER+/PR-/HER2- phenotype occurred more often in MED and PL. ER-/PR+/HER2- phenotype rarely occurred, but was most frequent in MED and MET. ER+/PR+/HER2+ accounted for 0.4% of our total sample. Conclusions: Here, we demonstrate histologic subtypes of IDC have a wide continuous range of RS. ODX assay may be used to further stratify patients with IDC and its histologic subtypes; however, further studies are needed to better understand the predictive capability of ODX in the histologic subtypes. Table 1. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma Table 2. Biomarker profile in histologic subtypes of invasive breast carcinoma Citation Format: Nhu Thuy Can, Cynthia A. Flannery, Jess Hoag, Alekhya Akkunuri, Helen Bailey, Frederick Baehner. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-11.

Prediction of Clinical Molecular Typing of Breast Invasive Ductal Carcinoma Using 18F-FDG PET/CT Dual-Phase Imaging

To investigate the diagnostic value of Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (18F-FDG PET/CT) dual-phase imaging for the different molecular subtypes of invasive ductal carcinoma of the breast. Clinical imaging data of 164 women with invasive ductal carcinoma of the breast confirmed by pathology who underwent 18F-FDG PET/CT dual-phase imaging were retrospectively analyzed. The maximum standard uptake values (SUVmax) of the early and delayed phases of the lesion were measured and recorded as SUVmax1 and SUVmax2, respectively, and the retention index (RI) was calculated. We analyzed the change rule of SUVmax1, SUVmax2, and RI for the different molecular subtypes and molecular marker expression groups. The diagnostic threshold of different molecular marker expression status was determined using receiver operating characteristic curve analysis. SUVmax1 and SUVmax2 were highest in the TNBC group and lowest in the luminal A group (p<0.001). TNBC and HER2 overexpression groups had higher RI than the luminal A and B groups (p<0.001), with no significant difference between the TNBC and HER2 overexpression groups or between the luminal A and B groups (p=0.640 and 0.345, respectively). The ER- and PR-negative groups had significantly higher SUVmax1, SUVmax2, and RI than the PR-positive group (p<0.001). The HER2-positive group had higher SUVmax1 and SUVmax2 than the negative group (p<0.001). The Ki67 overexpression group had higher SUVmax1 and SUVmax2 levels than the low expression group (p<0.001). There was no significant difference in RI between HER2-positive and negative groups or between Ki67 high and low expression groups (p=0.904 and 0.216, respectively). For ER-negative and positive expression status, the maximum area under the curve (AUC) of SUVmax2 was 0.852, diagnostic threshold was 10.87, sensitivity was 79.6%, and specificity was 74.5%. For PR-negative and positive expression status, the AUC of SUVmax2 was 0.858, diagnostic threshold was 10.45, sensitivity was 83.1%, and specificity was 75.3%. For HER2-negative and positive expression status, the AUC of SUVmax1 was 0.714, diagnostic threshold was 9.28, sensitivity was 79.6%, and specificity was 60.9%. For Ki67 high- and low expression status, the AUC of SUVmax2 was 0.915 at maximum, diagnostic threshold was 10.21, sensitivity was 83.4%, and specificity was 93.9%. 18F-FDG PET/CT dual-phase imaging facilitates the prediction of the expression of molecular markers and subtypes of invasive ductal carcinoma of the breast and the development of more tailored treatment plans for patients with this disease.

Case Report: Invasive micropapillary ductal breast carcinoma

Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare variant of invasive ductal breast carcinoma (IDC), with most cases characterized by lymph node metastasis and lymphatic vascular invasion. It is a ductal breast cancer subtype with a very high risk of recurrence and therefore requires special attention from breast cancer physicians and radiologists. Case: We present a case of an IMPC that has been followed up for two years since diagnosis and management. Based on clinical breast examination, ultrasound, and mammography, the initial diagnosis was a suspicious mass that required further investigation. Radiological and histological findings informed the diagnosis of a highly suspicious lesion, which turned out to be IMPC. The patient underwent surgery, left mastectomy with nodal dissection. During the 24-month follow-up, ultrasound and mammography revealed no evidence of local recurrence or involvement of the contralateral breast. Conclusions: This case reveals that invasive micropapillary carcinoma is a distinct but poorly recognized variant and subtype of invasive ductal carcinoma.

A Diagnostic Revelation: Case of a Mucinous Carcinoma of the Breast.

Mucinous or colloid cancers are a rare subtype of invasive ductal carcinoma, making up only 2-3% of infiltrating carcinomas. Prevalence of pure mucinous breast cancer(PMBC) among infiltrating duct carcinomas in less than 60year olds is 2-7%, and in less than 35year olds, it is 1%. Mucinous carcinoma of the breast is divided into 2 subtypes, the pure type and mixed type. PMBC is characterized by a lower incidence of nodal involvement, favourable histological grade, and higher ER/PR expression. Axillary metastases are rare, though found in 12-14%. It has a better prognosis than infiltrative ductal cancer with 10-year survival being more than 90%. Here is the case of a 70-year-old female who presented with lump in the left breast since 3years. On examination, we detected a left breast lump occupying the whole breast except lower outer quadrant, measuring 10 × 8cm with overlying skin stretched with puckering and engorged veins seen, nipple displaced laterally and higher by 1cm, firm to hard in consistency, and mobile with breast tissue. Sonomammography, mammography, FNAC and biopsy were suggestive of benign phyllodes tumour. Patient was hence posted for simple mastectomy on the left side with removal of attached lymph nodes (near axillary tail). Histopathological examination revealed pure mucinous breast carcinoma with nine lymph nodes, free from tumour and showing reactive hyperplasia. Immunohistochemistry studies demonstrated ER + , PR + , HER-2-NEU-. The patient was started on hormonal therapy. Therefore, mucinous carcinoma of the breast is a rare entity with imaging features sometimes mimicking a benign tumour such as Phyllodes tumour, hence making it important to include it as a differential diagnosis in our daily practice. It is especially important in the subtyping of carcinoma of the breast since it carries a favourable risk profile with less chances of lymph node involvement, higher hormone receptor positivity and good response to endocrine treatment.

Defining transcriptomic profiles of early-stage mucinous breast cancers: A FLEX sub study.

3134 Background: Mucinous breast cancer (MuBC) is a rare subtype of invasive ductal carcinoma (IDC) that accounts for less than 2% of all breast cancers and is associated with a favorable prognosis. Since MuBCs are rare in clinical trials, current treatment guidelines are extrapolated from IDC-no special type (IDC-NST). To provide better understanding of MuBCs and factors contributing to their clinical behavior, we examined the transcriptomic profiles of MuBCs in our FLEX study. Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III breast cancer patients who receive MammaPrint (MP)/BluePrint (BP) testing and consent to full transcriptome and clinical data collection. For this study, histologically confirmed MuBCs (n = 102) in the FLEX database were included. All patients examined were ER+/HER2- by immunohistochemistry and Luminal by BP. MuBC was compared with IDC matched for Age, MP, and BP index (n = 97). Differential gene expression analyses (DGEA) were performed with R package ‘limma’ and differentially expressed genes (DEGs) were considered significant if they had an adjusted p &lt; 0.05 and fold change ≥ 2. Results: DGEA comparing MuBC (n = 102) with IDC (n = 97) revealed 60 DEGs, regardless of the genomic risk, of which 42 genes were upregulated and 18 were downregulated in MuBC relative to IDC. Genes associated with MuBC, such as MUC2, TFF1, CARTPT were among the upregulated genes. Of the 102 MuBC patients, 56 were Luminal A (MP Low Risk-LR) and 46 were Luminal B (MP High Risk-HR) by MammaPrint and BluePrint. Comparison of LR MuBC with LR IDC revealed 111 DEGs. Functional enrichment showed upregulation of pathways involved in estrogen response (early &amp; late) and androgen response and a downregulation of the epithelial to mesenchymal transition (EMT) and E2F pathways in LR MuBC compared to LR IDC. DGEA between HR MuBC and HR IDC revealed only 22 DEGs with immune pathways being downregulated in HR MuBC. DGEA comparing LR MuBC with HR MuBC resulted in 63 DEGs, indicating LR and HR MuBC are biologically distinct types. Interestingly in LR MuBC, the tumor suppressor marker SCUBE2 is upregulated. Over expression of SCUBE2 is associated with better prognosis. Conclusions: Although MuBCs are often expected to have low clinical risk, MP revealed that half of the MuBCs examined in this study were MP High Risk (Luminal B). MP low risk MuBC is biologically different from MP low risk IDC, and downregulation of E2F and EMT pathways might lead to favorable prognoses in MP low risk MuBC. MP high risk MuBC showed limited DEGs compared to high-risk IDCs indicating these tumor types are highly genomically similar and likely to benefit from chemotherapy. The downregulation of immune pathways in MP high risk MuBC may lead to immune surveillance escape resulting in metastasis and further investigation is needed. Clinical trial information: NCT03053193.

Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.

Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE‐MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype.A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1‐min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann–Whitney U‐test was used for the statistical analysis.The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A‐like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05).The sigmoid model analysis of breast DCE‐MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A‐like breast cancer.

Comparative analysis of phenotypic features in the primary tumor, tumour buds and metastatic lymph nodes within Luminal A and Luminal B molecular subtypes of invasive ductal carcinoma of the breast

The study included 55 cases of formalin-fixed and paraffin-embedded (FFPE) tissues of breast invasive ductal carcinoma. The following algorithm has been made for further discussion by using immunohistochemical examination: antibodies against hormonal receptors; HER2; E-cadherin, Vimentin, Beta-catenin; Ki-67; Tumour buds were evaluated by using H&amp;E stained slides and computer software Qupath (version 0.3.2). The results of the study show that estrogen expression is different in primary tumour mass and in tumour buds and its expression is diminished in the Luminal B molecular subtype respectively. Vimentin and Beta-catenin expression is showing similar changes, the quantity is much higher in tumour microclusters compared to the primary tumour and metastatic lymph nodes. It can demonstrate features of epithelial-mesenchymal transformation. Modifications in dynamics of proliferative activity are showing the lowest proliferative activity in tumour microclusters which can be discussed as the indirect manifestation of epithelial-mesenchymal transformation.

Diagnostic performance of superb microvascular imaging combined with shear-wave elastography in distinguishing invasive ductal carcinoma molecular subtypes

IntroductionTo explore the diagnostic value of combining superb microvascular imaging (SMI), shear-wave elastography (SWE), and Breast Imaging Reporting and Data System (BI-RADS) to distinguish different molecular subtypes of invasive ductal carcinoma (IDC).Material and methodsA total of 239 surgically confirmed IDC masses in 201 patients underwent conventional ultrasound, SMI, and SWE examination, the information such as echo pattern, posterior features, margins, SMI pixels, and hardness of the masses was recorded. According to the St. Gallen standard, breast masses were classified as Luminal A, Luminal B, HER2 overexpression, and triple-negative subtype. We further explored the differences between different molecular subtypes of IDC.ResultsLuminal A subtype had the following characteristics: low histologic grade, posterior acoustic shadowing (p= 0.019), spiculated margins (p&lt;0.001) , and relatively soft. Luminal B subtype was characterized by low histological grade (p &lt;0.0001), posterior acoustic shadowing or indifference, and indistinct margins. HER2 overexpression breast cancers were characterized by high histological grade, enhanced posterior acoustics or indifference, calcifications (p= 0.005), spiculated or indistinct margins, vascularity (p=0.005), and relative stiffness. Triple-negative breast cancers had the characteristics of high histological grade, posterior echogenic enhancement, lack of calcifications, circumscribed or microlobulated margins, low blood flow signals, and stiff tissue (p=0.013).ConclusionsOur study demonstrated the significant differences and trends among the IDC four subtypes by the combined application of SMI, SWE, and BI-RADS lexicon, which are of great significance for early diagnosis, selection of treatment methods, and evaluation of prognosis of IDC.

Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.

B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors. We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators. Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes. The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer. BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.

Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up.

Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.

Histogram analysis of quantitative parameters from synthetic MRI: Correlations with prognostic factors and molecular subtypes in invasive ductal breast cancer

PurposeTo evaluate intra-tumoral heterogeneity through a histogram analysis of quantitative parameters obtained from synthetic MRI (magnetic resonance imaging), and determine correlations of these histogram characteristics with prognostic factors and molecular subtypes of invasive ductal carcinoma (IDC). MethodsA total of 122 IDC from 122 women who underwent preoperative synthetic MRI and DCE (dynamic contrast enhancement)-MRI were investigated. The synthetic MRI parameters (T1, T2, and PD (proton density)) were obtained. For each parameter, the minimum, 10th percentile, mean, median, 90th percentile, maximum, skewness, and kurtosis values of tumor were calculated, and correlations with prognostic factors and subtypes were assessed. The Mann-Whitney U test or the Student's t test were utilized to analyze the association between the histogram features of synthetic MRI parameters and prognostic factors. The Kruskal-Wallis test followed by the post-hoc test was used to analyze differences of synthetic MRI parameters among molecular subtypes. ResultsIDC with high histopathologic grade showed statistically higher PDmaxium, T1mean and T1median values than those with low grade (p = 0.003, p = 0.007, p = 0.003). The T110th were significantly higher in cancers with PR (progesterone receptor) negativity than those with PR positivity (p = 0.005). ER-negative cancers had significant higher values of T210th, T2mean, and T2median than ER-positive cancers (p = 0.006, 0.002, and 0.006, respectively). The values of PDmedian were significantly higher in IDC with HER2 (human epidermal growth factor receptor 2) positivity than those with HER2 negativity (p = 0.001). When discriminating molecular subtypes of IDC, the T2mean achieved the highest performance. The T2mean values of TN (triple-negative), luminal B and luminal A types are arranged in descending order (p < 0.0001). ConclusionsHistogram features derived from synthetic MRI quantifies the distributions of tissue relaxation time and proton density, and may serve as a potential biomarker for discriminating histopathological grade, hormone receptor status, HER2 expression status and breast cancer subtypes.

Apocrine Breast Carcinoma - Pathohistological And Immunohistochemical Analysis, Prognosis and Complex Treatment

Apocrine breast cancer (ABC) is a rarely diagnosed pathomorphological subtype of invasive ductal carcinoma of the breast. We present a clinical case of apocrine breast cancer in a 36-year-old woman. A left-sided breast-preserving surgery (quadrantectomy am blok with underlying muscle fascia) and axillary lymph dissection at all three levels were performed. The complex treatment is continued with adjuvant chemotherapy, followed by radiotherapy of the left mammary gland. The pathomorphological and immunohistochemical characteristics of apocrine breast cancer, the prognosis and the necessary complex treatment are discussed. Immunohistochemical (IHC) analysis of apocrine carcinoma cells reported a characteristic steroid receptor profile with negative IHC expression for estrogen and progesterone receptors and positive for androgen receptors. ABC is prognostically similar to invasive ductal carcinoma / NOS. Apocrine breast cancer needs to be classified as a separate nosological unit, due to growing evidence of a different hormonal profile with different clinical behavior following androgen deprivation therapy.

The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.

Carcinoma of breast with apocrine differentiation: A distinct entity with typical histomorphology and molecular signature

Apocrine Carcinoma (APC) is a rare and distinct entity among all the histological variants of invasive ductal carcinoma(IDC) of breast. It is common to encounter focal apocrine differentiation, but only 4% of IDCs show extensive apocrine differentiation. In the 2012 WHO classification of tumors of breast, it is placed under specialized subtypes of IDC and named “carcinomas with apocrine differentiation.” Apocrine differentiation is seen with IDC-no specific type (IDC-NST) as well as in special type carcinomas such as tubular, lobular, micropapillary, and medullary and that's why it does not represent as a separate entity. Although clinical, radiological, and gross appearance is indistinguishable from IDC-NST (the most common form), APC has a typical histomorphological picture with distinct molecular apocrine signature and immunohistochemistry. It is characterized by increased androgen expression overlapping with HER2/neu expression and estrogen receptor (ER) as well as progesterone receptor (PR) negativity. It is thought to have worse prognosis; hence, diagnosing this entity at the earliest is very important for implementation of new treatment modalities. Here, we report two such cases of carcinomas with apocrine features – 47-year-old and 52-year-old patients showing features of apocrine carcinoma and positivity for androgen receptor with negativity for ER and PR.

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

PurposeStudies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications.MethodsIn total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data.ResultsEMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index.ConclusionEMP2 may be involved in the early stage of tumor development in hormone-positive breast cancer.

Differential Expression of Autophagy-Related Marker (Beclin-1) in Relation to Clinicopathological Parameters in Different Breast Cancer Molecular Subtypes

AbstractBackground: Beclin-1 plays a vital role in the vesicle nucleation in the process of autophagy and has an important role in development, tumorigenesis, and neurodegeneration.Aim of Study: Study the role of beclin-1 and correlate the degree of its expression with available clinic-pathological data in different molecular types of breast cancer.Material and Methods: Immunohistochemistry was per-formed to examine the expression of Beclin-1 different mo-lecular subtypes of invasive ductal carcinoma and correlating it to clinicopathological parameter.Results: The expression of Beclin-1 was decreased in breast cancer in relation to normal tissue. High expression was significantly correlated with tumor grade, distant metas-tasis and stage. All the cases with high Beclin-1 expression were triple negative breast cancer cases.Conclusions: Triple negative breast cancer cases showed the highest tumor stage, grade, distant metastasis and beclin-1 expression suggesting that the overexpression of Beclin 1 may by itself confer an aggressive biological course. It could be a therapeutic target.

Correlation of the Strain Elastography-Derived Elasticity Scores with Prognostic Histologic Features, Immunohistochemical Markers, and Molecular Subtypes of Invasive Ductal Carcinoma

Correlation of the Strain Elastography-Derived Elasticity Scores with Prognostic Histologic Features, Immunohistochemical Markers, and Molecular Subtypes of Invasive Ductal Carcinoma

Neoadjuvant chemotherapy reduces the expression rates of ER, PR, HER2, Ki67, and P53 of invasive ductal carcinoma.

To analyze whether neoadjuvant chemotherapy (NAC) changes the expression rates of invasive ductal carcinoma (IDC) markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and P53.This was a retrospective study of 112 IDC patients who underwent NAC (docetaxel+epirubicin/pirarubicin+cyclophosphamide) but without pathological complete response (pCR) in 2012 to 2013 at the First Affiliated Hospital of Chongqing Medical University. The IDC subtypes and tumor protein markers were analyzed by immunohistochemistry (IHC). Specific changes in tumor protein markers before/after NAC were compared.The decrease in the positive rate of Ki-67 was the most significant, from 75.9% before NAC to 41.1% after NAC (P < .001). The positive rate of HER2 decreased from 42.0% before NAC to 32.1% after NAC (P = .04). The positive rate of ER decreased from 66.1% before NAC to 56.2% after NAC (P = .04). Increased number of metastatic lymph nodes (P = .006) and body mass index (BMI) (P = .028) seemed to be related to conversion of PR (positive to negative). There was statistical association between the Ki-67 (positive to negative) with the age greater or equal to 50 (P = .015). The BMI greater or equal to 24 (P = .021), age greater or equal to 50 (P = .047), and blood type A (P = .038) were independently associated with conversion of P53 (positive to negative). The BMI greater or equal to 24 (P = .004), number of metastatic lymph nodes greater or equal to 1 (P = .029) and TNM stages I–II (P = .008) were statistically associated with change of HER2 (positive to negative).In patients without pCR, NAC leads to changes in Ki-67, HER2, and hormone receptor (HR) expression. Age, BMI, number of metastatic lymph nodes, and TNM stage are associated with some changes of markers.