PET Molecular Imaging in Breast Cancer: Current Applications and Future Perspectives.

Positron emission tomography (PET) plays a crucial role in breast cancer management. This review addresses the role of PET imaging in breast cancer care. We focus primarily on the utility of 18F-fluorodeoxyglucose (FDG) PET in staging, recurrence detection, and treatment response evaluation. Furthermore, we delve into the growing interest in precision therapy and the development of novel radiopharmaceuticals targeting tumor biology. This includes discussing the potential of PET/MRI and artificial intelligence in breast cancer imaging, offering insights into improved diagnostic accuracy and personalized treatment approaches.

Real-World Data Analysis of CDK4/6 Inhibitor Therapy-A Patient-Centric Single Center Study.

BACKGROUND: The quest to comprehend the real-world efficacy of CDK4/6 inhibitors (CDKis) in breast cancer continues, as patient responses vary significantly. METHODS: This single-center retrospective study evaluated CDKi use outside the trial condition from November 2016 to May 2020. Progression-free survival (PFS), time-to-treatment failure (TTF), short-term and prolonged treatment benefit (≥4 and ≥10 months), as well as prognostic and predictive markers were assessed with Kaplan-Meier and multivariate regression analyses. RESULTS: Out of 86 identified patients, 58 (67.4%) had treatment failure of which 40 (46.5%) were due to progression. Median PFS and TTF were 12 and 8.5 months, respectively. A total of 57 (66.3%) and 42 (48.8%) patients experienced short-term and prolonged treatment benefit. Independent, significant predictors for PFS were progesterone receptor expression (HR: 0.88), multiple metastatic sites (HR: 2.56), and hepatic metastasis (HR: 2.01). Significant predictors for TTF were PR expression (HR: 0.86), multiple sites (HR: 3.29), adverse events (HR: 2.35), and diabetes (HR: 2.88). Aside from tumor biology and adverse events, treatment modifications like pausing and switching of CDKi were predictive for short-term (OR: 6.73) and prolonged (OR: 14.27) therapeutic benefit, respectively. CONCLUSIONS: These findings emphasize the importance of tailored treatment strategies, highlighting the role of PR expression, metastatic burden, and therapeutic adjustments in optimizing patient outcomes in real-world breast cancer management.

Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Validation of a new Custom Polyclonal Progesterone Receptor Antibody for Immunohistochemistry in the Female Mouse Brain.

Immunohistochemical visualization of progesterone receptor (PR)-expressing cells in the brain is a powerful technique to investigate the role of progesterone in the neuroendocrine regulation of fertility. A major obstacle to the immunohistochemical visualization of progesterone-sensitive cells in the rodent brain has been the discontinuation of the commercially produced A0098 rabbit polyclonal PR antibody by DAKO. To address the unavailability of this widely used PR antibody, we optimized and evaluated 4 alternative commercial PR antibodies and found that each lacked the specificity and/or sensitivity to immunohistochemically label PR-expressing cells in paraformaldehyde-fixed female mouse brain sections. As a result, we developed and validated a new custom RC269 PR antibody, directed against the same 533-547 amino acid sequence of the human PR as the discontinued A0098 DAKO PR antibody. Immunohistochemical application of the RC269 PR antibody on paraformaldehyde-fixed mouse brain sections resulted in nuclear PR labeling that was highly distinguishable from background, specific to its antigen, highly regulated by estradiol, matched the known distribution of PR protein expression in the female mouse hypothalamus, and nearly identical to that of the discontinued A0098 DAKO PR antibody. In summary, the RC269 PR antibody is a specific and sensitive antibody to immunohistochemically visualize PR-expressing cells in the mouse brain.

Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.

Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions.

Cutaneous Metastasis in Breast Cancer: A Case Series.

The most frequent reason for cutaneous metastases is breast cancer in females. Breast cancer patients can present with cutaneous manifestations of breast disease at the time of their initial diagnosis; however, cutaneous metastases more often present well after the initial diagnosis and treatment of the breast disease. We described three cases of carcinoma of breast metastasis to the skin of the breast and the chest wall, each with a unique dermatological presentation. A 52-year-old woman presented with a cutaneous erythematous papule for the past month. She underwent a modified radical mastectomy one year before. On presentation, she was diagnosed to have erythematous papule near the operative scar and surrounding chest wall and referred to the dermatology outdoor department, where a skin biopsy was done, which confirmed erysipeloides carcinoma. The second case includes a 38-year-old premenopausal lady who was diagnosed with carcinoma of the right breast with a locally advanced stage. She was treated with neoadjuvant chemotherapy (NACT) followed by modified radical mastectomy and subsequently presented with biopsy-proven multiple skin nodules on the chest wall at the same side. She was discussed in a multidisciplinary tumor board and planned for palliative chemotherapy followed by hormonal therapy. In the third case, a 42-year-old perimenopausal woman diagnosed with locally advanced left breast carcinoma presented in the surgical oncology outdoor patient department (OPD) with multiple skin erythema over the left breast. Biopsy was done from the skin erythema site showing metastasis to the skin. She was discussed in a multidisciplinary tumor board and planned for systemic chemotherapy followed by assessment for surgery. Skin erythema and erythematous papules are rare manifestations of cutaneous metastasis in patients with carcinoma of the breast; typically, patients present with a chest wall nodule. Careful examination and early detection of these uncommon skin lesions can lower morbidity and slow the progression of diseases in these patients.

Prevalence of Breast Cancer Subtypes Among Different Ethnicities and Bangladeshi Women: Demographic, Clinicopathological, and Integrated Cancer Informatics Analysis.

Background: The molecular subtyping of breast cancer is related to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The present study aimed to systematically analyze the expression, function, and prognostic value of ER, PR, HER2, and their prevalence in different ethnic groups and among Bangladeshi breast cancer (BC) patients. Method: This study included 25 BC patients and 25 healthy controls, aged between 25 and 70 years. The study characteristics were compared using the ANOVA and Chi-square tests. Also, the multi-Omics dataset of 775 BC patients from TCGA was analyzed for ER, PR, and HER2 in breast cancer subtypes and compared among different ethnicities. Results: For most BD breast cancer cases, the age at diagnosis was ⩾40 years, had only a histopathological diagnosis (P-value .004), and no history of mammography or other pathological tests. For treatment, had only chemotherapy (P-value .004) and no hormone therapy (P-value <.001). The majority of patients (>60%) were of stage-II cancer and TNBC (40%) subtype. The BC ethnicity-stratified data of ER, PR, and HER2 indicated a strong correlation across all ethnicities (P-value 4.99e-35; P-value 3.79e-18). The subtypes stratified data indicated a higher percentage of Luminal A (58.3%) in Caucasians whereas Luminal B (24.3%) and HER2 (25.2%) subtypes were found higher in Asians and TNBC (36.0%) were found in Africans. However, a significantly higher frequency of TNBC (52.2%) compared to Asians (14.8%) was found in BD patients (P-value <.001). The overall survival analysis of BC subtypes demonstrated that Luminal B (P-value .005) and HER2 enriched (P-value .015) were significantly more aggressive and were dominant in the Asian population. Conclusion: A significant association was found between BC subtypes with different ethnicities and Bangladeshi women and these findings might aid in the prevention, management, and raising of awareness against risk factors in the near future.

C11-hydroxy and C11-oxo C19 and C21 Steroids: Pre-Receptor Regulation and Interaction with Androgen and Progesterone Steroid Receptors.

C11-oxy C19 and C11-oxy C21 steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation of C11-oxy steroids by 11ß-hydroxysteroid dehydrogenase (11ßHSD) interconversion and potential agonist and antagonist activity associated with the androgen (AR) and progesterone receptors (PRA and PRB). Steroid conversions were investigated in transiently transfected HEK293 cells expressing 11ßHSD1 and 11ßHSD2, while CV1 cells were utilised for agonist and antagonist assays. The conversion of C11-hydroxy steroids to C11-oxo steroids by 11ßHSD2 occurred more readily than the reverse reaction catalysed by 11ßHSD1, while the interconversion of C11-oxy C19 steroids was more efficient than C11-oxy C21 steroids. Furthermore, 11-ketodihydrotestosterone (11KDHT), 11-ketotestosterone (11KT) and 11ß-hydroxydihydrotestosterone (11OHDHT) were AR agonists, while only progestogens, 11ß-hydroxyprogesterone (11ßOHP4), 11ß-hydroxydihydroprogesterone (11ßOHDHP4), 11α-hydroxyprogesterone (11αOHP4), 11α-hydroxydihydroprogesterone (11αOHDHP4), 11-ketoprogesterone (11KP4), 5α-pregnan-17α-diol-3,11,20-trione (11KPdione) and 21-deoxycortisone (21dE) exhibited antagonist activity. C11-hydroxy C21 steroids, 11ßOHP4, 11ßOHDHP4 and 11αOHP4 exhibited PRA and PRB agonistic activity, while only C11-oxo steroids, 11KP4 and 11-ketoandrostanediol (11K3αdiol) demonstrated PRB agonism. While no steroids antagonised the PRA, 11OHA4, 11ß-hydroxytestosterone (11OHT), 11KT and 11KDHT exhibited PRB antagonism. The regulatory role of 11ßHSD isozymes impacting receptor activation is clear-C11-oxo androgens exhibit AR agonist activity; only C11-hydroxy progestogens exhibit PRA and PRB agonist activity. Regulation by the downstream metabolites of active C11-oxy steroids at the receptor level is apparent-C11-hydroxy and C11-oxo metabolites antagonize the AR and PRB, progestogens the former, androgens the latter. The findings highlight the intricate interplay between receptors and active as well as "inactive" C11-oxy steroids, suggesting novel regulatory tiers.

Unraveling the Role of Guanylate-Binding Proteins (GBPs) in Breast Cancer: A Comprehensive Literature Review and New Data on Prognosis in Breast Cancer Subtypes.

At least one member of the Guanylate-Binding Protein (GBP) family of large interferon-induced GTPases has been classified as both a marker of good prognosis and as a potential drug target to treat breast cancers. However, the activity of individual GBPs appears to not just be tumor cell type-specific but dependent on the growth factor and/or cytokine environment in which the tumor cells reside. To clarify what we do and do not know about GBPs in breast cancer, the current literature on GBP-1, GBP-2, and GBP-5 in breast cancer has been assembled. In addition, we have analyzed the role of each of these GBPs in predicting recurrence-free survival (RFS), overall survival (OS), and distance metastasis-free survival (DMFS) as single gene products in different subtypes of breast cancers. When a large cohort of breast cancers of all types and stages were examined, GBP-1 correlated with poor RFS. However, it was the only GBP to do so. When smaller cohorts of breast cancer subtypes grouped into ER+, ER+/HER2-, and HER2+ tumors were analyzed, none of the GBPs influenced RFS, OS, or DMSF as single agents. The exception is GBP-5, which correlated with improved RFS in HER2+ breast cancers. All three GBPs individually predicted improved RFS, OS, and DMSF in ER- breast cancers, regardless of the PR or HER2 status, and TNBCs.

Nanotechnological Approaches for the Treatment of Triple-Negative Breast Cancer: A Comprehensive Review.

Breast cancer is the most prevalent cancer in women around the world, having a sudden spread nowadays because of the poor sedentary lifestyle of people. Comprising several subtypes, one of the most dangerous and aggressive ones is triple-negative breast cancer or TNBC. Even though conventional surgical approaches like single and double mastectomy and preventive chemotherapeutic approaches are available, they are not selective to cancer cells and are only for symptomatic treatment. A new branch called nanotechnology has emerged in the last few decades that offers various novel characteristics, such as size in nanometric scale, enhanced adherence to multiple targeting moieties, active and passive targeting, controlled release, and site-specific targeting. Among various nanotherapeutic approaches like dendrimers, lipid-structured nanocarriers, carbon nanotubes, etc., nanoparticle targeted therapeutics can be termed the best among all for their specific cytotoxicity to cancer cells and increased bioavailability to a target site. This review focuses on the types and molecular pathways involving TNBC, existing treatment strategies, various nanotechnological approaches like exosomes, carbon nanotubes, dendrimers, lipid, and carbon-based nanocarriers, and especially various nanoparticles (NPs) like polymeric, photodynamic, peptide conjugated, antibody-conjugated, metallic, inorganic, natural product capped, and CRISPR based nanoparticles already approved for treatment or are under clinical and pre-clinical trials for TNBC.

Breast Cancer Subtype-Specific miRNAs: Networks, Impacts, and the Potential for Intervention.

The regulatory and functional roles of non-coding RNAs are increasingly demonstrated as critical in cancer. Among non-coding RNAs, microRNAs (miRNAs) are the most well-studied with direct regulation of biological signals through post-transcriptional repression of mRNAs. Like the transcriptome, which varies between tissue type and disease condition, the miRNA landscape is also similarly altered and shows disease-specific changes. The importance of individual tumor-promoting or suppressing miRNAs is well documented in breast cancer; however, the implications of miRNA networks is less defined. Some evidence suggests that breast cancer subtype-specific cellular effects are influenced by distinct miRNAs and a comprehensive network of subtype-specific miRNAs and mRNAs would allow us to better understand breast cancer signaling. In this review, we discuss the altered miRNA landscape in the context of breast cancer and propose that breast cancer subtypes have distinct miRNA dysregulation. Further, given that miRNAs can be used as diagnostic and/or prognostic biomarkers, their impact as novel targets for subtype-specific therapy is also possible and suggest important implications for subtype-specific miRNAs.

Epidemiology and clinicopathological features of lung cancer in patients with prior history of breast cancer.

Breast cancer is the most common malignancy in women, and lung cancer, the leading cause of cancer-related mortality in the United States, is the most common subsequent primary cancer among breast cancer survivors. In this review, we examine the risk factors that cause subsequent primary lung cancer after breast cancer (referred to herein as BCLC patients) as well as the prognostic factors that may affect survival. Notable clinicopathological features include patient characteristics such as age, smoking history, and the presence of EGFR or BRCA mutations, as well as factors related to the treatment of breast cancer such as radiation, surgery, chemotherapy, stage, anti-estrogen therapy, and ER/PR/HER2 status.

Expression and significance of estrogen receptor and progesterone receptor in endometrial tissue of patients with intrauterine adhesions.

BACKGROUND: Our study aims to analyze the expression and significance of estrogen receptor (ER) and progesterone receptor (PR) in endometrial tissues of patients with intrauterine adhesion (IUA). METHODS: Fifty-four patients with IUAs examined in our hospital from January 2017 to January 2019 were selected as the research object (observation group), 54 healthy women who had physical examinations during the same period were selected as the control group, and the immunohistochemical EnVision was used. Two-step and real-time fluorescent quantitative PCR methods were used to detect the expression levels of ER and PR in the endometrial tissues of the two groups of subjects. RESULTS: The immunohistochemical test results showed that ER's expression level in the observation group was significantly higher than that in the control group, and the difference between the two groups was statistically significant (P<0.05). The difference in PR expression levels between the two groups was insignificant (P<0.05). Real-time fluorescent quantitative PCR results showed ER and PR's expression levels in the observation group were significantly higher than those in the control group, and the difference between the two groups was statistically significant (P<0.05). CONCLUSIONS: After IUA can detect ER and PR expression, we can formulate a personalized hormone treatment plan to improve the clinical treatment effect.

Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression.

Progression of cells through cell cycle consists of a series of events orchestrated in a regulated fashion. Such processes are influenced by cell cycle regulated expression of various proteins where multiple families of transcription factors take integral parts. Among these, the steroid hormone receptors (SHRs) represent a connection between the external hormone milieu and genes that control cellular proliferation. Therefore, understanding the molecular connection between the transcriptional role of steroid hormone receptors and cell cycle deserves importance in dissecting cellular proliferation in normal as well as malignant conditions. Deregulation of cell cycle promotes malignancies of various origins, including breast cancer. Indeed, SHR members play crucial role in breast cancer progression as well as management. This review focuses on SHR-driven cell cycle regulation and moving forward, attempts to discuss the role of SHR-driven crosstalk between cell cycle anomalies and breast cancer.

Clinical study of first-line endocrine therapy for type ER+/PR+ and ER+/PR- advanced breast cancer.

BACKGROUND: This study was designed to evaluate the relationship between estrogen receptor (ER) and progesterone receptor (PR) expression status and clinical outcomes in advanced breast cancer patients undergoing first-line endocrine therapy. METHODS: Data from 225 advanced breast cancer patients admitted to Henan Cancer Hospital from February 2010 to October 2019 were collected and compared using Chi-squared tests, with Cox regression models being used to identify relevant prognostic factors in these patients. RESULTS: PR+ and PR- patients had significantly different median progression-free survival (PFS) times of 25 months (95% CI: 13.50-36.50) and 7 months (95% CI: 4.03-9.97), respectively (P<0.001). Clinical benefit rates (CBR) were also significantly different between these 2 groups (80.9% and 55.6%, respectively; P<0.001). A subgroup analysis of PR+ and PR- patients that underwent aromatase inhibitor (AI) treatment revealed a median PFS of 25.0 months (95% CI: 14.28-35.72) and 7 months (95% CI: 4.18-9.82), respectively (P<0.001), and CBR values of 81.3% and 54.5%, respectively (P<0.001). In addition, for both the whole cohort and the AI subgroup, the total survival of patients with ER+/PR+ breast cancer was longer than that of patients with ER+/PR- breast cancer, and the difference was statistically significant (P<0.001). CONCLUSIONS: ER+/PR+ advanced breast cancer patients had a better prognosis than ER+/PR- advanced breast cancer patients undergoing first-line endocrine therapy. In addition, we found that PR status was an independent predictor of first-line endocrine therapy responses in hormone receptor-positive HER2 negative patients.

Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP.

Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.

Negative progesterone receptor status correlates with increased risk of breast cancer recurrence in luminal B HER2-positive and -negative subtypes.

OBJECTIVES: The prognostic significance of the progesterone receptor (PR) has been widely investigated in luminal A and luminal B [human epidermal growth factor receptor 2 (HER2)-] breast cancer subtypes, both of which are estrogen receptor (ER)-positive and HER2-negative. In contrast, few studies have focused on PR status in luminal B (HER2+) tumors. The aim of this study was to evaluate the impact of positive PR status on outcomes in patients with luminal B (HER2-) or luminal B (HER2+) breast cancer. METHODS: Survival analysis was performed to estimate the likelihood of distant recurrence and death in 469 breast cancer patients with the luminal B (HER2-) or luminal B (HER2+) subtype. The relationship between PR and HER2 status was also assessed. RESULTS: Of 387 luminal B (HER2-) and 82 luminal B (HER2+) cancers, PR+ was significantly more frequent in the former than the latter (86.3% vs. 61.0%, respectively; P<0.001). In univariate analysis, PR was identified as a significant favorable prognostic factor for distant disease-free survival and overall survival in both subtypes, but in multivariate analysis PR was not an independent prognostic factor. CONCLUSIONS: After patients with luminal B subtype were divided into two subgroups according to HER2 status, there was evidence of a relatively good prognosis in the PR+ subgroup. Further studies with a larger number of patients are recommended to validate these findings.

Encapsulated Papillary Carcinoma of Breast: Clinicopathological Features and Prognostic Parameters.

Introduction Encapsulated papillary carcinoma (EPC) is a rare malignant papillary breast tumor that, despite a lack of distinct myoepithelial layer, is considered an in situ carcinoma unless associated with a frank invasive component. Data regarding clinicopathologic features of rare breast tumors like EPC are especially scarce. Therefore, in this study, we evaluated the clinicopathologic features of EPC and performed a clinicopathological comparison with conventional invasive ductal carcinoma (IDC). Methods It was a retrospective study conducted in the Department of Pathology, Liaquat National Hospital and Medical College, from January 2013 to December 2019 over a period of seven years. During this period, 16 cases were diagnosed as EPC, and 634 cases were labeled as IDC. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) immunohistochemical (IHC) stains were performed on both EPC and IDC cases. Moreover, myoepithelial IHC stains were performed on all cases of EPC. Clinicopathologic features of EPC were compared with IDC. Results The mean age of the EPC patients was 51.81±13.94 years, with a mean tumor size of 2.97±2.46 cm. The majority of cases were grade II, and axillary metastasis was present in 18.8% of cases. About 56.3% of cases were in situ, and 43.8% showed foci of invasion in the form of IDC. Recurrence was noted in 12.5% of cases with a survival rate of 93.8%. ER, PR, and HER2/neu positivity was noted in 81.3%, 75%, and 12.5% cases, respectively. EPC was significantly noted to have lower tumor grade and pathological T-stage than IDC. Similarly, a lower frequency of axillary metastasis was noted in EPC than IDC.  Conclusion EPC is a rare distinct subtype of papillary breast tumors with overall good survival and low recurrence rate. Compared to IDC, we found EPC to be associated with better prognostic parameters such as lower tumor grade and T-stage and lower frequency of axillary metastasis.

Molecular Cytogenomic Characterization of the Murine Breast Cancer Cell Lines C-127I, EMT6/P and TA3 Hauschka.

BACKGROUND: To test and introduce effective and less toxic breast cancer (BC) treatment strategies, animal models, including murine BC cell lines, are considered as perfect platforms. Strikingly, the knowledge on the genetic background of applied BC cell lines is often sparse though urgently necessary for their targeted and really justified application. METHODS: In this study, we performed the first molecular cytogenetic characterization for three murine BC cell lines C-127I, EMT6/P and TA3 Hauschka. Besides fluorescence in situ hybridization-banding, array comparative genomic hybridization was also applied. Thus, overall, an in silico translation for the detected imbalances and chromosomal break events in the murine cell lines to the corresponding homologous imbalances in humans could be provided. The latter enabled a comparison of the murine cell line with human BC cytogenomics. RESULTS: All three BC cell lines showed a rearranged karyotype at different stages of complexity, which can be interpreted carefully as reflectance of more or less advanced tumor stages. CONCLUSIONS: Accordingly, the C-127I cell line would represent the late stage BC while the cell lines EMT6/P and TA3 Hauschka would be models for the premalignant or early BC stage and an early or benign BC, respectively. With this cytogenomic information provided, these cell lines now can be applied really adequately in future research studies.