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Background: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. Research design and methods: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. Result: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). Conclusion: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making. [ABSTRACT FROM AUTHOR]

Background Breast cancer is the most common cancer in Indian women, with a mortality rate of 12.7 per 100,000 women and an age adjusted incidence of up to 25.8 per 100,000 women. The breast cancer projection for India in 2020 predicts a potential occurrence of up to 1,797,900 cases. (1) Breast cancer incidence peaks in the 40–50 years age group in Indian women. Most of these cancers are HER2 positive and ER/PR negative, or triple negative, with poor prognosis.(2)In developing nations, the majority of breast cancer cases are detected at an advanced stage, and 50% of patients undergoing certain treatments have locally advanced breast cancer (3) The current methods of treatment consist of surgery, radiotherapy, chemotherapy, and hormonal therapy. Hormone treatment is determined by the tumor tissue's hormone receptor (ER, PR) status. The objective of this study is to establish a relationship between expression of conventional hormone receptors and HER-2/neu status and GATA 3 expression. this study also aims to find associations if any between GATA 3 expression and AJCC 8th edition prognostic staging. Methods This prospective study included 30 locally advanced breast cancer patients admitted to KR Hospital Mysuru (Mysore) from September 2022 to March 2024. Age, gender, lump duration, parity, and clinical stage were recorded, BIRADS score, pathological type, stage, grade, ER, PR, and HER2/Neu status were determined. The AJCC 8th edition breast carcinoma staging guidelines were used for clinical, pathological, and prognostic staging. Postoperative histopathological Parafin blocks were stained with GATA 3 on microarray slides. Data was tabulated and coded in Microsoft® Excel before IBM® SPSS ver18.0 statistical analysis. Results This study examined 30 clinical/pathological locally advanced breast cancer cases, focusing on GATA 3 expression and its relationship with prognostic factors and hormone receptors. The majority of patients were women (96.7%). They were 46–60 years old and 37% had clinical stage 3B. 86% had invasive ductal carcinoma and 84% were moderately to poorly differentiated. About 50% of patients were HER2 positive, while 80% were ER and PR positive. GATA 3 expression was measured using immunohistochemistry, resulting in a mean score of 17.4 ± 12.048. ER-positive tumors had significantly higher GATA 3 scores (19.8 ± 11.4) compared to ER-negative tumors (5.2 ± 7.3), with a significant correlation (p = 0.012). GATA 3 predicted ER status with 76.7% accuracy and 75% to 99.8% sensitivity. The relationship between GATA 3 positivity and PR status was not significant (p = 0.141). A significant correlation (p=0.011) showed higher GATA 3 scores for PR-positive. GATA 3 scores were higher in HER2-positive tumors (22.1 ± 10.6) compared to HER2-negative tumors (13.3 ± 12.5), but the correlation was weaker (p = 0.044). The GATA 3 scores did not vary with clinical or pathological stages, suggesting they may not be reliable indicators. Further research is needed on these findings. Conclusion The study demonstrates that GATA 3 expression is significantly associated with ER and PR status, making it a valuable marker for these receptors. However, GATA 3's role in predicting clinical or pathological stages is less clear, as it does not show strong correlations with these prognostic factors. The high sensitivity of GATA 3 for ER status suggests it could be a useful tool in identifying ER-positive tumors. The findings also highlight the need for further research to explore the potential role of GATA 3 in HER2-positive tumors and its overall utility in breast cancer prognosis [ABSTRACT FROM AUTHOR]

Aims: In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC. Materials and methods: Two large cohorts of luminal early‐stage BC (n = 2864) were included. PR and Ki67 expression were assessed using full‐face resection samples using immunohistochemistry. NPx was calculated and correlated with clinical variables and outcome, together with Oncotype DX recurrence score (RS), that is frequently used as a risk stratifier in luminal BC. Results: In the whole cohort, 38% of patients were classified as high risk using NPx which showed significant association with parameters characteristics of aggressive tumour behaviour and shorter survival (P < 0.0001). NPx classified the moderate Nottingham Prognostic Index (NPI) risk group (n = 1812) into two distinct prognostic subgroups. Of the 82% low‐risk group, only 3.8% developed events. Contrasting this, 14% of the high‐risk patients developed events during follow‐up. A strong association was observed between NPx and Oncotype Dx RS (P < 0.0001), where 66% of patients with intermediate risk RS who had subsequent distant metastases also had a high‐risk NPx. Conclusion: NPx is a reliable prognostic index in patients with luminal early‐stage BC, and in selected patients may be used to guide adjuvant chemotherapy recommendations. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor in women, posing a serious threat to women's health. HER2 has been identified as a key oncogene and prognostic factor in breast cancer. Recent studies have reported inconsistencies in ER, PR, and/or HER2 expression between primary breast tumors and metastatic lesions. Rarely is it reported that all three biomarkers experience conversion. In this report, we present the case of a female patient with relapsed and metastatic breast cancer, whose histology transformed from initially triplenegative to Luminal-B type (HER2 positive) (i.e., ER, PR, and HER2 positive). She underwent systematic chemotherapy, targeted therapy, and cranial radiotherapy, which was followed by maintenance treatment with targeted and endocrine therapy. Currently, she has been in nearly complete remission (nCR) for more than 12 months. For recurrent and metastatic breast cancer, it is necessary to perform the second biopsy for metastases, which would contribute to precision treatment and prognosis improvement. [ABSTRACT FROM AUTHOR]

Background/Aim: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immunohistochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece. Patients and Methods: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm. Results: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triplenegative phenotype (p=0.001). Conclusion: The study provided valuable insights into the histopathological and immunohistochemical characteristics involved in the development and progression of breast cancer. [ABSTRACT FROM AUTHOR]

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the seven parameters including three biomarkers routinely assessed in all the newly diagnosed breast cancers (BC), oestrogen receptor (ER), progesterone receptor (PR) and HER-2 and an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2 and KIF23. Taken together, the data are used to produce a molecular subtype for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridisation (ISH) in breast cancer patients. The data were presented at the weekly breast multidisciplinary team (MDT) meeting. A total of 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsies of nodal metastases yielding 100 cases were assessed. IHC and APIS results were available for 100 and 99 cases. ER was concordant in 97% cases, PR was concordant in 89% and HER-2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% of cases when compared with MK167 alone but discordant in 24% when compared with the four-gene proliferation signature. In conclusion, our study indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER-2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnosed breast cancer (BC) specimens. [ABSTRACT FROM AUTHOR]

BackgroundBreast cancer (BC) survivors experience an increased burden of long-term comorbidities, including heart failure (HF). However, there is limited understanding of the risk for the development of HF subtypes, such as HF with preserved ejection fraction (HFpEF), in BC survivors.ObjectivesThis study sought to estimate the incidence of HFpEF and HF with reduced ejection fraction (HFrEF) in postmenopausal BC survivors and to identify lifestyle and cardiovascular risk factors associated with HF subtypes.MethodsWithin the Women's Health Initiative, participants with an adjudicated diagnosis of invasive BC were followed to determine the incidence of hospitalized HF, for which adjudication procedures determined left ventricular ejection fraction. We calculated cumulative incidences of HF, HFpEF, and HFrEF. We estimated HRs for risk factors in relation to HF, HFpEF, and HFrEF using Cox proportional hazards survival models.ResultsIn 2,272 BC survivors (28.6% Black and 64.9% White), the cumulative incidences of hospitalized HFpEF and HFrEF were 6.68% and 3.96%, respectively, over a median of 7.2 years (IQR: 3.6-12.3 years). For HFpEF, prior myocardial infarction (HR: 2.83; 95% CI: 1.28-6.28), greater waist circumference (HR: 1.99; 95% CI: 1.14-3.49), and smoking history (HR: 1.65; 95% CI: 1.01-2.67) were the strongest risk factors in multivariable models. With the exception of waist circumference, similar patterns were observed for HFrEF, although none were significant. In relation to those without HF, the risk of overall mortality in BC survivors with hospitalized HFpEF was 5.65 (95% CI: 4.11-7.76), and in those with hospitalized HFrEF, it was 3.77 (95% CI: 2.51-5.66).ConclusionsIn this population of older, racially diverse BC survivors, the incidence of HFpEF, as defined by HF hospitalizations, was higher than HFrEF. HF was also associated with an increased mortality risk. Risk factors for HF were largely similar to the general population with the exception of prior myocardial infarction for HFpEF. Notably, both waist circumference and smoking represent potentially modifiable factors.

Background: Breast cancer is a chronic complex disease. Its progression depends partly on the interaction between tumor and immune cells. Whilst immunotherapy is the new promising treatment, many patients with breast cancer acquire resistance. Interferon gamma (IFN-γ) is a pleiotropic cytokine that is primarily released by T cells and natural killer (NK) cells and has always been praised for its antitumor activities. However, IFN-γ may induce different modulations in breast cancer cells that are expressing or not expressing the hormone receptors estrogen and progesterone. Methods: In this study, to examine the effect of IFN-γ on the subtypes of breast cancer in relation to the expression of estrogen and progesterone genes, we performed RNA-sequencing on the triple negative cells MDA-MB231 and ER/PR transfected MDA-MB231 cells (untreated or treated with 100 ng/ml IFN-γ). Various bioinformatics analyses were performed to investigate the affected functional pathways, and immune genes related to the different types of breast cancer cells. Results: The set of differentially expressed genes (DEGs) that are regulated by IFN-γ were unique, and specific to each breast cancer subtype. These unique DEG patterns in hormone-positive cells ( GBP3, HLA-DPA1, HLA-DRB1, HLA-E, IL6) and triple negative cells ( IFI6, ISG15, CCL5) showed significant but distinct effects on patients’ overall survival as well as noticeable differences in immune modulation and regulation. Conclusions: IFN-γ signaling can differentially affect the pattern of gene expression in breast cancer cells in an estrogen receptor (ER) / progesterone receptor (PR)-dependent manner. IFN-γ treatment of ER+/PR+ breast cancer cells upregulated the expression of genes related to immune cells and showed improved patient prognosis, while TNBC showed negative regulation of the expression of genes related to immune cells and worse patient prognosis.

Background: The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its prognostic significance as compared to Ki67 expression. Methods: A large cohort (n = 1924) of estrogen receptor (ER)‐positive/HER2‐negative BC was included. PR was immunohistochemically (IHC) stained on full face sections and core needle biopsies (CNB) where the optimal scoring cutoff was evaluated. In addition, the association of PR with other clinicopathological factors, cellular proliferation, disease outcome, and response to adjuvant therapy were analyzed. Results: Although several cutoffs showed prognostic significance, the optimal cutoff to categorize PR expression into two clinically distinct prognostic groups on CNB was 10%. PR negativity showed a significant association with features of aggressive tumor behavior and poor outcome. Multivariate analyses indicated that the association between PR negativity and poor outcome was independent of tumor grade, size, node stage, and Ki67. PR negativity showed independent association with shorter survival in patients who received endocrine therapy whereas Ki67did not. Conclusion: PR IHC expression provides independent prognostic value superior to Ki67. Routine assessment of PR expression in BC using 10% cutoff in the clinical setting is recommended. Plain Language Summary: In this study, we have established an optimal approach to determine the prognostic value of progesterone receptor expression in estrogen receptor‐positive breast cancer patients.To do this, the levels of progesterone receptor were measured in a large cohort of estrogen receptor‐positive breast cancer patients.We have refined the definition of progesterone receptor positivity in estrogen receptor‐positive breast cancer.We show that progesterone receptor expression adds prognostic and predictive value of endocrine therapy in estrogen receptor‐positive breast cancer patients, and our results show that the absence of progesterone receptor is associated with poorer outcomes independent of tumor grade, size, node stage, and Ki67 expression. This study provides further evidence that assessment of progesterone receptor status in the luminal breast cancer can provide valuable prognostic and predictive information independent of other clinicopathological variables comparable to that provided by Ki67 and can outperform it in certain situations. Using a 10% rather than a 1% cutoff for progesterone receptor expression provides the optimal prognostic significance. [ABSTRACT FROM AUTHOR]

Only few studies reported in literature that has elucidated in detail the implications of molecular typing in metastatic and recurrent breast cancer. In this prospective study, we have analysed in depth the pattern of expression, discordances of molecular markers in various metastatic sites, and recurrent cases and their response to chemotherapy/targeted agents and the prognostic outcome. The primary aim of the study was to determine ER, PR, HER2/NEU, and Ki-67 from recurrent and metastatic carcinoma breast to study the expression pattern and discordance and also to study the degree of discordance in relation to the site of metastasis and pattern of metastasis (synchronous vs metachronous) and discordance pattern with the response to chemotherapy and median overall survival rates in months in available subset of patients. Prospective open-label study done at the Government Rajaji Hospital, Madurai Medical College, and Government Royapettah Hospital, Kilpauk Medical College, India, from November 2014 to August 2021. All breast carcinoma patients with recurrence or oligo metastasis (defined as one organ with less than 5 metastases in our study) with known receptor status were eligible and 110 patients were enrolled in the study. ER (ER + to ER −) discordance was seen in 19 (26.38%) cases. PR (PR + to PR -Ve) discordance was seen in 14 (19.17%) cases. HER2/NEU (HER2/NEU + Ve to -Ve) discordance was seen in 3 (16.6%) cases. Ki-67 discordance was seen in 54 (49.09%) cases. High Ki-67 as a proliferative marker has increased response to chemotherapy but earlier relapse and disease progression especially in Luminal B type. In further subset analysis, ER, PR, and HER2/NEU discordance is higher for lung metastasis (ER, PR 61.1%, p value.001, HER2/NEU 5.5%), followed by liver metastasis (ER, PR 50%, p value.0023, 1 case turning ER -ve to + ve, HER2/NEU 1 (10%)). In lung, discordance is more for metachronous metastasis. In liver, discordance is 100% for synchronous metastasis. Synchronous metastasis with discordance in ER and PR is associated with rapid disease progression. High Ki-67 subset of Luminal B–like tumors progressed rapidly than triple negative and HER2/NEU positive subset. Complete clinical response rate in contralateral axillary node metastasis group was 87.8%, followed by local only recurrence with high Ki-67 where chemotherapy had response rate of 81% and 2 years DFS of 93.12% after excision. Certain subsets like contralateral axillary nodes and supraclavicular nodes which present as oligo metastatic disease with discordance and high Ki-67 respond well to chemotherapeutics and targeted agents improving the OS in this subset of patients. Molecular markers and their expression and discordance pattern determine the therapeutic outcome and prognosis of the disease. Early identification and targeting the discordance would go a long way in improving the outcome and DFS and OS of breast cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: To date there is no specific analysis providing comprehensive available evidence that can guide clinical treatment options for patients with hormone receptor-positive and human epidermal growth factor receptor-2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). We conducted a retrospective study with 3070 consecutive HR+/HER2− BC patients after NAC and indicated that progesterone receptor (PR) negativity BC has a higher complete pathological response (pCR) and lower survival than PR positivity BC. PR may be used as an independent predictor for pCR and a prognosis of HR+/HER2− BC in the NAC setting. HER2-low tumors are not significantly associated with pCR or disease-free survival (DFS), but these patients have significantly lower overall survival (OS) than those with HER-0 tumors. Our research confirms the significance of PR and HER2 status associated with pCR and prognosis. Purpose: To evaluate the clinical characteristics, pathological response, and prognostic significance of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). Methods: A survival analysis was performed to detect the factors related to recurrence and death in 3070 consecutive patients with HR+/HER2− BC who received NAC from 2011 to 2022. All patients received current "standard of care" following neoadjuvant therapy based on guidelines, including surgery and adjuvant endocrine therapy. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC 2+ and fluorescence in-situ hybridization-negative. Results: The complete pathological response (pCR) (ypT0/is ypN0) rate was 14.5%. The clinical tumor size (cT), ER scores, PR status, and Ki67 levels were related to pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 82.6% and 90.4%, respectively. PR, Ki67 levels, and postmastectomy radiotherapy were independent factors for DFS and OS, and the extranodal extension (ENE) correlated with DFS. However, pCR and HER2 status were related to OS. The pCR rate in PR negativity BC was significantly higher than that in PR positivity BC (21.1% vs. 12.2%, p = 0.000), but PR negativity BC had a poorer prognosis than PR positivity BC. HER2-low BC showed high ER scores (over 50%), PR positivity, large ypT, ENE, and lymphovascular invasion but a lower pCR rate than HER2-zero BC. Patients with HER2-low BC had shorter OS than those with HER2-zero BC (p = 0.037). However, there was no difference in DFS. Conclusions: Depending on PR status and HER2 status, patients with ER positivity and HER2 negativity exhibit different pathologic complete response rates to neoadjuvant chemotherapy and long-term outcomes, especially patients with PR negativity or HER2-low status. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) plays a major public health in Egyptian woman. In Upper Egypt, there is an increase in incidence of BC compared to other Egyptian areas. Triple-negative BC, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-neu-negative, is a high-risk BC that lacks the benefit of specific therapy that targets these proteins. Accurate determination of Caveolin-1(Cav-1), Caveolin-2 (Cav-2) and HER-2/neu status have become of major clinical significance in BC by focusing about its role as a tumor marker for response to different therapies. Methods: The present study was performed on 73 female BC patients in the South Egypt Cancer Institute. Blood samples were used for Cav-1, Cav-2, and HER-2/neu genes amplification and expression. In addition, immunohistological analysis of mammaglobin, GATA3, ER, PR, and HER-2/neu was done. Results: There was a statistically significant association between Cav-1, 2 and HER-2/neu genes expression and the age of patients (P< 0.001). There are increase in the level of Cav-1, 2 and increase in HER-2/neu mRNA expression in groups treated with chemotherapy and group treated with both chemotherapy and radiotherapy compared to each group baseline level of genes mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy and hormonal therapy revealed increase on the level of Cav-1, 2 and HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment. Conclusions: Noninvasive molecular biomarkers such as Cav-1 and Cav-2 have been proposed for use in the diagnosis and prognosis for women with BC. [ABSTRACT FROM AUTHOR]

Introduction: The most common cancer among women in the urban Indian population is breast cancer and it is second only to cancer of the cervix in the rural population. Currently, routine clinical management of breast cancer incorporates specific molecular markers; namely ER- Estrogen Receptor, PR-Progesterone Receptor, HER2-human epidermal growth factor receptor 2, that have been proven to provide therapeutic, predictive and prognostic value. Aims: To detect the mean age of patients diagnosed with breast cancer (in early, locally advanced breast cancer (LABC) & metastatic and the ER, PR Her2 neu status and Ki67 indices among them. To observe whether different type of breast cancer among the different age group bears any correlation against receptors status and correlate the receptor status with the different histopathological type of breast cancer. Materials And Method: This prospective observational study was conducted in CA breast patients attending General surgery OPD Burdwan Medical College Within 1 year 3 months period (May 2019-August 2020). 80 patients were included in this study. Result: 80 cases of breast carcinoma were assessed for clinicopathological parameter and for expression of ER, PR, Her2 neu and Ki 67 index status. In our study it has been seen that younger age group patients are more susceptible for her2 neu receptor positivity. It has been seen that only 33.3% patients are her2 neu positive in 51-60 yrs age group, whereas the percentage is 64.3% in 31-40 yrs age group and we observed that, it has been noted that more of the ER, PR positive status were seen in lower grade tumors. As in the grade 1 tumors have 71.4% ER,PR positivity where as 27.3 % of grade 3 tumor shows Er positivity.In case of Her2 neu receptor status, more the higher grade more the chance of her 2 receptor positivity. As 90.9% of grade 3 tumor showed Positive result for Her2 neu receptor. We found a inverse correlation between ER, PR and Her2 neu receptor status. Conclusion: Estrogen, Progesterone receptor positive tumors are common in post-menopausal women and Her2 neu receptor is common in pre-menopausal women. Her2 neu receptors are more prone to seen in grade 3 tumors than lower grade tumor. Her2 neu and er pr status has an inverse correlation with each other. The ki 67 index has proportionately seen in higher grade tumors. We have not found any correlation between ki67 index, age, receptor status. The survival of ER, PR positive tumors are more thant Receptor negative tumors. [ABSTRACT FROM AUTHOR]

To identify the most effective combination of DCE-MRI (K trans ,K ep) and IVIM (D,f) and analyze the correlations of these parameters with prognostic indicators (ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size) to improve the diagnostic and prognostic efficiency in breast cancer. This is a prospective study. We performed T1WI, T2WI, IVIM, DCE-MRI at 3 T MRI examinations on benign and malignant breast lesions that met the inclusion criteria. We also collected pathological results of corresponding lesions, including ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size. The diagnostic efficacy of DCE-MRI, IVIM imaging, and their combination for benign and malignant breast lesions was assessed. Correlations between the DCE-MRI and IVIM parameters and prognostic indicators were assessed. Overall,59 female patients with 62 lesions (22 benign lesions and 40 malignant lesions) were included in this study. The malignant group showed significantly lower D values (p < 0.05) and significantly higher K trans , K ep , and f values (p < 0.05). The AUC values of DCE, IVIM, DCE + IVIM were 0.828, 0.882, 0.901. K trans , K ep , D and f values were correlated with the pathological grade (p < 0.05); K trans was negatively correlated with ER expression (r = −0.519, p < 0.05); K ep was correlated with PR expression and the Ki-67 index (r = −0.489, 0.330, p < 0.05); the DCE and IVIM parameters showed no significant correlations with the HER2 and ALN (p > 0.05). Tumor diameter was correlated with the K ep , D and f values (r = 0.246, −0.278, 0.293; p < 0.05). IVIM and DCE-MRI allowed differential diagnosis of benign and malignant breast lesions, and their combination showed significantly better diagnostic efficiency. DCE- and IVIM-derived parameters showed correlations with some prognostic factors for breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Purpose Estrogen-receptor (ER) and progesterone-receptor (PR) expression levels in breast cancer, which have been principally compared via binomial descriptors, can vary widely across tumors. We sought to characterize ER and PR expression levels using semi-quantitative analyses of receptor staining in germline pathogenic variant (PV) carriers of cancer predisposition genes. Methods We conducted a retrospective chart review of patients who underwent germline genetic testing for cancer predisposition genes at a tertiary cancer center genetics clinic. We performed comparisons of semi-quantitative ER and PR percentage staining levels across carriers and non-carriers of cancer predisposition genes. Results Breast cancers from BRCA1 PV carriers expressed significantly lower ER (15.2% vs 78.2%, p

Simple Summary: Breast cancer is a heterogeneous disease and treatment needs to be adapted to individual tumors. Two thirds of breast tumors may benefit from treatment with drugs targeting a specific protein, the estrogen receptor alpha, a regulator of gene expression activated by female sex hormones. However, a significant percentage of tumors will recur and progress. To help detect more accurately the expression status and activity of this protein, a gene that it upregulates, the progesterone receptor (PR), is routinely used in the clinic as an additional marker. Here, we show that PR status is an imperfect reflection of the expression and/or overall activity of estrogen receptor alpha and identify another marker that can perform this task more consistently. Overall, use of CAXII as a marker of ER+ tumors should reinforce the diagnosis of ER status and prediction of its activity and enhance the accuracy of hormonal therapy delivery. Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by PGR) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR− status in ER+ tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower PGR expression, the clinical PR status does not correlate accurately with the expression of ESR1 or of ER target genes, including PGR itself. We identified carbonic anhydrase 12 (CA12) as an estrogen target gene better correlated with ESR1 than PGR, reflecting CA12 regulation by both ERα and the luminal factor and upstream ESR1 regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ER+PR− tumors expressed CAXII at levels similar to those of ER+PR+ tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ER+PR− breast cancer cell lines. The few ER−PR+ tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index in the brain metastatic lesions and primary lesions in Chinese patients with breast cancer brain metastasis (BCBM) and determine the correlation between their changes and patients' survival. Methods: A retrospective analysis was performed on patients with BCBM. The clinical characteristic of these patients was collected. The differences in the expression levels of the ER, PR, HER-2, and Ki-67 index between the primary lesions and brain lesions were evaluated, and the association between the differences and survival was analyzed. Results: The conversion rate of anyone receptor (ER, PR, or HER2) between the primary lesions and brain metastatic lesions was 45.0% (18/40), of which the ER inconsistency rate was 25.0%, the PR inconsistency rate was 22.5%, and the HER-2 inconsistency rate was 15.0%, and the receptor conversion resulted in a subtype conversion of 27.5% (11/40). The patients with HER-2 expression discordance between the primary lesions and the brain metastatic lesions had significantly longer survival times (58.9 vs. 26.4 months, P = 0.04) after diagnosis of brain metastases. Conclusion: In this study, 45.0% of breast cancer patients developed biomarker-conversion between the primary lesions and brain metastatic lesions, and the differences in the expression levels of the ER, PR, and HER-2, the change in Ki-67 index between the primary lesions and brain lesions may predict patients' survival. [ABSTRACT FROM AUTHOR]

Purpose: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes. Methods: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results. Results: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR. Conclusion: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer. [ABSTRACT FROM AUTHOR]

Forkhead box protein A1 (FOXA1) is pioneer factor has a dual role either as growth stimulator or a repressor and the significance role of this protein as a therapeutic biomarker still controversial, so the aim of this study was to identify the precise role of FOXA1 protein expression in treatment of BC patients by immunohistochemical (IHC) staning method. In this study, seventy three tissues samples embedded in wax block were taken from BC patients with (52.71+11.55) years who had surgery between 2014-2020 and thirty eight of normal (non tumoral) breast tissues samples with (54.17+10.84) years as a control group. There was a significant association between positive FOXA1 protein expression and Luminal A and Luminal B of BC (P=0.011). Moreover, FOXA1 positivity was elevated significantly in patients with positive Estrogen receptors (ER) expression (P=0.0001), positive Progesterone receptor (PR) expression (P=0.016). Furthermore, there was no significant correlation between FOXA1 expression in BC patients and Her2 expression (P=0.764). FOXA1 positive expression can be employed as a therapeutic marker to predict hormone responsiveness. [ABSTRACT FROM AUTHOR]

Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status.

Purpose: Estrogen-receptor (ER) and progesterone-receptor (PR) expression levels in breast cancer, which have been principally compared via binomial descriptors, can vary widely across tumors. We sought to characterize ER and PR expression levels using semi-quantitative analyses of receptor staining in germline pathogenic variant (PV) carriers of cancer predisposition genes.Methods: We conducted a retrospective chart review of patients who underwent germline genetic testing for cancer predisposition genes at a tertiary cancer center genetics clinic. We performed comparisons of semi-quantitative ER and PR percentage staining levels across carriers and non-carriers of cancer predisposition genes.Results: Breast cancers from BRCA1 PV carriers expressed significantly lower ER (15.2% vs 78.2%, p < 0.001) and lower PR (6.8% vs 41.1%, p < 0.001) staining compared to non-PV carriers. Similarly, breast cancers of BRCA2 (66.7% vs 78.2%, p = 0.005) and TP53 (50.6% vs 78.2%, p = 0.015) PV tumors also displayed moderate decreases in ER staining. Conversely, CHEK2 tumors displayed higher ER (93.1% vs 78.2%, p = 0.005) and PR (72% vs 48.8%, p = 0.001) staining when compared to non-PV carriers. We observed a wide range of dispersion across the ER and PR staining levels of the carriers and noncarriers. ER and PR ranges of dispersion of CHEK2 tumors were uniquely narrower than all other groups.Conclusion: The findings of our study suggest that precise expression levels of ER and PR in breast cancers can vary widely. These differences are further augmented when comparing expression staining across PV and non-PV carriers, suggesting potentially unique tumorigenesis and progression pathways influenced by germline cancer predisposition genes. [ABSTRACT FROM AUTHOR]

Ultrasound is commonly used in breast cancer screening and diagnosis. The use of ultrasound features to predict the subtypes of invasive breast cancer is of great clinical significance, since it facilitates a fast and early diagnosis and treatment. The correlation between breast lesion ultrasound features and the breast cancer subtypes requires further investigation. 388 patients with invasive breast cancer were retrospectively analyzed by two sonographers. The tumor size, shape, margin, echogenicity, echotexture, posterior echo attenuation microcalcification, and blood vessel density were recorded. The correlation between the tumor ER, PR, HER2, and Ki67 status, the molecular subtypes, and the ultrasound features was analyzed using the chi-square test, Fisher's exact test, and multiple logistic regression. ER and PR positivity were correlated with a low histologic grade, lymph node metastasis, and smaller-sized tumors. A hyperechoic or a mixed echogenicity was rare in the tumors of all groups but was enriched in the ER and PR tumors (9.57% and 7.64%, respectively, p < 0.01). A high percentage of posterior echo attenuation was found in the Ki67 low (53.94%) and ER+ (51.28%) tumors. Furthermore, heterogeneous and microcalcifications were enriched in HER2-positive tumors. In terms of the molecular subtypes, the luminal A subtype group had the lowest lymph node positivity and the smallest primary tumor size. The luminal B subtype had the lowest percentage of hyperechoic or mixed tumors. The HER2 subtype was positively correlated with microcalcification. Finally, TNBC showed the highest percentage of hyperechoic or mixed tumors and the lowest percentage of posterior echo attenuation and microcalcification. Tumor pathologic and ultrasound features were correlated with invasive breast tumor molecular marker positivity and its molecular subtypes. • The usage of ultrasound features to predict subtypes of invasive breast cancer is of great clinical significance, as it will facilitate fast and early diagnosis and treatment • Tumor pathologic and ultrasound features correlated with invasive breast tumor molecular marker positivity and molecular subtypes • The study provide valuable resource for using ultrasound features to predict invasive breast cancer molecular subtypes and contribute to breast cancer early diagnosis. [ABSTRACT FROM AUTHOR]

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Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.

Amaç: Bu çalışmada lokal ileri evre meme kanserli hastalarda neoadjuvan kemoterapi ile tümör çapı, tümörlü dokuda çalışılan vasküler endotelyal büyüme faktörü (VEGF), östrojen reseptörü (ER), progesteron reseptörü (PR), Ki-67 ve Cerb-B2 ekspresyonlarındaki değişimin gösterilmesi amaçlanmıştır.Gereç ve Yöntem: Cukurova University Tıp Fakültesi Genel Cerrahi ve Tıbbi Onkoloji Bilim Dalı’nda 2008 ve 2013 yılları arasında lokal ileri meme kanseri nedeniyle tedavi gören 69 hastanın verileri prospektif olarak araştırılmıştır. Tümör çapı, tümörlü dokuda çalışılan VEGF, Ki-67, ER, PR ve Cerb-B2 ekspresyonları immunhistokimyasal (İHK) yöntem ile neoadjuvan kemoterapi öncesi ve sonrası dönemde karşılaştırmalı olarak değerlendirilmiştir.Bulgular: Neoadjuvan kemoterapi sonrası tümör çapı, VEGF, Ki-67, ER, PR ve Cerb-B2 ekspresyonlarında istatistiksel olarak anlamlı düşüş saptandı. Sonuç: Tümör dokusunda çalışılan VEGF düzeyindeki anlamlı düşme, tümörün anjiyogenezinin ve bu yolla metastaz yapabilme yeteneğinin neoadjuvan kemoterapi etkisiyle azalabileceği sonucunu telkin etmektedir. Tümör dokusunda çalışılan Ki-67 proliferasyon indeksinde anlamlı değişim; malign hücre proliferasyonunun neoadjuvan kemoterapi etkisiyle azaldığını gösterebilir.

Background: Cancer research was focused on the studying of proper tumor cells for a long time. Despite the huge progress, there are still a lot of questions, that’s why new molecular markers must be identified. These could reveal new information about tumorigenesis. Material and methods: 15 cases of ductal invasive breast carcinomas have been analyzed and researched on tumor associated macrophages via immunohistochemistry. CD68 was used as a macrophage marker and CD68+ cells were evaluated in tumor nest and peritumoral area, as well as hormone receptors (ER, PR) and HER2 protein. Results: Most of tumors (10 cases out of 15/ 66.7%) were moderately differentiated (G2). The mean and std. error of mean of intratumoral CD68+ cells were 2.0±0.2, of peritumoral CD68+ cells – 1.4±0.2. Intratumoral CD68+ cells registered higher scores than those located in the peritumoral area. Conclusions: CD68+ cells are more likely to be present in the tumor nest rather than in the peritumoral area. This research did not establish any significant correlations between intratumoral and peritumoral CD68+ cells and patients’ age, tumor grade, expression of ER and PR. The content of peritumoral CD68+ cells inversely correlated with the number of HER2+ carcinoma cells.

Objective: To evaluate the correlation between traditional ultrasound and the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (Her-2), and Ki-67 expression in breast carcinoma.Methods: A retrospective analysis of 400 cases of breast cancer, which were confirmed by pathology. The expression of postoperative specimens by immune-histochemical staining was used to evaluate the immune molecules ER, PR, Her-2, and Ki-67. The correlation between the ultrasound findings (size, boundary, sand calcification, and blood flow grade), as well as the expression of ER, PR, Her-2, and Ki-67 were analyzed.Results: Of the 400 cases, there were no correlations between the boundary, the classification, or the blood flow of the tumor with the expression of ER, PR, Her-2, and Ki-67. The size of tumor was correlated with Her-2 and Ki-67. The tumor is the bigger, and the expression of Her-2 and Ki-67 is higher.Conclusion: There is a correlation between tumor size and expression of Her-2 and Ki-67 in breast cancer. The combination of them was important for the treatment and prognosis of breast cancer.

Background: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death.Methods: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up.Results: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes.Conclusions: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is considered the commonest cancer in Egyptian females. Established prognostic parameters of breast cancer patients are size, grade and stage of the tumor, presence of lymph nodes and distant metastasis in addition to assessment of hormonal receptors status. Aim of the current study was to assess ER, PR, Her2neu, Ki67 and AR status, to assess association between them, morphological and prognostic parameters in a large cohort of Egyptian females diagnosed with breast cancer. Patients and methods: This study was performed on 250 Egyptian female patients with breast cancer. All patients' data were collected and statistically analyze all data for detection of the association between ER, PR, Her2-neu, Ki 67 labeling index, AR, clinicopathological and prognostic data. Results: we found an association between positive ER and positive PR, with low grade of the tumor, absence of lymphovascular invasion, little number of metastatic lymph nodes, early stage and absence of distant metastases, favorable survival rates and lower rate of recurrence and disease progression (p<0.001). We found an association between positive AR, positive Her2-neu, high ki67 labeling index with; higher grade of the tumor, large number of metastatic lymph nodes and presence of distant metastases, unfavorable survival rates and higher rate of recurrence and disease progression (p<0.001). Conclusion: expression of ER, PR and Her2neu could be considered other prognostic parameters for patients with breast cancer and must be routinely performed for all cases to detect the prognosis and expect progression of the tumor and survival rates. [ABSTRACT FROM AUTHOR]

Purpose: Patients presenting with lymphovascular space invasion (LVSI) had an absolute decrease in survival. In our present study, the potential roles of LVSI on tumor characteristics was explored to predict the difference in the prognosis of ER and HER2 positive T1 tumors. Methods: A total of 142 breast cancer patients diagnosed with ER+ and HER2+ tumors whose tumor size was ≤ 2 cm were included in this analysis. One hundred forty-two patients were divided into four groups, group 1 (lymph nodes+ and LVSI+), group 2 (lymph nodes+ and LVSI−), group 3 (lymph nodes− and LVSI+), group 4 (lymph nodes− and LVSI−). Univariate and multivariate Cox proportional hazard models were used to identify independent prognostic factors and calculate the HR and 95% CI. Kaplan–Meier and Cox regression models were used to test the prognostic significance. Results: LVSI positivity was significantly associated with patient age, menopausal status, tumor size, lymph node status, Ki67, PR, and tumor grade. In the univariate and multivariate model, LVSI, PR, and Ki67 were significantly associated with DFS, and LVSI, lymph node status, PR, and Ki67 were significantly associated with OS. LVSI was significantly related to increased risk of DFS and OS only in the PR-negative and low-positive subgroups. It was a prognostic factor for DFS but not for OS in women with low Ki67 and was associated with DFS and OS in high-Ki67 tumors. Furthermore, patients who presented with only LVSI had a significantly worse survival rate than those with lymph node metastasis without LVSI in small tumors. Conclusion: The presence of LVSI was highlighted as a variable significant to survival. In further clinical practice, patients with LVSI may need more intensive treatment in certain populations. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS). Results 86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER negative and 86% were PR negative, respectively as compared to ductal carcinoma NOS, which were 40% ER negative and 54% were PR. Similarly, 86.7% micropapillary cancers were ER positive and 73.3% were PR positive. Moreover, 66.7% micropapillary carcinoma showed nodal metastasis and 77.8% showed lymphovascular invasion, which was significantly higher than that of IDC, NOS micropapillary and metaplastic carcinomas accounts for less than 2 and 1% of the breast cancer burden in our population and highly correlates with poor prognosis parameters therefore, require more intensive management in our population.

Abstract Background Prognosis of breast cancer and success of therapeutic interventions largely rely on the clinico-pathologic and biological characteristics of the tumor and vary due to the heterogeneous nature of breast cancers. The aim of this study was to determine the frequency and prognostic parameters of luminal breast cancers in our population to devise targeted and personalized therapeutic regimens tailored to the needs of the loco-regional population. Methods A retrospective cross-sectional study including 1951 cases of primary breast cancer treated at Liaquat National Hospital Karachi was conducted during the year 2011–2016. The clinico-pathologic characteristics were observed and semiquantitative immunohistochemical analysis was performed to study the luminal subtypes A and B. The cross-tabulated statistics of the observed characteristics were performed between the two subtypes. The significance level of each characteristic was estimated utilizing the chi-square test. Results Luminal cancers comprised 62.7% of the total number of cases diagnosed with breast cancers in the study period. Out of these 1224 cases of luminal cancers, 845 cases (69%) were luminal B, while 379 (31%) cases were of luminal A. Luminal B cancers were significantly more common in younger age groups as compared to luminal A cancers. Comparison of the two subtypes of luminal breast cancers revealed significant differences. Luminal B cancers were associated with higher grade (26% grade III in luminal B compared to 8% in luminal A), micropapillary histology, and high frequency of nodal metastasis (54 vs. 43%). Conclusions Luminal B comprised the most frequent subtype of breast cancer in our study and they were found more constantly in a younger age group. Moreover, they were associated with adverse clinico-histologic parameters like higher grade and nodal metastasis. Therefore, we suggest that, despite lack of widespread availability of molecular studies in our setup, IHC-based typing should be done in every case of breast cancer to individualize therapy.

Purpose: The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2. Experimental design: Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR. Results: In ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2−. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identified as responsible for the differential phosphorylation between PR− and PR+ in ER+/HER2− tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2− breast cancers. Twenty four kinase-encoding genes were identified as differentially expressed between PR+ and PR−, dividing ER+/HER2− samples in two distinct clusters with significant differences in survival (p < 0.05). Four kinase genes, LCK, FRK, FGFR4, and MST1R, were identified as potential direct targets of PR. Conclusions: Our results suggest that the PR status has a profound effect on tyrosine kinases, especially for FGFR4 and LCK genes, in ER+/HER2− breast cancer patients. The influence of these genes on the PI3K/AKT signaling pathway may potentially lead to novel drug targets for ER+/PR− breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the commonest malignancy of females all over the world and the second leading cause of death due to malignancy among females. Breast cancer is regarded as a unique disease in oncology and the specific markers such as ER, PR, HER-2/neu and others are used to predict the prognosis and the treatment response to guide the therapeutic plan. Aim of the Study: To clarify if there is any significant difference in the intrinsic molecular profile of breast cancer in old age patients in comparison to young age patients. Material & Methods: Samples of primary carcinoma of breast, obtained from 211 female patients with breast cancer. The patients are divided into two group. Immunohistochemical analysis was done for the specimens by using Envision method for detection of estrogen receptor, progesterone receptor, Her2/neu. Statistical analysis was done by using SPSS. In which we use frequency, percentage and mean as descriptive statistics while chi square and Yates corrected chi square as analytic statistics. Result: We found molecular intrinsic breast cancer subtypes have a significant difference in distribution of elderly breast cancer compared to their younger counterparts where elderly patients more frequently Luminal A and Luminal B tumor subtypes and less frequently HER2+ and basal molecular subtypes. Conclusion old age breast cancer patients have better prognosis in comparison to young age patients according to the biological profile, histopathological type and Immunohistochemical prognostic parameters. [ABSTRACT FROM AUTHOR]

Based on our knowledge about the importance of some prognostic factors in breast cancers, a retrospective study on 101 Iraqi female patients was done, using the following parameters; patient’s age, tumor grade, hormones Estrogen receptor (Er.) status, and human epidermal growth factor receptor 2 (Her2/neu) expression. A significant relationship between younger age group (< or = 35 years) and high grade tumors was detected. Significant number of those patients in the study had Er+ve tumors. No significant relationship has been found between Er-ve tumors and high grade histology. Most of postmenopausal women in this study were with Er+ve breast cancers, which is significantly higher than that in premenopausal women. Also a significant increase in Her2/neu expression is seen in tumors with high grade histology. No inverse relationship between Er. concentration and Her2/neu expression was seen. We did comparison between these findings and the results of others over the world to see if behaviors of breast tumors in Iraqi female are the same to that over the world. Unfortunately no similar work on Iraqi females was performed previously for comparison. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between magnetic resonance imaging (MRI) findings and histopathologic findings, including histologic type, histologic grade, extensive intraductal component (EIC), estrogen receptor (ER), progesterone receptor (PR), Ki-67, P53, and molecular subtypes in breast cancer. Materials and Methods: The present data was a retrospective review of the patients that underwent breast MRI at King Chulalongkorn Memorial Hospital between January 1, 2014 and December 31, 2016. MRI was assessed for shape, margin, and internal enhancement of the mass lesion, distribution and internal enhancement of the non-mass enhancement lesions, and kinetic curve type and restricted diffusion of both mass and non-mass enhancement lesions. The association between MRI findings and histologic type, histologic grade, EIC, ER, PR, human epidermal growth factor receptor 2 (HER2), Ki-67, P53, and molecular subtypes were evaluated. Results: One hundred seven patients with invasive breast cancers were included in the present study with 99 mass lesions and 8 non-mass enhancement lesions. Rim enhancement of the mass was a significant independent predictor of grade III (high) histologic grade (p=0.001, odd ratio 4.552), negative ER (p=0.001, odd ratio 4.644), negative PR (p=0.021, odd ratio 2.679), and positive Ki-67 status (p=0.022, odd ratio 3.373). Internal enhancement was significantly associated with molecular subtypes such as luminal A subtype appearing as heterogeneous enhancement for 78.3%, HER2-overexpressed and triple negative subtypes dominantly presented with rim enhancement for 76.9% and 75%, respectively. The authors found that spiculated tumor margin of the mass was significantly associated with negative EIC (p=0.006). Restricted diffusion of all lesions was also a significant independent predictor of negative EIC (p=0.022, odd ratio 7.417) and Ki-67 positive (p=0.028, odd ratio 7.182). Conclusion: The consistency of the association between rim enhancement and high histologic grade, negative ER/PR, positive Ki-67 statuses in the present study may help to determine that rim enhancement was likely to predict poor pathologic prognosis of breast cancer. Rim enhancement may also predict poor molecular subtypes including HER2-overexpressed and triple negative subtypes. These results suggest that rim enhancement is the most useful MRI finding to predict histopathology and molecular subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is heterogeneous disease. From this; a special group of tumors, triple negative tumors, has a distinct interest from having its unique behaviors regarding biological, clinical, histological, hormone receptors status, Her2/neu expression, and therapeutic modalities. We made a study on Iraqi women, with triple negative tumors, focusing on some important parameters in this group of patients, comparing our results with the others (from the world). We conclude that most of these parameters are identical except the tumor grade, where we found that it is significantly low. Results from studies done before on Iraqi women, for the same purpose, showed some differences from ours. These differences include percentage of these tumors among other types of breast tumors (our results looked less), grade of tumors (our results showed medium grade), and lymph nodes metastasis which looked less in our study. [ABSTRACT FROM AUTHOR]

The adoption of neoadjuvant chemotherapy (NACT) for breast cancer (BC) is increasing. The need to repeat the biomarkers on a residual tumor after NACT is still a matter of debate. We verified estrogen receptors (ER), progesterone receptors (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) status changes impact in a retrospective monocentric series of 265 BCs undergoing NACT. All biomarkers changed with an overall tendency toward a reduced expression. Changes in PR and Ki67 were statistically significant (p = 0.001). Ki67 changed in 114/265 (43.0%) cases, PR in 44/265 (16.6%), ER in 31/265 (11.7%) and HER2 in 26/265 (9.8%). Overall, intrinsic subtype changed in 72/265 (27.2%) cases after NACT, and 10/265 (3.8%) cases switched to a different adjuvant therapy accordingly. Luminal subtypes changed most frequently (66/175; 31.7%) but with less impact on therapy (5/175; 2.8%). Only 3 of 58 triple-negative BCs (5.2%) changed their intrinsic subtype, but all of them switched treatment. No correlation was found between intrinsic subtype changes and clinicopathological features. To conclude, biomarkers changes with prognostic implications occurred in all BC intrinsic subtypes, albeit they impacted therapy mostly in HER2 negative and/or hormone receptors negative BCs. Biomarkers retesting after NACT is important to improve both tailored adjuvant therapies and prognostication of patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are cytokines of particular interest in oncology from the perspective of neutropenia management (Mehta et al., 2015 [1]) and also as indirect activators of tumor-associated macrophages and modifiers of tumor microenvironment. Associated with poor breast cancer survival and unfavorable hormone receptor status (Wintrob et al., 2017 [2]), insulin may also influence hematopoiesis, thus interfering with colony stimulating factor production. Although G-CSF has been linked to exacerbating insulin resistance (Ordelheide et al., 2016 [3]), thus far no study linked insulin treatment and hematopoietic cytokines production. Additionally, IL-7 is the primary driver of T and B cell differentiation, maturation, and response (Corfe and Paige, 2012 [4]) and its elevated levels have been associated with poor prognosis in breast cancer. The data presented here is among the first to show a relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, hematopoietic cytokine profiles at time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between G-CSF, GM-CSF, and IL-7 stratified by insulin use, controls, as well as by estrogen and progesterone receptor status is also provided.

This study is descriptive exploratory in Thi

Although the function of microRNA-21 and microRNA-206 in breast cancer cells have been investigated in vitro, their association with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are not reported. ER, PR, HER2, and Ki-67 staining pattern were utilized to classify 75 breast cancer patients recruited. The malignancy was predicted with tumor nodes metastases (TNM) classification. RT-qPCR was performed to detect the relative expression of ER, PR, and HER2 in tumor samples and microRNA-21 and microRNA-206 in the serum. Spearman's correlation analysis was used to determine the association between different molecules. According to the staining pattern, the breast cancer patients were classified into five types. microRNA-21 was up-regulated in HER2 positive and Basal-like breast cancer types, while microRNA-206 was up-regulated in Luminal A and B types of breast cancer. microRNA-21 expression negatively correlated with the level of ER and PR but positively correlated with HER2 expression and tumor malignancy, while microRNA-206 showed the opposite trend. Neither microRNA-21 nor microRNA-206 showed any significant correlation with the age of the patients. Both microRNA-21 and microRNA-206 closely correlate with ER, PR, and HER2 expression, which can be considered as clinical biomarkers. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in household materials. Their environmental persistence has led to continuous human exposure and significant tissue levels. Three PBDE congeners (BDE-47, BDE-100, and BDE-153) have been frequently detected in human serum. Although these compounds appear to possess endocrine disrupting activity, studies are largely missing to determine the biological mechanisms of PBDEs in breast cancer cells. Here, we assessed PBDE bioactivities with three complementary strategies: receptor binding/activity assays; nonbiased RNA-sequencing analysis using an estrogen-dependent breast cancer cell line MCF-7aroERE; and in vivo assessments using patient-derived xenograft (PDX) models of human breast cancer. According to the results from in vitro experiments, the PBDE congeners regulate distinct nuclear receptor signaling pathways. BDE-47 acts as a weak agonist of both estrogen receptor α (ERα) and estrogen-related receptor α (ERRα); it could stimulate proliferation of MCF-7aroERE and induced expression of ER-regulated genes (including cell cycle genes). BDE-153 was found to act as a weak antagonist of ERα. BDE-100 could act as (1) an agonist of aryl hydrocarbon receptor (AhR), inducing expression of CYP1A1 and CYP1B1 and (2) as a very weak agonist/antagonist of ERα. In vivo, a mixture of the three congeners with ratios detected in human serum was tested in an ER+ PDX model. The mixture exhibited estrogenic activity through apoptosis/cell cycle regulation and increased the expression of a proliferation marker, Ki-67. These results advance our understanding of the mechanisms of PBDE exposure in breast cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is aimed to demonstrate the changes in the tumor diameter and expressions of vascular endothelial growth factor (VEGF), estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Cerb-B2 status after neoadjuvant chemotherapy in the patients with locally advanced breast cancer. Materials and Methods: Sixty-nine patients who diagnosed with locally advanced breast cancer and treated with were prospectively evaluated. The tumor diameter and VEGF, Ki-67, E R, P R, a nd C erb-B2 expressions tested by immunohistochemistry (IHC) were evaluated before and after neoadjuvant chemotherapy. Results: There was a statistically significant reduction in the tumor diameter and in the expression of VEGF, Ki- 67, ER, PR, and Cerb-B2 after neoadjuvant chemotherapy. Conclusion: The significant reduction in VEGF expression suggests that the tumor angiogenesis and its metastatic ability may be reduced by neoadjuvant chemotherapy. The significant change in the Ki-67 proliferation index may suggest the reduced proliferative activity of malignant cells with neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Some breast carcinomas (BC) of the HER-2 type respond poorly to endocrine therapy, indicating that hormonal receptor (HR) status possibly impacts the biological criteria of this tumor class. The aim of this study was to compare the clinicopathological characteristics of HR-positive and HR-negative tumors occurring in HER-2 and non-HER-2 BC. Methods Tissue microarray sections from 336 primary invasive BC specimens were stained immunohistochemically with antibodies against HER-2, ER, and PR. Proliferation was assessed using Ki67 and the P53 status was identified. Results The HER-2 phenotype was identified in 42/336 (12.5%) specimens, while 293/336 (87.5%) were of the non-HER-2 phenotype. In the non-HER-2 group , 103/293 (35%) were HR-negative tumors. HR negativity was significantly associated with higher tumor grades (P < 0.0001), higher proliferation rates (P < 0.0001), presence of necrosis (P < 0.0001), and with a higher P53 expression (P < 0.0001). There were no differences in patient age, tumor size, LN status, or presence of vascular invasion (VI) between the HR-negative and HR-positive groups. In the HER-2 group , 16/42 (38%) had HR-negative tumors. No significant difference in clinicopathological characteristics, except for tumor grade, was detected between the HR-positive and HR-negative tumors in this group. Conclusion Loss of HR does not influence the biological features of HER-2 BC. This finding may indicate that some tumors will 'biologically' move from being HER-2-positive/HR-positive tumors to behaving more like HER-2-positive/HR-negative tumors even when ER are present on the cell surface. Further studies are needed to explore this hypothesis and to identify the subset of tumors that will benefit from endocrine therapy. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cause of cancer in women. This tumor is hormone dependent tumor and oncologists use estrogen receptor (ER), progesterone receptor (PR) and HER2 for treatment of this malignancy. Androgens like testosterone and their receptors (AR) have a role in the pathophysiology of breast cancer but their clinical values are not clear. Method: AR expression was evaluated in 49 patients with breast cancers using immunohistochemistry. Testosterone was evaluated with ELISA. The relation of clinical characteristics and biomarkers with AR and testosterone were analyzed. According to the percentage of stained cells AR categorized to: AR-absent (0%), AR-poorly (1%-10%), AR-moderately (>10%-50%), and AR-highly (>50%) positive. Results: Among 49 patients with breast cancer, 34% were AR-positive and 44% of ERpositive and 22% of ER negative patients were AR-positive. There was no significant association between mean of testosterone and AR, ER, PR and HER2. AR was positive more frequently but not significantly statistically in older patients and patients less than 45 years of age. Testosterone level was higher in ER positive patients than ER negative and lower in AR positive patients than AR negative patients, but these findings were not statistically significant. ten persent of breast cancers were triple negative and AR was negative in all of them. Conclusion: Androgens and AR have role in pathophysiology of breast cancer and in the future one can use the potency of this pathway for the treatment of breast cancer.

Breast cancer is one of the leading causes of morbidity and mortality that is in need of novel diagnostics and therapeutics. Meta-analysis of microarray data offers promise to combine studies and provide more robust results. We report here a molecular classification of pathological subtypes (estrogen receptor [ER], progesterone receptor [PR], and Human Epidermal Growth Factor Receptor 2 [HER2]) of breast cancers with microRNA (miRNA)-dependent signatures. A ranking-based meta-analysis approach was applied to eight independent microarray data sets and meta-miRNA lists were obtained that are specific to each breast cancer subtype. The comparison of the lists with miRCancer and the PhenomiR 2.0 databases pointed out nine prominent miRNAs: let-7b-5p, let-7c-5p, let-7e-5p, miR-130a-3p, miR-30a-5p, miR-92a-1-5p, miR-211-5p, miR-500a-3p, and miR-516b-3p. Further analysis conducted with the TCGA data showed that these miRNAs can differentiate tumors from normal samples as well as discriminate the molecular subtypes of breast cancer. According to the PAM50 classification, three of these miRNAs (let-7b-5p, let-7c-5p, and miR-30a-5p) downregulated significantly, whereas miR-130a-3p, miR-92a-1-5p, miR-211-5p, and miR-500a-3p upregulated in tumors from the luminal A to the basal-like subtypes. When the prominent meta-miRNAs and their targets were analyzed, they appeared to be taking part in important signaling pathways in cancer such as the PI3K-Akt signaling and the p53 signaling pathways. Furthermore, the regulatory genes, which are key players for ER, PR, and ErBb signaling pathways, were found to be under control of several meta-miRNAs. These meta-miRNAs and the genes they are regulating offer new promise for future translational research and potential targets for precision medicine diagnostics. [ABSTRACT FROM AUTHOR]