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The percentage of tumours exhibiting positive and negative response to oestrogen and progesterone receptors in tumour cells according to histological type of tumour
Source publication
Aim of the study:
Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to horm...
Context in source publication
Context 1
... women over 50 years old (postmenopausal) ER was detected in 73% of patients, while PR expression was observed in 64%, but there was no expression of PR in 36% of cases. Taking into account the histological type of tumour, a positive reaction for oestrogen receptor was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC (Table 2, Fig. 1). Considering the histological grading, ER expression in the greatest percentage (72%) was observed in invasive sec- ond grade (G2) carcinomas. ...
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Purpose
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Citations
... In breast cancer, the presence of ER serves as a favorable prognostic marker, as it is associated with less aggressive tumors, leading to higher overall survival rates and longer disease-free survival compared to ER-negative tumors [25]. Given the importance of ER in breast cancer and considering the differential effect of EB1089 on ERα expression in ER-positive and ER-negative breast cancer cells (as depicted in Figure 1 These results indicate that the addition of EB1089 to treatments with lapatinib and antiestrogens and their combinations decreases ERα protein expression in HER2-positive breast cancer cells expressing ER. ...
... ER is a favorable prognostic marker in breast cancer, and its presence is associated with less aggressive tumors, leading to higher overall survival rates and longer diseasefree survival than ER-negative tumors [25]. Patients with ER-negative/HER2-positive breast cancer experience earlier relapses than those with ER-positive/HER2-positive disease [45]. ...
HER2-positive breast cancer is associated with aggressive behavior and reduced survival rates. Calcitriol restores the antiproliferative activity of antiestrogens in estrogen receptor (ER)-negative breast cancer cells by re-expressing ERα. Furthermore, calcitriol and its analog, EB1089, enhance responses to standard anti-cancer drugs. Therefore, we aimed to investigate EB1089 effects when added to the combined treatment of lapatinib and antiestrogens on the proliferation of HER2-positive breast cancer cells. BT-474 (ER-positive/HER2-positive) and SK-BR-3 (ER-negative/HER2-positive) cells were pre-treated with EB1089 to modulate ER expression. Then, cells were treated with EB1089 in the presence of lapatinib with or without the antiestrogens, and proliferation, phosphorylation array assays, and Western blot analysis were performed. The results showed that EB1089 restored the antiproliferative response to antiestrogens in SK-BR-3 cells and improved the inhibitory effects of the combination of lapatinib with antiestrogens in the two cell lines. Moreover, EB1089, alone or combined, modulated ERα protein expression and reduced Akt phosphorylation in HER2-positive cells. EB1089 significantly enhanced the cell growth inhibitory effect of lapatinib combined with antiestrogens in HER2-positive breast cancer cells by modulating ERα expression and Akt phosphorylation suppression. These results highlight the potential of this therapeutic approach as a promising strategy for managing HER2-positive breast cancer.
... This is following the report on Polish women that showed an association between tumour grades and HR positivity. 17 The present study showed that grade II tumours had a higher ER and PR positive frequency than grade III. Meanwhile, a previous report indicated that the number of cells expressing ER and/or PR gradually decreases with disease progression. ...
... 18 This was substantiated by Badowska-Kozakiewicz et al. who showed an inverse correlation between ER expression and the size of the primary tumour. 17 Specifically, in addition to positively predicting therapeutic outcomes, ERα is believed to inhibit epithelial-mesenchymal transition by promoting epithelial phenotype and preventing tumour invasion in breast cancer. 19 Moreover, higher HR positivity was observed than in many African populations, including Guinea, Ghana, South Africa and Mali. ...
Objectives
Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.
Methods
In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.
Results
Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.
Conclusion
Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.
... Invasive breast cancer with oestrogen receptor positivity has been associated with a favourable prognosis since it suggests a less aggressive tumour. Compared to oestrogen receptor-negative tumours, survival and disease-free duration are relatively long (17). Two extensive studies of 4,444 and 348 cases of invasive breast carcinoma, using c-KIT to stain the mast cells, concluded that stromal mast cells in invasive breast carcinoma were associated with a favourable prognosis (18,19). ...
Background
Mast cells influence tumour growth, neo-angiogenesis and the propensity for metastasis by contributing to innate and adaptive immune responses in the tumour microenvironment. The number of mast cells has increased in various malignant tumours and their abundance has been associated with either a favourable or unfavourable prognosis. This study investigated the significant difference in stromal mast cell density among multiple prognostic factor groups in invasive breast carcinoma.
Methods
CD117 (c-KIT) antibodies were used to stain 160 formalin-fixed and paraffin-embedded invasive breast carcinoma tissues to demonstrate the presence of mast cells. Then the labelled mast cells were counted in 10 fields at 400× magnification and the mean value was used to represent the mast cell density.
Results
The demographic distribution revealed that most patients were 40 years old or older (92.5%) and of Malay ethnicity (66.3%). With regard to prognostic factors, the most prevalent subtype was invasive carcinoma of no special type (80.6%), followed by tumour grade 3 (41.3%), T2 tumour size (63.1%), N0 lymph node stage (51.3%), presence of lymphovascular invasion (59.4%), positive oestrogen (64.4%) and progesterone receptors (53.1%), and negative human epidermal growth factor receptor 2 (HER2) expression (75.0%). However, there was no significant difference in stromal mast cell density among the different demographic and prognostic factor groups in invasive breast carcinoma.
Conclusion
The findings from this study suggest that stromal mast cells do not play a significant role in preventing or promoting tumour growth in invasive breast carcinoma.
... This type is negative for hormone receptors and HER2, and thus, both endocrine therapy and HER2-targeted therapy are ineffective for its treatment. Generally, only chemotherapy drugs can be used [6][7][8]. ...
Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE–RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine–AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol–AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.
... Other dysregulated enzymes involved in cancer cell metabolism reprogramming and detected by proteomics technics are listed in Table 1. Nuclear receptors/TFs that regulates transcription of estrogen target genes [67]; ERα is a promoter of cell proliferation/tumorigenesis in BC, and ERβ suppresses cell proliferation [68] IHC [116], MALDI-TOF MS [67], LC-SRM MS [27]; multiplex IHC-MALDI-MSI (MALDI-IHC) [17] More than 70% of all BC are ERα [117] Diagnostic biomarkers, classification of BC subtypes [67] nLC/ESI-MS/MS; MALDI-MS/MS (MS n ) [70] PTMs and PPI modulate activity: ubiquitination [117]; phosphorylation [70] Tamoxifen resistance [72] Progesterone receptors PR isoforms: PRA & PRB TFs that modulate ERα action in BC [118]; exhibits both activatory and repressive effect on gene transcription [119] IHC [116]; LC-SRM MS [27]; multiplex IHC-MALDI-MSI (MALDI-IHC) [17] Association between ERα/PR induces cell proliferation and tumor growth [120] Predictive biomarker [121], prognostic and predictive biomarker of response to endocrine therapy [118] Androgen receptor AR Nuclear TF that mediates the biological effects of androgens; tumor suppressor in ER+ BC and inducer of tumor progression in ER-BC, including HER2+ and TNBC [68], it has a crucial role in BC pathology and progression [122] IHC [123], PRM targeted proteomic [124] Expressed in 70-90% of the BCs [122]; upregulated in luminal A & B subtypes of BC and a subset of TNBC; positive immunostaining was associated with smaller tumor size [123] Possible prognostic biomarker [123]; potential therapeutic target in AR+ BC patients [122] Human epidermal growth factor receptor 2 HER2/neu, c-erbB2 ...
Immunohistochemistry (IHC) is still widely used as a morphology-based assay for in situ analysis of target proteins as specific tumor antigens. However, as a very heterogeneous collection of neoplastic diseases, breast cancer (BC) requires an accurate identification and characterization of larger panels of candidate biomarkers, beyond ER, PR, and HER2 proteins, for diagnosis and personalized treatment, without the limited availability of antibodies that are required to identify specific proteins. Top-down, middle-down, and bottom-up mass spectrometry (MS)-based proteomics approaches complement traditional histopathological tissue analysis to examine expression, modification, and interaction of hundreds to thousands of proteins simultaneously. In this review, we discuss the proteomics-based identification of dysregulated proteins in BC that are essential for the following issues: discovery and validation of new biomarkers by analysis of solid and liquid/non-invasive biopsies, cell lines, organoids and xenograft models; identification of panels of biomarkers for early detection and accurate discrimination between cancer, benign and normal tissues; identification of subtype-specific and stage-specific protein expression profiles in BC grading and measurement of disease progression; characterization of new subtypes of BC; characterization and quantitation of post-translational modifications (PTMs) and aberrant protein–protein interactions (PPI) involved in tumor development; characterization of the global remodeling of BC tissue homeostasis, diagnosis and prognostic information; and deciphering of molecular functions, biological processes and mechanisms through which the dysregulated proteins cause tumor initiation, invasion, and treatment resistance.
... 6 Approximately 75% of all BC patients have oestrogen-receptor-positive cancer, which is predictive of the effect of antihormonal therapy. 7 Since patients diagnosed with early-stage BC are at risk of longterm cancer recurrence (>5 years after the diagnosis), prevention treatment with anti-oestrogens is indicated to decrease the risk of recurrence and improve BC-specific survival. 8 Main adjuvant treatments include tamoxifen (selective oestrogen receptor modulator [SERM]) and aromatase inhibitors (AIs). ...
Introduction
Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment are increasingly in the spotlight. The beneficial effects of anti-oestrogen therapy with tamoxifen and letrozole in the prevention of BC recurrence are well documented. While the most common side-effects of this therapy are well-defined, less is known about its effects on thyroid function. In women treated for early BC, an average of 1–5 kg weight gain has been observed after treatment with chemotherapy/anti-oestrogens. We aim to evaluate the current knowledge on the side effects of tamoxifen and letrozole treatments on thyroid function, followed by its potential influence on the observed weight gain.
Methods
We searched PubMed and found 16 publications on thyroid function and tamoxifen treatment in pre- and post-menopausal women with early- and advanced BC, whereas five publications on letrozole treatment in post-menopausal women with advanced BC.
Results
According to the current literature, there is an overall tendency towards a mild and transient thyroid dysfunction, that is, subclinical hypothyroidism in tamoxifen-treated patients. Only one publication reported further significant changes in thyroid hormones beyond one year of tamoxifen treatment. No significant changes in thyroid function have been observed among letrozole-treated patients.
Conclusion
Tamoxifen-treated patients can develop mild and transient thyroid dysfunction within the first 12 months, yet further significant changes in thyroid function beyond one year of tamoxifen treatment have been reported in a single study. There is no evidence of thyroid dysfunction in letrozole-treated patients. Current literature does not focus on subclinical hypothyroidism as a possible cause of weight gain in patients with BC. Subgrouping of BC patients and studies with a longer observation of thyroid hormones and weight changes during and after anti-oestrogen treatment are needed to further elucidate how anti-oestrogens affect thyroid function.
... However, they may show some toxicity in cancer cells. Thus, they are considered to be attractive candidates for patients treatment, including adjuvant cancer therapy and gene therapy strategies [23,24]. Due to the similar structure of ecdysones and steroid hormones, one of the hypothesis assumes that estrogen receptors (beta type) can mediate the biological activity of ecdysones. ...
The present study was designed to identify the biological activity of three ecdysones, i.e., 20-hydroxyecdysone (20-HE), ajugasterone C, and polypodine B isolated from Serratula coronata. The main objective was to investigate the molecular mechanism of the biological activity of those compounds and to assess their impact on breast cancer cell survival and cell cycle. Cell lines were selected according to their hormone receptor status since this factor is perceived as a crucial one in the cancer prognosis as well as cancer cell response to therapy. Consequently, MCF7 (ER/PR+, HER2-), T-47D (ER/PR+, HER2-/+), and MDA-MB-231 (ER/PR-, HER2-) were enrolled in the study. Additionally, a non-tumorigenic, MCF10A cells were selected to verify any potential specificity to cancer cells. Interestingly, none of the studied compounds affected the viability of MCF10A cells while cancer cells were altered, albeit in different ways. Polypodine B did not affect the viability or cell cycle distribution of studied breast cancer cells. By contrast, 20-HE and ajugasterone C significantly inhibited the viability of triple-negative cell line, MDA-MB-231. Interestingly, 20-HE revealed proapoptotic activity in MDA-MB-231 and T-47D cells that was manifested by alterations in PARP, Bax, and Bcl-2 levels as well as caspase-3 activation. Moreover, 20-HE induced autophagy that was mediated by modification of autophagy-associated proteins, i.e., LC3, p62, and mTOR, but only in MDA-MB-231 cells. This study is the first to report diverse biological activity of phytoecdysones in different breast cancer cells, that suggests association with molecular characteristics including receptor status but also other biological properties and genetic markers.
... Although no previous studies have reported on patients from the Sudan or neighboring countries, this result is in line with many studies in more developed countries, either prospective or retrospective, regarding the frequency of ERβ expression in breast cancer. 15 ERβ was detected in 48% of samples from 67 breast cancer patients. 16 In comparison, a study by Gruvberger-Saal et al, 11 investigated 353 breast tumors, concluding that 74% of the cases stained positive for ERβ. ...
... This finding is in agreement with results reported by Marotti et al, 18 where 85% of grade I, 71% of grade II, and 49% of grade III breast cancers showed positive ERβ staining. Moreover, another study concluded that ERβ was associated with lower tumor grade; 15 however, others have shown no correlation between the presence of ERβ and better grade. 30 The expression of ERβ was significantly associated with negative lymph node involvement as the highest level of expression (62.6%) was detected among node-negative breast cancer. ...
... 19,21 There was no evidence of significant relationship between ERβ expression and age group in this study. This result is in agreement with studies, 15,21 which found that the expression of ERβ was normally distributed irrespective of patient age. ...
Two estrogen receptor isoforms (ERα and ERβ) have been characterized with variable and sometimes contrasting responses to estrogens, partially explained by different receptor signaling pathways in estrogen-sensitive tissues. This is a retrospective, descriptive, cross-sectional study, aiming to evaluate the expression pattern of ERβ, employing immunohistochemical techniques using specific monoclonal antibody for ERβ, to correlate its expression with that of ERα in a Sudanese population. Two-hundred and fifty formalin-fixed paraffin-wax-embedded breast tissue blocks were used in this study. Of these, 200 were taken from breast cancer patients ascertained as study cases, and the remaining 50 were noninvolved surgical margin considered as normal breast tissue. Receptor expression was demonstrated using immunohistochemical techniques. The immune expression of ERβ was detected in 57.5% of breast cancers. It was differentially expressed in breast tissues encompassing normal, noninvasive, as well as invasive carcinoma ( P = .02). There was no evidence of a significant relationship between ERβ and ERα expression. Among the ERα-negative tumor, 60.4% expressed ERβ. The expression of ERβ among this subgroup was significantly associated with good clinicopathological parameters such as negative Her2/neu, lower grade, and negative lymph node metastasis ( P = .002). This study concludes that ERβ was commonly expressed among Sudanese patients with breast cancer, either co-expressed with ERα or expressed alone. In the ERα-negative subgroup, it was associated with better tumor outcomes suggesting ERβ should be included in the diagnostic protocol as an independent marker for favorable prognosis.
... Comprehensive gene expression profiling revealed five major molecular subtypes of breast cancer which are luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive, basal like, and normal like [2]. Luminal breast cancer is hormone dependent and characterized by the expression of estrogen receptor (ER) and/or progesterone (PR) [3]. Endocrine therapy is essential in the treatment of hormone-dependent breast cancer [4]. ...
Hormone-dependent breast cancer is the most abundant molecular subtype of the disease. Despite the availability of endocrine treatments, the use of these drugs is limited by their serious adverse reactions and development of acquired resistance often mediated by growth factor receptors. The hepatocyte growth factor receptor, MET, is a receptor tyrosine kinase known for its oncogenic activity and mediating resistance to targeted therapies. Crizotinib is a small-molecule tyrosine kinase inhibitor of MET. In this study, the anticancer effects of combined crizotinib and endocrine drugs were investigated in breast cancer cells in vitro along with the molecular mechanisms associated with these effects. Results showed that crizotinib inhibited growth of MCF7 and T-47D breast cancer cells in a dose-dependent manner with IC50 values of 2.88 μM and 0.93 μM, respectively. Combined treatment of crizotinib and 4-hydroxytamoxifen resulted in synergistic growth inhibition of MCF7 and T-47D cells with combination index values of 0.39 and 0.8, respectively. The combined treatment significantly suppressed migration and colony formation of MCF7 and T-47D cells. Immunofluorescence showed a significant reduction of the expression of the nuclear protein Ki-67 with the combination of crizotinib and 4-hydroxytamoxifen in both cell lines. Western blotting indicated that the combination treatment reduced the levels of active and total MET, estrogen receptor α (ERα), total and active levels of AKT, ERK, c-SRC, NFĸB p65, GSK-3β, and the anti-apoptotic BCL-2 protein. Findings from this study suggest a potential role of MET inhibitors in breast cancer treatment as monotherapy or combination with endocrine drugs.
... [9,10] In general, it was estimated that 70%-80% of BC in women express high ER. [11] In healthy women, ER expression is largely heterogeneous within different areas of breast tissue. Only a small fraction of epithelial cells in ducts and lobules are ER-positive. ...
... P = 0.01) which implies that BC women with T2 stage are 3.7-time less likely to have high ER expression compared with women with T1 stage. In accordance with this result is the study of Badowska Kozakiewicz et al. [11] among Polish women. Analysis of ER and PgR expression showed that the greater expression of ER was in the T1 stage (51%), while only 1%-2% of T3 and T4 stages, respectively, expressed ER. Almost similar result was also obtained by Faheem et al. [19] among Pakistani women. ...
... Sofi et al. [18] found that patients with no involvement of lymph node and lower tumor grade were more likely have high expression of ER/PgR compared to patients with multiple lymph node involvement and advance stage. Almost similar results were obtained by Badowska-Kozakiewicz et al., [11] suggesting the inverse relationship between the high expression of steroid hormonal receptor and the aggressiveness of BC. ...
Background: The detection of the estrogen receptor (ER) and progesterone receptor (PgR) in women with breast cancer (BC) is considered a crucial step for prognostic evaluation and treatment choice in clinical practice. Objectives: This study aimed to evaluate the expression of the hormonal receptors (ER and PgR), their distribution, and their association with clinicopathologic prognostic parameters in a sample of Iraqi women with BC. Materials and Methods: The paraffin-embedded blocks from a total of 80 women diagnosed with primary invasive breast carcinomas with BC were examined by immunohistochemistry to assess the expression of ER and PgR status. Demographic and clinical data were collected from each patient in the preformed questionnaire. The association of steroid receptor expression with clinicopathologic parameters was assessed using binary logistic regression. Results: Among 80 BC women involved in the study, 54 (67.5%) and 39 (48.75%) had high expression of ER and PgR, respectively. High ER expression was significantly associated with older age (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.16-19.81, P = 0.03), postmenopausal status (OR = 3.6, 95% CI = 1.25–10.33, P = 0.015), smaller tumor (OR = 0.27, 95% CI = 0.09–0.75, P = 0.01), and with noninvolvement of lymph node (OR = 0.11, 95% CI = 0.02–0.51, P = 0.005). High PgR expression, on the other hand, was significantly associated with older age (OR = 4.44, 95% CI = 1.02–19.39) and postmenopausal status (OR = 3.13, 95% CI = 1.24–7.88, P = 0.016). Concomitant overexpression of both receptors was significantly associated with postmenopausal status and noninvolvement of lymph nodes. Conclusion: High expression of ER and PgR seems to be a good prognostic indicator because it was associated with less aggressive tumors.
