PR Levels Research Articles

Mechanistic Regulation of Epidermal Growth Factor and Hormonal Receptors by Kinase Inhibitors and Organofluorines in Breast Cancer Therapy.

Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC50 of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

Serum miRNA-1 may serve as a promising noninvasive biomarker for predicting treatment response in breast cancer patients receiving neoadjuvant chemotherapy

BackgroundMicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with drug sensitivity. Circulating miRNAs have been proven to be potential biomarkers with predictive and prognostic value. However, studies of miR-1 expression in the serum of breast cancer (BC) patients are relatively scarce, especially in patients receiving neoadjuvant chemotherapy (NAC).MethodsSerum samples from 80 patients were collected before chemotherapy, and RT-PCR was performed to detect the serum expression of miR-1. The correlation between miR-1 expression in serum and clinicopathological factors, including pathological complete response (pCR), was analyzed by the chi-squared test and logistic regression. KEGG and GSEA analysis were also performed to determine the biological processes and signalling pathways involved.ResultsThe miR-1 high group included more patients who achieved a pCR than did the miR-1 low group (p < 0.001). Higher serum miR-1 levels showed a strong correlation with decreased ER (R = 0.368, p < 0.001) and PR (R = 0.238, p = 0.033) levels. The univariate model of miR-1 for predicting pCR achieved an AUC of 0.705 according to the ROC curve. According to the interaction analysis, miR-1 interacted with Ki67 to predict the NAC response. According to the Kaplan–Meier plot, a high serum miR-1 level was related to better disease-free survival (DFS) in the NAC cohort. KEGG analysis and GSEA results indicated that miR-1 may be related to the PPAR signalling pathway and glycolysis.ConclusionsIn summary, our data suggested that miR-1 could be a potential biomarker for pCR and survival outcomes in patients with BC treated with NAC.

BREAST CANCER SUBTYPES IN PAKISTANI POPULATION: DATA FROM A SINGLE CENTER

Breast cancer is a complex disease that includes different types of tumors. These tumors can vary in their characteristics, such as the levels of estrogen, progesterone, and HER2/neu receptors. These differences can impact how the tumors respond to treatment, progress, and change over time. The study conducted at the Department of Oncology, Jinnah Hospital, Lahore, from May to November 2019, was a cross-sectional study that involved 90 female patients with breast cancer aged 25 to 75. The researchers analyzed the tumor samples using immunohistochemistry to evaluate ER, PR, and HER2neu levels. FISH was used to evaluate models that had equivocal HER2 by IHC. The participants in this study were 25 to 75 years old, with an average age of 47.10 ± 11.55 years. The average duration of the disease before presenting to the hospital was 6.71 ± 2.63 months. The study found that 74.44% of the female patients had tumors that were ER-positive, 56.67% had tumors that were PR-positive, and 20.0% had tumors that were HER2neu-positive. In conclusion, this study showed that the frequency of positive expression of estrogen, progesterone, and HER2neu in breast cancer patients in this population was consistent with international rates. However, more extensive studies are necessary to determine the exact prevalence of these tumors.

Association between light rare earth elements in maternal plasma and the risk of spontaneous preterm birth: a nested case-control study from the Beijing birth cohort study

BackgroundParental exposure to rare earth elements (REEs) could increase the risk of premature rupture of membranes, a major cause of spontaneous preterm birth (SPB). In addition, different subtypes of SPB, such as spontaneous preterm labor (SPL) and preterm premature rupture of membranes (PPROM), may have different susceptibility to environmental exposure. Therefore, we investigated the potential associations between REE exposure in different trimesters and SPB and its subtypes.MethodsA nested case-control study was performed. We included 244 women with SPB as cases and 244 women with full-term delivery as controls. The plasma concentrations of light REEs were measured in the first and third trimesters. Logistic regression was used to analyze the associations between single REE levels and SPB, and Bayesian kernel machine regression (BKMR) was used to analyze the mixed-exposure effect.ResultsExposure to light REEs was associated with SPB and its subtypes only in the third trimester. Specifically, the intermediate- and highest-tertile concentration groups of La and the highest-tertile concentration group of Sm were associated with an increased risk of SPL, with adjusted odds ratios (AORs) of 2.00 (95% CIs: 1.07–3.75), 1.87 (95% CIs: 1.01–3.44), and 1.82 (95% CIs: 1.00–3.30), respectively. The highest-tertile concentration group of Pr was associated with an increased risk of PPROM, with an AOR of 1.69 (95% CIs: 1.00–2.85). Similar results were also found in BKMR models.ConclusionsLa and Sm levels in plasma may be associated with the risk of SPL, and Pr levels in plasma may be associated with the risk of PPROM.

Biocomposites based on poly(lactic acid)/Aloe Vera/Priplast. Effects of UVA radiation on the crystallization

AbstractBiocomposites based on poly(lactic acid) (PLA), Aloe Vera (AV), and Priplast (Pr), were produced with AV and Pr levels of 5% and 10%, and submitted to UVA radiation for a time interval up to 28 days. Chemical changes were investigated using Fourier transform infrared spectroscopy (FTIR) and the thermal behavior was elucidated using differential scanning calorimetry (DSC); the non‐isothermal crystallization kinetics was modeled using the Pseudo‐Avrami model. FTIR spectra evidenced the formation of chromophore groups resulting from the photodegradation, which it was less intense in biocomposites with 10% Pr. AV addition promoted the cold crystallization, whereas the crystallization rate () displayed higher values for PLA/10%AV, with slight increases in the degree of crystallinity (Xc); while Pr addition decreased the Xc and of PLA, and protected it more intensely against the photodegradation effects. Pseudo‐Avrami model presented R2 ≥ 0.9909 and a low discrepancy between experimental and theoretical data, being adequate to describe the cold crystallization of PLA biocomposites. Summing up, AV and Pr addition protect PLA against the harmful effects of photodegradation, with AV subtly interfering in the crystalline parameters while Pr provides greater amorphicity to PLA biocomposites.

Abstract CT144: Randomized phase II trial of preoperative fulvestrant with or without enzalutamide for ER+/Her2- breast cancer

Abstract Background: Most estrogen receptor alpha positive (ER+) breast cancers (BCs) express androgen receptor (AR) protein, but its function is unclear. High AR relative to ER is associated with endocrine resistance. This randomized phase II trial of neoadjuvant fulvestrant (F) with or without the anti-androgen enzalutamide (E) was designed to determine if the addition of E to F in women with ≥T2 ER+/Her2- primary BC would increase the % patients (pts) with limited residual disease at time of surgery as measured by modified preoperative endocrine predictive index (PEPI). Methods: 4 months of therapy was given prior to surgery (F 500 mg IM weeks 1, 3, 5, 9, and 13) and pts were randomized to receive E 160 mg po daily for 16 weeks, stratified by node status and T-stage. Tumor biopsies were required at study entry and after 4 weeks on therapy (Wk5). PEPI score at time of surgery was the primary endpoint for efficacy. The minimax two-stage design had 80% power with type I error rate of 0.08. Reverse phase phosphoprotein array (RPPA), IHC for ER/PR/AR/GR/Ki67, and Polaris multiplex immunofluorescence (IF) panel for myeloid lineage immune cells were performed. Average signal levels were compared across arms, PEPI score (0, &amp;gt;0), PEPI by arm, and Ki67 (&amp;lt;10%, ≥10%). Comparisons at both baseline and with treatment were considered. Significance was assessed with empirical Bayes moderated t-statistics. Since exploratory, p-values were not adjusted for multiple testing. Results: 69 pts consented; 59 evaluable. 95% completed surgery. PEPI=0 observed in 10 (17%). Of 33 pts on FE arm, 21 had T3/T4 tumors, 91% ER+/PR+, median AR expression 80%, Ki67 15%. Of 26 patients on F arm, 19% had T3/T4 tumors, 96% ER+/PR+, median AR expression 85%, Ki67 10%. PEPI=0 was achieved more frequently on the FE arm (8, 24%) than the F arm (2, 8%) (p=0.16). Toxicity was as expected with endocrine therapy. IHC of baseline vs Wk5 biopsies showed decreased ER, PR, and Ki67 levels by Wk5 that remained decreased at time of surgery. AR and GR were significantly decreased only in the FE arm at the time of surgery. RPPA revealed that baseline EGFR (Y1604 and Y992) was higher in tumors with PEPI=0 tumors, whereas the average baseline mTOR activation was higher among pts with PEPI&amp;gt;0. Significant changes detected by RPPA upon treatment included a significant decrease in AR. Myeloid-derived suppressor cells (MDSC) were significantly reduced by treatment only in the FE arm. Conclusions: The combination FE had manageable side effects. PEPI=0 was achieved more frequently on the FE arm (8/33) than the F arm (2/26). Activated EGFR was higher pretreatment in tumors achieving PEPI=0. mTOR pathway was elevated pretreatment in PEPI&amp;gt;0 tumors (also observed with resistance to FE in ER+/HER2- metastatic disease (SABCS 2021). When comparing pretreatment tumor to Wk5, total AR by RPPA was the most differentially decreased protein in PEPI=0 tumors. AR signaling is known to support immunosuppressive cells and we observed a marked decrease in MDSCs with treatment only on the FE arm. Citation Format: Anthony D. Elias, Alyse Staley, Monica Fornier, Gregory A. Vidal, Sharon Sams, Nicole Spoelstra, Peter Kabos, Jennifer R. Diamond, Elena Shagisultanova, Rosa I. Gallagher, Julia Wulfkuhle, Emanuel Petricoin, Kathryn Zolman, Stephanie Biller, Vida Alami, Tessa McSpadden, Virginia Borges, Lyndsey S. Crump, Dexiang Gao, Jennifer K. Richer. Randomized phase II trial of preoperative fulvestrant with or without enzalutamide for ER+/Her2- breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT144.

Investigation of pectolytic and PR genes expression, quality and phytochemical contents in organic and non-organic table grapes at harvest and during storage

The demand for organic table grapes is increasing worldwide. However, comprehensive information of quality parameters and phytochemical compounds in organically grown fruit remain unclear. Furthermore, table grapes are perishable and postharvest quality retention and waste prevention is very important. In this study we have compared the differences between organic and non-organic table grapes in terms of phytochemical compounds and quality parameters as well as the changes in the expression levels of pathogen related and lytic genes during storage. Organic fruit showed higher levels of phenolics, flavonoids, caffeic acid, hydrogen peroxide, protein content, antioxidant and anti-stress enzymes and total antioxidant activities at harvest and during storage. Although, the expression levels of polygalactronases, pectin methyl esterase, chitinase and glucanase genes was lower in organically grown table grapes at harvest, but the expression of all these genes was significantly increased during cold storage. After 60 days of cold storage the expression levels of pectin methyl esterase, chitinase and glucanase genes was significantly higher than the conventionally grown grape berries in organic ones. The highest expression of polygalacturonase was recorded in organic samples after 30 days of storage. There was no significant difference between the two types of table grapes for decay extension and tissue deterioration rate. The results of this study indicate that due to higher levels of phytochemicals and antioxidant compounds the organic table grapes have a higher nutritional quality. Furthermore, the increase in PR and pectolytic genes expression levels is enough for decreasing the fruit susceptibility to decay pathogens and enhancing the postharvest life of organic grapes.

Abstract P3-08-05: Correlation of Trop2 expression with in vivo sensitivity to sacituzumab govitecan in a panel of breast XPDX models

Abstract Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop2 with an SN-38 payload recently approved for pretreated patients with locally advanced or metastatic triple-negative breast cancer (TNBC). The XenoSTART Patient-Derived Xenograft (XPDX) breast cancer platform includes over 180 models spanning all subtypes characterized with immunohistochemistry (IHC) including ER, PR, and HER2 protein levels, genomic and transcriptomic sequencing, and in vivo drug sensitivity. To better understand potential benefit of SG in breast cancers other than TNBC and further annotate our platform, Trop2 protein levels were determined in all breast models by IHC. We evaluated tumor growth inhibition by SG in 125 of our XPDX breast models and compared protein expression with agent activity. Methods: 180 breast XPDX models were evaluated for Trop2 expression (AF650, R&amp;D Systems) and 125 were evaluated in vivo against SG; responses were grouped by ER and Trop2 status (+/-). Models were grown subcutaneously in female athymic nude mice and ER+ models supplemented with estradiol. Models were also characterized for PR, HER2, and AR protein expression by IHC and profiled using WES and RNAseq. For in vivo studies, SG was administered by intravenous injection biweekly for two cycles at 1 mg, flat; endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C&amp;lt; 0%) versus Day 0 tumor volume was also reported. Results: 180 breast models were examined by IHC with 75/180 (42%) classified as ER+ and 105/180 (58%) ER-. In ER+ models 38/75 (51%) were Trop2+ and 37/75 (49%) Trop2-, and in ER- models 41/105 (39%) were Trop2+ and 64/105 (61%) Trop2-. In vivo, 20% of ER+/Trop2+ models reported sensitivity to SG, most notably models from patients with acquired resistance to CDK4/6 inhibitors, including STM001 and ST4316B. Interestingly, &amp;gt;70% of ER+/HER2+/Trop2+ models were insensitive to SG, including ST225 and ST340. Of 41 ER-/Trop2+ models, approximately 40% reported some response to SG with 50% of these sensitive to therapy, including ST5954 established from a patient who began treatment with SG following sample collection and is currently in remission. &amp;gt;75% of Trop2- models were insensitive to SG regardless of ER status. Conclusion: We screened 180 models in our XPDX breast cancer platform for Trop2 expression and compared expression with in vivo SG efficacy in 125 models. Analysis is underway to correlate receptor and molecular profiles with SG sensitivity in breast models and we are expanding expression and in vivo testing to additional indications. Citation Format: Alyssa Simonson, Johnnie Flores, Ebony Anderson, Crystal Moreno, George Plasko, Kyriakos P. Papadopoulos, Amita Patnaik, Drew Rasco, Gladys Rodriguez, Amy Lang, Muralidhar Beeram, Luis Rodriguez, Ronald Drengler, Steven Abbate, Hanni Salih, Lon Smith, Maryam Elmi, Brittany DeBerry, Arthur Rosenthal, Tatiana Hernandez, Nehal Lakhani, Manish Sharma, Michael Wick. Correlation of Trop2 expression with in vivo sensitivity to sacituzumab govitecan in a panel of breast XPDX models [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-08-05.

Clinical Features and Prognosis Analysis of Hormone Receptor-Positive, HER2-Negative Breast Cancer with Differential Expression Levels of Estrogen and Progesterone Receptors: A 10-Year Retrospective Study.

Estrogen and progesterone receptor status can predict breast cancer patient prognosis and treatment sensitivity, but research on low ER and PR levels and expression balance remains limited. From January 2010 to October 2016, 283 ER+/PR+/HER2-breast cancer patients who met the inclusion criteria were enrolled and divided into the H group (ER > 10%, N = 261) and the L group (1% ≤ ER ≤ 10%, N = 22). Groups were further divided into the HH group (ER > 10%/PR > 20%, N = 201), the HL group (ER > 10%/ER 1% ≤ PR ≤ 20% PR, N = 60), the LH group (1% ≤ ER ≤ 10%/PR > 20%, N = 5), and the LL group (1% ≤ ER ≤ 10%/1% ≤ PR ≤ 20%, N = 17). The LH group was excluded due to its small size, leaving the clinical and prognostic characteristics of 2 large groups and 3 subgroups to be analyzed. L group patients had significantly more stage N2 axillary lymph nodes than H group patients (31.8% vs. 9.2%, P = 0.007). Age (P = 0.011), menopause status (P = 0.001), and tumor size (P = 0.024) were significantly different in the HL vs. HH and LL groups. Five-year DFS (94.6% vs. 77.0%, P < 0.001) and 5-year OS (97.2% vs. 85.8%, P = 0.001) rates significantly differed between HH and HL. No significant differences in 5-year DFS (77.0% vs. 81.9%, P = 0.564) or 5-year OS (85.8% vs. 87.8%, P = 0.729) rates were observed between HL and LL; the OS rates of HL and LL were similar. In the group of ER+/PR+/HER2-patients, there was no significant prognostic difference between ER-low positive and ER-high positive groups, but low PR expression was significantly associated with a worse prognosis. The role of ER and PR balance in breast cancer progression and individualized treatment requires further investigation.

337 (PB117) - Identification and molecular characterization of invasive lobular breast cancer models in a panel of 180 breast XPDX models

Background: Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Invasive lobular cancer (ILC) characteristics include somatic alterations in the CDH1 gene leading to loss of E-cadherin expression, low HER2 expression, frequent loss of PTEN, increased AKT expression and mutations in PIK3CA, TBX3 and FOXA1 genes. Invasive ductal cancers (IDC) express E-cadherin and more often include HER2+ cancers and ESR1 mutations. The XenoSTART Patient-Derived Xenograft (XPDX) breast cancer platform includes over 180 models spanning all subtypes characterized with immunohistochemistry (IHC) including ERα, PR and HER2 protein levels, genomic and transcriptomic sequencing and in in vivo drug sensitivity. To further annotate our platform, we classified each breast XPDX model as ILC or IDC based on clinical history, E-cadherin staining, presence of variants in target genes and HER2 expression or amplification. Methods: XPDX models were established and validated as previously described and further characterized using IHC to determine E-cadherin protein levels (Abcam a-Rabbit ab15148). Analysis was performed on WES to identify variants in CDH1, PIK3CA, TBX3, FOXA1 and PTEN. RNAseq data was used to determine expression levels of AKT and HER2. Clinical histology data was also used for ILC versus IDC classification. Resulting models classified as ILC by our analysis were histologically confirmed by a clinical pathologist. Results: 180 breast models were examined by IHC and 25/180 (14%) lacked E-cadherin staining. Six of these 25 models (24%) reported CDH1 variants including deletions, frameshifts and point mutations. PIK3CA mutations, most notably H1047R, were reported in 5/25 models and FOXA1 (Q209E) was co-mutated in 2 of these models (ST2167 and ST2167/TDR). High AKT1 expression was reported in 5/25 models. While most E-cadherin-negative models were from clinically HER2 negative patients, 4/25 were from clinically HER2+ patients and corresponding models retained HER2 staining and amplification. 3/25 models were clinically classified as metaplastic and did not contain any target gene variant. Conclusion: We screened 180 models in our XPDX breast cancer platform and identified at least twenty-two ILC models based on E-cadherin staining, genomics and clinical histology, and confirmed heterogeneity of this subtype of breast cancer. Additonal analysis is underway to compare sensitivity of chemotherapy and targeted agents in ILC and IDC-classified breast models. No conflict of interest.

SUMOYLATION MEDIATES PROGESTERONE RESISTANCE IN ENDOMETRIOSIS TREATMENT FAILURE AND IMPAIRED IMPLANTATION

Endometriosis is a debilitating gynecologic disease affecting up to 1-in-10 reproductive-aged women. Progesterone resistance is the primary cause of endometriosis treatment failure as well as contributes to endometriosis related infertility, however the mechanisms mediating progesterone resistance are not completely known. We have previously categorized human endometriotic lesions as having high, medium, or low PR expression in women undergoing surgery for endometriosis. While those with low PR failed to respond to P, some with moderate PR levels also failed to respond, suggesting that posttranslational modifications may mediate progesterone resistance.

What's beyond BRCA Mutational Status in High Grade Serous Ovarian Cancer? The Impact of Hormone Receptor Expression in a Large BRCA-Profiled Ovarian Cancer Patient Series: A Retrospective Cohort Study.

Simple SummaryOvarian hormones are involved in ovarian cancer pathogenesis. However, few reports have investigated the hormone receptor pattern according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the relationship between hormone receptor status and BRCA1/2 mutation in a cohort of 207 high-grade serous ovarian carcinoma (HGSOC) patients. Interesting differences emerged between BRCA-mutated and BRCA wild-type women, in terms of pattern of receptor expression and its association to the outcome. On the whole, our findings, though needing further validation, extend our understanding of the complex interplay between BRCA1/2 protein and hormone signaling, suggesting new pathways to be exploited in order to develop future personalized therapy.Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA1/2-mut as compared to BRCA-wt patients (p = 0.02). None of the examined hormone receptors has revealed a significant prognostic role in the whole sample, apart from the ratio ERα/ERβ5 nuclear, for which higher values disclosed a positive role on the outcome in BRCA-wt subgroup (HR 0.77; CI 0.61–0.96; p = 0.019). Conversely, it negatively affected overall survival in the presence of BRCA1/2-mut (HR 1.41; CI 1.06–1.87; p = 0.020). Finally, higher PR levels were associated with platinum sensitivity in the whole sample (p = 0.019). Our data, though needing further validation, suggest a potential role of oestrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, thus revealing a possible therapeutic potential for targeting this interaction.

Unequal, undiversified and underrepresented: women on the backburner in local decision making in South Africa’s local government

The object of research: Firstly, the study highlights that women are still underrepresented in local government at the district level in leadership positions remaining on the backburner as decision makers. Secondly, the study examines the notion of patriarchy and male dominance that results in the marginalization and exclusion of women in municipal decision making. The study contributes to the current body of knowledge through identifying the challenges that prevent the equal representation of women as decision makers in local government.&#x0D; Investigated problem: South Africa has been consistently praised for its advcancement in drafting a progressive constitution and legislation that provides for gender equality. Despite the progressive achievements, women remain underrepresented at the municipal level, as South Africa has not attained the target of 50/50 equal representation as far as women mayors, women are more likely to be underemployed in comparison to men; women do not receive the same and/or fair remuneration in comparison to their male counterpart and women are not able to progress as fast as men in their careers once in local government structures , into leadership role that grant women equal access to become decision makers alike their male counterpart. The reasons for the low proportion of women to men in leadership is attributed to intersecting oppressions that women remain confronted with and can be seen to be connected to historical patriarchal norms and institutional values, which excludes and marginalizes women and institutional culture is stronger than the process of changing this culture.&#x0D; The main scientific results: The findings of the study suggest that women are lagging behind in decision making. Secondly, organizational structures that are attributed to the presence of dominant behaviours in the workplace can be seen to be linked to patriarchy and male dominance exclude and marginalize women. Thirdly, women’s representation within South Africa at the municipal ward and PR levels is on a downward spiral, when comparing the 2021 electoral results to previous electoral results in 2016. Notably, there is a lack of practicality of women's status in local government, policy enacted such as the Women Empowerment and Gender Equality Bill contains the key element that failure to comply with the Constitution justifies punitive action against the defaulting unit. This includes local councils and executive officers. Clause 11 requires 50 percent representation of women. Highlighting instances of failure to comply, with no punitive actions taken. South African women are passive recipients of male-dominated decision making in local government.&#x0D; The area of practical use of the research results: South African public and private sector institutions. Any persons connected to gender justice within society

167MO Association between ER, PR and HER2 levels and outcome under palbociclib (Pal) + aromatase inhibitors (AIs) as first-line therapy for ER+ HER2- metastatic breast cancer (MBC): An exploratory analysis of the PADA-1 trial

In 1st-line trials, the relative Progression Free Survival (PFS) benefit of adding CDK4/6 inhibitors to AI was consistent across all subgroups of patients (pts), including those with lower ER expression. However, little is known about the absolute PFS obtained under CDK4/6i and AI in pts with low ER expression and whether PR and HER2 expression impact PFS in this setting.

Concentration and temperature dependence behaviors of photoluminescence and scintillation properties of Lu2O3:Pr single crystals

Praseodymium doped lutecia (Lu1−xPrx)2O3 (x = 0.003, 0.006 and 0.01) single crystals have been prepared by optical floating zone (OFZ) method. The concentration and temperature dependence of photoluminescence and scintillation properties, including photoluminescence excitation (PLE) and photoluminescence (PL), PL decay, X-ray excited luminescence (XEL) and afterglow curves were systematically investigated. Both onward (Pr(S6)→Pr(C2)) and inverse (Pr(C2)→Pr(S6)) energy transfers are observed in Lu2O3:Pr. It is found that with the increasing of Pr3+ concentration, the Pr(S6)→Pr(C2) energy transfers efficiency increases. And the PL decay time becomes faster due to the increasing cross relaxation transition. Meanwhile, as the temperature increases (78–500 K), the onward and inverse energy transfer efficiencies between the two kinds of Pr3+ are enhanced simultaneously. The highest scintillation efficiency is Lu2O3:0.6%Pr and afterglow levels of obtained single crystals were comparable.

The deep infiltrating endometriosis tissue has lower T-cadherin, E-cadherin, progesterone receptor and oestrogen receptor than endometrioma tissue

ObjectiveTo compare the T-cadherin, E-cadherin, PR and ER staining levels of deep infiltrating endometriosis (DIE) tissue, ovarian endometriomas and normal endometrial tissues. Materials and methodsDIE tissue of 24 cases, endometrioma of 30 cases and normal endometrial tissues of 30 cases were examined. T-cadherin, E-cadherin, ER-α and PR-α staining levels of DIE, endometrioma tissues and endometrial tissues were compared immunohistochemically. H-score was calculated to compare the expression of T-cadherin, E-cadherin, ER-α, PR-α in IHC staining based on the percentage of cells stained at each intensity level. ResultsT-cadherin, E-cadherin, ER and PR H-score were found lowest in DIE tissue and the highest in endometrial tissue (p < 0.0001, <0.0001, <0.0001 and < 0.0001, respectively). In correlation analysis, a positive correlation was found between T-cadherin, E-cadherin, PR and ER H-score (p < 0.0001 for each). No correlation was found between age, body mass index (BMI), visual analog scale (VAS) score, CA125, endometrioma size and the severity of dysmenorrhea, dyspareunia and dystonia (p > 0.05). ConclusionT-cadherin, E-cadherin, ER and PR H-score were found lowest in DIE tissue, the highest in endometrium tissue. The finding of lower expression of PR-α in endometriotic nodule in our study may be related to decrease in progesterone effect which could not inhibit the decrease in the expression of T-cadherin and E-cadherin, thus the invasiveness of DIE tissue. These findings suggest that DIE tissue and ovarian endometrioma tissues have a different biology.

The Unfavorable Impact of DR9/DR9 Genotype on the Frequency and Quality of Partial Remission in Type 1 Diabetes.

Partial remission (PR) is a specific stage in type 1 diabetes (T1D). Although human leukocyte antigen (HLA) class II loci are the strongest genetic determinants in T1D, the relationship between PR and HLA remains unclear. To investigate the association between PR status and HLA genotypes in patients with T1D. A total of 237 patients with T1D were included. PR was defined according to C-peptide ≥300 pmol/L. The frequency of PR and peak C-peptide levels during remission phase were compared according to HLA status. Clinical characteristics including age of onset and diabetes autoantibodies were collected. All analyses were duplicated when subjects were divided into childhood- and adult-onset T1D. The median follow-up time was 24 months, 65.8% (156/237) of patients with T1D went into PR. DR9/DR9 carriers had a lower PR rate (44.2% vs 70.6%, P = .001) and were less likely to enter PR (OR = 0.218, 95% CI 0.098-0.487, P < .001) than the non-DR9/DR9 carriers, observed in both childhood- and adult-onset T1D. Besides, the peak C-peptide level during PR phase was also lower in DR9/DR9 carriers, and more notable in adult-onset T1D. When compared with non-DR9/DR9 carriers, T1D with DR9/DR9 genotype presented an older age of onset and a lower positivity of zinc transporter 8 antibody (ZnT8A), and the lower trend of ZnT8A was only found in adult-onset T1D (P = .049). Patients with T1D carrying susceptible DR9/DR9 are less prone to undergo PR. Additionally, the recovery extent of β-cell function during the PR phase tends to be lower in adults carrying DR9/DR9, which might be associated with ZnT8A.

Clinical characteristics and disease outcomes in ER+ breast cancer: a comparison between HER2+ patients treated with trastuzumab and HER2- patients

BackgroundTrastuzumab has changed the prognosis of HER2+ breast cancer. We aimed to investigate the prognosis of ER+/HER2+ patients treated with trastuzumab, thus to guide escalation endocrine treatment in ER+ breast cancer.MethodsER-positive early breast cancer patients operated at Ruijin Hospital between Jan. 2009 and Dec. 2017 were retrospectively included. Eligible patients were grouped as HER2-negative (HER2-neg) or HER2-positive with trastuzumab treatment (HER2-pos-T). Kaplan-Meier analysis and Cox proportional hazards model were used to compare the disease-free survival (DFS) and overall survival (OS) between these two groups.ResultsA total of 3761 patients were enrolled: 3313 in the HER2-neg group and 448 in the HER2-pos-T group. Patients in the HER2-pos-T group were associated with pre/peri-menopause, higher histological grade, LVI, higher Ki-67 level, lower ER and PR levels (all P < 0.05). At a median follow-up of 62 months, 443 DFS events and 191 deaths were observed. The estimated 5-year DFS rate was 89.7% in the HER2-neg group and 90.2% in the HER2-pos-T group (P = 0.185), respectively. Multivariable analysis demonstrated that patients in the HER2-pos-T group had a better DFS than patients in the HER2-neg group (HR 0.52, 95% CI: 0.37–0.73, P < 0.001). The estimated 5-year OS rates were 96.0% and 96.3% in the two groups, respectively (P = 0.133). Multivariate analysis found that HER2-pos-T group was still associated with significantly better OS compared with the HER2-neg group (HR 0.38, 95% CI: 0.22–0.67, P = 0.037).ConclusionER+/HER2+ breast cancer patients treated with trastuzumab were associated with superior outcome compared with ER+/HER2- patients, indicating HER2-positivity itself may not be an adverse factor for ER+ patients in the era of trastuzumab.

Analyzing the relationship between the cytokine profile of invasive breast carcinoma, its histopathological characteristics and metastasis to regional lymph nodes

This study was aimed at analyzing the relations of metastasis to regional lymph nodes (RLNs) with histopathological indicators of invasive breast carcinoma of no special type (IC-NST) and its cytokine profile. Enzyme-linked immunosorbent assays were performed to determine concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A, and MCP-1 in the culture supernatant of IC-NST samples from 48 female patients. Histopathological indicators (degree of tumor cell differentiation, mitoses, and others) and ER, PR, Her2/neu, Ki-67, and CD34 expression levels were determined. By means of three types of neural network models, it was shown that for different parameters of the output layer, different groups of parameters are involved that have predictive value regarding metastasis to RLNs. As a result of multi-dimensional cluster analysis, three clusters were formed with different cytokines profiles of IC-NST. Different correlations between indicators of cytokine production by IC-NST and its histopathological parameters were revealed in groups with different cytokine profiles. It was shown that at simultaneous evaluation of the production of even two cytokines, the importance of which relationship with metastasis was revealed by neural network modeling, can increase the probability of determining the presence of metastasis in the RLNs.

Automated immunostaining-free prediction of breast carcinoma ER and PR status, Ki67 count, patient therapy stratification index and quantification of prognostic quiescence burden in TNBC from pretreatment H&amp;E stained histopathology images in breast cancer.

e12535 Background: Categorical combinations of ER, PR, HER2, and Ki67 levels are traditionally used to classify patients into luminal A and B-like subtypes in order to inform treatment choice. Accounting for nearly 70% of all breast malignancies, luminal cancer is heterogeneous, harboring subtypes with distinct molecular profiles and clinical outcomes. Although most patients with luminal-type disease respond well to endocrine therapy alone, some develop recurrences benefiting from additional cytotoxic therapy. Identifying such cases a priori remains a challenge but would enable patients to be spared the debilitating side-effects of ineffective chemotherapy. In this regard, the efficacy of chemotherapy and disease recurrence relate to (i) ER driven G1/S perturbations and/or (ii) quiescent cell populations arrested in the G0/G1 phase of cell cycle. This study aimed to develop a histopathology whole slide image (WSI)-based, low cost, rapid and automated approach to: (i) predict ER/PR/Ki67 status, (ii) quantify quiescence burden, (iii) develop a G1/S-based patient stratification system for luminal A/B patients, and (iv) achieve a quiescence burden-based stratification of TNBC patients. Methods: This investigation centered on the initial clinical validation of a novel, immunostaining-free technology which uses information extracted from pre-treatment hematoxylin and eosin (H&amp;E) stained slide WSIs alone to achieve these aims. Unlike conventional artificial intelligence-based approaches, the underlying proprietary algorithm and its prediction criteria are based on deterministic, hard-coded observational relationships of continuous scales drawn from WSI morphological features. In this instance, these represent tumor-related biological pathway disruptions and mitotic checkpoint perturbations, where G1/S perturbations enable luminal subtype stratification, and G0/G1 perturbations reflect quiescence burden. Back projecting the algorithm’s quiescence burden output on to the original WSIs enables morphological patterns to be mapped to quiescence burden.