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Premature birth (PTB) is the most common cause of perinatal mortality and morbidity. We performed a case–control study to determine whether two selected single-nucleotide polymorphisms (SNPs) of the progesterone receptor gene (PGR) (rs4754732 and rs653752) play a role in the modulation of the risk for spontaneous PTB. This study included 400 mothers (199 with premature delivery and 201 with term delivery) and 400 newborns (201 term-born and 199 premature-born) of European descent. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. We found no statistically significant difference in the distribution of genotypes and allele frequencies between prematurely born newborns and newborns at term for either investigated SNP. There was no statistically significant difference in the distribution of genotypes and allele frequencies between groups of mothers with extremely early and early PTB compared to the group of mothers with term births. Potential association of the mothers' C allele of rs653752 with lower odds of PTB (p = 0.03; odds ratio 1.36; 95% confidence interval 1.02–1.81; Chi-square test), and association of the mothers' CC genotype of rs653752 in the recessive inheritance model with lower odds of PTB in general (p = 0.02; odds ratio 0.54; 95% confidence interval 0.32–0.91; Chi-square test) and with a late PTB (p = 0.005, odds ratio 0.45, 95% confidence interval 0.23–0.79; Chi-square test), were found. It was also found that the mothers who were carriers of the haplotype T-G combination of rs4754732 and rs653752 were 1.5 times more likely to have PTB, even after correcting the p-value for multiple comparisons (p = 0.008; odds ratio 1.59; 95% confidence interval 1.13–2.24, Chi-square test). Further research on a larger number of subjects of these and other PGR SNPs will be needed in order to confirm the presented results. [ABSTRACT FROM AUTHOR]

• Reproductive hormones may affect cognition by rapidly modulating synaptic responses in the infralimbic cortex. • Stimulation of infralimbic cortex layer I evoked field EPSPs generated by a current sink in layer I. • Both progesterone and allopregnanolone increased EPSP amplitudes in layer I. • The membrane progesterone receptor agonist Org OD 02–0 increased synaptic responses. • Org OD 02–0 also occluded increases in synaptic responses induced by progesterone or allopregnanolone. Estrogens and progesterone can have rapid effects on neuronal function and can modify the use of spatial navigation strategies dependent upon the prefrontal cortex, striatum, and hippocampus. Here, we assessed the effects of 17β-estradiol (E2), progesterone, and its metabolite allopregnanolone, on evoked excitatory postsynaptic potentials in the infralimbic region of the female rat prefrontal cortex. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of layer I were first characterized by recording responses at multiple depths between the cortical surface and the underlying white matter. Current source density analysis showed that the short-latency negative component was generated by activation of synaptic currents within layer I, and that putative polysynaptic responses were generated in layers III to V. The amplitude of evoked field EPSPs in layer I was not significantly affected by 20 min application of 17β-estradiol (10 nM), but both 100 nM progesterone and 1 µM allopregnanolone caused lasting increases in field EPSP amplitude. The effects of progesterone were not blocked by the nuclear progesterone receptor antagonist RU486 (1 µM). Both progesterone and allopregnanolone are known to activate membrane progesterone receptors, and we found that the membrane progesterone receptor agonist Org OD 02–0 facilitated EPSPs, and also occluded further increases induced by either progesterone or allopregnanolone. These results provide evidence that both progesterone and allopregnanolone facilitate synaptic responses in layer I of the infralimbic cortex by activating membrane progesterone receptors. [ABSTRACT FROM AUTHOR]

Background: Although several risk factors have been suggested for uterine torsion, the pathogenesis is still unclear. Therefore, the current study aims to investigate the pathogenesis of uterine torsion by assessing the histological, histochemical, and immunohistochemical changes that occur in the placenta obtained from uterine torsion cases. Immunohistochemical changes include investigation of the expression of estrogen receptors (ERs), progesterone receptors (PRs), and the vascular endothelial growth factor (VEGF) in the placental tissue. Methods: Forty intrapartum dairy cows were included in this investigation. The cows were divided into two equal groups. The first group was the uterine torsion (UT) group, while the second group was the normal control group (Ctrl). After caesarian section treatment, placentas were collected from all animals in the study. Histopathological, histochemical, and immunohistochemical examinations were performed. Estrogen receptors, progesterone receptors, and vascular endothelial growth factor expression in the placenta were evaluated. Results: The results revealed numerous trophoblast giant or binucleate cells in the trophoblastic epithelium. Through Masson's trichrome technique, the distribution of collagen fibers as shiny, blue-colored stripes on the fetal mesenchyme was observed. Additionally, the results showed a strong, intense PAS-positive reaction in the cytoplasmic vesicles of most trophoblastic cells due to mucopolysaccharides. The immunohistochemical findings of the UT placenta revealed moderate to weak staining for ERs in contrast to those of the Ctrl placenta, which revealed moderate staining for ERs. In addition, non-statistical differences in the expression of PRs were found between the two tested groups. For VEGF, strong positive immunoreactivity was found in the Ctrl group compared to the UT group, which exhibits a general absence in many trophoblast cells. Conclusion: It can be concluded that significant variation was observed in the placentas obtained from buffaloes suffering from UT compared to those obtained from normal pregnant ones. These significant variations were involved in the decreased expression of ERs and VEGF in the UT group compared to the normal Ctrl one. Investigating the expression of these placental molecules may monitor the changes in the placental tissue and provide insight into the pathogenesis of UT. [ABSTRACT FROM AUTHOR]

The incidence of breast cancer in young women (aged under 40) is on the rise and is associated with more aggressive tumor characteristics and lower survival rates. Breast cancer is most frequently diagnosed in the sixth decade, and most research presents results based on data from older patients. By using large-scale clinico-pathologic and transcriptomic data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1932), we aimed to explore age-related differences in treatment, tumor characteristics, and gene expression signatures. Young patients presented more aggressive clinico-pathologic features such as higher histological grade, more frequent lymph node metastasis involvement, and estrogen receptor negativity. Accordingly, age below 40 years was associated with lower mRNA expression of the estrogen- and progesterone receptors, encoded by ESR1 and PGR, a higher proportion of the basal-like subtype, and increased transcription patterns reflecting stemness. Young breast cancer patients showed reduced survival, also within the basal-like subtype. We observed age-related differences in treatment, with more patients receiving chemotherapy among the young. Our results confirm a more challenging disease in young patients with breast cancer despite the more abundant use of chemotherapy. This argues for increased attention to young patients in current management and future research in breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the expression and clinical relevance of the androgen receptor (AR) in breast cancer. Methods: This retrospective study examined the expression of AR in breast cancer and its correlation with patients' clinicopathological and immunohistochemical characteristics. A total of 521 patient records were gathered and assessed. Patients were categorized as either positive or negative for AR expression, and statistical analyses were conducted using the chi-square test, logistic regression in SPSS 26.0, and Kaplan-Meier analysis. Results: AR was detected in 83.7% of the 521 patients studied. There was a statistically significant difference in the prevalence of AR positivity among different molecular subtypes, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and epidermal growth factor receptor (EGFR) (P < 0.05). Logistic regression analysis further revealed that ER and PR positivity were identified as risk factors for AR expression, and Kaplan-Meier curve analysis demonstrated the potential of AR as a prognostic indicator for breast cancer outcomes. Additionally, AR positivity was associated with a favorable prognosis. Conclusions: The results suggest a strong correlation between AR expression and ER and PR co-expression in breast cancer. Additionally, AR positivity in the absence of ER and PR expression is associated with a favorable prognosis, indicating potential therapeutic value as a novel target in breast cancer treatment. Particularly in endocrine resistance or triple-negative breast cancer (TNBC), AR may serve as a significant prognostic indicator, warranting further investigation. [ABSTRACT FROM AUTHOR]

Simple summary: We investigated the role of Ki67, a ubiquitous marker in cancer, within the context of ductal carcinoma in situ (DCIS), a precursor of invasive breast cancer. Through rigorous analysis of histopathological and immunopathological samples from a substantial cohort, this study revealed robust correlations between heightened Ki67 expression, diminished progesterone (PR) levels, and HER2 overexpression, indicative of aggressive DCIS phenotypes. These findings offer novel insights into the surrogate immunomolecular subtyping landscape of DCIS, potentially refining risk stratification and therapeutic approaches. This elucidation underscores the translational significance of Ki67 as a prognostic and predictive biomarker in DCIS, with implications for personalized treatment paradigms and patient outcomes. Background: The Ki67 proliferation index is widely used in various tumors, including invasive breast carcinoma (IBC). However, its prognostic utility is often constrained by technical complexity. Its diagnostic and clinical significance in ductal carcinoma in situ (DCIS) remains uncertain. We studied Ki67 immunohistochemistry interobserver diagnostic agreement at different cutoff values in high-grade DCIS. Additionally, we investigated the associations between Ki67 expression, PR levels, and human epidermal growth factor receptor 2 (HER2) in high-grade DCIS among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched, and triple-negative)). Methods: Using histopathological specimens from 484 patients diagnosed with DCIS between 1996 and 2018, we implemented the 2013 St. Gallen recommendations for surrogate immunomolecular subtyping of IBC. Subtypes were classified, and the Ki67 interobserver diagnostic agreement between Counting Pathologist 1 (CP1) and CP2 was calculated using Cohen's kappa coefficient at various cutoff values. Results: The Cohen's kappa coefficient for interobserver agreement between CP1 and CP2 was κ = 0.586, indicating moderate agreement. Ki67 levels varied significantly among subtypes (p < 0.0001), with a median Ki67% being higher in cases with invasive components (p = 0.0351). Low PR combined with high Ki67% was significantly associated with HER2 overexpression (p = 0.0107). Conclusions: Interobserver agreement for the Ki67 count was moderate. Ki67 expression showed considerable variability in high-grade DCIS. Low PR levels combined with high Ki67 expression were linked to HER2 overexpression, showing possible clinical implications for identifying high-risk DCIS. [ABSTRACT FROM AUTHOR]

Introduction: Dysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) physiology, oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs), a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues, stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids). Areas covered: The present review examines the development of the clinical trials and observational studies done with the different SPRMs for the treatment of dysmenorrhea in patients with uterine diseases. Expert opinion: Mifepristone, telapristone acetate and vilaprisan have antagonistic activity on PRs, whereas ulipristal acetate and asoprisnil have both potent antagonist and partial agonist effects. Since no studies have been done on primary dysmenorrhea, the different SPRMs have been evaluated in the treatment of endometriosis, adenomyosis and uterine fibroid-related dysmenorrhea. [ABSTRACT FROM AUTHOR]

The metastasis of breast cancer to the colon is a rare occurrence, especially in the presence of changes in estrogen and progesterone receptors. To date, literature has only reported two cases of invasive ductal carcinoma and two cases of invasive lobular carcinoma metastasizing to the colon with concurrent changes in hormone receptors. This report describes a 65-year-old woman with a history of left breast cancer, who presented with symptoms of bloody stools and abdominal pain. CT and colonoscopy results revealed a malignant tumor in the ascending colon, and the patient underwent surgery. Pathological results post-surgery indicated changes in hormone receptors, differing from the previous breast cancer pathology, ultimately leading to the diagnosis of breast cancer metastasis to the colon. The patient was found to have liver metastasis 14 months after right hemicolectomy, and systemic metastases in various locations were discovered at the 19-month mark. [ABSTRACT FROM AUTHOR]

Mammography is the recommended imaging modality for breast cancer screening. Expressions of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) are critical to the development of therapeutic strategies for breast cancer. In this study, a deep learning model (CBAM ResNet-18) was developed to predict the expression of these three receptors on mammography without manual segmentation of masses. Mammography of patients with pathologically proven breast cancer was obtained from two centers. A deep learning-based model (CBAM ResNet-18) for predicting HER2, ER, and PR expressions was trained and validated using five-fold cross-validation on a training dataset. The performance of the model was further tested using an external test dataset. Area under receiver operating characteristic curve (AUC), accuracy (ACC), and F1-score were calculated to assess the ability of the model to predict each receptor. For comparison we also developed original ResNet-18 without attention module and VGG-19 with and without attention module. The AUC (95% CI), ACC, and F1-score were 0.708 (0.609, 0.808), 0.651, 0.528, respectively, in the HER2 test dataset; 0.785 (0.673, 0.897), 0.845, 0.905, respectively, in the ER test dataset; and 0.706 (0.603, 0.809), 0.678, 0.773, respectively, in the PR test dataset. The proposed model demonstrates superior performance compared to the original ResNet-18 without attention module and VGG-19 with and without attention module. The model has the potential to predict HER2, PR, and especially ER expressions, and thus serve as an adjunctive diagnostic tool for breast cancer. [ABSTRACT FROM AUTHOR]

This study aims to comprehensively evaluate the clinical utility of five diffusion models, including conventional mono-exponential (Mono), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), stretched exponential (SEM), and continuous-time random-walk (CTRW), for preoperatively predicting of breast lesion pathology, prognostic biomarkers, and molecular subtypes. We retrospectively analyzed 132 patients with pathologically verified breast lesions (41 benign and 91 malignant) who underwent a full protocol preoperative breast MRI protocol, including a diffusion-weighted imaging (DWI) sequence with nine b values (0 to 2000 s/mm2) on a 3.0T MR scanner. The diffusion parameters from each model—Mono (ADC), IVIM (D, D*, f), DKI (MD, MK), SEM (DDC, α) and CTRW (Dm, α, β)—were quantitatively calculated and compared between benign and malignant breast lesions, as well as across different prognostic biomarker statuses in breast cancer, using Mann–Whitney U-tests. For molecular subtypes comparisons, we employed the Kruskal-Wallis test followed by Bonferroni. All parameters, except IVIM-D*, significantly differentiated benign from malignant lesions. Notably, IVIM-D and DKI-MK values were significantly different between estrogen receptor (ER)-positive and ER-negative tumors. Progesterone receptor (PR)-positive cancers exhibited lower Mono-ADC, IVIM-D, DKI-MD, SEM-DDC, CTRW-Dm, and CTRW-α values, alongside higher DKI-MK value compared to PR-negative cancers (p < 0.05). Significant differences in IVIM-D, IVIM-D*, and DKI-MK values were observed between human epidermal growth factor receptor 2 (HER2)-negative and HER2-positive tumors. Furthermore, higher SEM-α and CTRW-β values, along with lower DKI-MD and SEM-DDC values, were noted in the high Ki-67 expression group compared to the low Ki-67 group (p < 0.05). All five diffusion models proved valuable for breast cancer diagnosis, with the CTRW model exhibiting the highest diagnostic performance, although the difference was not statistically significant. The diffusion parameters derived from these models can effectively assist in distinguishing prognostic factors and molecular subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) involvement, as an important prognostic factor in breast cancer (BC) patients, has a crucial role in their therapeutic approach. Consequently, a great desire is to thoroughly assess the patients based on their axillary LN status. The present study evaluated the characteristics and survival rate of axillary metastatic BC patients in a Tertiary and referral center. Method: The overall survival, disease-free survival, and clinicopathological characteristics of axillary metastatic BC patients referred to the Cancer Research Center in Tehran, Iran, from 1991 to 2022 were assessed retrospectively. We obtained patients' clinical data from prospectively maintained registries. Result: Among the total 3399 recruited patients, 49.1%, 26.3%,13.1%, and 6.4% were pN0, pN1, pN2 and pN3, respectively. The pN0 group patients showed a significantly lower Hazard Ratio (HR) for DFS and OS compared to others. Moreover, estrogen and progesterone receptors, human epidermal growth factor2, tumor pathology type and tumor grade were prognostic factors of axillary LN status. Accordingly, pN0 patients had a lower recurrence risk than the others (P = 0.01). Conclusion: The axillary lymph node status has been considered as one of the fundamental factors determining the therapeutic strategy and prognosis of BC patients, which has an association with tumor characteristics. Regarding the crucial impact of the LN status on the survival landscape of breast cancer patients, accurate detection of the involved one and close screening follow-up of patients with more metastatic LNs during the surgery have a high value. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (EBC) is a heterogenous disease. Identification of better clinical and molecular biomarkers is essential to guide optimal therapy for each patient. We analyzed rates of pathologic complete response (pCR) and distant recurrence-free survival (DRFS) for patients with HR+/HER2-negative EBC in eight neoadjuvant arms in the I-SPY2 trial by clinical/molecular features: age, stage, histology, percentage estrogen receptor (ER) positivity, ER/progesterone receptor status, MammaPrint (MP)-High1 (0 to −0.57) versus MP-High2 (<−0.57), BluePrint (BP)-Luminal-type versus BP-Basal-type, and ImPrint immune signature. We quantified the clinical/molecular heterogeneity, assessed overlap among these biomarkers, and evaluated associations with pCR and DRFS. Three hundred and seventy-nine patients with HR+/HER2-negative EBC were included in this analysis, with an observed pCR rate of 17% across treatment arms. pCR rates were higher in patients with stage II versus III disease (21% versus 9%, P = 0.0013), ductal versus lobular histology (19% versus 11%, P = 0.049), lower %ER positivity (≤66% versus >66%) (35% versus 9%, P = 3.4E-09), MP-High2 versus MP-High1 disease (31% versus 11%, P = 1.1E-05), BP-Basal-type versus BP-Luminal-type disease (34% versus 10%, P = 1.62E-07), and ImPrint-positive versus -negative disease (38% versus 10%, P = 1.64E-09). Patients with lower %ER were more likely to have MP-High2 and BP-Basal-type disease. At a median follow-up of 4.8 years, patients who achieved pCR had excellent outcomes irrespective of clinical/molecular features. Among patients who did not achieve pCR, DRFS events were more frequent in patients with MP-High2 and BP-Basal-type disease than those with MP-High1 and BP-Luminal-type disease. Among patients with high molecular-risk HR+/HER2-negative EBC, the MP-High2, BP-Basal-type, and ImPrint-positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy ± targeted agents or immunotherapy compared to patients with MP-High1, BP-Luminal-type, and ImPrint-negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection. • We characterized the clinical and molecular heterogeneity of patients with HR+/HER2-negative EBC in I-SPY2. • We quantified overlap in MP, BP, and ImPrint signatures and associations with rates of pCR and DRFS. • The MP-High2, BP-Basal, and ImPrint+ signatures identify a partially overlapping subset of patients with higher rate of pCR. • Patients who achieved pCR had low rates of DRFS events at 4.8 years irrespective of clinical or molecular features. • Among patients who did not achieve pCR, DRFS events were more frequent in patients with MP-High2 and BP-Basal disease. [ABSTRACT FROM AUTHOR]

Estrogens have been associated with an increase in breast cancer risk. Yet emerging clinical and experimental evidence points to progestogens [endogenous progesterone or synthetic progesterone (progestin)] as the primary hormonal driver underlying seemingly estrogen-associated breast cancer risk. Estrogens may contribute to breast cancer risk indirectly by induction of the progesterone receptor and thus amplifying progesterone signaling. Large studies of hormonal contraceptives suggest that the small increase in breast cancer risk from hormonal contraceptives is mainly attributable to progestins, not estrogens. Estrogen-plus-progestin hormone replacement therapy (HRT) has consistently shown an increase in breast cancer risk among postmenopausal women, whereas estrogen-alone HRT has little impact on breast cancer risk in naturally or surgically menopausal women. In particular, the long-term follow-up of the Women's Health Initiative (WHI) randomized trials suggests a benefit of estrogen alone. Recent data further indicate that endogenously elevated estrogen during assisted reproductive technology (ART) exhibits little adverse effect on or potentially a reduction in breast cancer risk and recurrence. Also, accumulating evidence suggests that inhibition of progesterone signaling is a critical mechanism underlying the risk-reducing and therapeutic effects of antiestrogens. Estrogen HRT has shown an array of proven benefits, including ameliorating menopausal symptoms and improving bone health. Collective evidence thus suggests that estrogen HRT is likely to offer health benefits to perimenopausal or postmenopausal women, including breast cancer survivors, as well as young BRCA 1/2 carriers with prophylactic oophorectomy for ovarian cancer prevention. • Without a progestogen, estrogen alone appears to have little or no impact on breast cancer risk. • Estrogen may increase breast cancer risk by inducing the progesterone receptor and augmenting progesterone signaling. • Progestins—not estrogens—from hormonal contraceptives appear to be responsible for a small increase in breast cancer risk. • In postmenopausal women using HRT, progestins are likely the primary hormonal agent that elevates breast cancer risk. • Estrogen HRT, coupled with minimal progestogen, might be acceptable for women in need of HRT, including BRCA1/2 carriers. [ABSTRACT FROM AUTHOR]

The article discusses a rare association between benign brain tumors like Vestibular Schwannoma and meningioma with breast cancer, highlighting two cases where patients developed breast cancer after surgery for their brain tumors. The study aims to explore potential links between these conditions and suggests the need for closer surveillance of breast cancer risk in patients with large symptomatic brain tumors. Shared genetic pathways, particularly involving hormone receptors like estrogen and progesterone, are proposed as potential factors contributing to the increased risk of breast cancer in patients with these benign brain tumors. The cases emphasize the importance of further research into the connection between benign brain tumors and breast cancer, as well as the consideration of early breast cancer screening for patients with these tumors. [Extracted from the article]

Purpose: To investigate the chemoprotective potential of karanjin against 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast cancer. Methodology: Thirty-six female rats were utilized for the study. Breast cancer was induced through a subcutaneous injection of 35 mg/kg DMBA. The animals were allocated to six groups. Three groups were allocated for karanjin (50 mg/kg, 100 mg/kg, and 200 mg/kg), and received daily treatment for 20 weeks (including 2 weeks as pre-treatment). Doxorubicin (4 mg/kg) was administered to the standard control group twice a week for 20 weeks. The disease control (DC) and normal control (NC) groups received daily treatment with saline. After the treatment, oxidative stress parameters, biochemical parameters, and inflammatory parameters were estimated. CCAAT-displacement protein/cut homeobox (CUP/Cux) and scaffold/matrix attachment region binding protein 1 (SMAR1) expression levels were measured through gene expression analysis. Immunohistochemical (IHC) analysis was performed to estimate the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Results: Tumor growth reduced significantly (P-value < 0.01) in karanjin-treated animals compared to the DC group. Karanjin significantly (P-value < 0.01) regulated the levels of oxidative stress parameters, biochemical parameters, and inflammatory parameters compared to the DC group. Karanjin treatment significantly (P-value < 0.001) regulated the expression levels of SMAR1 and CDP/Cux. A notable reduction in the IHC scores was observed for ER, PR, and HER2 expression in karanjin groups. Conclusion: Karanjin demonstrated chemoprotective activity against DMBA-induced breast cancer in animals potentially through modulation of SMAR1 and CDP/Cux gene expression and reduction of ER, PR and HER2 expression levels. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a type of breast cancer with lack the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is the most aggressive breast cancer and the most difficult to treat due to its poor response to treatments and extremely invasive characteristics. The typical treatment for TNBC frequently results in relapse because of the lack of particular treatment choices. It is urgent to focus on identifying a workable and effective target for the treatment of TNBC. Cancer metastasis is significantly influenced by epithelial-mesenchymal transition (EMT). Ferroptosis is an iron-dependent cell death form, and changes its key factor to affect the proliferation and metastasis of TNBC. Several reports have established associations between EMT and ferroptosis in TNBC metastasis. Furthermore, non-coding RNA (ncRNA), which has been previously described, can also control cancer cell death and metastasis. Thus, in this review, we summarize the correlation and pathways among the ferroptosis, EMT, and ncRNAs in TNBC metastasis. Also, aim to find out a novel strategy for TNBC treatment through the ncRNA-ferroptosis-EMT axis. [ABSTRACT FROM AUTHOR]

Triple-positive breast cancer (TPBC), defined by the co-expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), poses unique therapeutic challenges due to complex signaling interactions and resulting treatment resistance. This review summarizes key findings on the molecular mechanisms and cross-talk among ER, PR, and HER2 pathways, which drive tumor proliferation and resistance to conventional therapies. Current strategies in TPBC treatment, including endocrine and HER2-targeted therapies, are explored alongside emerging approaches such as immunotherapy and CRISPR/Cas9 gene editing. Additionally, we discuss the tumor microenvironment (TME) and its role in treatment resistance, highlighting promising avenues for intervention through combination therapies and predictive biomarkers. By addressing these interdependent pathways and optimizing therapeutic strategies, precision medicine holds significant potential for improving TPBC patient outcomes and advancing individualized cancer care. [ABSTRACT FROM AUTHOR]

Abdominal wall endometriosis (AWE) is a clinical disorder with unknown pathogenesis with an incidence between 0.03% and 1% in women affected by cutaneous/scar endometriosis. We investigated the pathological, molecular cytogenetic and cell proliferation features of a primary AWE developed in rectus abdominis muscle in a patient without co-existing pelvic endometriosis. An investigational model of cultured stromal cells was additionally established. Histologically, the lesion revealed areas of endometrial-like glands surrounded by a thick stromal layer in addition to numerous disseminated foci composed exclusively of stromal cells. Beyond the strong expression of Estrogen (ER) and Progesterone receptors (PRs), consistent immunolabeling for several mesenchymal stromal/stem cell antigens and oncoproteins was revealed in both the endometrioma as well as in the cultured stromal cells. The Fluorescence in situ hybridization (FISH) analysis of the endometrioma demonstrated a structural alteration of the c-MYC protooncogene, with a mean of three gene copies in 3% to 5% of both glandular and stromal cells. The FISH assay applied on the cultured cells showed c-MYC gene amplification, with an average number of more than six gene copies in 18% to 25% of the cellular nuclei. Altogether, these results markedly highlight the pathological and molecular features of idiopathic AWE essential for histo-pathogenetic categorization. [ABSTRACT FROM AUTHOR]

Hypothyroidism causes ovarian dysfunction and infertility in women and animals and impairs the hypothalamic expression of kisspeptin (Kp). However, kisspeptin is also expressed in the genital system, and the lack of the Kp receptor (Kiss1r) in the uterus is linked to reduced implantation rates. This study investigated the impact of hypothyroidism on the uterine expression of Kp and Kiss1r in female rats throughout the estrous cycle and the associated changes in uterine activity modulators. Hypothyroidism was induced through daily administration of propylthiouracil (PTU) over a period of 14 days. Plasma levels of LH, E2, and P4, cyclicity, body and uterine weight, uterine histomorphometry, and the gene and/or protein expression of Kiss1, Kiss1r, estrogen receptor α (ERα), progesterone receptor (PR), and thyroid hormone receptor α (TRα) were assessed. Additionally, proliferative activity (CDC-47) and the gene expression of uterine receptivity mediators (SMO, WNT4, BMP2, HAND2, MUC1, and LIF) were evaluated. Hypothyroidism prolonged the diestrus and increased progesterone levels during this phase, while decreasing luteinizing hormone and estradiol on proestrus. In the uterus, hypothyroidism reduced Kp immunostaining on diestrus and KISS1R mRNA levels on proestrus. These changes were accompanied by reduced endometrial glands, reduced uterine proliferative activity, and reduced ERα gene and protein expression. Additionally, hypothyroidism led to reduced uterine gene expression of LIF, BMP2, WNT4, and HAND2. On the other hand, thyroid hypofunction increased uterine PR and TRα immunostaining, while it reduced PGR gene expression on diestrus. These findings demonstrate that hypothyroidism reduces the expression of Kiss1/Kiss1r system in the uterus, which is associated with disrupted uterine estrogen and progesterone signaling and reduced expression of uterine receptivity mediators across the rat estrous cycle. [ABSTRACT FROM AUTHOR]

Background: Saidi sheep are one of the most important farm animals in Upper Egypt, particularly in the Assiut governorate. Since they can provide meat, milk, fiber, and skins from low-quality roughages, sheep are among the most economically valuable animals bred for food in Egypt. Regarding breeding, relatively little is known about the Saidi breed. In mammals, the uterus is a crucial reproductive organ. Therefore, the purpose of this work was to provide further details on the histological, histochemical, and immunohistochemical analyses of superoxide dismutase 2 (SOD2), glutathione reductase (GR), and progesterone receptor alpha (PRA) as well as terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling assay (TUNEL) of the uterus during the follicular phase of estrous cycle in Saidi sheep. Thus, 11 healthy Saidi ewes (38.5 ± 2.03 kg weight) ranging in age from 2 to 5 years were used to examine the histological changes in the uterus. Results: In Saidi sheep, the uterine histological and immunological picture during the follicular phase of the estrous cycle was characterized by epithelial and stromal proliferation and apoptosis. Leucocytic recruitment (lymphocytes, plasma, and mast cells) was also observed. Uterine gland adenogenesis, vascular angiogenesis, oxidative marker expression, and PRA expression in the muscles, stroma, and epithelium were the most noticeable features of the follicular phase. Conclusion: This study provides new evidence of the role of PRA, SOD2, GR, and mast cells in controlling uterine epithelial proliferation and apoptosis in the Saidi sheep during the follicular phase of the estrus cycle. These findings have growing significance in understanding the key mechanisms that characterize successful reproduction and enhancing the fertility and reproductive efficiency in Saidi Sheep. [ABSTRACT FROM AUTHOR]

Nowadays, the incidence of allergic diseases is increasing worldwide, which seriously affects the quality of human life. Recent studies have shown that sex hormones are closely related to the occurrence of allergic diseases. Sex hormones can directly affect the function and development of immune cells, as well as the susceptibility to autoimmune cell responses, resulting in different prevalence and clinical manifestations of allergic diseases in men and women. This article reviews the different roles and potential mechanisms of sex hormones in the occurrence and development of common allergic diseases. In atopic dermatitis, the amount of dehydroepiandrosterone sulfate into dehydroepiandrosterone sulfate is higher in females than in males. Therefore, females are more susceptible to the influence of dehydroepiandrosterone, which inhibits the proliferation of Th2, resulting in a series of clinical symptoms. In allergic asthma, estrogen can aggravate type 2 airway inflammation and androgens can reduce type 2 airway inflammation. Studies have found that there are estrogen and progesterone receptors in the nasal mucosa. When the estrogen concentration increases, the two receptors are also up-regulated, resulting in clinical manifestations such as increased nasal secretions and nasal mucosal swelling. [ABSTRACT FROM AUTHOR]

Triple negative breast cancers (TNBCs) lacking estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) on their cell surfaces are highly aggressive, difficult‐to‐treat and often relapse. Herein, we report on the self‐assembled lipid nanoparticles (LNPs) of two new pegylated lipopeptides for killing TNBCs (MDA‐MB‐231). The pegylated lipopeptides were synthesized by conjugating an n‐hexadecyl hydrophobic tail to one end of a (PEG)27 unit the other distal end of which was covalently grafted with two previously reported tumor targeting RGDK‐ and CGKRK‐ peptides. The SEM images of the self‐assembled LNPs formed upon dissolution of the pegylated lipopeptides in aqueous medium revealed formation of spherical aggregates. The degree of cellular uptake for the self‐assembled LNPs formed by the pegylated CGKRK‐lipopeptide were found to be significantly higher than that for the self‐assembled LNPs formed by the pegylated RGDK‐lipopeptide in MCF‐7, MDA‐MB‐231, HEK‐293 and HFF cells. Notably, about 60 % TNBCs (MDA‐MB‐231 cells) were killed upon treatment with commercially available potent JAK2 inhibitor (WP 1066) loaded LNPs of the pegylated RGDK‐lipopeptide. Contrastingly, the same treatment killed only about 20 % non‐cancerous HEK‐293 cells. The self‐assembled pegylated LNPs described herein open the door for undertaking preclinical studies in animal models for TNBCs. [ABSTRACT FROM AUTHOR]

Context.--Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. Objective.--To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. Design.--Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. Results.--A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 31) rate was 9.0%. The aggregate HER2 equivocal (score 21) rate was 14.5%. Of 81 equivocal (score 21) cases, 70 (86.4%) were nonamplified. Conclusions.--The data from this study provide multiinstitutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower. [ABSTRACT FROM AUTHOR]

Breast cancer is a substantial source of morbidity and mortality worldwide. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the primary biomarkers which inform breast cancer treatment. Although endocrine therapy for ER+ patients is widely available, there is a need for increased access to low‐cost, rapid, and accurate ER testing methods. In this work, we designed a near‐infrared optical nanosensor using single‐walled carbon nanotubes (SWCNT) as the transducer and an anti‐ERα antibody as the recognition element. We evaluated the nanosensor in vitro prior to testing with 26 breast cancer samples which were collected by scraping the cut surface of fresh, surgically resected tumors. Twenty samples were ER+, and six ER−, representing 13 unique patients. We found that the nanosensor can differentiate ER− from ER+ patient biopsies through a shift in its center wavelength upon sample addition. Receiver operating characteristic area under the curve analyses determined that the strongest classifier with an AUC of 0.94 was the (7,5) SWCNT after direct incubation and measurement, and without further processing. We anticipate that further testing and development of this nanosensor may push its utility toward field‐deployable, rapid ER subtyping with the potential for additional molecular marker profiling. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) heterogeneity determines appropriate drug selection and affects efficacy of treatment. Effective therapy design can benefit from a combination of drugs directed against a specific type of BC with compounds that modulate components of crucial cellular regulatory systems, including the ubiquitin-proteasome system (UPS), which is responsible for the maintenance of protein homeostasis. Here, we revealed mutual influence and a correlation between the proteasome pool heterogeneity and the intratumoral expression of markers determining the BC subtype. Obtained results facilitate the development of novel BC subtype-specific therapy. Background: Proteasomes degrade intracellular proteins. Different proteasome forms were identified. Proteasome inhibitors are used in cancer therapy, and novel drugs directed to specific proteasome forms are developed. Breast cancer (BC) therapy depends on the subtype of the tumor, determined by the expression level of Ki67, HER-2, estrogen and progesterone receptors. Relationships between the presence of specific proteasome forms and proteins that determine the BC subtype remain unclear. Here, using gene expression data in 19,145 tumor samples from 144 datasets and tissues from 159 patients with different subtypes of BC, we investigated the association between the activity and expression of proteasomes and levels of BC subtype markers. Methods: Bioinformatic analysis of proteasome subunit (PSMB1-10) gene expression in BC was performed. Proteasome heterogeneity in BC cell lines was investigated by qPCR. By Western blotting, proteasome composition was assessed in cells and patient tissue lysates. Proteasome activities were studied using fluorogenic substrates. BC molecular subtypes were determined by immunohistochemistry. Results: BC subtypes demonstrate differing proteasome subunit expression pattern and strong PSMB8-10 co-correlation in tumors. A significant increase in chymotrypsin- and caspase-like proteasome activities in BC compared to adjacent tissues was revealed. The subunit composition of proteasomes in tumor tissues of BC subtypes varied. Regression analysis demonstrated a positive correlation between proteasome activities and the expression of Ki67, estrogen receptors and progesterone receptors. Conclusion: BC subtypes demonstrate differences within the proteasome pool. Correlations between the proteasome activity, hormone receptors and Ki67 indicate possible mutual influence. Obtained results facilitate development of novel drug combinations for BC therapy. [ABSTRACT FROM AUTHOR]

The detection of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human epidermal growth factor receptor 2 (HER-2) is important for the stratification of breast cancer and the selection of therapeutic modalities. This study aimed to determine the quantitative expression of ER, PR and HER-2 using Immunohistochemistry and their correlation with quantitative baseline Ct values measured using Quantitative Polymerase Chain Reaction (PCR). This study also assessed the use of fresh breast tissue biopsies preserved in RNAlater solution in the quantitative detection of these receptors using PCR technique. The study evaluated 20 matched formalin fixed paraffin embedded and RNAlater preserved samples for ER, PR, and HER-2 using IHC and quantitative PCR technique. One portion of the breast tissue biopsy was fixed immediately in 10% neutral buffered formalin and another was preserved in RNAlater. After the histological confirmation of breast cancer by the H&E technique, formalin fixed paraffin embedded tissues (FFPE)—positive cases were matched with their corresponding RNAlater samples for IHC and qPCR. The extracted RNA was quantified using Nanodrop technology, resulting into complementary DNA. ER and PR using IHC were expressed in 60% (n = 12) of the study samples and were negative in 40% (n = 8) of samples. HER-2 was negative in 70% (n = 14) of study samples, 25% (n = 5) positive, and 5% (n = 1) equivocal. With the quantitative expression of ER, PR, and HER-2 being reported in the IHC triple—negative breast cancer cases. The mean Ct values for the hormonal receptors correlated with what has been previously studied with ER at 19.631, PR at 25.410 and HER-2 at 25.695. There was no statistically significant difference between the mean Ct values of RNAlater and FFPE with their P-values being 0.9919, 0.0896 and < 0.0001 for ER, PR, and HER-2 respectively. P-values; 0.9919 and 0.0896 for ER and PR respectively being greater than 0.05 it's a borderline significance although HER-2 had a statistical significance. With a concordance in the detection of these breast cancer hormonal receptors, qPCR can be used in our setting considering the delays that may be associated in following the samples through IHC processing. [ABSTRACT FROM AUTHOR]

Background: Drugs used in chemotherapy specifically target and kill the cancer cells during the breast cancer treatment. However, the majority of anti-cancer therapies are non-specific, which will harm the innate cells. Our research work assessed the impact of chemotherapy with adriamycin/cytoxan (AC) on the influence of antioxidant enzymes and hematopathological profiles in the diagnosis and prognosis of breast cancer treated with chemotherapy. Methods: 40 breast cancer patients treated with AC chemotherapy (Adriamycin 60 mg/m2, Cytoxan 600 mg/m2) between July 2020 and March 2021 are part of this prospective study. The first sample was taken prior to chemotherapy, the second after the intervention's three cycles, and the third after the intervention's last cycle. Spectrophotometric technique was used to evaluate the amounts of antioxidant enzymes in serum samples. Patients' demographic variables, clinical features, biochemical andhematogical parameters data were noted. The data was compared before and after treatment using the Paired-t test. Results: 55% of the patients were detected with carcinoma on left breast and majority was in Grade 3 clinical stage 37.5%. Most of the patients express estrogen and progesterone receptors 72.5%. Our findings demonstrated that a significant decrease in the mean values of antioxidant enzymes MDA, NO, TAS, CAT, GPx, GR, SOD and GST along with hematological parameters after three cycles of AC treatment in breast carcinoma individuals. The p-value is < 0.05. Conclusion: Our research demonstrates that the body's oxidant/antioxidant system, particularly reduction levels and antioxidant enzyme activity, is drastically altered by AC chemotherapy in breast carcinoma individuals. [ABSTRACT FROM AUTHOR]

In brief: The HIPPO signaling effectors YAP1 and WWTR1 are required for murine pregnancy initiation, and mutation of these factors compromises the decidualization response and overall pregnancy success. Abstract: Endometrial stromal cell decidualization is required for pregnancy success. Although this process is integral to fertility, many of the intricate molecular mechanisms contributing to decidualization remain undefined. One pathway that has been implicated in endometrial stromal cell decidualization in humans in vitro is the HIPPO signaling pathway. Two previously conducted studies showed that the effectors of the HIPPO signaling pathway YAP1 and WWTR1 are required for decidualization of primary endometrial stromal cells in vitro. To investigate the in vivo role of YAP1 and WWTR1 in decidualization and pregnancy initiation, we generated progesterone receptor Cre-mediatedmutation of a combination of Yap1 and Wwtr1 alleles. Female Yap1 and Wwtr1 triple allele mutants exhibited subfertility, a compromised decidualization response, decreased endometrial receptivity, delayed embryonic development and a unique transcriptional profile at 7.5 days post-coitus (dpc). Bulk mRNA sequencing revealed aberrant maternal remodeling evidenced by significant alterations in extracellular matrix-encoding genes at 7.5 dpc in mutant dams and enrichment for terms associated with fertility-compromising diseases such as pre-eclampsia and endometriosis. In addition, differentially expressed genes overlapped directionally with estrogen receptor- and epidermal growth factor receptor-regulated genes as identified by microarray. Our results indicate that Yap1 and Wwtr1 are necessary for successful mammalian pregnancy initiation. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a significant burden on healthcare systems, especially in low- and middle-income countries where access to diagnosis and treatment is challenging. Objectives: The purpose of this study was to assess the diagnostic accuracy and cost using tissue microarray (TMA) instead of traditional immunohistochemical (IHC) evaluation for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and the proliferation marker Ki-67 and BC subtyping within the Brazilian public health system. Design: This is a retrospective cohort study comparing TMA slides with traditional whole-slide evaluation for IHC markers in 242 BC cases. Methods: We used formalin-fixed tissue blocks for TMA assembly. Clinical data and IHC scores for ER, PR, HER2, and Ki-67 were obtained from pathology reports. Cohen's kappa (k) was used to assess TMA performance. Results: BC samples were distributed in 10 TMAs and 968 cores were scored (242 BC cases × 4 markers). In 97% of these, TMA reached high quality to adequate IHC scoring with minimal technical issues. Inter-examiner agreement was almost perfect for all markers (ranging from 0.85 for HER2 to 0.91 for ER, p < 0.001). The intratumoral heterogeneity ranged from almost perfect agreement for ER and HER2 to moderate to substantial for PR and Ki-67. TMA offers substantial time and cost savings, with an approximately 11-fold reduction compared to traditional methods. The concordance between TMA and original reports was almost perfect, with 93% overall agreement (k = 0.81, p < 0.001). However, TMA performance varied between markers, with intratumoral heterogeneity significantly impacting discordant results, particularly for Ki-67 and HER2. This ultimately affected the accuracy of BC subtyping. TMA performed well in identifying luminal A and triple-negative cases, but misclassification was common for luminal B and HER2-positive cases. Conclusion: TMA offers accurate and lower-cost results in the individualized IHC assessment of BC markers. However, we do not recommend the use of TMA in the subtyping of BC, where analysis of the whole section remains necessary for more accurate results. We advocate more studies using the TMA approach in the Brazilian public health system to advance women's health care. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of progesterone and estrogen receptors and low (or absent) HER2 expression. TNBC accounts for 15-20% of all breast cancers. It is associated with younger age, a higher mutational burden, and an increased risk of recurrence and mortality. Standard treatment for TNBC primarily relies on cytotoxic agents, such as taxanes, anthracyclines, and platinum compounds for both early and advanced stages of the disease. Several targeted therapies, including bevacizumab and sunitinib, have failed to demonstrate significant clinical benefit in TNBC. The emergence of immune checkpoint inhibitors (ICI) has revolutionized cancer treatment. By stimulating the immune system, ICIs induce a durable anti-tumor response across various solid tumors. TNBC is a particularly promising target for treatment with ICIs due to the higher levels of tumor-infiltrating lymphocytes (TIL), increased PD-L1 expression, and higher mutational burden, which generates tumor-specific neoantigens that activate immune cells. ICIs administered as monotherapy in advanced TNBC yields only a modest response; however, response rates significantly improve when ICIs are combined with cytotoxic agents, particularly in tumors expressing PD-L1. Pembrolizumab is approved for use in both early and advanced TNBC in combination with standard chemotherapy. However, more research is needed to identify more potent biomarkers, and to better elucidate the synergism of ICIs with other targeted agents. In this review, we explore the challenges of immunotherapy in TNBC, examining the mechanisms of tumor progression mediated by immune cells within the tumor microenvironment, and the signaling pathways involved in both primary and acquired resistance. Finally, we provide a comprehensive overview of ongoing clinical trials underway to investigate novel immune-targeted therapies for TNBC. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer liver metastasis presents a significant challenge in clinical oncology, with limited treatment options and poor prognosis. This case series study explores the extended survival achieved in breast cancer patients with liver metastases through a combination of surgical and medical interventions. Case presentation: We present three cases of Javanese female patients with breast cancer (51 years old, 42 years old, and 55 years old) with liver metastases who underwent hepatic resection followed by systemic therapy. The cases illustrate successful outcomes with disease-free survival ranging from 5 to 31 months post-surgery. Key prognostic factors associated with improved survival include prolonged interval between initial diagnosis and detection of liver metastasis, liver-limited disease, positive response to preoperative systemic therapy, and expression of estrogen and progesterone receptors in the metastatic lesions. Conclusion: These findings underscore the potential efficacy of a multidisciplinary approach integrating local hepatectomy with systemic therapy in selected patients with breast cancer liver metastasis. Further research is warranted to identify optimal patient selection criteria and refine treatment strategies for improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Uterine carcinosarcoma (UCS), or malignant mixed Müllerian tumor, is a cancer that include both carcinomatous and sarcomatous components, resembling endometrial carcinoma. A 55-year-old woman was admitted to the hospital with postmenopausal vaginal bleeding. Gross examination of the specimen revealed brittle tissue in the fundus and the left wall of the endometrium. Postoperative pathology revealed a mixture of well-differentiated endometrioid adenocarcinoma and osteosarcoma. The patient was never given birth, which may be relevant to the diagnosis. Literature review suggests that being nulliparous may be a significant risk factor for developing uterine carcinosarcoma. Case description: In December 2023, a 55-year-old female patient was admitted to the hospital with postmenopausal vaginal bleeding. Hysteroscopic surgery was performed, and the postoperative pathology showed endometrial cancer accompanied by ossified tissue with necrosis. The immunohistochemical results indicated positive Estrogen receptors (ER), positive Progesterone receptors (PR), ki67 positivity at 70%, negative PTEN, mutated positive p53, focal positive Pax-8, positive SATB2, positive Cytokeratin 7 (CK7), positive EMA and positive Vimentin (Vim). The patient was diagnosed with Uterine carcinosarcoma. On December 18, 2023, the patient underwent partial vaginal resection, bilateral salpingo-oophorectomy, pelvic lymph node dissection, and a sub-extensive laparoscopic hysterectomy. Postoperatively, the patients received radiotherapy and four cycles of chemotherapy in the DC regimen. As of July 2024, laboratory and impact test results showed no tumor recurrence. The patient's disease-free survival (DFS) was seven months. Conclusion: The rate of childless in patients with uterine carcinosarcoma is at a high level. [ABSTRACT FROM AUTHOR]

Background: Müllerian cysts of the posterior mediastinum are rare, benign lesions typically discovered incidentally via routine medical exams. Case presentation: We present a distinctive case of a 49-year-old asymptomatic woman, illustrating a rare Müllerian cyst located in the posterior mediastinum with serous papillary cystadenoma-like features, a novel finding in the medical literature. Identified during a routine health screening in December 2020, a 20 mm cystic lesion adjacent to the T4-5 vertebral body was detected through chest CT and MRI, initially suggesting a neurogenic tumor. Histopathological analysis revealed a Müllerian cyst characterized by an epithelium resembling serous papillary cystadenoma, with positive immunohistochemical markers for Paired Box 8 (PAX8), Estrogen Receptor (ER), and Progesterone Receptor (PR), indicative of Müllerian differentiation. The papillary growth pattern initially raised concerns about malignancy, yet the benign nature was confirmed by minimal cellular atypia, well-defined borders, absence of invasion, and a low proliferation index. Conclusion: This case underscores the significance of detailed pathological analysis and immunohistochemical profiling in managing atypical Müllerian cysts, adding to the limited knowledge on Müllerian cysts. Future research should explore the mechanisms leading to Müllerian cysts with serous papillary cystadenoma-like features in the posterior mediastinum. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most diagnosed cancers worldwide. The insulin-like growth factor (IGF) system promotes proliferation and survival in breast cancer cells and is regulated by 6 insulin-like growth factor binding proteins (IGFBPs). The IGFBPs sequester IGFs to prolong their half-life and attenuate binding to insulin-like growth factor 1 receptor (IGF1R). While IGFBP-6 has been studied in some cancers it has not been studied extensively in hormone receptor positive breast cancer. Survival analysis using available databases indicated that high IGFBP-6 levels improve overall survival in progesterone receptor positive breast cancers. IGFBP-6 is transcriptionally induced by progesterone in T47D breast cancer cells resulting in increased intracellular and extracellular IGFBP-6 protein. Knockdown of IGFBP-6 resulted in reduced proliferative antagonism when estradiol stimulated T47D cells were cotreated with progesterone and protein levels of both progesterone receptor isoforms (PR-A and PR-B) were decreased following knockdown of IGFBP-6. P21(Cip1/Waf1), which is progesterone responsive, was not induced in response to progesterone following knockdown of IGFBP-6. Cyclin E2, a cell cycle regulator, is induced by progesterone only when IGFBP-6 is knocked down. Stable overexpression of IGFBP-6 in MCF-7 cells resulted in an increase in Epidermal Growth Factor Receptor (EGFR) and this expression was further enhanced when cells were cotreated with progesterone and estradiol. These results indicate that IGFBP-6 is a regulator of progesterone action, and that PR is required for the observed protective effects of IGFBP-6 in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistance (MDR), mainly caused by ATP-binding cassette transporters (ABCTs) efflux, makes it difficult for many anticancer drugs to treat breast cancer (BC). Phytochemicals can reverse cancer's MDR by modifying ABC transporter expression and function, as well as working synergistically with anticancer drugs to target other molecules. The reversal effect of the isoquinoline alkaloid coptisine (COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDB-MB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR. Methods: The cytotoxicity of COP and its ability to improve doxorubicin (DOX) cytotoxicity were assessed using the MTT assay. The effectiveness of COP in reversing DOX resistance was evaluated by calculating resistance ratio (RR) values, combination index (CI), and isobologram (IB). The inhibitory effect of COP on ABCT efflux function in comparison to verapamil (VER) was evaluated by measuring the cellular accumulation of Rho123 using flow cytometry. The impact of COP, either alone or in combination with DOX, on the gene expression of ABCTs (P-gp/MDR1, BCRP, and MRP1) of investigated cell lines was assessed by RT-PCR. Results: The COP showed modest cytotoxicity on the examined cell lines. In MCF-7/ADR and MDA-MB-231/ADR cells, COP (31 μM) enhanced DOX cytotoxicity with CI (0.77 and 0.75), RR (2.58 and 3.33), and IB suggesting synergism. COP significantly inhibits ABCT function in resistant BC cell lines, increases Rho123 accumulation, and decreases efflux more than VER; 2.1 and 1.2-fold, respectively. The combination of COP and DOX had a strong inhibitory effect on ABCT function (3.1 and 3.9 times VER, P< 0.001) and downregulated the genes and protein expression of ABCT. Conclusion: COP reversed ABCT-mediated multidrug resistance in vitro , indicating its potential as a multidrug resistance-reversing agent in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

There are conflicting data regarding the prognostic effect of microvascular density (MVD) in breast cancer and its molecular subtypes. It is thought that high levels of FOXP3 + T cells in breast cancer are associated with poor prognosis. However, data regarding FOXP3 show significant variability in the literature. In our study, we aim to measure MVD and FOXP3 + T cells in breast cancer cases and investigate their relationship with each other and their effects on breast cancer patients' clinical and prognostic features. In our study, the results of 207 female breast cancer patients whose excisional tumoral tissue was obtained are presented. The study evaluated the findings under a light microscope using antibodies against CD34 for measuring MVD and FOXP3 for measuring FOXP3-positive T cells. CD34 ≥ 17 was categorized as high MVD, and CD34 < 17 was classified as low MVD. FOXP3 + cell count ≥ 20/mm2 was categorized as high FOXP3 positivity and < 20/mm2 as low FOXP3 positivity. The SPSS program (version 22) was used to evaluate the results statistically, and p < 0.05 was considered significant. The median age was 54.0 (27–86) years, and the median follow-up period was 60.0 (IQR: 42.6–86.5) months. In the high MVD group, a higher progesterone receptor (PR) positivity rate was detected (p = 0.035). High FOXP3 positivity was significantly associated with high nuclear grade (p = 0.003). High FOXP3 positivity was significantly associated with PR negativity and high Ki67 values ​​(p = 0.009, p = 0.012, respectively). No statistically significant correlation was found between MVD elevation and FOXP3 positivity (r = 0.063, p = 0.36). A weakly significant positive correlation was detected between high Ki67 and FOXP3 positivity (r = 0.0146, p = 0.04). A weak inverse correlation was detected between high FOXP3 positivity and PR percentage values ​​(r=-0.182, p = 0.01). While there was no significant difference in disease-free survival in cases with high MVD and high FOXP3 + T cells compared to groups with low levels, the results were not mature enough because the median values ​​in overall survival could not be reached. A significant correlation was found between high FOXP3 positivity and some aggressive tumor features; no effect on survival was detected. In contrast to literature data on luminal A breast cancer, high MVD in the luminal B (HER2-) subgroup was associated with a lower risk of recurrence. Our study is the first in the literature to evaluate the relationship between MVD measured using CD34 and FOXP3 positive T cells in breast cancer. Our study found no correlation between MVD and FOXP3 positivity, while literature data show significant correlations in some other cancers. [ABSTRACT FROM AUTHOR]

Objective: To explore the improvement effect of acupoint application of seed of Chinese dodder at Sanyinjiao acupoint on pregnancy outcome in rats with recurrent abortion, and its influence on the balance of Th1/Th2 at maternal-fetal interface. Methods: SD female pregnant rats were randomly divided into normal pregnant rats group, abortion model group, acupoint application of seed of Chinese dodder group, gavage of seed of Chinese dodder group, acupoint application of starch group, with 15 rats in each group. Except for normal pregnant rats group, pregnant rats of other groups were injected subcutaneously with 0.3 mg/kg bromocriptine on 6~8 days of gestation, for once a day, the abortion model was established, the treatment was given from the first day of pregnancy, and the blood was taken from the abdominal aorta on the 12th day of pregnancy to detect levels of serum prolactin(PRL) and progesterone (P); pregnant rats were sacrificed, the uterus was taken out, the embryo abortion rate was calculated and the uterus weight was weighed to evaluate changes of pregnancy outcome of pregnant rats; the decidua tissue was taken, and the positive expression of progesterone receptor(PR) was detected by immunohistochemical method; Th1 type(TNF-α, IFN-γ)/Th2 type(IL-4, IL-10) cytokines mRNA and protein expressions in decidua tissue were detected by RT-PCR and Western blot. Results: Compared with normal pregnant rats group, abortion model group had an increased embryo abortion rate, and decreased uterine weight, progesterone PRL, P and PR expressions, the decidual tissue Th1 type (TNF-α, IFN-γ) cytokines mRNA and protein expressions were increased, while Th2 type (IL-4, IL-10) cytokines mRNA and protein expressions were decreased (P<0.05). Acupoint application of seed of Chinese dodder and gavage of seed of Chinese dodder could reduce the abortion rate, increase expressions of PRL, P and PR, and correct the Th1/Th2 imbalance, and the therapeutic effect of acupoint application of seed of Chinese dodder is better than that of gavage of seed of Chinese dodder (P<0.05). Conclusion: Application of the seed of Chinese dodder at Sanyinjiao acupoint can improve the adverse pregnancy outcome of abortion model rats, correct Th1/Th2 imbalance, and reduce the abortion rate, and its effect is better than gavage of seed of Chinese dodder. [ABSTRACT FROM AUTHOR]

PURPOSE: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)–low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM). METHODS: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)–negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS). RESULTS: In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor–positive/HER2-negative (HR+/HER2–) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; P =.07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS. CONCLUSION: Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2– disease have HER2-low BrM with potential to benefit from HER2-targeted therapy. HER2 status of breast cancer brain metastases—a target among patients whose extracranial disease is HER2-0. [ABSTRACT FROM AUTHOR]

Adenosarcoma of the uterus with Sarcomatous Overgrowth (SO) and Heterologous Elements (HE) is a rare and aggressive neoplasm that shares common clinical and radiological presentations. It is also referred to as Müllerian adenosarcoma, a slow-growing neoplasm characterised by a classical biphasic pattern comprising benign epithelial and malignant mesenchymal tissue. Adenosarcoma with a high-grade stromal component has an increased risk of recurrence. Hereby the authors present a case of 39-year-old female who was nulliparous, reported to the Department of Obstetrics and Gynaecology with abdominal pain, menorrhagia, and burning micturition. Her medical history included diabetes, hypertension, hypothyroidism, and morbid obesity. She had a past history of similar complaints, during which an endometrial biopsy had shown hyperplasia without atypia. She was lost for follow-up and returned after one and a half years, having developed endometrial hyperplasia with atypia. She returned only after six months with similar but more severe complaints. Clinically and radiologically, there was a polypoidal mass protruding through the cervical canal. The hysterectomy specimen revealed a tumour with histopathological features of Müllerian adenosarcoma with SO. Interestingly, both ovaries were enlarged, exhibiting marked stromal hyperplasia. A panel of immunohistochemical markers, including CD10, Ki67, S-100, desmin, Estrogen Receptor (ER), and Progesterone Receptor (PR), was used, and the findings were unusual for an adenosarcoma with high-grade stromal histology. The chronological progression from endometrial hyperplasia without atypia to hyperplasia with atypia in a nulliparous woman, along with bilateral ovarian stromal hyperplasia, represents a classical pattern of events. [ABSTRACT FROM AUTHOR]

Background: Inconclusive epidemiological evidence suggests that diet quality indices may influence breast cancer (BC) risk; however, the evidence does not consider the molecular expression of this cancer. Purpose: We aimed to evaluate if diet quality is related to molecular subtypes of BC, in women residing in Northern Mexico. Methods: This is a secondary analysis of 1,045 incident cases and 1,030 population controls from a previous case-control study, conducted between 2007 and 2011 in Northern Mexico. Information about the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) was obtained from medical records to classify BC as luminal (ER + and/or PR+/HER2–), HER2+ (ER+/–and/or PR+/–/HER2+), or triple-negative (TN) (ER– and PR–/HER2–) cases. Food consumption was assessed with a semi-quantitative food frequency questionnaire. Diet quality was evaluated using the Mexican Diet Quality Index (MxDQI) and the Mexican Alternative Healthy Eating Index (MxAHEI). We used unconditional logistic regression models to estimate the association between Mexican diet quality indices and BC molecular subtypes. Results: The MxDQI was related to lower odds of BC (ORT3vsT1=0.24; 95%CI: 0.18, 0.31). Similarly, MxAHEI was negatively associated with BC (ORT3vsT1=0.43; 95%CI: 0.34, 0.54). The associations of both indices remained significant in the ER + and ER- tumors, and in the BC luminal and HER2 + molecular subtypes, except in the TN molecular subtype for MxAHEI, which was not statistically significant. Conclusions: Our findings showed that MxDQI and MxAHEI were negatively associated with BC risk regardless of its molecular subtype. [ABSTRACT FROM AUTHOR]

Objective: To analyze differences between screen-detected and non-screen-detected invasive breast cancers by tumour characteristics and age at diagnosis in the nationwide population-based mammography screening program in Sweden. Methods: Data were retrieved from the National Quality Register for Breast Cancer for 2008–2017. Logistic regression analysis was used to estimate the likelihood for a tumour to be screen-detected by tumour characteristics and age group at diagnosis. Results: In total there were 51,429 invasive breast cancers in the target age group for mammography screening of 40–74 years. Likelihood of screen detection decreased with larger tumour size, lymph node metastases, higher histological grade and distant metastasis. Odds ratios (ORs) for negative oestrogen (ER) and progesterone (PgR) were 0.41 and 0.57; for positive HER2, 0.62; for Ki-67 high versus low, 0.49. Molecular sub-types had OR of 0.56, 0.40 and 0.28, respectively, for luminal B-like, HER2-positive and triple negative versus luminal A-like. Adjusting for tumour size (T), lymph node status (N), age, year and county at diagnosis slightly elevated the ORs. Statistically significant interactions between tumour characteristics and age were found (p < 0.05) except for ER and PgR. The age group 40–49 deviated most from the other age groups. Conclusions: Our study demonstrates that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected after adjusting for age, year and county of diagnosis, and even after adjusting for T and N. The trend towards favourable tumour characteristics was less pronounced in the 40–49 age group compared to the other age groups, except for ER and PgR. [ABSTRACT FROM AUTHOR]

Background: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, β (ERα,β) and prostate-specific antigen (PSA). Materials and methods: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted. Results: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERβ expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERβ expression levels. Conclusion: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml). [ABSTRACT FROM AUTHOR]

Background and Clinical Significance: Abnormal uterine bleeding during the postmenopausal years is a pathological sign that may be due to simultaneous intrauterine and ovarian pathology. Granulosa cell tumours of the ovary are malignant neoplasms producing oestradiol, which leads to the abnormal proliferation of the endometrium, precancerous lesions, and endometrial carcinoma type I. Case Presentation: The authors present a clinical case of a 67-year-old woman with postmenopausal bleeding who underwent a total abdominal hysterectomy with bilateral adnexectomy, pelvic lymphadenectomy, and partial omentectomy. The histopathological examination showed a granulosa cell adult-type ovarian tumour and a malignant endometrial polyp with atypical hyperplasia of the endometrium. Conclusions: The immunohistochemical analysis of the malignant endometrial polyp confirmed the expression of oestrogen, progesterone receptors, and the biomarker Ki-67. [ABSTRACT FROM AUTHOR]

Chronic diseases may be associated with adverse clinical characteristics of breast cancer outcomes. This study determined the descriptive association of some chronic diseases and clinicopathological characteristics of breast cancer patients in women diagnosed in a single center in Jeddah, KSA. Retrospective data of 196 patients diagnosed with breast cancer (from 2015-2021) was analyzed. Demographics, patients' health conditions, and tumor properties were investigated. Most women diagnosed with breast cancer were 40-69 years of age. Women with a body mass index (BMI) classification of overweight/obese were extremely significantly more than those who were classified as lean. The tumors reported show that a significant number of samples (87.0%) had tumors between T1 and T2. Significantly more tumors (61.0%) were of grade V, and ~81.0% were histopathologically classified as invasive ductal carcinoma. A significant majority of breast cancers in this population were human epidermal growth factor receptor 2 negative (70%), progesterone receptor positive (58%), and non-triple negative (~93%). In these patients, a BMI classification of overweight/obese is possibly associated with breast cancer. Awareness and knowledge about the correlation of breast cancer with obesity may help to reduce or delay its presence. [ABSTRACT FROM AUTHOR]

Objective: In this study, we investigated the clinical characteristics and survival outcomes of patients diagnosed with special types of breast cancer who presented to our clinic. Methods: The demographic, clinicopathological, and survival characteristics of all rare, histologically special subtype breast cancer patients who applied to Sivas Cumhuriyet University Oncology Center between 2010 and 2020 were retrospectively reviewed. Results: The records of 1198 patients with invasive breast cancer were examined, and 104 of them (8%) were identified as having other histological special subtypes. Of these, 19 (8%) had apocrine cancer, 19 (8%) had mucinous type, 17 (7%) had invasive cribriform, 15 (6%) had invasive papillary, 11 (4%) had metaplastic type, 9 (4%) had invasive micropapillary, 6 (2%) had neuroendocrine, 3 (1%) had tubular type, 3 (1%) had microinvasive type, and 2 (1%) had undifferentiated carcinoma. The majority of these patients, 102 (98%), were female, with a median age of 52 years (range 26-82). Of the women, 60 (59%) were postmenopausal, and 42 (41%) were premenopausal. The ECOG Performance Score (PS) was 0 in 79 (76%) patients, 1 in 17 (16%) patients, and 2 in 8 (8%) patients. Upon evaluation, 50 patients (48%) had comorbid conditions, and 26 patients (25%) had a family history of breast cancer. At diagnosis, 25 patients (24%) were stage I, 50 (48%) were stage II, 26 (25%) were stage III, and 3 (3%) were stage IV. Histopathologically, 75 patients (72%) were estrogen receptor (ER)-positive, 69 (66%) were progesterone receptor (PR)-positive, and 26 (25%) were HER2-positive. An intraductal component was detected in 54 (60%) patients, and multicentricity was observed in 15 (16%) patients. A modified radical mastectomy was performed on 56 (54%) patients, while breast-conserving surgery was performed on 45 (43%) patients. Adjuvant chemotherapy was administered to 76 (73%) patients, hormonal therapy to 73 (70%), and radiotherapy to 72 (68%). The median follow-up period was 54 months (range 1-201). During follow-up, metastasis was detected in 13 patients (13%), and recurrence was detected in 7 patients (7%). The 5-year and 10-year overall survival rates were 86% and 77%, respectively, while the 5-year and 10-year event-free survival rates were 79% and 70%, respectively. Conclusion: In our study, the majority of patients with special type breast carcinoma were non-metastatic, and histopathologically, they were hormone receptor-positive with low grade. There was no statistically significant difference in 5-year and 10-year overall survival or event-free survival among the pecial types. [ABSTRACT FROM AUTHOR]

Background: CDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor‐positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes. Methods: Patients with HR+ MBC who received CDK4/6i‐based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression‐free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0). Results: This study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4–15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki‐67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C‐index of 0.714 (95% confidence interval: 0.640–0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions. Conclusions: This real‐world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment. [ABSTRACT FROM AUTHOR]