Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China.

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.

Modulatory effect of vitamin B6 on sex hormone receptors, thyroid, and kisspeptin/kiss1r system in the uterus of pseudopregnant bitches.

This study evaluated whether the treatment of pseudopregnancy in bitches with vitamin B6 modulates uterine expression of receptors for progesterone (PR), oestrogen (ERα), androgen (AR), thyroid hormone (TRα) and the kisspeptin/Kiss1r system. Eighteen pseudopregnant bitches were treated for 20 days in groups receiving placebo (n = 6); cabergoline (5 µg/kg/day; n = 6); or vitamin B6 (50 mg/kg/day; n = 6). Blood was collected on the 1st day of drug administration and 120 h later to measure serum prolactin (PRL). After treatment, they were ovariohysterectomized and uterine fragments were collected for histomorphometry and immunohistochemical evaluation of PR, ERα, AR, TRα, Kiss1 and Kiss1r. After 120 h of cabergoline or vitamin B6 treatment, PRL levels were reduced in the bitches, confirming the antiprolactinemic effect of these drugs. Furthermore, regardless of treatment, the animals exhibited uterine histomorphometry consistent with dioestrus. The PR showed strong immunostaining in all regions and an increase in scores was observed for this receptor in animals treated with vitamin B6 in deep glands. In contrast, ERα and Kiss1R receptors showed weak to no immunostaining in all uterine regions and no changes between groups. Regarding AR, most animals treated with vitamin B6 showed increased trends in the deep gland and myometrium marking scores. In contrast, in both vitamin B6 and cabergoline treatments, a reduction in TRα marking scores was observed compared to the control group. In addition, on the endometrial surface, a reduction was observed in the marked area of Kiss1 after administration of cabergoline when compared to the pseudopregnant control group. These findings shed valuable insight into the use of vitamin B6 as a drug with actions similar to cabergoline in reducing PRL and uterine modulation in bitches.

Association between pathologic complete response and biochemical indicators after neoadjuvant therapy for HER2-positive breast cancer.

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center.

Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS). Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients. Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki-67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes). Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.

Correlation of Ki-67 proliferative index with oncotype DX recurrence score in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer with low-burden axillary nodal disease - a review of 137 cases.

The use of chemotherapy in breast cancer management has significantly contributed to the decrease in its mortality. Currently, the prognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, the increasing use of advanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided the ability to estimate the risk of recurrence. Research has demonstrated that the ODX-RS helps to predict recurrence risk and the potential benefit of chemotherapy in breast cancer. As a result, it can assist clinicians in making decisions regarding using the chemotherapy. The goal of work is to explore the correlation between the ODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In the high Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, the results show no significant correlation between the ODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Isolation and Characterization of a Novel Mammary Adenocarcinoma, MCa-P1362, with Hormone Receptor Expression, Human Epidermal Growth Factor Receptor 2 Positivity, and Enrichment in Cancer and Mesenchymal Stem Cells.

Preclinical models that display spontaneous metastasis are necessary to improve the therapeutic options for hormone receptor-positive breast cancers. Within this study, detailed cellular and molecular characterization was conducted on MCa-P1362, a newly established mouse model of metastatic breast cancer that is syngeneic in BALB/c mice. MCa-P1362 cancer cells express estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2. MCa-P1362 cancer cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for growth and tumor progression. Analysis of MCa-P1362 tumor explants revealed the tumors contained a mixture of cancer cells and mesenchymal stromal cells. Through transcriptomic and functional analyses of both cancer and stromal cells, stem cells were detected within both populations. Functional studies demonstrated that MCa-P1362 cancer stem cells drove tumor initiation, whereas stromal cells from these tumors contributed to drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of breast tumor progression and therapeutic resistance.

Molecular Imaging of Steroid Receptors in Breast Cancer.

ABSTRACT: Steroid receptors regulate gene expression for many important physiologic functions and pathologic processes. Receptors for estrogen, progesterone, and androgen have been extensively studied in breast cancer, and their expression provides prognostic information as well as targets for therapy. Noninvasive imaging utilizing positron emission tomography and radiolabeled ligands targeting these receptors can provide valuable insight into predicting treatment efficacy, staging whole-body disease burden, and identifying heterogeneity in receptor expression across different metastatic sites. This review provides an overview of steroid receptor imaging with a focus on breast cancer and radioligands for estrogen, progesterone, and androgen receptors.

Systematic literature review of real-world evidence for treatments in HR+/HER2- second-line LABC/mBC after first-line treatment with CDK4/6i.

BACKGROUND: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC. METHODS: MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens. RESULTS: Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics. CONCLUSIONS: The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.

Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model.

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo.

The effect of parity, breastfeeding history, and duration on clinical and pathological characteristics of breast cancer patients.

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.

Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2- metastatic breast cancer: A single center real-world study in China.

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC. METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). CONCLUSION: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.

The value of whole tumor apparent diffusion coefficient histogram parameters in predicting meningiomas progesterone receptor expression.

PURPOSE: This study investigated the value of whole tumor apparent diffusion coefficient (ADC) histogram parameters and magnetic resonance imaging (MRI) semantic features in predicting meningioma progesterone receptor (PR) expression. MATERIALS AND METHODS: The imaging, pathological, and clinical data of 53 patients with PR-negative meningiomas and 52 patients with PR-positive meningiomas were retrospectively reviewed. The whole tumor was outlined using Firevoxel software, and the ADC histogram parameters were calculated. The differences in ADC histogram parameters and MRI semantic features were compared between the two groups. The predictive values of parameters for PR expression were assessed using receiver operating characteristic curves. The correlation between whole-tumor ADC histogram parameters and PR expression in meningiomas was also analyzed. RESULTS: Grading was able to predict the PR expression in meningiomas (p = 0.012), though the semantic features of MRI were not (all p > 0.05). The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were able to predict meningioma PR expression (all p < 0.05). The predictive performance of the combined histogram parameters improved, and the combination of grade and histogram parameters provided the optimal predictive value, with an area under the curve of 0.849 (95%CI: 0.766-0.911) and sensitivity, specificity, ACC, PPV, and NPV of 73.08%, 81.13%, 77.14%, 79.20%, and 75.40%, respectively. The mean, Perc.01, Perc.05, Perc.10, Perc.25, and Perc.50 histogram parameters were positively correlated with PR expression (all p < 0.05). CONCLUSION: Whole tumor ADC histogram parameters have additional clinical value in predicting PR expression in meningiomas.

The diagnostic potentiality of the RNA aptamer against progesterone receptor isolated by crush and soak (CRUSOAK)-SELEX.

Aptamers are a class of molecular recognition elements that exhibit high binding affinity and specificity against their respective targets. In view of the many advantages aptamers harbor over their counterpart antibodies, we were impelled to isolate an RNA aptamer against progesterone receptor, particularly its DNA binding domain. A total of eight SELEX cycles were executed against the recombinant Progesterone Receptor DNA-binding domain (PR DBD). The RNA-protein complex in the gel shift assay was subjected to crush and soak method to elute the binders prior to conventional sequencing, the step of which was based upon to coin the term CRUSOAK-SELEX. The sequencing revealed three different classes of sequences, with one class termed, PRapt-3, showing the strongest binding against PR DBD. The dissociation constant of PRapt-3 RNA aptamer was estimated at 380 nM ± 35 nM. PRapt-3 was successfully used to develop aptamer-based diagnostic assays such as ELASA, aptamer-based dot blot, and aptamer-based western blot. The prominent highlight is the performance of the aptamer in aptacytostaining, which was unachievable with antibodies. Compared to its counterpart antibodies, PRapt-3 has a better penetration capacity in aptahistostaining using the formalin-fixed paraffin-embedded (FFPE) breast cancer cells and tissue blocks. This study represents the first ever demonstration of an aptamer against progesterone receptor and its diagnostic capacity.

Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report.

BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Is neoadjuvant chemotherapy necessary for T2N0-1M0 hormone receptor-positive/HER2-negative breast cancer patients undergoing breast-conserving surgery?

INTRODUCTION: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. METHODS: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. RESULTS: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. CONCLUSION: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.