19,795 results on '"Receptors, Progesterone"'
Search Results
2. Cáncer de mama metastásico y embarazo: reporte de caso.
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Salas Gil, Elide Berenisse, Barbabosa Vilchis, Jorge Arturo, and Palestino Rojas, Guillermo
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CANCER in pregnancy ,METASTATIC breast cancer ,PERICARDIAL effusion ,HYPOVENTILATION ,PROGESTERONE ,TUMOR growth ,BREAST abnormalities ,CANCER diagnosis - Abstract
Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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3. 子宫内膜异位症中雌、孕激素及其受体基因甲基化的研究进展.
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王湘炼, 朱姝, 徐炜, and 王秀丽
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Endometriosis (EMs) is a common and frequent disease in women of reproductive age. The main clinical manifestations are dysmenorrhea and infertility, and there is a high recurrence rate and a potential risk of malignant transformation. EMs is an estrogen-dependent disease, with progesterone-resistant properties. The local synthesis of estrogen and progesterone in the ectopic lesions and the interactions with the receptors play an essential role in the development and progression of EMs. The local high estrogen environment favors the proliferation, migration, adhesion and invasion of ectopic endometrial cells, promoting the development of EMs and even malignancy. Progesterone resistance can affect endometrium tolerance and is closely associated with endometriosis-associated infertility. Recent studies have identified DNA methylation plays an important regulatory process in the synthesis of estrogen and progesterone and the expression of their receptors in eutopic endometrium and ectopic lesions of EMs. Understanding the role of gene methylation related to estrogen and progesterone and their receptors in the development of EMs, endometriosis-associated infertility and endometriosis-associated malignancy can provide a basis for diagnosis and drug-targeted therapy studies for EMs. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma
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Jin Hwan Lee, Han Kyeom Kim, and Bong Kyung Shin
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adenocarcinoma of lung ,receptors, estrogen ,erα ,erβ ,receptors, progesterone ,prognosis ,Pathology ,RB1-214 - Abstract
Background Adenocarcinoma (ADC) of the lung exhibits different clinicopathological characteristics in men and women. Recent studies have suggested that these differences originate from the expression of female sex hormone receptors in tumor cells. The aim of the present study was to evaluate the immunohistochemical expression of female sex hormone receptors in lung ADC and determine the expression patterns in patients with different clinicopathological characteristics. Methods A total of 84 patients with lung ADC who underwent surgical resection and/or core biopsy were recruited for the present study. Immunohistochemical staining was performed for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), epidermal growth factor receptor (EGFR), EGFR E746-A750 del, and EGFR L858R using tissue microarray. Results A total of 39 (46.4%) ERα-positive, 71 (84.5%) ERβ-positive, and 46 (54.8%) PR-positive lung ADCs were identified. In addition, there were 81 (96.4%) EGFR-positive, 14 (16.7%) EGFR E746-A750 del–positive, and 34 (40.5%) EGFR L858R–positive cases. The expression of female sex hormone receptors was not significantly different in clinicopathologically different subsets of lung ADC. Conclusions Expression of female sex hormone receptors is not associated with the prognosis and clinicopathological characteristics of patients with lung ADC.
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- 2020
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5. Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer
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Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, and Ahwon Lee
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breast neoplasms ,core needle biopsy ,receptors, estrogen ,receptors, progesterone ,human epidermal growth factor receptor 2 ,immunohistochemistry ,Pathology ,RB1-214 - Abstract
Background Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens. Methods This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers. Results In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p
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- 2020
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6. Age-related phenotypes in breast cancer: A population-based study.
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Svanøe AA, Humlevik ROC, Knutsvik G, Sæle AKM, Askeland C, Ingebriktsen LM, Hugaas U, Kvamme AB, Tegnander AF, Krüger K, Davidsen B, Hoivik EA, Aas T, Stefansson IM, Akslen LA, and Wik E
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- Humans, Female, Ki-67 Antigen, Receptor, ErbB-2 genetics, Prognosis, Cell Proliferation, Receptors, Progesterone, Biomarkers, Tumor genetics, Breast Neoplasms pathology
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Breast cancer in young (<40 years) is associated with a higher frequency of aggressive tumor types and poor prognosis. It remains unclear if there is an underlying age-related biology that contributes to the unfavorable outcome. We aim to investigate the relationship between age and breast cancer biology, with emphasis on proliferation. Clinico-pathologic information, immunohistochemical markers and follow-up data were obtained for all patients aged <50 (Bergen cohort-1; n = 355, not part of a breast screening program) and compared to previously obtained information on patients aged 50 to 69 years (Bergen cohort-2; n = 540), who participated in the Norwegian Breast Cancer Screening Program. Young breast cancer patients presented more aggressive tumor features such as hormone receptor negativity, HER2 positivity, lymph-node metastasis, the HER2-enriched and triple-negative subtypes and shorter survival. Age <40 was significantly associated with higher proliferation (by Ki67). Ki67 showed weaker prognostic value in young patients. We point to aggressive phenotypes and increased tumor cell proliferation in breast cancer of the young. Hence, tumors of young breast cancer patients may present unique biological features, also when accounting for screen/interval differences, that may open for new clinical opportunities, stratifying treatment by age., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
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7. White matter volume and treatment with selective progesterone receptor modulator in patients with premenstrual dysphoric disorder.
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Kaltsouni E, Wikström J, Lanzenberger R, Sundström-Poromaa I, and Comasco E
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- Female, Humans, Receptors, Progesterone, Brain diagnostic imaging, Brain pathology, Gray Matter diagnostic imaging, Gray Matter pathology, Premenstrual Dysphoric Disorder diagnostic imaging, Premenstrual Dysphoric Disorder drug therapy, White Matter diagnostic imaging, White Matter pathology
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Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD., Competing Interests: Declaration of Competing Interest The study drugs were provided by Gedeon Richter, but they had no further involvement in the study design, data collection, analysis, findings’ interpretation, or manuscript preparation. RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. ISP has served occasionally on advisory boards or acted as invited speaker at scientific meetings for Asarina Pharma, Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, Sandoz, and Lundbeck A/S. All other authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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8. Association of estrogen receptor and progesterone receptor genetic polymorphisms with recurrent pregnancy loss: A systematic review and meta-analysis.
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Huang X, Yin T, Song M, and Pan J
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- Female, Humans, Pregnancy, Estrogen Receptor alpha genetics, Estrogen Receptor beta genetics, Genetic Predisposition to Disease, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Receptors, Progesterone, Abortion, Habitual genetics, Receptors, Estrogen
- Abstract
Objective: Estrogen and progesterone play key roles in the maintenance of pregnancy, and their function is mediated via estrogen receptor 1 (ESR1)/estrogen receptor 2 (ESR2) and progesterone receptor (PGR), respectively. It has been suggested the genetic variations in ESR1, ESR2, and PGR may contribute to recurrent pregnancy loss (RPL); however, the available evidence remains controversial. This meta-analysis aimed to explore the relation of various polymorphisms in ESR1, ESR2, and PGR genes to the risk of RPL., Methods: A systematic literature search was conducted using PubMed and Scopus up to August 2023 to obtain relevant studies. The odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed and pooled with the use of random-effects models to test the associations., Results: A total of 31 studies with 12 different polymorphisms, including 5 polymorphisms for ESR1, 3 polymorphisms for ESR2, and 4 polymorphisms for PGR, were analyzed in this meta-analysis. Overall, no significant relationship was found between various polymorphisms of ESR1 and ESR2 with RPL in any of the genetic analysis models. PGR rs590688 (C > G) polymorphism was significantly related to the elevated risk of RPL under the dominant (OR = 1.67; 95 %CI: 1.15-2.44), allelic (OR = 1.55; 95 %CI: 1.13-2.12), and GC vs. CC (OR = 1.55; 95 %CI: 1.07-2.23) models. No significant association was identified for other variants of PGR gene., Conclusion: Unlike estrogen receptors, variations in PGR rs590688 (C > G) may be linked to the increased risk of RPL. More studies are required to confirm this finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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9. Design, Synthesis, and Evaluation of B -(Trifluoromethyl)phenyl Phosphine-Borane Derivatives as Novel Progesterone Receptor Antagonists.
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Miyajima Y, Ochiai K, and Fujii S
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- Computer Simulation, Drug Discovery, Receptors, Progesterone, Boranes pharmacology, Phosphines
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We previously revealed that phosphine-boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and synthesize a series of B -(trifluoromethyl)phenyl phosphine-borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine-borane derivatives exhibited Log P values in a predictable manner and that the P-H group in the phosphine-borane was almost nonpolar. Among the synthesized phosphine-boranes, which exhibited PR antagonistic activity, B -(4-trifluoromethyl)phenyl tricyclopropylphosphine-borane was the most potent with an IC
50 value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand-receptor interactions. These results support the idea that phosphine-boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists.- Published
- 2024
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10. Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.
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Mao C, Hu L, Jiang W, Qiu Y, Yang Z, Liu Y, Wang M, Wang D, Su Y, Lin J, Yan X, Cai Z, Zhang X, and Shen J
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- Female, Humans, Prospective Studies, Receptors, Progesterone, Diffusion Magnetic Resonance Imaging, Receptors, Estrogen metabolism, Breast Neoplasms pathology, Receptor, ErbB-2
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Objectives: To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC)., Methods: This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, α
CTRW , βCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic (ROC) curves were used to evaluate their discriminative ability., Results: The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877., Conclusions: The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs., Clinical Relevance Statement: Human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue., Key Points: • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW , DCTRW , βFROC , DFROC , μFROC , αSEM , and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)- Published
- 2024
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11. Placental histology for targeted risk assessment of recurrent spontaneous preterm birth.
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Suresh S, Freedman A, Adams M, Hirsch E, and Ernst LM
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- Infant, Newborn, Pregnancy, Female, Humans, Infant, 17 alpha-Hydroxyprogesterone Caproate, Progesterone, Receptors, Progesterone, Retrospective Studies, Placenta, 17-alpha-Hydroxyprogesterone, Risk Assessment, Gravidity, Inflammation drug therapy, Hydroxyprogesterones therapeutic use, Premature Birth prevention & control
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Background: Spontaneous preterm birth significantly increases the risk for a recurrent preterm birth. Only a few identifiable clinical risk factors can be referenced in counseling for recurrent preterm birth. Furthermore, treatment using progesterone supplementation has not consistently prevented preterm birth among high-risk patients, but it may be effective in a subset of those patients. Placental pathology from a previous pregnancy may be used to predict which patients will experience a recurrent preterm birth or to identify a subset of patients more likely to respond to treatment with antenatal progesterone., Objective: This study aimed to determine if histologic patterns are associated with recurrent preterm birth among patients with an index spontaneous preterm birth. A secondary objective was to determine if placental histologic types and/or progesterone receptor density in the decidua are associated with the response to progesterone supplementation with intramuscular 17-hydroxyprogesterone caproate., Study Design: This was a retrospective cohort study at a single institution of women with singleton pregnancies with an index spontaneous preterm birth and a subsequent birth within the same hospital system between 2009 and 2019. Patients were included if placental pathology was available for the index spontaneous preterm birth. A logistic regression was used to determine if there were independent associations between 4 histologic types (acute inflammation, maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammation) and recurrent preterm birth. For the secondary endpoint, 17-hydroxyprogesterone caproate response was defined as prolonging gestation by >3 weeks beyond the gestational age at delivery in the index pregnancy. Patients who delivered <3 weeks beyond the gestational age in the index pregnancy but at ≥39 weeks' gestation were excluded. A logistic regression was used to assess the independent association between placental histology and 17-hydroxyprogesterone caproate response. Sensitivity analyses were completed using only patients with an index birth <36 weeks' gestation, and then excluding those with medically indicated preterm birth in a subsequent pregnancy. A nested case-control immunohistochemical study was done among 20 patients with a subsequent term birth and 20 patients with a subsequent spontaneous preterm birth. The percentage of cells in the maternal decidua positive for progesterone receptors was correlated with the subsequent pregnancy outcome., Results: A total of 352 patients were included. Acute inflammation was the most common histologic type seen among patients with spontaneous preterm birth (44.1%), followed by chronic inflammation (40.9%) and maternal vascular malperfusion (31.3%). No histologic type was independently associated with recurrent preterm birth. A total of 155 patients received 17-hydroxyprogesterone caproate in a second pregnancy. Low-grade acute inflammation was significantly associated with a decreased likelihood of 17-hydroxyprogesterone caproate response. Low-grade maternal vascular malperfusion among those with an index pregnancy delivered at <36 weeks' gestation was significantly associated with a more than 4 times increased likelihood of 17-hydroxyprogesterone caproate response when excluding those with a subsequent iatrogenic preterm birth. Progesterone receptor staining was not associated with recurrent preterm birth., Conclusion: Although acute inflammation was prevalent among spontaneous preterm births, more than half of the spontaneous preterm births were not associated with acute inflammation. Low-grade acute inflammation was associated with a significantly decreased response to 17-hydroxyprogesterone caproate supplementation. Low-grade maternal vascular malperfusion was associated with a 4-fold increased likelihood of 17-hydroxyprogesterone caproate response among those with index deliveries <36 weeks' gestation. Further work is needed to determine if placental pathologic examination can be used to target treatment in subsequent pregnancies to prevent recurrent preterm birth., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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12. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
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Lajos Pusztai, Gabriel N. Hortobagyi, Bryan T. Hennessy, Massimo Cristofanilli, Chafika Mazouni, Fabrice Andre, Attila Tordai, W. Fraser Symmans, Cornelia Liedtke, Marjorie C. Green, Ana M. Gonzalez-Angulo, Kenneth R. Hess, and Jaime A. Mejia
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Adult ,Oncology ,medicine.medical_specialty ,Cancer Research ,Neoplasm, Residual ,Neoplasms, Hormone-Dependent ,Receptor, ErbB-2 ,medicine.medical_treatment ,Estrogen receptor ,Breast Neoplasms ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,Survival rate ,Neoadjuvant therapy ,Triple-negative breast cancer ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gynecology ,business.industry ,Carcinoma, Ductal, Breast ,Cancer ,Triple Negative Breast Neoplasms ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Survival Rate ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,Female ,Breast disease ,Neoplasm Recurrence, Local ,Receptors, Progesterone ,business - Abstract
PURPOSE Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates ( P < .0001) and 3-year overall survival (OS) rates ( P < .0001). TNBC was associated with increased risk for visceral metastases ( P = .0005), lower risk for bone recurrence ( P = .027), and shorter postrecurrence survival ( P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival ( P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC ( P < .0001). CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.
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- 2023
13. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer
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Zohreh Ghoreishi, Seyedali Keshavarz, Mohammad Asghari Jafarabadi, Zahra Fathifar, Karyn A Goodman, and Ali Esfahani
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Peripheral nervous system diseases ,Paclitaxel ,Breast neoplasms ,Receptors, progesterone ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Paclitaxel induced peripheral neuropathy (PIPN) is a major debilitating side effect of paclitaxel in patients with breast cancer with no fully known mechanisms. The aim of the study was to find out the possible risk factors for PIPN. Methods Eligible patients with node positive breast cancer undergoing chemotherapy with paclitaxel were assessed. They belonged to an initial randomized controlled trial in which the effectiveness of omega-3 fatty acids in preventing and reducing severity of PIPN was evaluated (protocol ID: NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN. All analyses were performed adjusting for intervention effect. The association between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was evaluated. Results Fifty-seven patients with breast cancer were investigated. Age was significantly associated with risk of PIPN (RR:1.50, P value = .024). Body mass index and BSA had significant association with severity of PIPN (B:1.28, P = .025; and B: 3.88, P = .010 respectively). Also, BSA showed a significant association with the risk of PIPN (RR: 2.28, P = .035; B: 3.88, P = .035). Incidence and severity of PIPN were much more pronounced in progesterone receptor positive (PR+) patients (RR:1.88, P = .015 and B:1.54, P = .012). Multivariate analysis showed that age and the status of PR+ were independent risk factor for incidence and the status of PR+ was the only independent risk factor for severity of PIPN. Conclusion Age, BSA and the status of PR+, should be considered as the risk factors for PIPN before commencement of chemotherapy with paclitaxel in patients with breast cancer. Older patients, those with greater BSA and PR+ patients may need closer follow up and more medical attention due to greater incidence and severity of PIPN.
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- 2018
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14. A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy
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Erdoğan Selçuk Şeber, Yakup İriagac, Eyyup Çavdar, Kubilay Karaboyun, Okan Avcı, Ahmet Yolcu, Sibel Özkan Gürdal, and Meltem Öznur
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Subtypes ,Patients ,Neoadjuvant therapy ,Antineoplastic agents ,Receptors ,estrogen ,Receptors, progesterone ,Therapy ,General Medicine ,Breast neoplasms ,progesterone ,Receptors, estrogen - Abstract
SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48–6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07–5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.
- Published
- 2023
15. [Association between reproductive history, breast cancer subtype, and survival in premenopausal women].
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Bernal-Gómez M, Núñez-Álvarez V, Lluch-Gómez J, de la Torre-Hita C, Campini-Bermejo A, Perdomo-Zaldívar E, Rodríguez-Pérez L, Calvete-Candenas J, Benítez-Rodríguez E, and Baena-Cañada JM
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- Female, Humans, Middle Aged, Pregnancy, Parity, Receptor, ErbB-2, Receptors, Progesterone, Reproductive History, Retrospective Studies, Risk, Risk Factors, Young Adult, Adult, Breast Neoplasms
- Abstract
Background and Objective: Reproductive history influences breast cancer risk. We analysed its association with tumour subtype and survival in premenopausal women., Patients and Methods: Retrospective, observational study of premenopausal women with stage I-III breast carcinoma in the last 20 years. Review of reproductive history, clinical data, and treatments in health records., Results: In 661 premenopausal women (32.40% of 1377 total cases), median age was 47 years (19-53), menarche 12 (7-17), first delivery 28 (16-41) and number of deliveries 2 (0-9). One hundred and eleven (18.20%) were nulliparous. Three hundred and fifty-nine (58.80%) used natural lactation, with a median duration of 6 months. Anovulatory drugs were used by 271 (44.40%), with a median duration of 36 months. Associations were found between menarche <10 years and lower risk of luminal subtype (OR: 0.52, 95% CI: 0.28-0.94; P=.03), between menarche >11 years and lower risk of HER2 subtype (OR: 0.50, 95% CI: 0.26-0.97; P=.04) and between first birth >30 years and lower risk of triple negative subtype (OR: 0.40, 95% CI: 0.17-0.93; P=.03). The 20-year overall and disease-free survival probabilities were 0.80 (95% CI: 0.71-0.90) and 0.72 (95% CI: 0.64-0.79) respectively. Patients with ≥1 delivery had better overall survival than nulliparous patients (HR: 0.51, 95% CI: 0.27-0.96, P=.04)., Conclusions: The findings suggest an association between age at menarche and age at first delivery and breast cancer subtype. Nulliparity is associated with worse survival., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)
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- 2024
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16. Ribociclib plus Endocrine Therapy in Early Breast Cancer.
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Slamon D, Lipatov O, Nowecki Z, McAndrew N, Kukielka-Budny B, Stroyakovskiy D, Yardley DA, Huang CS, Fasching PA, Crown J, Bardia A, Chia S, Im SA, Ruiz-Borrego M, Loi S, Xu B, Hurvitz S, Barrios C, Untch M, Moroose R, Visco F, Afenjar K, Fresco R, Severin I, Ji Y, Ghaznawi F, Li Z, Zarate JP, Chakravartty A, Taran T, and Hortobagyi G
- Subjects
- Female, Humans, Aminopyridines administration & dosage, Aminopyridines adverse effects, Aminopyridines therapeutic use, Purines administration & dosage, Purines adverse effects, Purines therapeutic use, Receptor, ErbB-2 metabolism, Receptors, Estrogen, Receptors, Progesterone, Goserelin administration & dosage, Goserelin adverse effects, Goserelin therapeutic use, Antineoplastic Agents, Hormonal, Male, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms mortality, Breast Neoplasms pathology, Letrozole administration & dosage, Letrozole adverse effects, Letrozole therapeutic use, Aromatase Inhibitors administration & dosage, Aromatase Inhibitors adverse effects, Aromatase Inhibitors therapeutic use
- Abstract
Background: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear., Methods: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy., Results: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals., Conclusions: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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17. Targeting human progesterone receptor (PR), through pharmacophore-based screening and molecular simulation revealed potent inhibitors against breast cancer.
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Shahab M, Ziyu P, Waqas M, Zheng G, Bin Jardan YA, Fentahun Wondmie G, and Bouhrhia M
- Subjects
- Humans, Female, Molecular Dynamics Simulation, Molecular Docking Simulation, Pharmacophore, Receptors, Progesterone, Progesterone therapeutic use, Early Detection of Cancer, Ligands, Breast Neoplasms drug therapy, Breast Neoplasms metabolism
- Abstract
Breast cancer, the prevailing malignant tumor among women, is linked to progesterone and its receptor (PR) in both tumorigenesis and treatment responsiveness. Despite thorough investigation, the precise molecular mechanisms of progesterone in breast cancer remain unclear. The human progesterone receptor (PR) serves as an essential therapeutic target for breast cancer treatment, warranting the rapid design of small molecule therapeutics that can effectively inhibit HPR. By employing cutting-edge computational techniques like molecular screening, simulation, and free energy calculation, the process of identifying potential lead molecules from natural products has been significantly expedited. In this study, we employed pharmacophore-based virtual screening and molecular simulations to identify natural product-based inhibitors of human progesterone receptor (PR) in breast cancer treatment. High-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases was performed, leading to the identification of potential lead compounds. The analysis of binding modes for the top five compounds from both database provides valuable structural insights into the inhibition of HPR for breast cancer treatment. The top five hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as HPR inhibitors., (© 2024. The Author(s).)
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- 2024
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18. Development of an International Virtual Multidisciplinary Tumor Board for Breast Cancer in Mongolia.
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Brownson KE, Flores-Huidobro Martinez A, Ganbayar J, Sorensen LM, Darelli-Anderson AM, Prathibha S, Hoven N, Nansalmaa E, Mahlow J, Pushkin B, Potter D, Tuttle T, and Price RR
- Subjects
- Humans, Female, Adult, Mongolia epidemiology, Mastectomy, Receptor, ErbB-2, Neoadjuvant Therapy, Receptors, Progesterone, Breast Neoplasms therapy, Breast Neoplasms drug therapy, Carcinoma surgery
- Abstract
Introduction: Breast cancer is the most diagnosed cancer among Mongolian women and mortality rates are high. We describe a virtual multi-institutional and multidisciplinary tumor board (MTB) for breast cancer created to assist the National Cancer Center of Mongolia., Materials and Methods: A virtual MTB for breast cancer was conducted with participation of two United States and 1 Mongolian cancer centers. A standardized template for presentations was developed. Recommendations were summarized and shared with participants. Collected data included patient demographics, tumor characteristics, stage, imaging and treatments performed, and recommendations. Questions were categorized as treatment, diagnosis, or palliative questions., Results: Fifteen patients were evaluated. Median age was 39 y. 86.7% of breast cancers were invasive ductal cancers and 13.3% were metaplastic carcinomas. 53.3% were estrogen and progesterone receptor positive (ER+/PR+), 60% were HER2+, 13.3% were triple negative, and 26.7% were recurrent. 40% of patients were evaluated with mammography. 6% received positron emission tomography scans for metastatic evaluation. 66.7% of surgical patients received neoadjuvant chemotherapy. Herceptin was administered to 55.6% of patients with Her2+ cancers. Modified radical mastectomy was most commonly performed and reconstruction was rare. Sentinel lymph node biopsy was not performed. 66.7% of ER+/PR+ patients received endocrine therapy. 6.7% of patients received radiation. 75% of MTB questions pertained to treatment. Recommendations were related to systemic therapy (40%), surgical management (33.3%), pathology (13.3%), and imaging (13.3%)., Conclusions: This study illustrates the development of an international, virtual, multi-institutional breast cancer MTB and provides insight into challenges and potential interventions to improve breast cancer care in Mongolia., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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19. B-GOS alleviates olanzapine-induced lipid disturbances in mice by enriching Akkermansia and upregulation of PGRMC1-Wnt signaling.
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Zeng C, Chen H, Cao T, Wang L, Jiao S, Lin C, Zhang B, and Cai H
- Subjects
- Mice, Animals, Olanzapine adverse effects, Wnt Signaling Pathway, Akkermansia, Up-Regulation, Lipids, Membrane Proteins, Receptors, Progesterone, Antipsychotic Agents toxicity
- Abstract
Although olanzapine (OLZ) remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability issues related to its metabolic profile such as weight gain and dyslipidemia. Our previous studies have demonstrated that progesterone receptor membrane component 1 (PGRMC1) plays a key role in antipsychotic-induced metabolic side effects. Prebiotics showed positive effects on lipid metabolism, however, limited studies focused on their therapeutic potential and mechanisms in treating antipsychotic-induced lipid metabolic disorders. Herein, our study aims to explore the effects of the prebiotic B-GOS on lipid disturbances induced by OLZ and elucidate its underlying mechanisms via PGRMC1 pathway. In an 8-week study, long-term intraperitoneal administration of OLZ at a dosage of 8 mg/kg/day in mice induced lipid disturbances as manifested by significantly increased lipid indexes in plasma and liver. B-GOS effectively alleviated the OLZ-induced abnormal lipid metabolism by enhancing the diversity of the gut microbiota, with a 100-fold increase in Akkermansia abundance and a 10-fold decrease in Faecalibaculum abundance. Followed by the B-GOS related changes of gut microbiota, OLZ-induced substantial hepatic inhibition of PGRMC1, and associated protein factors of Wnt signaling pathway (Wnt3a, β-catenin, and PPAR-γ) were reversed without affecting plasma levels of short-chain fatty acids. Taken together, prebiotics like B-GOS enriching Akkermansia offer a promising novel approach to alleviate antipsychotic-induced lipid disturbances by modulating the PGRMC1-Wnt signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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20. Alcohol, Smoking, and Risks of Breast Cancer Recurrence and Mortality among Women with Luminal, Triple-Negative, and HER2-Overexpressing Breast Cancer.
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Loroña NC, Othus M, Malone KE, Linden HM, Tang MC, and Li CI
- Subjects
- Female, Humans, Prospective Studies, Receptor, ErbB-2, Breast, Smoking adverse effects, Ethanol, Receptors, Progesterone, Biomarkers, Tumor, Breast Neoplasms
- Abstract
Background: This study evaluates the relationship between smoking, alcohol, and breast cancer outcomes according to molecular subtype., Methods: This population-based prospective cohort consisted of 3,876 women ages 20 to 69 diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 expressions: luminal (ER+), triple-negative (TN; ER-/PR-/HER2-), and HER2-overexpressing (H2E; ER-/HER2+). We fit Cox proportional hazards models to assess the association between alcohol consumption and smoking status at diagnosis and risks of recurrence, breast cancer-specific mortality, and all-cause mortality., Results: Histories of ever smoking [HR, 1.33; 95% confidence interval (CI), 1.01-1.74] and current smoking (HR, 1.59; 95% CI, 1.07-2.35) were associated with greater risk of breast cancer recurrence among TN cases. Smoking was also associated with greater risk of recurrence to bone among all cases and among luminal cases. Elevated risks of breast cancer-specific and all-cause mortality were observed among current smokers across all subtypes. Alcohol use was not positively associated with risk of recurrence or mortality overall; however, TN patients who drank four or more drinks per week had a decreased risk of recurrence (HR, 0.71; 95% CI, 0.51-0.98) and breast cancer-specific mortality (HR, 0.73; 95% CI, 0.55-0.97) compared with non-current drinkers., Conclusions: Patients with breast cancer with a history of smoking at diagnosis have elevated risks of recurrence and mortality., Impact: These findings underscore the need to prioritize smoking cessation among women diagnosed with breast cancer., (©2023 American Association for Cancer Research.)
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- 2024
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21. Lifetime alcohol consumption patterns and young-onset breast cancer by subtype among Non-Hispanic Black and White women in the Young Women's Health History Study.
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Hirko KA, Lucas DR, Pathak DR, Hamilton AS, Post LM, Ihenacho U, Carnegie NB, Houang RT, Schwartz K, and Velie EM
- Subjects
- Female, Humans, Case-Control Studies, Receptor, ErbB-2, Receptors, Progesterone, Risk Factors, Black or African American, White, Age of Onset, Alcohol Drinking epidemiology, Alcohol Drinking adverse effects, Breast Neoplasms epidemiology, Breast Neoplasms etiology, Triple Negative Breast Neoplasms epidemiology, Triple Negative Breast Neoplasms etiology
- Abstract
Purpose: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age., Methods: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative)., Results: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all p
trend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed., Conclusions: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2024
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22. Developing therapies for triple-negative breast cancer subtypes.
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Okines A and Turner N
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- Humans, Female, Receptor, ErbB-2 genetics, Receptors, Progesterone, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms genetics, Breast Neoplasms drug therapy, Breast Neoplasms genetics
- Abstract
Competing Interests: AO has received research funding from Pfizer and Roche; advisory fees from Roche; honoraria from AstraZeneca, Esai, Gilead, Lilly, Pfizer, Roche, and Seagen; conference support from AstraZeneca, Lilly, Novartis, and Roche; participated on advisory boards for AstraZeneca, Pfizer, Roche, and Seagen; and is a member of the trial steering committee for two Seagen studies. NT has received advisory board honoraria from AstraZeneca, Lilly, Pfizer, Roche/Genentech, Novartis, GlaxoSmithKline, Repare therapeutics, Relay therapeutics, Zentalis, Gilead, Inivata, Guardant, and Exact Sciences; and research funding from AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Guardant Health, Invitae, Inivata, Personalis, and Natera.
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- 2024
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23. Significant Palliative Benefits Following Therapy With Mifepristone for Advanced Treatment Resistant Small Cell Lung Cancer.
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Check JH, Check DL, DO TP, Srivastava M, and Check E
- Subjects
- Male, Humans, Middle Aged, Mifepristone therapeutic use, Mifepristone pharmacology, Receptors, Progesterone, Progesterone pharmacology, Lung Neoplasms drug therapy, Small Cell Lung Carcinoma drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy
- Abstract
Background/aim: Progesterone receptor antagonists have been found to provide significant extension of life and considerable palliative benefits in a large variety of very advanced cancers. Most of these treated cancers lack the classical nuclear progesterone receptor (nPR). The hypothesized targets are membrane (m) PRs to inhibit progesterone induced blocking factor (PIBF). To date, there have been no case reports documenting the efficacy of PR antagonists for small cell lung cancer (SCLC) confirmed by pathological analysis. The case reported here demonstrates the efficacy of the single oral agent mifepristone in treating resistant SCLC., Case Report: A 58-year-old man, presenting with a persistent cough, dyspnea on exertion, and marked weakness, was diagnosed with stage IV non-SCLC (NSCLC) that tested positive for the EGFR mutation. He was treated with the single agent osimertinib. When symptoms returned eight months later, along with radiographic evidence of marked cancer progression, a lung biopsy showed SCLC. He failed to respond to pembrolizumab and subsequently to atezolizumab. He was then treated with the single agent mifepristone 200 mg per day orally. He showed marked clinical improvement associated with marked radiographic improvement. Though clinically doing very well, after one year, his dominant lesion increased in size. His oncologist elected to stop mifepristone and treat with camrelizumab with anlototinib. His clinical condition deteriorated on these drugs, and he died five months later., Conclusion: SCLC can be added to the long list of very advanced cancers that are treatment resistant to standard therapy, but respond well to PR antagonists., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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24. Prenatal arsenite exposure alters maternal cardiac remodeling during late pregnancy.
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Taube N, Kabir R, Ebenebe OV, Garbus H, Alam El Din SM, Illingworth E, Fitch M, Wang N, and Kohr MJ
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- Humans, Animals, Mice, Female, Pregnancy, Receptors, Progesterone, Maternal Exposure adverse effects, Ventricular Remodeling, Mice, Inbred C57BL, Arsenic metabolism, Arsenites toxicity, Cardiovascular Diseases, Prenatal Exposure Delayed Effects metabolism
- Abstract
Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6 J mice were exposed to 0 (control), 100 or 1000 μg/L sodium arsenite (NaAsO
2 ) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that maternal heart size was smaller and transcript levels of Esr1 (estrogen receptor alpha), Pgrmc1 (progesterone receptor membrane component 1) and Pgrmc2 (progesterone receptor membrane component 2) reduced during late pregnancy with exposure to 1000 μg/L iAs vs. non-exposed pregnant controls. Both 100 and 1000 μg/L iAs also reduced transcription of Nppa (atrial natriuretic peptide). Akt protein expression was also significantly reduced after 1000 μg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mark Kohr reports financial support was provided by National Heart Lung and Blood Institute. Nicole Taube reports financial support was provided by National Institute of Environmental Health Sciences. Haley Garbus reports financial support was provided by National Heart Lung and Blood Institute. Mark Kohr reports a relationship with National Heart Lung and Blood Institute that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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25. Progesterone receptor distribution in the human hypothalamus and its association with suicide.
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Zhang L, Verwer RWH, van Heerikhuize J, Lucassen PJ, Nathanielsz PW, Hol EM, Aronica E, Dhillo WS, Meynen G, and Swaab DF
- Subjects
- Humans, Progesterone, Analgesics, Opioid, Pro-Opiomelanocortin, Hypothalamus, Receptors, Progesterone, Suicide
- Abstract
The human hypothalamus modulates mental health by balancing interactions between hormonal fluctuations and stress responses. Stress-induced progesterone release activates progesterone receptors (PR) in the human brain and triggers alterations in neuropeptides/neurotransmitters. As recent epidemiological studies have associated peripheral progesterone levels with suicide risks in humans, we mapped PR distribution in the human hypothalamus in relation to age and sex and characterized its (co-) expression in specific cell types. The infundibular nucleus (INF) appeared to be the primary hypothalamic structure via which progesterone modulates stress-related neural circuitry. An elevation of the number of pro-opiomelanocortin
+ (POMC, an endogenous opioid precursor) neurons in the INF, which was due to a high proportion of POMC+ neurons that co-expressed PR, was related to suicide in patients with mood disorders (MD). MD donors who died of legal euthanasia were for the first time enrolled in a postmortem study to investigate the molecular signatures related to fatal suicidal ideations. They had a higher proportion of PR co-expressing POMC+ neurons than MD patients who died naturally. This indicates that the onset of endogenous opioid activation in MD with suicide tendency may be progesterone-associated. Our findings may have implications for users of progesterone-enriched contraceptives who also have MD and suicidal tendencies., (© 2024. The Author(s).)- Published
- 2024
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26. Estrogen receptor-negative/progesterone receptor-positive breast cancer has distinct characteristics and pathologic complete response rate after neoadjuvant chemotherapy.
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Dou H, Li F, Wang Y, Chen X, Yu P, Jia S, Ba Y, Luo D, Gao T, Li Z, and Xiao M
- Subjects
- Female, Humans, Receptors, Progesterone, Pathologic Complete Response, Neoadjuvant Therapy, Prognosis, Receptors, Estrogen analysis, Receptor, ErbB-2 analysis, Breast Neoplasms pathology
- Abstract
Purpose: The status of hormone receptors (HR) is an independent factor affecting survival and chemotherapy sensitivity in breast cancer (BC) patients, with estrogen receptor (ER) and progesterone receptor (PR) having the most significant effects. The ER-/PR + phenotype has been controversial in BC, and experts will face many challenges in determining treatment strategies. Herein, we systematically analyzed the clinicopathological characteristics of the ER-/PR + phenotype in BC patients and the response to chemotherapy., Patients and Methods: We included two cohorts. The first cohort counted the relationship between clinicopathologic data and survival outcomes for 72,666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort analyzed the relationship between clinicopathological data and pathologic complete response (pCR) rate in 879 patients at the Harbin Medical University Cancer Hospital. The classification data were compared by the chi-square test and Fister's exact test of the Logistic regression model, and predictor variables with P < 0.05 in the univariate analysis were included in the multivariate regression analysis. The Kaplan-Meier method evaluated breast cancer-specific survival (BCSS) and overall survival (OS) to investigate the relationship between different HR typing and survival and pCR., Results: In the two cohorts, 704 (0.9%) and 11 (1.3%) patients had the ER-/PR + phenotype, respectively. The clinicopathologic features of patients with the ER-/PR + phenotype are more similar to those of the ER-/PR- phenotype. The ER-/PR + phenotype is more common in younger and premenopausal women, and most ER-/PR + phenotypes exhibit higher histological grades. Survival analysis showed that there were significant differences in OS and BCSS among patients with different HR states (P < 0.001). The survival results of patients with the ER + /PR + phenotype were the best. The prognosis of the ER-/PR + phenotype was similar to that of the ER-/PR- phenotype. On the other hand, we found that HR status was also an independent predictor of post-NAC pCR rate in BC patients. The ER + /PR- and ER-/PR- phenotypes were more sensitive to chemotherapy than the ER + /PR + phenotypes., Conclusion: HR status is the main factor affecting BC's survival outcome and pCR rate. Patients with the ER-/PR + phenotype possess more aggressive biological factors and can benefit significantly from chemotherapy. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical treatment., (© 2023. The Author(s).)
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- 2024
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27. ER+/PR- phenotype exhibits more aggressive biological features and worse outcome compared with ER+/PR+ phenotype in HER2-negative inflammatory breast cancer.
- Author
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Luo Y, Li Q, Fang J, Pan C, Zhang L, Xu X, Qian S, Zhao X, and Hou L
- Subjects
- Humans, Middle Aged, Female, Receptors, Progesterone, Receptors, Estrogen, Prognosis, Phenotype, Receptor, ErbB-2, Breast Neoplasms pathology, Inflammatory Breast Neoplasms
- Abstract
The loss of progesterone receptor (PR) often predicts worse biological behavior and prognosis in estrogen receptor-positive (ER +) breast cancer. However, the impact of PR status on inflammatory breast cancer (IBC) has not been studied. Therefore, the purpose of our study was to investigate the influence of PR on IBC. Patients with ER+ and HER2-negative IBC were selected from the Surveillance, Epidemiology and End Results database. Pearson's χ
2 test was used to compare the clinicopathological characteristics between patients with estrogen receptor-positive/progesterone receptor-positive (ER+/PR +) and patients with estrogen receptor-positive/progesterone receptor-negative (ER+/PR-). Univariate and multivariate analyses were performed to investigate the effects of PR status on the breast cancer-specific survival (BCSS) and overall survival (OS) in IBC. Overall, 1553 patients including 1157 (74.5%) patients with ER+/PR+ and 396 (25.5%) patients with ER+/PR- were analyzed in our study. The patients with ER+/PR- were more likely to be high histological grade (p < 0.001) and liver metastasis (p = 0.045) compared to patients with ER+/PR+. Despite higher chance of receiving chemotherapy (83.6% vs 77.3%, P = 0.008), patients with ER+/PR- showed worse BCSS (5-year BCSS rate, 34.3% vs 51.3%, P < 0.001) and OS (5-year OS rate, 31.3% vs 46.1%, P < 0.001) compared with ER+/PR+ phenotype. Multivariate survival analysis showed that patients with ER+/PR- still had worse BCSS (hazard ratios [HR]: 1.764, 95% confidence intervals [CI] 1.476-2.109, P < 0.001) and OS (HR: 1.675, 95% CI 1.411-1.975, P < 0.001) than ER+/PR+ phenotype. Furthermore, patients with ER+/PR- showed worse outcomes than ER+/PR+ phenotype in most subgroups, especially in patients with younger age (≤ 60 years), lower histological grade, lymph node involved and distant metastasis. Patients with ER+/PR- had more aggressive biological behaviors and worse outcomes than patients with ER+/PR+ in IBC. Stronger treatments maybe needed for IBC patients with ER+/PR-., (© 2024. The Author(s).)- Published
- 2024
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28. Clinicopathological analysis of 38 male patients diagnosed with breast cancer.
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Sahin SI, Balci S, Guler G, and Altundag K
- Subjects
- Humans, Male, Aged, Prognosis, Lymph Nodes pathology, Receptors, Progesterone, Breast Neoplasms pathology, Breast Neoplasms, Male pathology, Bone Neoplasms, Carcinoma, Ductal, Breast pathology
- Abstract
Background: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival., Objectives: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes., Methods: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results., Results: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC., Conclusions: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach.
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- 2024
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29. Highly malignant endometrial stromal sarcoma in a cat.
- Author
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Hirota T, Yonemaru K, Hattori M, Murakami M, Sakai H, and Hirata A
- Subjects
- Humans, Female, Cats, Animals, Receptors, Progesterone, Sarcoma, Endometrial Stromal veterinary, Sarcoma, Endometrial Stromal diagnosis, Sarcoma, Endometrial Stromal pathology, Endometrial Neoplasms veterinary, Endometrial Neoplasms diagnosis, Endometrial Neoplasms pathology, Uterine Neoplasms veterinary, Uterine Neoplasms pathology, Cat Diseases
- Abstract
An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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30. [Comparative immunohistochemistry study of different antibodies clones for detection of breast cancer markers (estrogen receptor, progesterone receptor, HER2/neu, Ki-67)].
- Author
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Kalinin DV, Samoylova DV, Danilova NV, Germanovich NY, Kuznetsova OA, and Zavalishina LE
- Subjects
- Humans, Female, Receptors, Progesterone, Receptors, Estrogen, Immunohistochemistry, Receptor, ErbB-2 genetics, Ki-67 Antigen genetics, Clone Cells pathology, Biomarkers, Tumor, Breast Neoplasms diagnosis, Breast Neoplasms genetics, Breast Neoplasms pathology
- Abstract
Objective: A comparative study of detection of breast cancer markers (estrogen receptors, progesterone receptors, HER2/neu, Ki-67) by immunohistochemical method with antibodies produced by PrimeBioMed (Russia) and antibodies produced by Roche Ventana (USA)., Material and Methods: Surgical specimens and biopsies from 37 patients with invasive breast cancer were used. Sections were stained with antibodies of clones ER SP1 and GM030, PR 1E2 and PBM-5B8, HER2/neu 4B5 and PBM-46A6, Ki-67 30-9 and GM010., Results: There was a high positive and significant correlation between the immunohistochemistry results and antibodies of the clones ER-SP1 and GM030, PR1E2 and PBM-5B8, HER2/neu4B5 and PBM-46A6, Ki-67 30-9 and GM010., Conclusion: The study showed the possibility of using antibodies of clones GM030, HER2/neu 4B5, PBM-46A6, GM010 (PrimeBioMed) on the Ventana Bench Marck Ultra automatic immunostainer using the detection system UltraView Universal DAB Detection Kit.
- Published
- 2024
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31. Positive Progesterone Receptor Expression in Meningioma May Increase the Transverse Relaxation: First Prospective Clinical Trial Using Single-Shot Ultrafast T 2 Mapping.
- Author
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Li Z, Wang X, Zhang H, Yang Y, Zhang Y, Zhuang Y, Yang Q, Gao E, Ren Y, Zhang Y, Cai S, Chen Z, Cai C, Dong Y, Bao J, and Cheng J
- Subjects
- Humans, Diffusion Magnetic Resonance Imaging methods, Prospective Studies, Receptors, Progesterone, Magnetic Resonance Imaging methods, Retrospective Studies, Meningioma diagnostic imaging, Meningioma surgery, Meningioma pathology, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms surgery, Meningeal Neoplasms pathology
- Abstract
Rationale and Objectives: This project aims to investigate the diagnostic performance of multiple overlapping-echo detachment imaging (MOLED) technique-derived transverse relaxation time (T
2 ) maps in predicting progesterone receptor (PR) and S100 expression in meningiomas., Materials and Methods: 63 meningioma patients were enrolled from October 2021 to August 2022, who underwent a complete routine magnetic resonance imaging and T2 MOLED, which can characterize the whole brain transverse relaxation time within 32 seconds in a single scan. After the surgical resection of meningiomas, the expression levels of PR and S100 were determined by an experienced pathologist using immunohistochemistry techniques. Histogram analysis was performed in tumor parenchyma based on the parametric maps. Independent t test and Mann-Whitney U test were applied for the comparison of histogram parameters between different groups, with a significance level of P < .05. Logistic regression and receiver operating characteristic (ROC) analysis with 95% confidence interval were conducted for the diagnostic efficiency evaluation., Results: PR-positive group had significantly elevated T2 histogram parameters (P = .001-.049) compared to the PR-negative group. The multivariate logistic regression model with T2 showed the highest area under the ROC curve (AUC) for predicting PR expression (AUC=0.818). Additionally, the multivariate model also had the best diagnostic performance for predicting meningioma S100 expression (AUC=0.768)., Conclusion: The MOLED technique-derived T2 maps can distinguish PR and S100 status in meningiomas preoperatively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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32. Exploring the Prognostic Value of CS15-3 Tumor Marker in Breast Cancer Recurrence.
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Salih MJ, Al-Mansouri L, and Hasson HM
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- Humans, Female, Adolescent, Adult, Prognosis, Prospective Studies, Retrospective Studies, Neoplasm Recurrence, Local diagnosis, Biomarkers, Tumor, Receptor, ErbB-2, Receptors, Progesterone, Breast Neoplasms diagnosis, Breast Neoplasms pathology
- Abstract
Background: The most prevalent tumor marker for breast cancer is CS15-3. This marker's elevated serum levels have been proven to predict a patient's risk of developing the condition again., Purposes: The purpose of this study was to ascertain the sensitivity of blood CS15-3 levels in the identification of breast cancer recurrence., Patients and Methods: A prospective cohort follow-up analytical study was conducted at Basra Oncology Center from early 2016 to the end of 2022. The study included 178 females aged ≥18 years with histologically confirmed invasive ductal breast cancer. CS15-3 had been evaluated for all included cases on two occasions: the first, at the time of diagnosis or remission, and the second, at the time of progression. The tumor marker (CS15-3) was evaluated using a Cobas e411 analyzer (Roche Diagnostics International Ltd)., Results: The mean age showed no significant difference between the groups (P=0.581). The duration of progression was higher among those with the luminal group (40.60± 42.08). Those with bony and liver metastasis were mostly among luminal (50.0%) and HER 2+ (52.4%) groups respectively. At the time of diagnosis CS15-3 tumor marker showed no significant difference between the three groups, while at the time of progression, the luminal group showed higher means (120.74± 95.07) compared to others with a significant mean difference of (-99.84± 94.43)., Conclusions: Age, disease stages, and co-morbidity have no significant influence on the distribution between groups of luminal. The duration of progression was higher among those in the luminal group. Osseous and hepatic secondaries are mostly among luminal and hormonal receptors positive. Initially, at the time of diagnosis CS15-3 marker expressed no significant difference between the groups, whereas at the time of progression, the luminal group expressed a higher means of level of the CS15-3 marker.
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- 2024
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33. 孕激素及其受体与蜕膜化.
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蒋莎, 陈璐, 王炜, 常卓, 张杨, and 冯晓玲
- Abstract
Decidualization is a delicate and complex process, which is regulated by hormones and cellular and molecular signals. Progesterone plays a leading role in the process of decidualization and embryo implantation. In the late period of menstrual cycle (the day 24 -28 of menstrual cycle), the progesterone combined with progesterone receptor (PR) stimulates the synthesis of prolactin (PRL), a marker of endometrium decidualization, and mediates the occurrence of decidualization. In the complex mechanism of decidualization, progesterone and PR are mainly to control the epithelial cell proliferation to obtain uterine receptivity, and to stimulate stromal cell differentiation to establish pregnancy. The monitoring of progesterone and progesterone receptor has a guiding significance for the prediction of early embryo loss in those patients with habitual abortion. The role of progesterone and PR and the mechanism in decidualization were reviewed in this paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
34. Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances
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Cengiz, Yilmaz and Demet Kocatepe, Cavdar
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Clinical Relevance ,Ki-67 Antigen ,Neoplasm, Residual ,Receptors, Estrogen ,Receptor, ErbB-2 ,Biomarkers, Tumor ,Humans ,Female ,Breast Neoplasms ,Receptors, Progesterone ,breast cancer ,neoadjuvant chemotherapy ,biomarker discordance ,biomarker alteration ,chemosensitivity ,Neoadjuvant Therapy ,Retrospective Studies - Abstract
Purpose: Biomarker discordances and alterations can be encountered between tru-cut biopsy and residual tumor in breast cancer treated with neoadjuvant chemotherapy (NACTx). We aimed to investigate the effect of NACTx on major biomarker expression (ER, PR, HER2, Ki-67) and tumor grade, the frequency and causes of receptor discordances, and the clinical significance of changes in terms of adjuvant therapy need and chemosensitivity. Methods: In this retrospective study, ER, PR, HER2, and Ki-67 expression and tumor grades were compared between pre- and post-NACTx tumor samples using the Wilcoxon signed-rank test. The frequencies of receptor discordances and the need for new adjuvant therapy due to discordances were calculated. The effect of patient and tumor characteristics and NACTx regimens on discordances was investigated using multivariate analysis. Using histopathological examinations, residual tumors were divided into chemotherapy-responsive and chemotherapy-unresponsive tumors. Biomarker changes in both groups were analyzed for predictability of chemosensitivity. Results: Of the 169 patients who received NACTx, 102 patients having enough residual tumors in the surgical pathology specimen were enrolled in the study. Histopathologically, about 70% of tumors were partially responsive to NACTx and 30% were unresponsive (chemo-resistant). The concordance and discordance rates were 95.1% versus 4.9% for ER (p = 0.180), 97.1% versus 2.9% for PR (p = 0.083), and 89.2% versus 10.8% for HER2 (p = 0.763), respectively. In addition, 15% of hormone receptor (HR)-negative patients became HR(+) and 5.7% of HER2(−) patients became HER2(+) in the residual tumors, requiring adjuvant endocrine or anti-HER2 therapy. In particular, 18% of triple-negative patients became HR(+) and 12% became HER2(+). HER2 loss was detected in 40% of HER2(+) patients. Multivariate logistic regression analysis revealed that lower estrogen expression (p = 0.046), a smaller tumor size (p = 0.029), and anti-HER2 therapy (p < 0.001) have independent efficacy on ER discordance, PR discordance, and HER2 discordance, respectively. Ki-67 and PR expression significantly decreased in chemotherapy-responsive tumors (p = 0.001 and p = 0.004), and the tumor grade increased in chemotherapy-unresponsive tumors (p = 0.034). Conclusions: Approximately 3–5% of HR discordance and about 10% of HER2 discordance can be observed in breast cancer after currently used NACTx regimens. Discordances are bi-directional (from positive to negative and vice versa), and their causes are multifactorial; they should be assessed accordingly. The NACTx effect alone cannot explain observed discordances but can cause biomarker alterations. The change in receptor status from positive to negative, especially HER2 loss, is mainly associated with the NACTx effect. However, the shift from negative to positive is thought to be primarily related to intratumoral heterogeneity. Receptor statuses becoming positive are of more clinical importance due to adjuvant therapy requirements. Biomarker alterations in PR, Ki-67, and tumor grade can provide predictive information about tumor chemosensitivity.
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- 2022
35. Expressions of Progesterone Receptor of Orbital Meningiomas in Indonesia
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Raudatul Janah, Lantip Rujito, and Daniel Wahyono
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Cross-Sectional Studies ,Indonesia ,Eye Neoplasms ,Meningeal Neoplasms ,Humans ,RNA, Messenger ,General Medicine ,Neoplasm Recurrence, Local ,Meningioma ,Receptors, Progesterone ,Retrospective Studies - Abstract
Visual disturbances that can heal after a complete resection of orbital meningiomas are only about 2.9%. Grading and expression of the progesterone receptor (PR) in orbital meningiomas, according to World Health Organization (WHO) is a useful predictive value of recurrence in the treatment management of orbital meningiomas. This study aims to determine the relationship of PR expression on the grading of orbital meningiomas as tumour prognostic factors.This cross-sectional observational analysis observed 44 orbital meningioma in Cicendo Eye Hospital Bandung and Hasan Sadikin Hospital between 2017-2020. We performed of mRNA PR with RT-qPCR technique and calculation with the 2∆∆Ct formula. Statistical analysis used the Kruskal-Wallis Test, followed by the Mann-Whitney post hoc test with p0.005.Relative expression of mRNA PR in meningioma orbita grade I to grade III decreased significantly the expression of relative mRNA PR at grade I, II, III of 21.69±44.35, 20.39±26.30 and 1.25±0.85, with Kruskal-Wallis test, p =0.007. Mann Whitney's test results showed relative mRNA PR expression between grades I and II not different (p = 0.055), relative expression mRNA PR between grades I and III differed significantly (p = 0.024), and relative expression mRNA PR between grades I and III was not different (p = 0.638).mRNA PR expression is viable for prognostic value, predicting recurrence and implementing more effective management of subsequent therapy, it must be combined with other markers to determine the nature of the orbital meningioma.
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- 2022
36. Grey matter morphology in women with premenstrual dysphoric disorder treated with a selective progesterone receptor modulator
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Elisavet Kaltsouni, Manon Dubol, Johan Wikström, Rupert Lanzenberger, Inger Sundström-Poromaa, and Erika Comasco
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Pharmacology ,Grey matter ,Brain ,Reproduktionsmedicin och gynekologi ,Luteal Phase ,Voxel-based morphometry ,Premenstrual Syndrome ,Psychiatry and Mental health ,Magnetic resonance imaging ,Neurology ,Obstetrics, Gynecology and Reproductive Medicine ,Humans ,Female ,Surface-based morphometry ,Women ,Pharmacology (medical) ,Neurology (clinical) ,Gray Matter ,Premenstrual Dysphoric Disorder ,Receptors, Progesterone ,Premenstrual dysphoric disorder ,Menstrual Cycle ,Progesterone ,Biological Psychiatry - Abstract
Premenstrual dysphoric disorder (PMDD) is characterized by severe cyclic mood symptoms emerging in the luteal phase of the menstrual cycle. The variation in progesterone levels and its metabolites during the luteal phase seems critical to the occurrence of PMDD symptoms. Notably, the efficacy of selective progesterone receptor modulator (SPRM) treatment on the mental symptoms of PMDD has been recently demonstrated. In the present study, structural magnetic resonance imaging was used to assess the effects of SPRM treatment, compared with placebo, on grey matter morphology in women with PMDD. In total, 35 women were scanned during the luteal phase, before and after three months of treatment with SPRM or placebo. Symptom severity was assessed using the Daily Record of Severity of Problems (DRSP), while gonadal hormone levels were measured by liquid chromatography-tandem mass spectrometry. Region-of-interest and whole-brain approaches were employed to perform voxel-based morphometry analyses, subcortical volumetric analyses, and surface-based morphometry analyses. No interaction or main effects of treatment and time were observed on grey matter volume and cortical surface measures (cortical thickness, gyrification index, sulcal depth, and fractal dimension). The relationship between change in brain morphology and symptom severity was also explored but no treatment-dependant grey matter structure change was related to symptom severity change. These findings suggest that SPRM treatment does not impart macrostructural changes onto grey matter structure, at least in the short term. De två sista författarna delar sistaförfattarskapet.
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- 2022
37. Many or too many progesterone membrane receptors? Clinical implications
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Alexandra Wendler and Martin Wehling
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Endocrinology ,Hydrolases ,Endocrinology, Diabetes and Metabolism ,Humans ,Membrane Proteins ,Female ,Receptors, Progesterone ,Progesterone ,gamma-Aminobutyric Acid ,Signal Transduction - Abstract
Several receptors for nongenomically initiated actions of progesterone (P4) exist, namely membrane-associated P4 receptors (MAPRs), membrane progestin receptors (mPRs), receptors for neurosteroids [GABA
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- 2022
38. Clinical Features and Prognosis Analysis of Hormone Receptor-Positive, HER2-Negative Breast Cancer with Differential Expression Levels of Estrogen and Progesterone Receptors: A 10-Year Retrospective Study
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Jin Liu, Mingyu Gan, Zijing Lin, Qin Deng, Juan Deng, Bin Zeng, Yanling Shi, and Jia Ming
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Article Subject ,Receptor, ErbB-2 ,Breast Neoplasms ,Estrogens ,Prognosis ,Receptors, Estrogen ,Oncology ,Biomarkers, Tumor ,Internal Medicine ,Humans ,Female ,Surgery ,Receptors, Progesterone ,Retrospective Studies - Abstract
Background. Estrogen and progesterone receptor status can predict breast cancer patient prognosis and treatment sensitivity, but research on low ER and PR levels and expression balance remains limited. Methods. From January 2010 to October 2016, 283 ER+/PR+/HER2-breast cancer patients who met the inclusion criteria were enrolled and divided into the H group (ER > 10%, N = 261) and the L group (1% ≤ ER ≤ 10%, N = 22). Groups were further divided into the HH group (ER > 10%/PR > 20%, N = 201), the HL group (ER > 10%/ER 1% ≤ PR ≤ 20% PR, N = 60), the LH group (1% ≤ ER ≤ 10%/PR > 20%, N = 5), and the LL group (1% ≤ ER ≤ 10%/1% ≤ PR ≤ 20%, N = 17). The LH group was excluded due to its small size, leaving the clinical and prognostic characteristics of 2 large groups and 3 subgroups to be analyzed. Results. L group patients had significantly more stage N2 axillary lymph nodes than H group patients (31.8% vs. 9.2%, P = 0.007). Age ( P = 0.011), menopause status ( P = 0.001), and tumor size ( P = 0.024) were significantly different in the HL vs. HH and LL groups. Five-year DFS (94.6% vs. 77.0%, P P = 0.001) rates significantly differed between HH and HL. No significant differences in 5-year DFS (77.0% vs. 81.9%, P = 0.564) or 5-year OS (85.8% vs. 87.8%, P = 0.729) rates were observed between HL and LL; the OS rates of HL and LL were similar. Conclusion. In the group of ER+/PR+/HER2-patients, there was no significant prognostic difference between ER-low positive and ER-high positive groups, but low PR expression was significantly associated with a worse prognosis. The role of ER and PR balance in breast cancer progression and individualized treatment requires further investigation.
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- 2022
39. Aberrant upregulation of CDK1 contributes to medroxyprogesterone acetate (MPA) resistance in cancer-associated fibroblasts of the endometrium
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Intan Sofia, Omar, Noor Azmi, Mat Adenan, Alejandro, Godoy, Ik Hui, Teo, Yogeeta, Gunasagran, and Ivy, Chung
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Biophysics ,Medroxyprogesterone Acetate ,Cell Biology ,Biochemistry ,Endometrial Neoplasms ,Up-Regulation ,Endometrium ,Mifepristone ,Cancer-Associated Fibroblasts ,Drug Resistance, Neoplasm ,Neoplasms ,CDC2 Protein Kinase ,Humans ,Female ,RNA, Messenger ,Luciferases ,Receptors, Progesterone ,Molecular Biology - Abstract
The response to medroxyprogesterone acetate (MPA) decreases as endometrial disease progresses from the benign to malignancy. In a mouse model, progesterone receptor (PR) expression in normal fibroblasts is accountable for the MPA's inhibitory effects in cancer cells. However, it is still unclear, if and how, fibroblasts from human tumors respond to MPA. In this study, three benign-associated fibroblasts (BAFs) and four cancer-associated fibroblasts (CAFs) were isolated from human benign and cancerous endometrial tissues, respectively, to examine MPA activation on PR signaling. PR-B protein expression were heterogeneously expressed in both CAFs and BAFs, despite a lower mRNA expression in the former. In a luciferase reporter assay, MPA treatment stimulated some PR DNA-binding activity in BAFs but not in CAFs. Yet, activation of PR target gene was generally more pronounced in MPA-treated CAFs compared to BAFs. Cyclin-dependent kinase 1 (CDK1) was exclusively upregulated by 10 nM MPA in CAFs (5.1-fold vs. 1.1-fold in BAFs, P 0.05), leading to a higher CDK1 protein expression. Subsequently in a dose-response study, CAFs showed an average of ∼20% higher cell viability when compared to BAFs, indicative of drug resistance to MPA. MPA resistance was also observed in EC-CAFs co-culture, when MPA-treated cells showed greater tumor spheroid formation than in EC-BAFs co-culture (2-fold, P 0.01). The increased cell viability observed in CAFs was reversed with mifepristone (RU486), a PR antagonist which suppressed MPA-induced CDK1 expression. This indicates that MPA-induced abnormal upregulation of CDK1 may contribute to the enhanced CAFs cell proliferation, suggesting a new mechanism of MPA resistance within endometrial cancer microenvironment.
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- 2022
40. Utility of TRPS-1 immunohistochemistry in diagnosis of metastatic breast carcinoma in cytology specimens
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Mohammed Abdelwahed, Nalan Yurtsever, Deepika Savant, Priyanka Karam, Cecilia Gimenez, Kasturi Das, Silvat Sheikh-Fayyaz, and Seema Khutti
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Receptors, Estrogen ,Biomarkers, Tumor ,Humans ,Triple Negative Breast Neoplasms ,Receptors, Progesterone ,Immunohistochemistry ,Pathology and Forensic Medicine - Abstract
At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens.MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups.We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group.TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.
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- 2022
41. Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer
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Bo La Yun, Eunyoung Kang, Hee-Chul Shin, Sun Mi Kim, Eun Kyu Kim, Se Hyun Kim, Mijung Jang, Jee Hyun Kim, So Yeon Park, Yeshong Park, Kyung-Hwak Yoon, and Koung Jin Suh
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Estrogen receptor ,Breast Neoplasms ,medicine.disease_cause ,Breast cancer ,Internal medicine ,Humans ,Medicine ,Endocrine system ,Prospective Studies ,Stage (cooking) ,Prospective cohort study ,Retrospective Studies ,business.industry ,Estrogens ,Prognosis ,medicine.disease ,Ki-67 Antigen ,Receptors, Estrogen ,Hormone receptor ,Hormonal therapy ,Female ,Receptors, Progesterone ,business ,Carcinogenesis - Abstract
PurposeEstrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1-10%) of ER expression have been separately defined as ER Low Positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).MethodsRetrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative (ER-)).ResultsA total of 2162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2 (HER2), negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (P = 0.418).ConclusionERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.
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- 2022
42. Mixed epithelial and stromal tumours of the kidney with malignant transformation: a clinicopathological study of four cases
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Anna, Caliò, Liang, Cheng, Guido, Martignoni, Shaobo, Zhang, Matteo, Brunelli, and John N, Eble
- Subjects
Mucin-1 ,Estrogens ,Soft Tissue Neoplasms ,Adenocarcinoma ,Immunohistochemistry ,Actins ,Kidney Neoplasms ,Desmin ,Pathology and Forensic Medicine ,Sarcoma, Synovial ,Cell Transformation, Neoplastic ,Proto-Oncogene Proteins c-bcl-2 ,Receptors, Estrogen ,Biomarkers, Tumor ,Humans ,Receptors, Progesterone - Abstract
Mixed epithelial and stromal tumour of the kidney is a complex benign neoplasm in which malignancy rarely arises. In this study, we report four mixed epithelial and stromal tumours in which sarcoma or carcinoma developed. In the first, a multifocal adenocarcinoma arose and areas of transition from benign to malignant epithelium were observed. Oestrogen and progesterone receptors were diffusely present in the nuclei of the spindle cell stroma of the benign component. The second was a sarcoma in which benign epithelial elements were intermixed. Outside the renal parenchyma, clusters of small benign glands surrounded by oestrogen receptor-positive benign stroma were present, supporting the diagnosis of mixed epithelial and stromal tumour. Fluorescence in situ hybridisation for SYT-SSX translocation and immunohistochemical results, specifically TLE1 -ativity, argued against primary renal synovial sarcoma. The patient died 24 months after surgery. The third tumour consisted of small blue round cells, positive for epithelial membrane antigen, BCL2, CD99, and FLI1. Throughout the tumour, the presence of benign appearing branching tubules in fibromuscular stroma, reactive for smooth muscle actin, desmin and progesterone receptor, supported the diagnosis of mixed epithelial and stromal tumour in which a small round blue cell sarcoma with EWSR1 rearrangement arose. In the fourth tumour, adenocarcinoma with papillary architecture arose in a typical mixed epithelial and stromal tumour. In summary, we present four cases of mixed epithelial and stromal tumour with malignant transformation, two showing carcinomatous and the other two with sarcomatous transformation. Identification of typical benign looking elements and the absence of SYT-SSX translocation are helpful in recognition of this entity.
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- 2022
43. Prognostic Impact of Low Estrogen and Progesterone Positivity in Luminal B (HER2 Negative) Breast Cancer
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Jasmina Rajc, Irena Fröhlich, Milanka Mrčela, Ilijan Tomaš, and Josipa Flam
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Breast neoplasms ,Receptors, estrogen ,Receptors, progesterone ,Disease-free survival ,Croatia ,Medicine - Abstract
Luminal B (HER2 negative) subtype is the most diversiform type of breast cancers, with a high Ki-67 proliferation index (>20%) or/and low progesterone (PR;
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- 2018
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44. Reproductive history differs by molecular subtypes of breast cancer among women aged ≤ 50 years in Scotland diagnosed 2009–2016: a cross-sectional study
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Anushri Chitkara, Ines Mesa-Eguiagaray, Sarah H. Wild, Peter S. Hall, David A. Cameron, Andrew H. Sims, and Jonine D. Figueroa
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Cancer Research ,Receptor, ErbB-2 ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,Middle Aged ,Cross-Sectional Studies ,Receptors, Estrogen ,Oncology ,Pregnancy ,Biomarkers, Tumor ,Humans ,Female ,Receptors, Progesterone ,Reproductive History - Abstract
Background The aetiology of breast cancers diagnosed ≤ 50 years of age remains unclear. We aimed to compare reproductive risk factors between molecular subtypes of breast cancer, thereby suggesting possible aetiologic clues, using routinely collected cancer registry and maternity data in Scotland. Methods We conducted a cross-sectional study of 4108 women aged ≤ 50 years with primary breast cancer diagnosed between 2009 and 2016 linked to maternity data. Molecular subtypes of breast cancer were defined using immunohistochemistry (IHC) tumour markers, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumour grade. Age-adjusted polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of number of births, age at first birth and time since last birth with IHC-defined breast cancer subtypes. Luminal A-like was the reference compared to luminal B-like (HER2−), luminal B-like (HER2+), HER2-overexpressed and triple-negative breast cancer (TNBC). Results Mean (SD) for number of births, age at first birth and time since last birth was 1.4 (1.2) births, 27.2 (6.1) years and 11.0 (6.8) years, respectively. Luminal A-like was the most common subtype (40%), while HER2-overexpressed and TNBC represented 5% and 15% of cases, respectively. Larger numbers of births were recorded among women with HER2-overexpressed and TNBC compared with luminal A-like tumours (> 3 vs 0 births, OR 1.87, 95%CI 1.18–2.96; OR 1.44, 95%CI 1.07–1.94, respectively). Women with their most recent birth > 10 years compared to Conclusion Number of births and time since last birth differed by molecular subtypes of breast cancer among women aged ≤ 50 years. Analyses using linked routine electronic medical records by molecularly defined tumour pathology data can be used to investigate the aetiology and prognosis of cancer.
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- 2022
45. Breast cancer: an up‐to‐date review and future perspectives
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Ruoxi Hong and Binghe Xu
- Subjects
Phosphatidylinositol 3-Kinases ,Cancer Research ,Receptors, Estrogen ,Oncology ,Class I Phosphatidylinositol 3-Kinases ,Tumor Microenvironment ,Humans ,Triple Negative Breast Neoplasms ,Poly(ADP-ribose) Polymerase Inhibitors ,Phosphatidylinositols ,Receptors, Progesterone ,Immune Checkpoint Inhibitors ,B7-H1 Antigen - Abstract
Breast cancer is the most common cancer worldwide. The occurrence of breast cancer is associated with many risk factors, including genetic and hereditary predisposition. Breast cancers are highly heterogeneous. Treatment strategies for breast cancer vary by molecular features, including activation of human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen receptor [ER] and progesterone receptor [PR]), gene mutations (e.g., mutations of breast cancer 1/2 [BRCA1/2] and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA]) and markers of the immune microenvironment (e.g., tumor-infiltrating lymphocyte [TIL] and programmed death-ligand 1 [PD-L1]). Early-stage breast cancer is considered curable, for which local-regional therapies (surgery and radiotherapy) are the cornerstone, with systemic therapy given before or after surgery when necessary. Preoperative or neoadjuvant therapy, including targeted drugs or immune checkpoint inhibitors, has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer, followed by risk-adapted post-surgical strategies. For ER-positive early breast cancer, endocrine therapy for 5-10 years is essential. Advanced breast cancer with distant metastases is currently considered incurable. Systemic therapies in this setting include endocrine therapy with targeted agents, such as CDK4/6 inhibitors and phosphoinositide 3-kinase (PI3K) inhibitors for hormone receptor-positive disease, anti-HER2 targeted therapy for HER2-positive disease, poly(ADP-ribose) polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease. Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future. In this review, we summarized the latest scientific information and discussed the future perspectives on breast cancer.
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- 2022
46. Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations
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Mark R, Hopkins, Doreen N, Palsgrove, Brigitte M, Ronnett, Russell, Vang, Jeffrey, Lin, and Tricia A, Murdock
- Subjects
Papillomavirus Infections ,Uterine Cervical Neoplasms ,Estrogens ,Alphapapillomavirus ,Immunohistochemistry ,Endometrial Neoplasms ,Pathology and Forensic Medicine ,Carcinoma, Squamous Cell ,Humans ,Female ,Surgery ,Tumor Suppressor Protein p53 ,Anatomy ,Receptors, Progesterone ,Papillomaviridae ,Carcinoma, Endometrioid ,Cyclin-Dependent Kinase Inhibitor p16 - Abstract
Human papillomavirus (HPV)-independent primary endometrial squamous cell carcinoma (PESCC) is a rare but aggressive subtype of endometrial carcinoma for which little is known about the genomic characteristics. Traditional criteria have restricted the diagnosis of PESCC to cases without any cervical involvement. However, given that modern ancillary techniques can detect HPV and characteristic genetic alterations that should identify the more common mimics in the differential diagnosis, including endometrial endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma, those criteria may benefit from revision. To further characterize PESCC, we identified 5 cases of pure squamous cell carcinoma dominantly involving the endometrium that had the potential to be PESCC: 1 case involving only the endometrium and 4 cases with some involvement of the cervix. Clinicopathologic features were assessed and immunohistochemical analysis (p16, estrogen receptor, progesterone receptor, and p53), HPV RNA in situ hybridization (high-risk and low-risk cocktails and targeted probes for 16 and 18), and molecular studies were performed. All tumors showed aberrant/mutation-type p53 expression, were negative for estrogen receptor, progesterone receptor, and p16, and had no detectable HPV. Per whole-exome sequencing, 4 of the 5 tumors demonstrated comutations in TP53 and CDKN2A (p16). Four patients died of disease within 20 months (range, 1 to 20 mo; mean, 9 mo), and 1 patient had no evidence of disease at 38 months. PESCC represents a unique, clinically aggressive subtype of endometrial cancer with TP53 and CDKN2A comutations. This characteristic profile, which is similar to HPV-independent squamous cell carcinoma of the vulva, is distinct from endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma and can be used to distinguish PESCC from those mimics even when cervical involvement is present. Diagnostic criteria for PESCC should be relaxed to allow for cervical involvement when other pathologic features are consistent with, and ancillary techniques are supportive of classification as such.
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- 2022
47. A systematic study on phenotypical characteristics of invasive breast carcinoma and surrounding ductal carcinoma in situ in multifocal breast cancers
- Author
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Taesung Jeon, Hayeon Kim, Aeree Kim, and Chungyeul Kim
- Subjects
EGF Family of Proteins ,Carcinoma, Intraductal, Noninfiltrating ,Ki-67 Antigen ,Receptors, Estrogen ,Receptor, ErbB-2 ,Carcinoma, Ductal, Breast ,Biomarkers, Tumor ,Humans ,Breast Neoplasms ,Female ,Receptors, Progesterone ,Hormones ,Pathology and Forensic Medicine - Abstract
Multifocal breast cancers are heterogeneous in terms of histologic characteristics and molecular types. In this study, we annotated multiple foci of invasive lesions and ductal carcinoma in situ lesions of 17 cases of multifocal breast cancer and investigated their immunohistochemical phenotypes (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor 2 [HER2], and Ki-67 proliferative index). Tumor histologic grade, proliferative index, and phenotypes were varied within each patient. We observed that there were some cases in which the treatment consideration could be changed due to different phenotypes of lesions. The proliferative index tended to be higher in areas where the histologic grade was higher. The triple-negative (TN) type had the highest Ki-67 index, followed by luminal B/HER2-, HER2, luminal B/HER2+, and luminal A types sequentially. As the luminal B lesions comprised a considerable portion of multifocal cancer, we subcategorized them according to several criteria. The proliferation index of the luminal B group was significantly (P .001) higher in the low hormone receptor (HR) group than in the HR group. When compared by the phenotypes of the surrounding lesions, the proliferative index of luminal B lesions were intimately related to the coexisting phenotypes. In conclusion, the immunohistochemical phenotypes of multifocal breast cancer are heterogeneous, and luminal B type is the commonest of the heterogeneous phenotypes.
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- 2022
48. BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance
- Author
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Midas M. Kuilman, Architha Ellappalayam, Andrei Barcaru, Josien C. Haan, Rajith Bhaskaran, Diederik Wehkamp, Andrea R. Menicucci, William M. Audeh, Lorenza Mittempergher, and Annuska M. Glas
- Subjects
Cancer Research ,Oncology ,Receptor, ErbB-2 ,Biomarkers, Tumor ,Humans ,Breast Neoplasms ,Female ,Receptors, Progesterone - Abstract
Purpose BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, breast tumors have one dominant subtype, representative of a single activated pathway. However, some tumors show a statistically equal representation of more than one subtype, referred to as dual subtype. This study aims to identify and examine dual subtype tumors by BP to understand their biology and possible implications for treatment guidance. Methods The BP scores of over 15,000 tumor samples from EBC patients were analyzed, and the differences between the highest and the lowest scoring subtypes were calculated. Based upon the distribution of the differences between BP scores, a threshold was determined for each subtype to identify dual versus single subtypes. Results Approximately 97% of samples had one single activated BluePrint molecular subtype, whereas ~ 3% of samples were classified as BP dual subtype. The most frequently occurring dual subtypes were the Luminal-Basal-type and Luminal-HER2-type. Luminal-Basal-type displays a distinct biology from the Luminal single type and Basal single type. Burstein’s classification of the single and dual Basal samples showed that the Luminal-Basal-type is mostly classified as ‘luminal androgen receptor’ and ‘mesenchymal’ subtypes, supporting molecular evidence of AR activation in the Luminal-Basal-type tumors. Tumors classified as Luminal-HER2-type resemble features of both Luminal-single-type and HER2-single-type. However, patients with dual Luminal-HER2-type have a lower pathological complete response after receiving HER2-targeted therapies in addition to chemotherapy in comparison with patients with a HER2-single-type. Conclusion This study demonstrates that BP identifies tumors with two active functional pathways (dual subtype) with specific transcriptional characteristics and highlights the added value of distinguishing BP dual from single subtypes as evidenced by distinct treatment response rates.
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- 2022
49. Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype <scp>DX</scp> Recurrence Score in early breast cancer
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Rima Patel, Malin Hovstadius, Melanie W. Kier, Erin L. Moshier, Brittney S. Zimmerman, Krystal Cascetta, Shabnam Jaffer, Joseph A. Sparano, and Amy Tiersten
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Cancer Research ,Ki-67 Antigen ,Oncology ,Gene Expression Profiling ,Biomarkers, Tumor ,Humans ,Breast Neoplasms ,Female ,Neoplasm Recurrence, Local ,Prognosis ,Receptors, Progesterone ,Hormones ,Retrospective Studies - Abstract
The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG).The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic.The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ = 0.01-0.20) between Ki67 and RS (κ = 0.027) in the overall population, although this was not significant (p = .1985). There was fair agreement (κ = 0.21-0.40) between high Ki67 and RS values (κ = 0.280; p .0001). A higher progesterone receptor percentage was associated with lower RS values (p .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p = .0059 and p .0001) but not with RS.In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values.In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.
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- 2022
50. Strategies for Targeting CIB1: A Challenging Drug Target
- Author
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Guojun Zheng, Abdul Wadood, and Muhammad Shahab
- Subjects
Pharmacology ,Integrins ,Receptors, Estrogen ,Receptor, ErbB-2 ,Calcium-Binding Proteins ,Drug Discovery ,Humans ,Breast Neoplasms ,Calcium ,Female ,Triple Negative Breast Neoplasms ,Receptors, Progesterone - Abstract
Abstract: Breast cancer is a common malignancy in women and is a diverse disease. In women, 287,850 and in males 2710 cases are reported in 2022 by WHO. Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), accounted for 10-20% of all new cases discovered in the United States in 2017. Because calcium integrin-binding protein1 lacks a suitable pocket that could be used to create a chemical inhibitor, and because the breast cancer-causing protein is nearly identical to its necessary wild-type counterpart, it was thought to be druggable. The structure and function of the newly discovered calcium integrinbinding protein1 have been improved, paving the way for the designing of several therapeutic candidates. Currently, no FDA-approved drugs are available for CIB1-driven cancer. CIB1 has proven to challenge drug target due to several factors, including the fact that the CIB1 protein is highly resistant to small inhibitors. This study aimed to present various ways for targeting calcium integrin-binding protein1, which is an important target that could be useful to scientists.
- Published
- 2022
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