Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy.

Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy. Biochem Biophys Res Commun. 2017 Jul 12;: Authors: Louw-du Toit R, Perkins MS, Hapgood JP, Africander D Abstract Progestins used in endocrine therapies bind to multiple steroid receptors and are associated with several side-effects. It is thus important to understand the relationship between steroid receptor cross-reactivity and the side-effect profile of progestins. In cell lines that express negligible levels of steroid receptors, we report for the first time the binding affinities, potencies and efficacies of selected progestins from different generations determined in parallel. We show that the progestins bind to the androgen receptor (AR) with similar affinities to each other and progesterone, while none bind estrogen receptor (ER)-β, and only norethisterone acetate, levonorgestrel and gestodene bind ERα. Comparative dose-response analysis revealed that progestins from the first three generations display similar androgenic activity to the natural androgen dihydrotestosterone for transactivation, while norethisterone acetate, levonorgestrel and gestodene are ERα agonists. We show for the first time that the anti-androgenic properties of progesterone and drospirenone are similar to the well-known AR antagonist hydroxyflutamide, while nomegestrol acetate is more potent and nestorone less potent than both hydroxyflutamide and prog...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research

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Abstract Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p 
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
ns Verhaegh : Estrogen receptor positive (ER+) breast cancer patients are eligible for hormonal treatment, but only around half respond. A test with higher specificity for prediction of endocrine therapy response is needed to avoid hormonal overtreatment and to enable selection of alternative treatments. A novel testing method was reported before that enables measurement of functional signal transduction pathway activity in individual cancer tissue samples, using mRNA levels of target genes of the respective pathway-specific transcription factor. Using this method, 130 primary breast cancer samples were analyzed fro...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionsRa ‐223 with hormonal therapy showed possible efficacy in HR+ bone‐dominant breast cancer metastasis, and adverse events were tolerable. We plan to further investigate the clinical application of Ra‐223 in these patients. (NCT02366130).
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
A study led by UCLA researchers found that adding ribociclib, a targeted therapy drug, to standard hormone therapy significantly improves overall survival in postmenopausal women with advanced hormone-receptor positive/HER2- breast cancer, one of the most common types of the disease.The findings also show the combination treatment is beneficial at the time of recurrence and should become a first-line option in postmenopausal women with HR+/HER2- advanced breast cancer.The study was published today in the New England Journal of Medicine and presented earlier this year at the European Society for Medical Oncology Congress in...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Quantitative real-time PCR was used to investigate mRNA levels. Protein expression was measured by immunohistochemistry and Western blot. Glycolytic levels were measured by glucose consumption and lactic acid measurement. The antitumour activity of TAM alone or with cisplatin was examined with CCK8 assay, colony formation, flow cytometry and in vivo models. The results revealed that ERɑ expression was higher in GBC tissues and predicted poor clinical outcomes. TAM was showe...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.MethodsThe biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+  breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and e fficacy of endocrine therapy.ResultsHigh CDC20 mRNA expression was associated with poor c...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Two RCTs have been reported to date, with low certainty of evidence. In a recurrent disease setting, mTOR inhibitors may result in improved progression-free survival, but we found no clear benefit in overall survival or tumour response rate. We await the publication of at least five ongoing studies investigating the role of PI3K/AKT/mTOR inhibitors in advanced or recurrent endometrial cancer before any conclusions can be drawn on their use. PMID: 31588998 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
ConclusionsAmong patients with HR-positive advanced breast cancer treated with CDK4/6i combined with endocrine, the estimated PFS was comparable to previously reported data. Treatment was well tolerated, with a low drug discontinuation rate.Legal entity responsible for the studyHellenic Cooperative Oncology Group.FundingHellenic Cooperative Oncology Group (HeCOG).DisclosureE. Fountzilas: Travel / Accommodation / Expenses: K.A.M ONCOLOGY / HEMATOLOGY; Travel / Accommodation / Expenses: Merck; Shareholder / Stockholder / Stock options: Deciphera. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: Brist...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundA high percentage of breast cancer patients in the Asia-Pacific ( ∼42%) and Middle East (∼50%) regions are aged 50 years or younger. Although a high proportion of younger patients with endocrine-responsive metastatic disease are treated initially with cytotoxic chemotherapy (CT) in routine general practice, data from phase III trials have shown higher response rates and longer progression-free survival with endocrine therapy (ET) in combination with CDK4/6 inhibitor versus single agent ET. Due to lack of direct evidence, trials in pre-/perimenopausal advanced breast cancer are thus necessary to as...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsMLT and MTF showed encouraging results in combination with neoadjuvant hormonotherapy. However, these data require confirmation in larger randomized studies.Legal entity responsible for the studyT. Semiglazova.FundingFederal State Budget Institution "National Medical Research Center of Oncology na N.N. Petrov" Ministry of Healthcare of Russian Federation.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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