Cancers, Vol. 12, Pages 802: ER and PI3K Pathway Activity in Primary ER Positive Breast Cancer Is Associated with Progression-Free Survival of Metastatic Patients under First-Line Tamoxifen

Cancers, Vol. 12, Pages 802: ER and PI3K Pathway Activity in Primary ER Positive Breast Cancer Is Associated with Progression-Free Survival of Metastatic Patients under First-Line Tamoxifen Cancers doi: 10.3390/cancers12040802 Authors: Sieuwerts Inda Smid van Ooijen van de Stolpe Martens 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 from non-metastatic ER+ patients, treated with surgery without adjuvant hormonal therapy, who subsequently developed metastatic disease that was treated with first-line tamoxifen. Quantitative activity levels were measured of androgen and estrogen receptor (AR and ER), PI3K-FOXO, Hedgehog (HH), NFκB, TGFβ, and Wnt pathways. Based on samples with known pathway activity, thresholds were set to distinguish low from high activity. Subsequently, pathway activity levels were correlated with the tamoxifen treatment response and progression-free surv...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article 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
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
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
Abstract Endocrine therapy represents a mainstay adjuvant treatment of estrogen receptor-positive (ER+) breast cancer in clinical practice with an overall survival (OS) benefit. However, the emergence of resistance is inevitable over time and is present in one-third of the ER+ breast tumors. Several mechanisms of endocrine resistance in ER+/HER2- advanced breast cancers, through ERα itself, receptor tyrosine signaling, or cell cycle pathway, have been identified to be pivotal in endocrine therapy. The epigenetic alterations also contribute to ensuring tumor cells' escape from endocrine therapie...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
CONCLUSION: Collectively, these findings suggest that while FGFR1 amplification confers broad resistance to ER, PI3K, and CDK4/6 inhibitors, TORC1 inhibitors might have a unique therapeutic role in the treatment of patients with ER+/FGFR1+ MBC. PMID: 31371343 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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