scholarly journals Experimental treatment of oestrogen receptor (ER) positive breast cancer with tamoxifen and brivanib alaninate, a VEGFR-2/FGFR-1 kinase inhibitor: A potential clinical application of angiogenesis inhibitors

2010 ◽  
Vol 46 (9) ◽  
pp. 1537-1553 ◽  
Author(s):  
Roshani R. Patel ◽  
Surojeet Sengupta ◽  
Helen R. Kim ◽  
Andres J. Klein-Szanto ◽  
Jennifer R. Pyle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Application ◽  
Oestrogen Receptor ◽  
Kinase Inhibitor ◽  
Experimental Treatment ◽  
Angiogenesis Inhibitors ◽  
Potential Clinical Application ◽  
Brivanib Alaninate ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer

2017 ◽  
Vol 140 (7) ◽  
pp. 1633-1644 ◽  
Author(s):  
Lindsay Bennett ◽  
Jean Quinn ◽  
Pamela McCall ◽  
Elizabeth A. Mallon ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oestrogen Receptor ◽  
Cancer Specific Survival ◽  
Time To Recurrence ◽  
Er Positive ◽  
Reduced Time ◽  
Positive Breast Cancer

scholarly journals Clinical validity of clinical treatment score 5 (CTS5) for estimating risk of late recurrence in unselected, non-trial patients with early oestrogen receptor-positive breast cancer

2020 ◽  
Author(s):  
Juliet Richman ◽  
Alistair Ring ◽  
Mitch Dowsett ◽  
Ivana Sestak
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Oestrogen Receptor ◽  
Premenopausal Women ◽  
Clinical Validity ◽  
Er Positive ◽  
Extended Endocrine Therapy ◽  
Positive Breast Cancer

Abstract Purpose Clinical Treatment Score at 5 years (CTS5) is a prognostic tool to estimate distant recurrence (DR) risk after 5 years of endocrine therapy for postmenopausal women with oestrogen receptor-positive (ER-positive) breast cancer. Methods The validity of CTS5 was tested in a retrospective cohort of patients diagnosed with early ER-positive breast cancer. The primary endpoint was DR in years 5–10. The primary analysis cohort consisted of postmenopausal women, with premenopausal women as a secondary analysis cohort. Cox regression models were used to determine the prognostic value of CTS5 and Kaplan–Meier curves were used with associated 10-year DR risks (%). Results 2428 women were included with a median follow-up of 13.4 years. The CTS5 was significantly prognostic in both postmenopausal (N = 1662, HR = 2.18 95% CI (1.78–2.67)) and premenopausal women (N = 766, HR = 1.84 95% CI (1.32–2.56)). The 10-year DR risks were 2.9% (1.9–4.5), 7.2% (5.3–9.9), and 12.9% (10.0–16.7) for low, intermediate and high risk in postmenopausal women and 3.8% (2.2–6.7), 6.9% (4.4–10.8), and 11.1% (7.4–16.5) in premenopausal women, respectively. The number of observed DRs was significantly greater than expected in those predicted to be at high risk by CTS5 but this discordance was lost when those receiving more than 60 months of endocrine therapy were excluded. Conclusions The CTS5 demonstrated clinical validity for predicting late DR within a large cohort of unselected postmenopausal patients but less so in premenopausal patients. Calibration of the CTS5 was good in patients who did not receive extended endocrine therapy. The CTS5 low-risk cohort has risk of DR so low as to not warrant extended endocrine therapy.

scholarly journals Inducible upregulation of oestrogen receptor-β1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells

2005 ◽  
Vol 34 (2) ◽  
pp. 553-566 ◽  
Author(s):  
L C Murphy ◽  
B Peng ◽  
A Lewis ◽  
J R Davie ◽  
E Leygue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Growth Responses ◽  
Over Expression ◽  
Er Positive ◽  
Positive Breast Cancer ◽  
Tamoxifen Sensitivity

To investigate the effect of altered oestrogen receptor (ER)α and ERβ expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERβ1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERβ1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERβ1 did not affect endogenous levels of ERα but increased progesterone receptor (PR) levels. Over-expression of ERβ1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ERα. In oestrogen-replete conditions, over-expression of ERβ1 but not ERα reduced proliferation. Over-expression of ERβ1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERβ1 in the presence of an endogenously expressed ERα was associated with tamoxifen sensitivity but may negatively modulate ERα-mediated growth. However, not all ERα activities were inhibited since endogenous PR expression was increased by both ERα and ERβ1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERβ expression as well as ERβ expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERβ1 expression in ER-positive breast cancer.

Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Chuan Chen ◽  
Ziyue Zhao ◽  
Qian Dong ◽  
XueHui Gao ◽  
Huibin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Transcriptome Analysis ◽  
Mcf7 Cells ◽  
Er Positive ◽  
Induced Apoptosis ◽  
Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

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