Abstract PD3-8: Whole exome sequencing reveals early mutational change on endocrine and targeted therapy in estrogen receptor (ER)-positive breast cancer

2013 ◽  
Author(s):  
S Massarweh ◽  
E Romond ◽  
C Wang ◽  
Z Zeng ◽  
J Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Targeted Therapy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mutational Change ◽  
Whole Exome ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals Relationship Between Plasma Estradiol Levels and Estrogen-Responsive Gene Expression in Estrogen Receptor–Positive Breast Cancer in Postmenopausal Women

2010 ◽  
Vol 28 (7) ◽  
pp. 1161-1167 ◽  
Author(s):  
Anita K. Dunbier ◽  
Helen Anderson ◽  
Zara Ghazoui ◽  
Elizabeth J. Folkerd ◽  
Roger A'Hern ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Multivariable Analysis ◽  
Independent Set ◽  
Breast Cancers ◽  
Plasma Estradiol ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose To determine whether plasma estradiol (E2) levels are related to gene expression in estrogen receptor (ER)–positive breast cancers in postmenopausal women. Materials and Methods Genome-wide RNA profiles were obtained from pretreatment core-cut tumor biopsies from 104 postmenopausal patients with primary ER-positive breast cancer treated with neoadjuvant anastrozole. Pretreatment plasma E2 levels were determined by highly sensitive radioimmunoassay. Genes were identified for which expression was correlated with pretreatment plasma E2 levels. Validation was performed in an independent set of 73 ER-positive breast cancers. Results The expression of many known estrogen-responsive genes and gene sets was highly significantly associated with plasma E2 levels (eg, TFF1/pS2, GREB1, PDZK1 and PGR; P < .005). Plasma E2 explained 27% of the average expression of these four average estrogen-responsive genes (ie, AvERG; r = 0.51; P < .0001), and a standardized mean of plasma E2 levels and ER transcript levels explained 37% (r, 0.61). These observations were validated in an independent set of 73 ER-positive tumors. Exploratory analysis suggested that addition of the nuclear coregulators in a multivariable analysis with ER and E2 levels might additionally improve the relationship with the AvERG. Plasma E2 and the standardized mean of E2 and ER were both significantly correlated with 2-week Ki67, a surrogate marker of clinical outcome (r = −0.179; P = .05; and r = −0.389; P = .0005, respectively). Conclusion Plasma E2 levels are significantly associated with gene expression of ER-positive breast cancers and should be considered in future genomic studies of ER-positive breast cancer. The AvERG is a new experimental tool for the study of putative estrogenic stimuli of breast cancer.

scholarly journals Low Estrogen Receptor (ER)–Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy

2018 ◽  
Vol 150 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Alessandra Landmann ◽  
Daniel J Farrugia ◽  
Li Zhu ◽  
Emilia J Diego ◽  
Ronald R Johnson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Systemic Chemotherapy ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals PELP-1 regulates adverse responses to endocrine therapy in Estrogen Receptor (ER) positive breast cancer

Oncotarget ◽  
2020 ◽  
Vol 11 (51) ◽  
pp. 4722-4734
Author(s):  
Michael Rees ◽  
Chris Smith ◽  
Peter Barrett-Lee ◽  
Steve Hiscox
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals Searching for the missing genetic determinants of hereditary breast cancer risk by whole-exome sequencing of BRCA-negative patients: new candidate genes USP39, SLIT3, CREB3

2021 ◽  
Vol 67 (1) ◽  
pp. 111-116
Author(s):  
Kirill Zagorodnev ◽  
Aleksandr Romanko ◽  
Uliy Gorgul ◽  
Aleksandr Ivantsov ◽  
Anna Sokolenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Exome Sequencing ◽  
Candidate Genes ◽  
Whole Exome Sequencing ◽  
Hereditary Breast Cancer ◽  
Germ Line ◽  
Genetic Diagnosis ◽  
Clinical Signs ◽  
Causative Mutation ◽  
Whole Exome

The search for the new hereditary mutations and a precise molecular genetic diagnosis that determines the causative mutation in each specific case of hereditary breast cancer (BC) is a clinically important task since it helps to define the personal therapeutic approach and increase the effectiveness of preventive measures. Using whole-exome sequencing (WES) we analyzed the full spectrum of hereditary variations in 49 Russian patients with clinical signs of a hereditary disease which allowed us to compile a list of 229 candidate probably pathogenic germ-line variants. Then, the selected candidate mutations were validated by Sanger sequencing and molecular-epidemiological studies, the predisposing roles of three oncologically relevant mutations (USP39 c.*208G>C, SLIT3 p.Arg154Cys, and CREB3 p.Lys157Glu) were confirmed. Our candidate genes are first mentioned in connection with the hereditary risk of BC. The final proofs of the causative roles of these variants could be obtained through functional tests as well as via the analysis of the mutations segregation in BC families.

scholarly journals Estrogen Receptor Positive Breast Cancer with High Expression of Androgen Receptor has Less Cytolytic Activity and Worse Response to Neoadjuvant Chemotherapy but Better Survival

2019 ◽  
Vol 20 (11) ◽  
pp. 2655 ◽  
Author(s):  
Maiko Okano ◽  
Masanori Oshi ◽  
Ali Linsk Butash ◽  
Mariko Asaoka ◽  
Eriko Katsuta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Cytolytic Activity ◽  
Er Positive ◽  
Infiltrating Lymphocytes ◽  
Response To Neoadjuvant Chemotherapy ◽  
Positive Breast Cancer

Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives (p < 0.001, p < 0.001, respectively) and it correlated with ER expression (R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = −2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC (p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC.

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