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Markers of steroid ...
Markers of steroid receptor, kinase signalling pathways and Ki-67 expression in relation to tamoxifen sensitivity and resistance
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- Campbell, Christine (author)
- Frontier Science (Scotland) Ltd
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- Mathew, John (author)
- Peterborough City Hospital
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- Ellis, Ian O. (author)
- University of Nottingham
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- Bradbury, Ian (author)
- Frontier Science (Scotland) Ltd
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- Borgquist, Signe (author)
- Aarhus University
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- Elebro, Karin (author)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Bröstcancer - prevention & intervention,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröstcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery,Lund University Research Groups,Breast cancer prevention & intervention,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breastcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Green, Andrew R. (author)
- University of Nottingham
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- Finlay, Pauline (author)
- Cardiff University
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- Gee, Julia M. W. (author)
- Cardiff University
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- Robertson, John F. R. (author)
- University of Nottingham
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(creator_code:org_t)
- 2020-10
- 2020
- English.
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In: Translational Breast Cancer Research. - : AME Publishing Company. - 2218-6778. ; 1
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http://dx.doi.org/10... (free)
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Abstract
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- Background: It remains clinically important to identify ER positive breast cancers likely to respond to tamoxifen (TAM) and so we aimed to select a group of biomarkers able to predict response. We also assessed whether data from different sample types [tumor microarrays (TMAs) and core biopsies] or tumor sites could be combined for biomarker studies.Methods: A total of 123 endocrine treatment naïve patients with known ER and HER2 status treated with TAM had paraffin-embedded tumor tissue available either as TMAs (n=102) or core biopsies (n=21). TMA cores were collected from three different tumor sites, two central and one peripheral. Ten biomarkers were evaluated by immunohistochemistry, for % positivity and/or H-Score, comprising: ER, HER2, Ki-67, phosphorylated forms of ER (Ser118), IGF1R, PRAS40, Akt & MAPK (ERK1/2), and PTEN & androgen receptor expression (AR). Each tumor was analysed for Akt1 E17K somatic mutation using BEAMing technology. Patient outcome was assessed by clinical benefit (CB) rate & survival analyses [time to progression (TTP) and time to death (TTD)].Results: There was no significant difference in % positivity or H-Score between central & peripheral tumor sites for all biomarkers examined. After False Discovery Rate (FDR) correction differences (P<0.05) were observed between the two central samples only for HER2 & pER118 and pPRAS40. However, differences in biomarker expression were common between core biopsies and TMAs. Only 2/123 (1.6%) tumors had Akt1 E17K mutations. Univariate and multivariate analyses identified that lower levels of PTEN and higher levels of Ki-67 (% positivity) were predictive of poor outcome (TTP & TTD) following TAM. Higher ER. lower Ki-67 and AR/ER ratio <2 predicted increased CB rate.Conclusions: There were few differences in marker expression between TMAs from different intra-tumoral sites. More marked differences between TMAs and core biopsies suggest caution if combining such datasets. Loss of PTEN, a key regulator of the PI3K/Akt pathway, was the only RTK/kinase signaling biomarker related to poorer clinical outcome. PTEN along with ER & lower Ki-67 proved the most predictive markers for better outcome (TTP & TTD and/or CBR) following TAM treatment.Keywords: ER+ breast cancer; Akt pathway; tamoxifen
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- By the author/editor
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Campbell, Christ ...
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Mathew, John
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Ellis, Ian O.
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Bradbury, Ian
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Borgquist, Signe
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Elebro, Karin
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Green, Andrew R.
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Finlay, Pauline
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Gee, Julia M. W.
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Robertson, John ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Lund University