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Activation of Akt, ...
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Bostner, JosefineLinköpings universitet,Onkologi,Hälsouniversitetet
(författare)
Activation of Akt, mTOR, and the estrogen receptor as a signature to predict tamoxifen treatment benefit
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2012-12-15
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Springer Verlag (Germany),2013
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-88458
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-88458URI
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https://doi.org/10.1007/s10549-012-2376-yDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:125937544URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|Swedish Cancer Society||Swedish Research Council||King Gustaf V Jubilee Fund||
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The frequent alterations of the PI3K/Akt/mTOR-growth signaling pathway are proposed mechanisms for resistance to endocrine therapy in breast cancer, partly through regulation of estrogen receptor alpha (ER) activity. Reliable biomarkers for treatment prediction are required for improved individualized treatment. We performed a retrospective immunohistochemical analysis of primary tumors from 912 postmenopausal patients with node-negative breast cancer, randomized to either tamoxifen or no adjuvant treatment. Phosphorylated (p) Akt-serine (s) 473, p-mTOR-s2448, and ER phosphorylations-s167 and -s305 were evaluated as potential biomarkers of prognosis and tamoxifen treatment efficacy. High expression of p-mTOR indicated a reduced response to tamoxifen, most pronounced in the ER+/progesterone receptor (PgR) + subgroup (tamoxifen vs. no tamoxifen: hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.31-2.38; P = 0.78), whereas low p-mTOR expression predicted tamoxifen benefit (HR, 0.29; 95 % CI, 0.18-0.49; P = 0.000002). In addition, nuclear p-Akt-s473 as well as p-ER at -s167 and/or -s305 showed interaction with tamoxifen efficacy with borderline statistical significance. A combination score of positive pathway markers including p-Akt, p-mTOR, and p-ER showed significant association with tamoxifen benefit (test for interaction; P = 0.029). Cross-talk between growth signaling pathways and ER-signaling has been proposed to affect tamoxifen response in hormone receptor-positive breast cancer. The results support this hypothesis, as an overactive pathway was significantly associated with reduced response to tamoxifen. A clinical pre-treatment test for cross-talk markers would be a step toward individualized adjuvant endocrine treatment with or without the addition of PI3K/Akt/mTOR pathway inhibitors.
Ämnesord och genrebeteckningar
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mTOR
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Akt
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Estrogen receptor phosphorylation
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Tamoxifen resistance
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Immunohistochemistry
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Karlsson, ElinLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)elika34
(författare)
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Pandiyan, Muneeswaran J.Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
(författare)
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Westman, HannaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
(författare)
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Skoog, LambertKarolinska Institutet
(författare)
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Fornander, TommyKarolinska Institutet
(författare)
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Nordenskjöld, BoÖstergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Onkologiska kliniken US(Swepub:liu)bono64
(författare)
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Stål, OlleÖstergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Onkologiska kliniken US(Swepub:liu)ollst87
(författare)
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Linköpings universitetOnkologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Breast Cancer Research and Treatment: Springer Verlag (Germany)137:2, s. 397-4060167-68061573-7217
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