Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016077962> ?p ?o ?g. }
Showing items 1 to 92 of
92
with 100 items per page.
- W2016077962 abstract "Background. Not all patients (pts) with HER2-overexpressing metastatic breast cancer (MBC) respond to trastuzumab and most that initially respond, ultimately develop resistance to treatment. Activated PI3K signalling has been proposed to predict trastuzumab resistance.Patients and Methods. PI3K pathway activity was evaluated in tumor samples from pts with HER2-overexpressing MBC treated with first-line chemotherapy in combination with trastuzumab by: a) assessing PIK3CA mutation status by our recently developed High Resolution Melting Analysis (HRMA) for the detection of mutations in exons 9 and 20, performed in the HR-1 High Resolution Melter (Idaho Technology, USA) and b) PTEN expression levels using immunohistochemical analysis. All samples with mutant melting transitions were verified by DNA sequencing. PI3K pathway activation defined by the presence of PIK3CA hotspot mutations and/or low or absent PTEN was correlated to the response to trastuzumab-based therapy.Results. Fifty-six pts received trastuzumab in combination with vinorelbine (n=15) or taxane-based chemotherapy (n=41). Median age was 62 years, 55 pts (98.2%) had PS 0-1, 10 (17.9%) were premenopausal, 27 (48.2%) had hormone receptor negative tumors and 37 (66.1%) had visceral metastases. HRMA identified the presence of PIK3CA mutations in 22 (39.3%) pts [exon 9 mutations in 5 (8.9%) and exon 20 mutations in 17 (30.4%) pts]. Subsequent PIK3CA sequence analysis demonstrated exon 9 mutations (E542K and E545K) in 4 (7.1%) pts and exon 20 mutations in 17 (30.4%; H104R in 16, and H1047L in 1) corresponding to a PIK3CA hotspot mutation frequency of 35.7%. Only in one sample that showed a mutant melting transition by HRMA, DNA sequencing did not confirm the presence of a PIK3CA mutation in exon 9, possibly due to lower sensitivity. Absent or reduced PTEN expression was detected in 22 (39.3%) of 47 pts. In 9 (16.1%) pts, PTEN score could not be retrieved. A trend for lower response rates was observed for patients with PI3K hotspot mutations compared to pts with wild-type tumors (35% vs 60%, p= 0.074). No difference in response rates was identified for pts with low or absent compared to normal PTEN expression (p=0.920). However, activated PI3K pathway (presence of PI3K mutations and/or low or absent PTEN expression) was associated with significantly lower response rates compared to non-activated one (40.6% vs 72.2%; p=0.032).Conclusions. The activation of PI3K pathway is predictive of response to first-line chemotherapy plus trastuzumab in pts with HER2-overexpressing MBC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2022." @default.
- W2016077962 created "2016-06-24" @default.
- W2016077962 creator A5006337734 @default.
- W2016077962 creator A5019577278 @default.
- W2016077962 creator A5021554009 @default.
- W2016077962 creator A5031768538 @default.
- W2016077962 creator A5032132445 @default.
- W2016077962 creator A5046521246 @default.
- W2016077962 creator A5077485049 @default.
- W2016077962 creator A5084377238 @default.
- W2016077962 date "2009-12-15" @default.
- W2016077962 modified "2023-09-26" @default.
- W2016077962 title "PI3K Pathway Activity and Response to First-Line Chemotherapy in Combination with Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer." @default.
- W2016077962 doi "https://doi.org/10.1158/0008-5472.sabcs-09-2022" @default.
- W2016077962 hasPublicationYear "2009" @default.
- W2016077962 type Work @default.
- W2016077962 sameAs 2016077962 @default.
- W2016077962 citedByCount "1" @default.
- W2016077962 crossrefType "proceedings-article" @default.
- W2016077962 hasAuthorship W2016077962A5006337734 @default.
- W2016077962 hasAuthorship W2016077962A5019577278 @default.
- W2016077962 hasAuthorship W2016077962A5021554009 @default.
- W2016077962 hasAuthorship W2016077962A5031768538 @default.
- W2016077962 hasAuthorship W2016077962A5032132445 @default.
- W2016077962 hasAuthorship W2016077962A5046521246 @default.
- W2016077962 hasAuthorship W2016077962A5077485049 @default.
- W2016077962 hasAuthorship W2016077962A5084377238 @default.
- W2016077962 hasConcept C104317684 @default.
- W2016077962 hasConcept C121608353 @default.
- W2016077962 hasConcept C126322002 @default.
- W2016077962 hasConcept C143998085 @default.
- W2016077962 hasConcept C190283241 @default.
- W2016077962 hasConcept C2775930923 @default.
- W2016077962 hasConcept C2776694085 @default.
- W2016077962 hasConcept C2777511904 @default.
- W2016077962 hasConcept C2777609662 @default.
- W2016077962 hasConcept C2778239845 @default.
- W2016077962 hasConcept C2779786085 @default.
- W2016077962 hasConcept C2780350996 @default.
- W2016077962 hasConcept C36823959 @default.
- W2016077962 hasConcept C502942594 @default.
- W2016077962 hasConcept C530470458 @default.
- W2016077962 hasConcept C54355233 @default.
- W2016077962 hasConcept C71924100 @default.
- W2016077962 hasConcept C86554907 @default.
- W2016077962 hasConcept C86803240 @default.
- W2016077962 hasConceptScore W2016077962C104317684 @default.
- W2016077962 hasConceptScore W2016077962C121608353 @default.
- W2016077962 hasConceptScore W2016077962C126322002 @default.
- W2016077962 hasConceptScore W2016077962C143998085 @default.
- W2016077962 hasConceptScore W2016077962C190283241 @default.
- W2016077962 hasConceptScore W2016077962C2775930923 @default.
- W2016077962 hasConceptScore W2016077962C2776694085 @default.
- W2016077962 hasConceptScore W2016077962C2777511904 @default.
- W2016077962 hasConceptScore W2016077962C2777609662 @default.
- W2016077962 hasConceptScore W2016077962C2778239845 @default.
- W2016077962 hasConceptScore W2016077962C2779786085 @default.
- W2016077962 hasConceptScore W2016077962C2780350996 @default.
- W2016077962 hasConceptScore W2016077962C36823959 @default.
- W2016077962 hasConceptScore W2016077962C502942594 @default.
- W2016077962 hasConceptScore W2016077962C530470458 @default.
- W2016077962 hasConceptScore W2016077962C54355233 @default.
- W2016077962 hasConceptScore W2016077962C71924100 @default.
- W2016077962 hasConceptScore W2016077962C86554907 @default.
- W2016077962 hasConceptScore W2016077962C86803240 @default.
- W2016077962 hasLocation W20160779621 @default.
- W2016077962 hasOpenAccess W2016077962 @default.
- W2016077962 hasPrimaryLocation W20160779621 @default.
- W2016077962 hasRelatedWork W2011182661 @default.
- W2016077962 hasRelatedWork W2044348501 @default.
- W2016077962 hasRelatedWork W2054536628 @default.
- W2016077962 hasRelatedWork W2067582244 @default.
- W2016077962 hasRelatedWork W2104659222 @default.
- W2016077962 hasRelatedWork W2269020509 @default.
- W2016077962 hasRelatedWork W2317743587 @default.
- W2016077962 hasRelatedWork W2489012263 @default.
- W2016077962 hasRelatedWork W2589198558 @default.
- W2016077962 hasRelatedWork W2589793929 @default.
- W2016077962 hasRelatedWork W2592290895 @default.
- W2016077962 hasRelatedWork W2594389609 @default.
- W2016077962 hasRelatedWork W2651253263 @default.
- W2016077962 hasRelatedWork W2787874662 @default.
- W2016077962 hasRelatedWork W3001722046 @default.
- W2016077962 hasRelatedWork W3006792714 @default.
- W2016077962 hasRelatedWork W3092288103 @default.
- W2016077962 hasRelatedWork W3132576484 @default.
- W2016077962 hasRelatedWork W798751312 @default.
- W2016077962 hasRelatedWork W2738395440 @default.
- W2016077962 isParatext "false" @default.
- W2016077962 isRetracted "false" @default.
- W2016077962 magId "2016077962" @default.
- W2016077962 workType "article" @default.