PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab
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| Názov: | PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab |
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| Autori: | Jeanette Dupont Jensen, Anne Vibeke Lænkholm, Morten Grauslund, Maj-Britt Jensen, Marianne Ewertz, Michael Andersson, Ann Knoop, Eric Santoni-Rugiu |
| Zdroj: | Jensen, J D, Knoop, A, Laenkholm, A V, Grauslund, M, Jensen, M B, Santoni-Rugiu, E, Andersson, M & Ewertz, M 2012, ' PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab ', Annals of Oncology, vol. 23, no. 8, pp. 2034-42 . https://doi.org/10.1093/annonc/mdr546 |
| Informácie o vydavateľovi: | Elsevier BV, 2012. |
| Rok vydania: | 2012 |
| Predmety: | Phosphatidylinositol 3-Kinases/genetics, Receptor, erbB-2, Class I Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, Molecular Sequence Data, Epirubicin/administration & dosage, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Antibodies, Cyclophosphamide/administration & dosage, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Breast Neoplasms/drug therapy, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Humans, Phosphorylation, Humanized, Cyclophosphamide, Adjuvant, erbB-2, Epirubicin, Base Sequence, PTEN Phosphohydrolase, PTEN Phosphohydrolase/biosynthesis, Trastuzumab, Immunohistochemistry, 3. Good health, Survival Rate, ErbB-2/biosynthesis, Fluorouracil/administration & dosage, Chemotherapy, Adjuvant, Mutation, Humanized/administration & dosage, Female, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Fluorouracil, Receptor |
| Popis: | This study was conducted to determine the frequency of PIK3CA mutations and human epidermal growth factor receptor-2 (HER2) phosphorylation status (pHER2-Tyr1221/1222) and if PIK3CA, phosphatase and tensin homolog (PTEN), or pHER2 has an impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab.Two hundred and forty HER2-positive early-stage breast cancer patients receiving adjuvant treatment (cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2) before administration of 1 year trastuzumab were assessable. PTEN and pHER2 expression were assessed by immunohistochemistry. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing.Five-year overall survival (OS) and invasive disease-free survival were 87.8% and 81.0%, respectively. Twenty-six percent of patients had a PIK3CA mutation, 24% were PTEN low, 45% pHER2 high, and 47% patients had increased PI3K pathway activation (PTEN low and/or PIK3CA mutation). No significant correlations were observed between the clinicopathological variables and PIK3CA, PTEN, and pHER2 status. In both univariate and multivariate analyses, patients with PIK3CA mutations or high PI3K pathway activity had a significant worse OS [multivariate: hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.01-4.51, P=0.046; and HR 2.35, 95% CI 1.10-5.04, P=0.03].Patients with PIK3CA mutations or increased PI3K pathway activity had a significantly poorer survival despite adequate treatment with adjuvant chemotherapy and trastuzumab. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdr546 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/22172323 https://www.annalsofoncology.org/article/S0923-7534(19)38088-3/fulltext https://academic.oup.com/annonc/article/23/8/2034/135228 https://pure-portal.regsj.dk/da/publications/pik3ca-mutations-pten-and-pher2-expression-and-impact-on-outcome- https://www.sciencedirect.com/science/article/pii/S0923753419380883 https://paperity.org/p/40521382/pik3ca-mutations-pten-and-pher2-expression-and-impact-on-outcome-in-her2-positive-early http://europepmc.org/abstract/MED/22172323 https://portal.findresearcher.sdu.dk/da/publications/9a10b59a-3d6c-4729-8828-df65a78ac610 |
| Rights: | Elsevier Non-Commercial |
| Prístupové číslo: | edsair.doi.dedup.....a708dd43b136d288339d2340fa749c87 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | This study was conducted to determine the frequency of PIK3CA mutations and human epidermal growth factor receptor-2 (HER2) phosphorylation status (pHER2-Tyr1221/1222) and if PIK3CA, phosphatase and tensin homolog (PTEN), or pHER2 has an impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab.Two hundred and forty HER2-positive early-stage breast cancer patients receiving adjuvant treatment (cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2) before administration of 1 year trastuzumab were assessable. PTEN and pHER2 expression were assessed by immunohistochemistry. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing.Five-year overall survival (OS) and invasive disease-free survival were 87.8% and 81.0%, respectively. Twenty-six percent of patients had a PIK3CA mutation, 24% were PTEN low, 45% pHER2 high, and 47% patients had increased PI3K pathway activation (PTEN low and/or PIK3CA mutation). No significant correlations were observed between the clinicopathological variables and PIK3CA, PTEN, and pHER2 status. In both univariate and multivariate analyses, patients with PIK3CA mutations or high PI3K pathway activity had a significant worse OS [multivariate: hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.01-4.51, P=0.046; and HR 2.35, 95% CI 1.10-5.04, P=0.03].Patients with PIK3CA mutations or increased PI3K pathway activity had a significantly poorer survival despite adequate treatment with adjuvant chemotherapy and trastuzumab. |
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| ISSN: | 09237534 |
| DOI: | 10.1093/annonc/mdr546 |