OBJECTIVE: Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancer patients. METHODS: A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified. RESULTS: In HER2-positive locally advanced breast cancer patients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439-1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453-2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417-1.484, P = 0.459; RR = 0.772, 95% CI: 0.387-1.539, P = 0.462). In HER2-positive early stage breast cancer patients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706-1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancer patients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550-0.846, P = 0.000). CONCLUSIONS: In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.
OBJECTIVE: Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancerpatients. METHODS: A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified. RESULTS: In HER2-positive locally advanced breast cancerpatients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439-1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453-2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417-1.484, P = 0.459; RR = 0.772, 95% CI: 0.387-1.539, P = 0.462). In HER2-positive early stage breast cancerpatients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706-1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancerpatients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550-0.846, P = 0.000). CONCLUSIONS: In HER2-positive recurrent or metastatic breast cancerpatientsPTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.
Authors: Asunción Díaz-Serrano; Barbara Angulo; Carolina Dominguez; Roberto Pazo-Cid; Antonieta Salud; Paula Jiménez-Fonseca; Ana Leon; Maria Carmen Galan; Maria Alsina; Fernando Rivera; J Carlos Plaza; Luis Paz-Ares; Fernando Lopez-Rios; Carlos Gómez-Martín Journal: Oncologist Date: 2018-04-26
Authors: Katherine L Pogue-Geile; Nan Song; Jong-Hyeon Jeong; Patrick G Gavin; Seong-Rim Kim; Nicole L Blackmon; Melanie Finnigan; Priya Rastogi; Louis Fehrenbacher; Eleftherios P Mamounas; Sandra M Swain; D Lawrence Wickerham; Charles E Geyer; Joseph P Costantino; Norman Wolmark; Soonmyung Paik Journal: J Clin Oncol Date: 2015-01-05 Impact factor: 44.544
Authors: Michalina Janiszewska; Lin Liu; Vanessa Almendro; Yanan Kuang; Cloud Paweletz; Rita A Sakr; Britta Weigelt; Ariella B Hanker; Sarat Chandarlapaty; Tari A King; Jorge S Reis-Filho; Carlos L Arteaga; So Yeon Park; Franziska Michor; Kornelia Polyak Journal: Nat Genet Date: 2015-08-24 Impact factor: 38.330