EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab

Gori, Stefania; Sidoni, Angelo; Colozza, Mariantonietta; Ferri, Ivana; Mameli, Maria Grazia; Fenocchio, D.; Stocchi, Lucia; Foglietta, Jennifer; Ludovini, Vienna; Minenza, Elisa; Angelis, Verena De; Crinò, Lucio

doi:10.1093/annonc/mdn681

Cited by 66 publications

(54 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oncogenic mutations of PIK3CA and low expression or loss of the phosphatase and tensine homologue gene (PTEN), that antagonizes the action of PIK3CA, have both been described as factors that activate the PI3K/AKT pathway and contribute to trastuzumab resistance in breast tumors [6,7]. Investigation in cell lines and clinical studies have suggested the possible use of the PIK3CA and PTEN status as predictive factors of trastuzumab efficacy in breast cancer [7][8][9][10][11] and in one study PIK3CA mutations were found to be mutually exclusive with PTEN loss [12]. In the present study we analyzed samples from patients with presumed HER2-positive breast tumors that were treated with trastuzumab, after local evaluation for HER2 by IHC.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer

Razis

Bobos

Kotoula

et al. 2011

Breast Cancer Res Treat

166

150

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer

Razis

Bobos

Kotoula

et al. 2011

Breast Cancer Res Treat

166

150

View full text Add to dashboard Cite

“…25 On the other hand, some studies found no correlation between PTEN expression and trastuzumab response or survival in patients with HER2-positive breast cancer. 27,28 These contradictory findings prompted us to further investigate the association between PTEN status and clinical outcomes in a large cohort of patients with MBC who were treated with trastuzumab-based therapy. We tested the hypothesis that a comprehensive assessment of PI3K pathway activation status provides biomarkers that can identify patients who may not benefit from trastuzumab-based therapy.…”

mentioning

confidence: 99%

PTEN, PIK3CA, p-AKT, and p-p70S6K Status

Esteva

Guo

Zhang

et al. 2010

The American Journal of Pathology

262

111

View full text Add to dashboard Cite

Phosphatase and tensin homolog (PTEN) is a key modulator of trastuzumab sensitivity in HER2-overexpressing breast cancer. Because PTEN opposes the downstream signaling of phosphoinositide 3-kinase (PI3K) , we investigated the role of PTEN and other components of the PI3K pathway in trastuzumab resistance. We analyzed the status of PTEN , p-AKTSer473 , and p-p70S6K-Thr389 using immunohistochemistry. PIK3CA mutation status was analyzed by direct sequencing. Primary tumor tissue was available from 137 patients with HER2-overexpressing metastatic breast cancer who had received trastuzumabbased chemotherapy. We observed that each of the four biomarkers alone did not significantly correlate with trastuzumab response , whereas PTEN loss alone significantly correlated with shorter survival times (P ‫؍‬ 0.023). PI3K pathway activation , defined as PTEN loss and/or PIK3CA mutation , was associated with a poor response to trastuzumab (P ‫؍‬ 0.047) and a shorter survival time (P ‫؍‬ 0.015). PTEN loss was significantly associated with a poor response to trastuzumab (P ‫؍‬ 0.028) and shorter survival time (P ‫؍‬ 0.008) in patients who had received first-line trastuzumab and in patients with estrogen receptor-(P ‫؍‬ 0.029) and progesterone receptor-negative tumors (P ‫؍‬ 0.033). p-AKT-Ser473 and p-p70S6K-Thr389 each had a limited correlation with trastuzumab response. When these markers were combined with PTEN loss , an increased correlation with patient outcome was observed. In conclusion , PI3K path- Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% to 25% of invasive breast cancers. Patients with HER2-overexpressing tumors experience a shorter time to relapse and shorter overall survival than patients with tumors of normal HER2 levels.

show abstract

“…We discovered that patients with HER2-positive tumors with strong PTEN expression had a 100% survival rate. Some authors reported no relationship between PTEN loss in HER2-positive tumors and response to trastuzumab treatment [22,33], overall [33] as well as relapse/metastasis-free survival [32,33]. In other studies shorter survival for individuals with HER2 overexpressing tumors with PTEN loss [22,32] or shorter time to progression [12] was noted.…”

Section: Discussionmentioning

confidence: 99%

Original paper Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting

Adamczyk¹,

Niemiec²,

Janecka³

et al. 2015

pjp

View full text Add to dashboard Cite

Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN). HER2-overexpressing breast cancer patients (n = 75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry. In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p = 0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p = 0.042, p = 0.016, p = 0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2+3) stage (p = 0.040) and with tumors characterized by low Ki-67LI (≤ 50% vs. > 50%) (p = 0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p = 0.007). The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.

show abstract

EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab

Cited by 66 publications

References 22 publications

Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer

Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer

PTEN, PIK3CA, p-AKT, and p-p70S6K Status

Original paper Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting

Contact Info

Product

Resources

About