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

被引：65

作者：

Gori, S. ^{[1
]}

Sidoni, A. ^{[2
]}

Colozza, M. ^{[1
]}

Ferri, I. ^{[2
]}

Mameli, M. G. ^{[2
]}

Fenocchio, D. ^{[3
]}

Stocchi, L. ^{[1
]}

Foglietta, J. ^{[1
]}

Ludovini, V. ^{[1
]}

Minenza, E. ^{[1
]}

De Angelis, V. ^{[4
]}

Crino, L. ^{[1
]}

机构：

[1] Azienda Osped, Div Med Oncol, I-06122 Perugia, Italy

[2] Univ Perugia, Inst Pathol Anat & Histol, I-06100 Perugia, Italy

[3] Azienda Osped, Pathol Anat & Histol Serv, I-06122 Perugia, Italy

[4] Palliat Care Serv, Perugino ASL2, Perugia, Italy

来源：

ANNALS OF ONCOLOGY | 2009年 / 20卷 / 04期

关键词：

breast cancer; EGFR; pAkt; pMAPK; PTEN; trastuzumab; GROWTH-FACTOR RECEPTOR; PROTEIN EXPRESSION; 1ST-LINE TREATMENT; RESISTANCE; SURVIVAL; GENE; CONTRIBUTES; EFFICACY; SAFETY; HER2;

D O I：

10.1093/annonc/mdn681

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: In an attempt to identify markers of resistance to trastuzumab, we evaluated both the profiling of human epidermal growth factor receptor 2 (HER2)-positive tumor cells measuring the relative levels of EGFR, pMAPK, pAkt and PTEN and their correlations with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab. Patients and methods: Tumor tissues for this retrospective analysis were available from 45 out of 76 patients with metastatic breast cancer treated from April 1999 to March 2006 with trastuzumab-based therapy at our Institution. Evaluations of EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry (IHC) were carried out on all 45 tissue samples and their correlations with response to trastuzumab, incidence of central nervous system (CNS) metastases, time to progression (TTP), overall survival from diagnosis of breast cancer (OS1), from diagnosis of metastatic disease (OS2) and from the start of trastuzumab (OS3) were analyzed. Results: We observed that TTP (P = 0.001) and median OS2 and OS3 were significantly longer in patients responsive to trastuzumab-based regimen compared with nonresponsive patients. EGFR, pMAPK, pAkt and PTEN status by IHC were not significantly associated with response to trastuzumab, TTP, overall survival (OS1, OS2, OS3) and CNS metastases incidence. A trend for shorter OS3 was observed for pMAPK-positive patients compared with pMAPK-negative patients (22.8 versus 31.2 months; P = 0.076). Median OS1 resulted shorter in 22 pAkt-positive patients (69.8 months) compared with 23 pAkt-negative patients (108.2 months); P = 0.091. It is likely that high expression of pMAPK (pMAPK-positive status) or pAkt (pAkt-positive status) could identify a subgroup of HER2-positive tumors with high activity of proliferation and survival pathways and with resistance to trastuzumab. Conclusions: In HER2-positive metastatic breast cancers, EGFR, pMAPK, pAkt and PTEN status evaluated by IHC was not significantly associated with response to trastuzumab, TTP, OS and CNS metastases incidence. However, HER2 status determined by IHC and/or FISH assays may not be sufficient to predict response to trastuzumab-based therapy.

引用

页码：648 / 654

页数：7

共 23 条

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Epidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin-based neoadjuvant chemotherapy [J].