<i>HER2</i> Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer

Lee, Hee Jin; Seo, An Na; Kim, Eun Joo; Jang, Min Hye; Suh, Koung Jin; Ryu, Han Suk; Kim, Yu Jung; Kim, Jee Hyun; Im, Seock Ah; Gong, Gyungyub; Jung, Kyung Hae; Park, In Ae; Park, So Yeon

doi:10.1309/ajcpirl4guvgk3yx

Cited by 116 publications

(85 citation statements)

References 31 publications

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“…For example, discordant HER2 expression has been observed in the same biopsy from cancer patients54. This could be a major obstacle for conventional single-ligand targeted cancer therapy since subpopulations lacking expression of target receptors may repopulate the tumour after treatment.…”

Section: Discussionmentioning

confidence: 99%

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Burnouf

Chuang

et al. 2017

Nat Commun

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Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Burnouf

Chuang

et al. 2017

Nat Commun

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“…Studies of HER2 genetic heterogeneity in breast cancer generated inconsistent findings. Lee et al found out that the heterogeneity was a negative predictor of trastuzumab response [13, 27]. However, Gullo et al reported findings to the contrary [28].…”

Section: Discussionmentioning

confidence: 99%

Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type

Jiang

et al. 2017

Oncotarget

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IntroductionFactors affecting trastuzumab efficacy in advanced gastric cancer (GC) are largely unknown. Heterogeneity is a notable feature of HER2 in GC. Whether the heterogeneity influences trastuzumab efficacy is still unknown.ResultsThe HER2homogeneous group and HER2heterogeneous group showed no statistical difference in RR (46.4% vs 55.0%, P = 0.558), PFS (5.80 vs 6.30 months, P = 0.804) and OS (16.00 vs 16.00 months, P = 0.787). The Laurenintestinal group and Laurennon-intestinal group demonstrated no discrepancy in PFS (6.00 vs 6.00 months, P = 0.912) and OS (16.50 vs 14.00 months, P = 0.227). However, by combining HER2 heterogeneity and Lauren classification, PFS and OS of HER2homogeneous/Laurennon-intestinal subgroup was the shortest among the 4 subgroups (P = 0.012 and P = 0.037), which was much shorter than the other patients (PFS:3.00 vs 6.30 months, P = 0.003; OS: 4.50 vs 16.50 months, P = 0.004). Univariate and multivariate analysis showed that HER2 heterogeneity combined with Lauren classification was an independent prognostic factor in both PFS (P = 0.031 and P = 0.002) and OS (P = 0.039 and P = 0.013).Materials and Methods48 patients with HER2 positive advanced GCs accepting trastuzumab treatment were retrospectively analyzed. Based on HER2 heterogeneity, the patients were divided into a HER2homogeneous group and a HER2heterogeneous group. Response rate (RR), progression free survival (PFS), and overall survival (OS) were compared. Main clinicopathological factors including Lauren classification were subjected to subgroup analysis.ConclusionsHER2 heterogeneity alone may not correlate with trastuzumab efficacy in HER2 positive advanced GCs. HER2 heterogeneity combined with Lauren classification may help to identify a subgroup with poor response to trastuzumab which is homogeneous HER2 positive and non-intestinal type.

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“…HER2 is a therapeutic target in several tumors such as breast cancer (29)(30)(31)(32), and a predictive factor of response to chemotherapy in various solid malignancies (33)(34)(35)(36). In order to identify improved prognostic indicators for ESCC, the Table I.…”

Section: Discussionmentioning

confidence: 99%

Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

Yong¹,

Zhu²,

Xu³

et al. 2015

Oncology Letters

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Abstract. Esophageal squamous cell carcinoma (ESCC)is the eighth most frequent neoplasm in China. However, the expression levels of human epidermal growth factor receptor 2 (HER2) and multidrug resistance protein 1 (MRP1) in patients with ESCC remain to be determined. In the present study, 829 ESCC cases were evaluated using immunohistochemistry. The association between the expression levels of HER2 and MRP1 and the patient's clinicopathological factors was analyzed using Fisher's exact test or χ 2 test. Univariate analysis was performed via Kaplan-Meier survival curves, while the Cox proportional hazard model was used for multivariate analysis. A significant correlation was observed between the expression levels of HER2 and the patient's gender (P<0.050), tumor size (P=0.013) and venous/lymphatic invasion (P= 0.039). However, no significant correlation was identified between the expression levels of MRP1 and the clinicopathological factors of the patients. In univariate analysis, gender, differentiation, depth of invasion, clinical stage, adjuvant radiotherapy or chemotherapy and lymph node metastasis were significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients with ESCC (P<0.050). The graphical representation of the Kaplan-Meier estimate curves suggested that the expression levels of HER2 or MRP1 did not exert any influence on prognosis (log-rank test, P>0.050). In multivariate analysis, tumor location, gender, clinical stage, differentiation and lymph node metastasis were identified as independent factors of prognosis in patients with ESCC (P<0.050). However, the expression levels of HER2 or MRP1 were not independently associated with PFS or OS in these patients. In conclusion, the present large-scale study demonstrates that the protein expression levels of HER2 and MRP1 does not exert any influence on the prognosis of ESCC.

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HER2 Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer

Abstract: These results suggest that accurate assessment of HER2 status, including HER2 heterogeneity, is important in predicting trastuzumab responses and outcomes in patients with HER2-positive metastatic breast cancer.

Cited by 116 publications

References 31 publications

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type

Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

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