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Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer.

Toi M, Sperinde J, Huang W, Saji S, Winslow J, Jin X, Tan Y, Ohno S, Nakamura S, Iwata H, Masuda N, Aogi K, Morita S, Petropoulos C, Bates M - BMC Cancer (2010)

Bottom Line: Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Medicine, Kyoto University, Kyoto, Japan. toi@kuhp.kyoto-u.ac.jp

ABSTRACT

Background: We have recently described the correlation between quantitative measures of HER2 expression or HER2 homodimers by the HERmark assay and objective response (RR), time-to progression (TTP), and overall survival (OS) in an expanded access cohort of trastuzumab-treated HER2-positive patients with metastatic breast cancer (MBC) who were stringently selected by fluorescence in situ hybridization (FISH). Multivariate analyses suggested a continuum of HER2 expression that correlated with outcome following trastuzumab. Here we investigate the relationship between HER2 expression or HER2 homodimers and OS in a clinic-based population of patients with MBC selected primarily by IHC.

Methods: HERmark, a proximity-based assay designed to detect and quantitate protein expression and dimerization in formalin-fixed paraffin-embedded (FFPE) tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples from patients with MBC. Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.

Results: Initial analyses revealed a parabolic relationship between continuous measures of HER2 expression and risk of death, suggesting that the assumption of linearity for the HER2 expression measurements may be inappropriate in subsequent multivariate analyses. Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.

Conclusions: These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.

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Related in: MedlinePlus

Relationship between ICH results and HER mark measures of HER2. (a) Screening IHC results correlated with HER2 expression. (b) Repeat IHC results, all patients (compare to Figure S1).
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Figure 1: Relationship between ICH results and HER mark measures of HER2. (a) Screening IHC results correlated with HER2 expression. (b) Repeat IHC results, all patients (compare to Figure S1).

Mentions: In this cohort, we initially compared H2T to the screening IHC calls provided by the treating hospitals. The distribution of H2T measurements ranged over a 3-log dynamic range, and there was no significant difference between the H2T distributions of those samples scored as 2+ or 3+ by the screening IHC assays (Figure 1a). We repeated the IHC assays on all specimens. The repeat assays were performed centrally and read by a single pathologist. Approximately one-third of the specimens were scored as 0 or 1+ upon repeat. Comparison of the repeat IHC results with the HER2 expression levels by HERmark yielded a stair-step correlation (Figure 1b) reminiscent of previous comparisons with centralized IHC results (see Additional file 1, Figure S1).


Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer.

Toi M, Sperinde J, Huang W, Saji S, Winslow J, Jin X, Tan Y, Ohno S, Nakamura S, Iwata H, Masuda N, Aogi K, Morita S, Petropoulos C, Bates M - BMC Cancer (2010)

Relationship between ICH results and HER mark measures of HER2. (a) Screening IHC results correlated with HER2 expression. (b) Repeat IHC results, all patients (compare to Figure S1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837013&req=5

Figure 1: Relationship between ICH results and HER mark measures of HER2. (a) Screening IHC results correlated with HER2 expression. (b) Repeat IHC results, all patients (compare to Figure S1).
Mentions: In this cohort, we initially compared H2T to the screening IHC calls provided by the treating hospitals. The distribution of H2T measurements ranged over a 3-log dynamic range, and there was no significant difference between the H2T distributions of those samples scored as 2+ or 3+ by the screening IHC assays (Figure 1a). We repeated the IHC assays on all specimens. The repeat assays were performed centrally and read by a single pathologist. Approximately one-third of the specimens were scored as 0 or 1+ upon repeat. Comparison of the repeat IHC results with the HER2 expression levels by HERmark yielded a stair-step correlation (Figure 1b) reminiscent of previous comparisons with centralized IHC results (see Additional file 1, Figure S1).

Bottom Line: Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Medicine, Kyoto University, Kyoto, Japan. toi@kuhp.kyoto-u.ac.jp

ABSTRACT

Background: We have recently described the correlation between quantitative measures of HER2 expression or HER2 homodimers by the HERmark assay and objective response (RR), time-to progression (TTP), and overall survival (OS) in an expanded access cohort of trastuzumab-treated HER2-positive patients with metastatic breast cancer (MBC) who were stringently selected by fluorescence in situ hybridization (FISH). Multivariate analyses suggested a continuum of HER2 expression that correlated with outcome following trastuzumab. Here we investigate the relationship between HER2 expression or HER2 homodimers and OS in a clinic-based population of patients with MBC selected primarily by IHC.

Methods: HERmark, a proximity-based assay designed to detect and quantitate protein expression and dimerization in formalin-fixed paraffin-embedded (FFPE) tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples from patients with MBC. Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.

Results: Initial analyses revealed a parabolic relationship between continuous measures of HER2 expression and risk of death, suggesting that the assumption of linearity for the HER2 expression measurements may be inappropriate in subsequent multivariate analyses. Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.

Conclusions: These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.

Show MeSH
Related in: MedlinePlus