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. 2015 Jan 6;112(1):103-11.
doi: 10.1038/bjc.2014.556. Epub 2014 Oct 28.

Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer

H J Lee  1 , A N Seo  2 , E J Kim  2 , M H Jang  2 , Y J Kim  3 , J H Kim  3 , S-W Kim  4 , H S Ryu  5 , I A Park  5 , S-A Im  6 , G Gong  7 , K H Jung  8 , H J Kim  9 , S Y Park  10
Affiliations

Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer

H J Lee et al. Br J Cancer. .

Abstract

Background: Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.

Methods: We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.

Results: Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.

Conclusions: Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.

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Figures

Figure 1
Figure 1
EGFR fluorescence in situ hybridisation and EGFR immunohistochemistry. An example of EGFR amplification (A) showing strong (3+) EGFR overexpression (B). An example of EGFR high polysomy (C) showing strong (3+) but focal EGFR overexpression (D).
Figure 2
Figure 2
Disease-free and overall survival according to EGFR overexpression and EGFR copy number alteration in HER2-positive primary breast cancer. EGFR overexpression defined as 3+ (A) and EGFR overexpression defined as 2+ or more (B) were associated with poor disease-free survival, whereas high EGFR copy number (C) was not associated with disease-free survival. EGFR overexpression defined as 3+ (D) or as 2+ or more (E), or high EGFR copy number (F) was not associated with overall survival.
Figure 3
Figure 3
Disease-free and overall survival according to EGFR overexpression in HER2-positive primary breast cancer patients treated with adjuvant trastuzumab. EGFR overexpression defined as 3+ (A and C) and EGFR overexpression defined as 2+ or more (B and D) were associated with poor disease-free and overall survival.
Figure 4
Figure 4
Progression-free and overall survival according to EGFR expression in HER2-positive metastatic breast cancer. EGFR overexpression defined as 3+ (A) and 2+ or more (B) were not associated with progression-free survival. EGFR overexpression defined as 3+ (C) and 2+ or more (D) tends to be associated with decreased overall survival.
See this image and copyright information in PMC

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