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Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.

Koutras AK, Kalogeras KT, Dimopoulos MA, Wirtz RM, Dafni U, Briasoulis E, Pectasides D, Gogas H, Christodoulou C, Aravantinos G, Zografos G, Timotheadou E, Papakostas P, Linardou H, Razis E, Economopoulos T, Kalofonos HP, Fountzilas G, Hellenic Cooperative Oncology Group (HeCO - Br. J. Cancer (2008)

Bottom Line: At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS).These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer.However, HER2 mRNA expression did not predict clinical benefit from paclitaxel.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece. angkoutr@otenet.gr

ABSTRACT
The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT-PCR). The overall concordance between kRT-PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT-PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.

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Related in: MedlinePlus

Distribution of breast carcinoma specimens according to normalised expression of mRNA encoding for HER family receptors.
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fig1: Distribution of breast carcinoma specimens according to normalised expression of mRNA encoding for HER family receptors.

Mentions: The distribution of tumour samples according to the normalised expression of mRNA encoding for HER family receptors is shown in Figure 1. The median value for EGFR was 32.95 (range, 24.85–36.11), for HER2 35.56 (range, 30.32–40.98), for HER3 34.63 (range, 28.3–37.1), and for HER4 31.79 (range, 24.67–35.43).


Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.

Koutras AK, Kalogeras KT, Dimopoulos MA, Wirtz RM, Dafni U, Briasoulis E, Pectasides D, Gogas H, Christodoulou C, Aravantinos G, Zografos G, Timotheadou E, Papakostas P, Linardou H, Razis E, Economopoulos T, Kalofonos HP, Fountzilas G, Hellenic Cooperative Oncology Group (HeCO - Br. J. Cancer (2008)

Distribution of breast carcinoma specimens according to normalised expression of mRNA encoding for HER family receptors.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600696&req=5

fig1: Distribution of breast carcinoma specimens according to normalised expression of mRNA encoding for HER family receptors.
Mentions: The distribution of tumour samples according to the normalised expression of mRNA encoding for HER family receptors is shown in Figure 1. The median value for EGFR was 32.95 (range, 24.85–36.11), for HER2 35.56 (range, 30.32–40.98), for HER3 34.63 (range, 28.3–37.1), and for HER4 31.79 (range, 24.67–35.43).

Bottom Line: At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS).These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer.However, HER2 mRNA expression did not predict clinical benefit from paclitaxel.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece. angkoutr@otenet.gr

ABSTRACT
The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT-PCR). The overall concordance between kRT-PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT-PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.

Show MeSH
Related in: MedlinePlus