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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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OS (A1 and A2) and DFS (B1 and B2) for patients treated with (red line) or without (blue line) paclitaxel, according to HER2 mRNA expression. A1 and B1 (HER2 <median): 55 (41%) E-T-CMF and 79 (59%) E-CMF-treated patients. A2 and B2 (HER2⩾median): 62 (46%) E-T-CMF and 72 (54%) E-CMF-treated patients.
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fig3: OS (A1 and A2) and DFS (B1 and B2) for patients treated with (red line) or without (blue line) paclitaxel, according to HER2 mRNA expression. A1 and B1 (HER2 <median): 55 (41%) E-T-CMF and 79 (59%) E-CMF-treated patients. A2 and B2 (HER2⩾median): 62 (46%) E-T-CMF and 72 (54%) E-CMF-treated patients.

Mentions: The interaction between mRNA expression of HER2 and the addition of paclitaxel was not significant for OS (P=0.778). The HR for death in paclitaxel containing chemotherapy (E-T-CMF) among HER2-positive patients was 1.12 (95% CI: 0.60–2.11). With respect to the DFS, the interaction was also non-significant (P=0.976). Among HER2-positive cases the HR for recurrence of the paclitaxel containing treatment (E-T-CMF) was 1.05 (95% CI: 0.61–1.81) (Figure 3). In the subgroup of ER-positive patients, the interaction of HER2 mRNA expression and paclitaxel was still non-significant (P=0.952 and P=0.860 for OS and DFS, respectively). Similarly, the interaction of HER2 mRNA expression and paclitaxel was not found to be significant in the subgroup of ER-negative patients (P=0.408 for OS and P=0.654 for DFS). In addition, mRNA expression of EGFR, HER3 and HER4 was not predictive for benefit from adjuvant treatment with paclitaxel, neither for OS nor for DFS (data not shown).


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)

OS (A1 and A2) and DFS (B1 and B2) for patients treated with (red line) or without (blue line) paclitaxel, according to HER2 mRNA expression. A1 and B1 (HER2 <median): 55 (41%) E-T-CMF and 79 (59%) E-CMF-treated patients. A2 and B2 (HER2⩾median): 62 (46%) E-T-CMF and 72 (54%) E-CMF-treated patients.
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Related In: Results  -  Collection

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

fig3: OS (A1 and A2) and DFS (B1 and B2) for patients treated with (red line) or without (blue line) paclitaxel, according to HER2 mRNA expression. A1 and B1 (HER2 <median): 55 (41%) E-T-CMF and 79 (59%) E-CMF-treated patients. A2 and B2 (HER2⩾median): 62 (46%) E-T-CMF and 72 (54%) E-CMF-treated patients.
Mentions: The interaction between mRNA expression of HER2 and the addition of paclitaxel was not significant for OS (P=0.778). The HR for death in paclitaxel containing chemotherapy (E-T-CMF) among HER2-positive patients was 1.12 (95% CI: 0.60–2.11). With respect to the DFS, the interaction was also non-significant (P=0.976). Among HER2-positive cases the HR for recurrence of the paclitaxel containing treatment (E-T-CMF) was 1.05 (95% CI: 0.61–1.81) (Figure 3). In the subgroup of ER-positive patients, the interaction of HER2 mRNA expression and paclitaxel was still non-significant (P=0.952 and P=0.860 for OS and DFS, respectively). Similarly, the interaction of HER2 mRNA expression and paclitaxel was not found to be significant in the subgroup of ER-negative patients (P=0.408 for OS and P=0.654 for DFS). In addition, mRNA expression of EGFR, HER3 and HER4 was not predictive for benefit from adjuvant treatment with paclitaxel, neither for OS nor for DFS (data not shown).

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