Tags

Type your tag names separated by a space and hit enter

Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401.
J Clin Oncol. 2006 Jun 01; 24(16):2428-36.JC

Abstract

PURPOSE

Amplification of the HER-2/neu and topoisomerase IIalpha (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting the outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial.

PATIENTS AND METHODS

The present substudy of the Scandinavian Breast Group trial 9401, in which an epirubicin-based regimen (nine courses of tailored and dose-escalated fluorouracil, epirubicin, and cyclophosphamide [FEC]) was compared with three or four courses of standard FEC followed by bone marrow-supported high-dose chemotherapy (cyclophosphamide, thiotepa, and carboplatin), included high-risk breast cancer patients (with eight or more positive axillary lymph nodes or at least five nodes with additional poor prognostic indicators). Amplification of HER-2/neu was determined retrospectively in paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. TOP2A was tested only in HER-2/neu-amplified tumors.

RESULTS

HER-2/neu amplification alone, which was present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free (P = .0034) and overall survival (P = .0008) but showed no direct association with treatment assignment. TOP2A coamplification, which was present in 37% of HER-2/neu-amplified tumors, was associated with better relapse-free survival in patients treated with tailored and dose-escalated FEC (hazard ratio [HR] = 0.45; P = .049). A statistical multivariate Cox's regression analysis confirmed the predictive significance of TOP2A coamplification (HR = 0.30; P = .020) in HER-2/neu-amplified tumors. There was no such association in patients with HER-2/neu-amplified tumors without TOP2A gene amplification.

CONCLUSION

Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines.

Authors+Show Affiliations

Laboratory of Cancer Biology, Institute of Medical Technology, and Department of Oncology, Tampere University and Tampere University Hospital, Tampere, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16682728

Citation

Scandinavian Breast Group Trial 9401, et al. "Topoisomerase IIalpha Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-escalated Anthracycline-based Adjuvant Chemotherapy in HER-2/neu-amplified Breast Cancer: Scandinavian Breast Group Trial 9401." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 24, no. 16, 2006, pp. 2428-36.
Scandinavian Breast Group Trial 9401, Tanner M, Isola J, et al. Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol. 2006;24(16):2428-36.
Tanner, M., Isola, J., Wiklund, T., Erikstein, B., Kellokumpu-Lehtinen, P., Malmström, P., Wilking, N., Nilsson, J., & Bergh, J. (2006). Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 24(16), 2428-36.
Scandinavian Breast Group Trial 9401, et al. Topoisomerase IIalpha Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-escalated Anthracycline-based Adjuvant Chemotherapy in HER-2/neu-amplified Breast Cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol. 2006 Jun 1;24(16):2428-36. PubMed PMID: 16682728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. AU - ,, AU - Tanner,Minna, AU - Isola,Jorma, AU - Wiklund,Tom, AU - Erikstein,Björn, AU - Kellokumpu-Lehtinen,Pirkko, AU - Malmström,Per, AU - Wilking,Nils, AU - Nilsson,Jonas, AU - Bergh,Jonas, Y1 - 2006/05/08/ PY - 2006/5/10/pubmed PY - 2006/6/13/medline PY - 2006/5/10/entrez SP - 2428 EP - 36 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J Clin Oncol VL - 24 IS - 16 N2 - PURPOSE: Amplification of the HER-2/neu and topoisomerase IIalpha (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting the outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial. PATIENTS AND METHODS: The present substudy of the Scandinavian Breast Group trial 9401, in which an epirubicin-based regimen (nine courses of tailored and dose-escalated fluorouracil, epirubicin, and cyclophosphamide [FEC]) was compared with three or four courses of standard FEC followed by bone marrow-supported high-dose chemotherapy (cyclophosphamide, thiotepa, and carboplatin), included high-risk breast cancer patients (with eight or more positive axillary lymph nodes or at least five nodes with additional poor prognostic indicators). Amplification of HER-2/neu was determined retrospectively in paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. TOP2A was tested only in HER-2/neu-amplified tumors. RESULTS: HER-2/neu amplification alone, which was present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free (P = .0034) and overall survival (P = .0008) but showed no direct association with treatment assignment. TOP2A coamplification, which was present in 37% of HER-2/neu-amplified tumors, was associated with better relapse-free survival in patients treated with tailored and dose-escalated FEC (hazard ratio [HR] = 0.45; P = .049). A statistical multivariate Cox's regression analysis confirmed the predictive significance of TOP2A coamplification (HR = 0.30; P = .020) in HER-2/neu-amplified tumors. There was no such association in patients with HER-2/neu-amplified tumors without TOP2A gene amplification. CONCLUSION: Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/16682728/Topoisomerase_IIalpha_gene_amplification_predicts_favorable_treatment_response_to_tailored_and_dose_escalated_anthracycline_based_adjuvant_chemotherapy_in_HER_2/neu_amplified_breast_cancer:_Scandinavian_Breast_Group_Trial_9401_ L2 - https://ascopubs.org/doi/10.1200/JCO.2005.02.9264?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -