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The Pathological Response to Anthracycline is Associated with Topoisomerase IIα Gene Amplification in the HER2 Breast

Takashi Ishikawa1, Takeshi Sasaki1, Mikiko Tanabe1

  • 1Department of Breast Surgery, Tokyo Medical University (TI); Departments of Breast and Thyroid Surgery (TI, KN, KK, KS, DS, AY), Pathology (TS, MT, KK) and Biostatistics and Epidemiology (SM, MSO), Yokohama City University Medical Center, Yokohama, Japan; Department of Gastrointestinal Surgery and Clinical Oncology, Yokohama City University, Yokohama, Japan (YI, IE); and Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA, USA (KT).

Journal of Surgery and Science
|February 3, 2015
PubMed
Abstract

Insights

Topoisomerase IIα (TOP2A) amplification predicts response to anthracycline chemotherapy in HER2-positive breast cancer patients receiving neoadjuvant treatment. This finding suggests TOP2A amplification can guide treatment selection for this subtype.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • HER2-positive breast cancer exhibits enhanced sensitivity to anthracyclines when topoisomerase IIα (TOP2A) is co-amplified.
  • This association is established in adjuvant and metastatic settings.
  • The relationship in neoadjuvant settings remains unexplored.

Purpose of the Study:

  • To investigate the association between TOP2A amplification and anthracycline sensitivity in HER2-positive breast cancer patients undergoing neoadjuvant chemotherapy.
  • To determine if TOP2A amplification can predict pathological response to anthracycline-based neoadjuvant regimens.

Main Methods:

  • Analysis of TOP2A gene status using Fluorescence In Situ Hybridization (FISH).
  • Biopsies were obtained from 18 patients treated with anthracycline and cyclophosphamide prior to surgery.
  • Correlation of TOP2A gene status with pathological response.

Main Results:

  • TOP2A gene amplification was observed in 6 out of 17 evaluable patients.
  • A significant association was found between TOP2A amplification and pathological response to the neoadjuvant chemotherapy regimen.

Conclusions:

  • TOP2A amplification serves as a predictive biomarker for anthracycline sensitivity in HER2-positive breast cancer.
  • The HER2/TOP2A co-amplified subtype may benefit from anthracycline-containing neoadjuvant regimens as a standalone treatment.
Keywords:
Breast CancerFISHHER2NeoadjuvantPredictive factorTOP2A

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