Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting

Anna Di Benedetto, Cristiana Ercolani, Laura Pizzuti, Domenico Angelucci, Domenico Sergi, Camilla Marinelli, Laura Iezzi, Francesca Sperati, Irene Terrenato, Marco Mazzotta, Luciano Mariani, Enrico Vizza, Giancarlo Paoletti, Silverio Tomao, Marcello Maugeri-Saccà, Maddalena Barba, Nicola Tinari, Clara Natoli, Gennaro Ciliberto, Antonino GrassadoniaPatrizia Vici

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT). Methods: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered. Results: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both). Conclusions: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.

Original languageEnglish
JournalTherapeutic Advances in Medical Oncology
Volume11
DOIs
Publication statusPublished - Aug 1 2019

Keywords

  • DNA damage and repair
  • elderly patients
  • hormone-receptor-positive breast cancer
  • neoadjuvant hormone therapy
  • prognostic biomarkers

ASJC Scopus subject areas

  • Oncology

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