Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers

Xuan Liu, Zhongqi Ge, Fei Yang, Alejandro Contreras, Sanghoon Lee, Jason B. White, Yiling Lu, Marilyne Labrie, Banu K. Arun, Stacy L. Moulder, Gordon B. Mills, Helen Piwnica-Worms, Jennifer K. Litton, Jeffrey T. Chang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Germline mutations in BRCA1 or BRCA2 exist in ~2–7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy. We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature. These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.

Original languageEnglish (US)
Article number64
Journalnpj Breast Cancer
Issue number1
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)


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