Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• NPJ breast cancer, 2022-05, Vol.8 (1), p.64-64, Article 64

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.