Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study

Official Title

Determinants of Acquired Endocrine Resistance in Metastatic Breast Cancer: A Pilot Study

Summary:

This is a single-centre prospective study involving analysis of circulating tumour DNA (ctDNA) and the gut microbiome in patients with metastatic breast cancer on standard of care endocrine therapy with an aromatase inhibitor in combination with an inhibitor of the cyclin-dependent kinases 4 and 6 (CDK 4/6). Up to 20 patients with Estrogen Receptor positive (ER+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0-1 will be enrolled. This study involves the collection and analysis of patient samples and does not involve therapeutic intervention.

Trial Description

Primary Outcome:

• Time to treatment failure

Secondary Outcome:

• Correlation between specific mutations in ctDNA and in archival tissue samples (where available from prior testing) with time to treatment failure
• Diversity and composition of the gut microbiome in patients with ER+ HER2- metastatic breast cancer
• Dietary factors and composition of the gut microbiome
• Overall survival

Endocrine therapies have been associated with an overall survival benefit in breast cancer and are the preferred initial treatment approach in patients with ER+, HER2- metastatic breast cancer. Unfortunately, resistance to endocrine therapies eventually develops in the metastatic setting and metastatic breast cancer remains an incurable disease. Endocrine resistance may develop as a result of alterations in estrogen signaling and metabolism pathways, which may be modulated by gut bacteria. In addition, genomic profiling of archival tissues and circulating tumour DNA (ctDNA) in ER+ breast cancer has identified multiple somatic molecular alterations that may mediate response to endocrine therapies. This study is designed to identify markers of endocrine resistance in ctDNA and the gut microbiome in patients with ER+ HER2- metastatic breast cancer.

View this trial on ClinicalTrials.gov