Molecular relapse detection in early stage breast cancer

Breast cancer is the most frequently diagnosed cancer worldwide and in women the second most common cause of cancer death with approximately 95% of women with breast cancer presenting with early stage, primary breast cancer without macroscopic evidence of metastatic disease. Advances in diagnosis and treatment have resulted in substantial improvement in disease free survival in the last few decades but there is substantial need to develop better tools to establish who is at risk of relapse after primary treatment. Detecting which patients have minimal residual disease (MRD) that has not been eradicated by treatment would allow clinical trials of adjuvant therapies to prevent relapse focused on those who are at highest risk.

In blood malignancies, molecular-based testing to identify molecular residual disease (MRD), to assess for leukemic disease below levels identifiable by morphological changes, has become increasingly routine across different subsets of lymphoid and myeloid neoplasms. For patients with solid tumors, circulating tumor DNA (ctDNA) derived from the tumor can be detected in a high proportion of patients with advanced cancer, as well as patients presenting with primary cancer. Several small proof-of-principle studies have also shown that detection of ctDNA may present a strategy to identify MRD, with detection of ctDNA anticipating future relapse with high accuracy in patients with breast, colon and lung cancer.

Here, I will present our latest data to assess the clinical validity of MRD detection in a large prospective, multi-center series of patients with primary breast cancer. We demonstrate that analysis of ctDNA can be employed to detect MRD in breast cancer, and that MRD detection can accurately identify those patients that are at high risk of early relapse. We investigate the factors that associate with detection of ctDNA, and identify ‘dark’ sites of metastasis that may be missed by ctDNA MRD analysis.