Circulating methylated HOXA9 tumor DNA as a biomarker for mortality in recurrent breast cancer: An exploratory study

Methylated homeobox A9 (meth-<i>HOXA9</i>) circulating tumor DNA may be a relevant biomarker in breast cancer, although its clinical significance remains unknown. The present exploratory study aimed to investigate the association between meth-<i>HOXA9</i> and mortality in patients with recurrent breast cancer. The cohort study enrolled 51 patients with breast cancer recurrence from the Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark (Vejle, Denmark). Tissue samples from primary surgery and biopsies, and plasma samples obtained at the time of recurrence were analyzed for meth-<i>HOXA9</i> using a methylation-specific droplet digital polymerase chain reaction. Using Cox regression, hazard ratios (HRs) for mortality with 95% confidence intervals (CIs) comparing patients with detectable and undetectable meth-<i>HOXA9</i> in both tumor tissue and plasma were estimated. Among the 50 patients with data on tumor tissue meth-<i>HOXA9</i>, there was no association between meth-<i>HOXA9</i> in the primary tumor and mortality (HR 1.09, 95% CI 0.47-2.52). A total of 34 patients had data on plasma meth-<i>HOXA9</i> at the time of recurrence. Detectable plasma meth-<i>HOXA9</i> was associated with higher mortality (HR 3.95, 95% CI 1.50-10.37). Among the 20 patients with data on both plasma and metastatic tissue meth-<i>HOXA9</i>, meth-<i>HOXA9</i> was detectable in 90% of metastases and 65% of plasma samples. In conclusion, detectable plasma meth-<i>HOXA9</i> was significantly associated with higher mortality in recurrent breast cancer; therefore, plasma meth-<i>HOXA9</i> may prove useful as a prognostic marker in patients with breast cancer.