Advancements in breast cancer progression monitoring: Analysis of methylated circulating cell- free DNA.

person Chin-Sheng Hung Taipei Medical University Hospital, Taipei, Taiwan info_outline Chin-Sheng Hung, Ruo-Kai Lin

Authors person Chin-Sheng Hung Taipei Medical University Hospital, Taipei, Taiwan info_outline Chin-Sheng Hung, Ruo-Kai Lin Organizations Taipei Medical University Hospital, Taipei, Taiwan, Taipei Medical University, Taipei, Taiwan Abstract Disclosures Research Funding NSTC, Taiwan Background: Breast cancer is a leading cause of mortality among women, with a significant number developing metastasis. Existing markers like CA-153 and CEA have limited sensitivity. Circulating cell-free DNA (ccfDNA) in plasma can be used for the noninvasive sampling of cancer cells obtained from patients with breast cancer. Aberrant circulating methylated GCM2 and TMEM240 have been reported in patients with breast cancer. The study aims to evaluate the potential of simultaneous detection of methylated GCM2 and TMEM240 in plasma for enhanced prediction of residual disease and tumor progression. Methods: In a prospective study conducted in Taipei, Taiwan, we enrolled a total of 396 patients between 2016 and 2023. The retrospective study involving plasma samples from Western populations included a total of 134 samples. Utilizing the Monte Carlo replicates module within the R software, is employed to automate the random partitioning of 70% of the entire patient dataset into a training set, while the remaining 30% is assigned to the validation set. The model's performance, including sensitivity, specificity, accuracy, false positives, and false negatives, will be thoroughly assessed to ensure its robustness. Results: The test demonstrated an accuracy of 91.5%, a sensitivity of 95.7%, and a specificity of 90.3% for prediction of residual disease and tumor progression. CA15-3 and CEA markers show limited sensitivity (53.3% and 33.3%, respectively). The tests also assess the tumor burden dynamically through monitoring circulating methylated GCM2 and TMEM240 in plasma of patients with breast cancer following their treatment. Conclusions: The simultaneous detection of circulating methylated GCM2 and TMEM240 in plasma presents a novel and accurate noninvasive tool for predicting tumor progression. Clinical trial information: N201708049, N202105091, N202202061.