The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We analyzed a genome-wide methylation array in Taiwanese and The Cancer Genome Atlas (TCGA) breast cancer (BC) patients. Most breast cancer-specific circulating methylated CCDC181, GCM2 and ITPRIPL1 biomarkers were found in the plasma. An automatic analysis process of methylated ccfDNA was established. A combined analysis of CCDC181, GCM2 and ITPRIPL1 (CGIm) was performed in R using Recursive Partitioning and Regression Trees to establish a new prediction model. Combined analysis of CCDC181, GCM2 and ITPRIPL1 (CGIm) was found to have a sensitivity level of 97% and an area under the curve (AUC) of 0.955 in the training set, and a sensitivity level of 100% and an AUC of 0.961 in the test set. The circulating methylated CCDC181, GCM2 and ITPRIPL1 was also significantly decreased after surgery (all p < 0.001). The aberrant methylation patterns of the CCDC181, GCM2 and ITPRIPL1 genes means that they are potential biomarkers for the detection of early BC and can be combined with breast imaging data to achieve higher accuracy, sensitivity and specificity, facilitating breast cancer detection. They may also be applied to monitor the surgical treatment response.

Background: Endoscopy-assisted total mastectomy has been used for surgical intervention of breast cancer patients; however, large cohort studies with long-term follow-up data are lacking. Methods: Breast cancer patients who underwent endoscopy-assisted total mastectomy from May of 2009 to March of 2018 were collected prospectively from multiple centers. Clinical outcome, impact of different phases, oncologic results, and patient-reported aesthetic outcomes of endoscopy-assisted total mastectomy were reported. Results: A total of 436 endoscopy-assisted total mastectomy procedures were performed; 355 (81.4 percent) were nipple-sparing mastectomy, and 81 (18.6 percent) were skin-sparing mastectomy. Three hundred fourteen (75.4 percent) of the procedures were associated with immediate breast reconstruction; 255 were prosthesis based and 59 were associated with autologous flaps. The positive surgical margin rate for endoscopy-assisted total mastectomy was 2.1 percent. In morbidity evaluation, there were 19 cases (5.4 percent) with partial nipple necrosis, two cases (0.6 percent) with total nipple necrosis, and three cases (0.7 percent) with implant loss. Compared with the early phase, surgeons operating on patients in the middle or late phase had significantly decreased operation time and blood loss. With regard to patient-reported cosmetic outcomes, approximately 94.4 percent were satisfied with the aesthetic results. Patients who underwent breast reconstruction with preservation of the nipple had higher satisfaction rates. Over a median follow-up of 54.1 ± 22.4 months, there were 14 cases of locoregional recurrence (3.2 percent), three distant metastases (0.7 percent), and one mortality (0.2 percent). Conclusion: This multicenter study showed that endoscopy-assisted total mastectomy is a reliable surgical intervention for early breast cancer, with high patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.