An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing
ABSTRACT Background Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI‐RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early‐stage breast canc...
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Wiley
2025-06-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71004 |
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| author | Xianyu Zhang Yanling Yin Zhujia Ye Xingda Zhang Wei Wei Yi Hao Liuhong Zeng Ting Yang Dalin Li Jun Wang Dezhi Zhao Yanbo Chen Shan Lei Yongdong Jiang Youxue Zhang Shouping Xu Abiyasi Nanding Yajie Gong Siwei Li Yuanyuan Yu Shilu Zhao Siyu Liu Yashuang Zhao Zhiwei Chen Shihui Yu Jian‐Bing Fan Da Pang |
| author_facet | Xianyu Zhang Yanling Yin Zhujia Ye Xingda Zhang Wei Wei Yi Hao Liuhong Zeng Ting Yang Dalin Li Jun Wang Dezhi Zhao Yanbo Chen Shan Lei Yongdong Jiang Youxue Zhang Shouping Xu Abiyasi Nanding Yajie Gong Siwei Li Yuanyuan Yu Shilu Zhao Siyu Liu Yashuang Zhao Zhiwei Chen Shihui Yu Jian‐Bing Fan Da Pang |
| author_sort | Xianyu Zhang |
| collection | DOAJ |
| description | ABSTRACT Background Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI‐RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early‐stage breast cancer detection via circulating tumor DNA (ctDNA) methylation holds potential to bridge these diagnostic gaps. Methods We curated a breast cancer‐specific panel by harnessing methylation profiles from in‐house and public databases. Leveraging breast tissue‐plasma‐leukocyte samples, we identified breast cancer‐specific markers, culminating in a 103‐marker methylation model which underwent rigorous validation in two independent cohorts. To assess its performance, we compared it against the accuracy of ultrasonography, mammography, and CNB. Results The 103‐marker model exhibited remarkable proficiency in discerning benign from malignant breast tumors in plasma, with AUCs of 0.838, 0.838 and 0.823 in the validation set and two independent test sets, respectively. In BI‐RADS 4a breast cancer, when compared to ultrasonography or mammography, the model augmented breast cancer diagnostic accuracy by 40.58% and 25.49%, separately. Retrospective analyses suggested that our model achieved a sensitivity of 66.67% (4/6) and a specificity of 80.36% (45/56) for surgical patients in the BI‐RADS 4a category with tumors ≤ 10 mm, who did not undergo CNB, potentially sparing 45 benign patients from overtreatment. Notably, significant differences emerged in cancer scores between DCIS and invasive ductal carcinoma (p < 0.05). Higher cancer scores correlated with a more unfavorable prognosis (p < 0.05). Conclusions The 103‐marker methylation model demonstrates impressive performance in distinguishing between malignant and benign tumors, facilitating precise early diagnosis of BC, and holds promise as a prognostic tool. |
| format | Article |
| id | doaj-art-0f87597ee7ee4fa1b076cf6bf6383f2c |
| institution | Matheson Library |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-0f87597ee7ee4fa1b076cf6bf6383f2c2025-06-25T06:46:41ZengWileyCancer Medicine2045-76342025-06-011412n/an/a10.1002/cam4.71004An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation SequencingXianyu Zhang0Yanling Yin1Zhujia Ye2Xingda Zhang3Wei Wei4Yi Hao5Liuhong Zeng6Ting Yang7Dalin Li8Jun Wang9Dezhi Zhao10Yanbo Chen11Shan Lei12Yongdong Jiang13Youxue Zhang14Shouping Xu15Abiyasi Nanding16Yajie Gong17Siwei Li18Yuanyuan Yu19Shilu Zhao20Siyu Liu21Yashuang Zhao22Zhiwei Chen23Shihui Yu24Jian‐Bing Fan25Da Pang26Department of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Zhujiang Hospital, Southern Medical University Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Pathology Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaDepartment of Epidemiology Harbin Medical University Harbin ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaGuangzhou Kingmed Center for Clinical Laboratory Co., Ltd. Guangzhou ChinaAnchorDx Medical Co., Ltd. Guangzhou ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin ChinaABSTRACT Background Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI‐RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early‐stage breast cancer detection via circulating tumor DNA (ctDNA) methylation holds potential to bridge these diagnostic gaps. Methods We curated a breast cancer‐specific panel by harnessing methylation profiles from in‐house and public databases. Leveraging breast tissue‐plasma‐leukocyte samples, we identified breast cancer‐specific markers, culminating in a 103‐marker methylation model which underwent rigorous validation in two independent cohorts. To assess its performance, we compared it against the accuracy of ultrasonography, mammography, and CNB. Results The 103‐marker model exhibited remarkable proficiency in discerning benign from malignant breast tumors in plasma, with AUCs of 0.838, 0.838 and 0.823 in the validation set and two independent test sets, respectively. In BI‐RADS 4a breast cancer, when compared to ultrasonography or mammography, the model augmented breast cancer diagnostic accuracy by 40.58% and 25.49%, separately. Retrospective analyses suggested that our model achieved a sensitivity of 66.67% (4/6) and a specificity of 80.36% (45/56) for surgical patients in the BI‐RADS 4a category with tumors ≤ 10 mm, who did not undergo CNB, potentially sparing 45 benign patients from overtreatment. Notably, significant differences emerged in cancer scores between DCIS and invasive ductal carcinoma (p < 0.05). Higher cancer scores correlated with a more unfavorable prognosis (p < 0.05). Conclusions The 103‐marker methylation model demonstrates impressive performance in distinguishing between malignant and benign tumors, facilitating precise early diagnosis of BC, and holds promise as a prognostic tool.https://doi.org/10.1002/cam4.71004breast cancerbreast ultrasonographycore needle biopsyctDNAmammographymethylation |
| spellingShingle | Xianyu Zhang Yanling Yin Zhujia Ye Xingda Zhang Wei Wei Yi Hao Liuhong Zeng Ting Yang Dalin Li Jun Wang Dezhi Zhao Yanbo Chen Shan Lei Yongdong Jiang Youxue Zhang Shouping Xu Abiyasi Nanding Yajie Gong Siwei Li Yuanyuan Yu Shilu Zhao Siyu Liu Yashuang Zhao Zhiwei Chen Shihui Yu Jian‐Bing Fan Da Pang An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing Cancer Medicine breast cancer breast ultrasonography core needle biopsy ctDNA mammography methylation |
| title | An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing |
| title_full | An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing |
| title_fullStr | An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing |
| title_full_unstemmed | An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing |
| title_short | An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing |
| title_sort | approach for differential diagnosis of breast tumors by ctdna methylation sequencing |
| topic | breast cancer breast ultrasonography core needle biopsy ctDNA mammography methylation |
| url | https://doi.org/10.1002/cam4.71004 |
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