Yidong Zhou1, Yaping Xu2, Changjun Wang3, Yuhua Gong2, Yanyan Zhang2, Ru Yao3, Peng Li3, Xiuli Zhu2, Jing Bai2, Yanfang Guan2, Xuefeng Xia2, Ling Yang2, Xin Yi2, Qiang Sun4. 1. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China. zhouydpumch@163.com. 2. Geneplus-Beijing, Beijing, 102206, China. 3. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China. 4. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China. sunqiangpumch@sina.com.
Abstract
BACKGROUND: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. METHODS: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1021-gene panel. RESULTS: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, 1 versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904-290.9; p < 0.0001). CONCLUSIONS: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient recurrence. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome. TRIAL REGISTRATION: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).
BACKGROUND: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. METHODS: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1021-gene panel. RESULTS: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, 1 versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904-290.9; p < 0.0001). CONCLUSIONS: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient recurrence. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome. TRIAL REGISTRATION: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).
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