Abstract
Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. 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. 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 9.8months 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). 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. This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).
Highlights
Breast cancer is one of the most common malignancies for women
We aimed to explore the utility of Circulating tumor DNA (ctDNA) to evaluate the efficacy and prognosis of neoadjuvant chemotherapy for breast cancer
23 patients were excluded because they were ineligible for neoadjuvant chemotherapy
Summary
Breast cancer is one of the most common malignancies for women. According to 2018 global cancer statistics, over 2 million patients were diagnosed as having breast cancer and 630,000 died of the disease worldwide[1]. Neoadjuvant chemotherapy (NCT) is a useful treatment for locally advanced breast cancer (LABC) to downstage and render inoperable disease operable[2]. The efficacy evaluation of NCT has not yet been well developed. Because distant relapse is the major cause of cancer death[7, 8], more effective diagnostic tools that stratify patients by distant recurrence risk would be of great clinical significance to deliver personalized healthcare. The development of novel markers with high prognostic and predictive performance for postoperative relapse risk are crucial to further facilitate clinical decision-making. Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer
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