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Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer

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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).

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Yidong Zhou, Yaping Xu and Changjun Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China

    Yidong Zhou, Changjun Wang, Ru Yao, Peng Li & Qiang Sun

  2. Geneplus-Beijing, Beijing, 102206, China

    Yaping Xu, Yuhua Gong, Yanyan Zhang, Xiuli Zhu, Jing Bai, Yanfang Guan, Xuefeng Xia, Ling Yang & Xin Yi

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  1. Yidong Zhou
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Contributions

Totally 14 authors are listed in manuscript. YZ and YX are the main experimental designers and writers; CW, RY and LP have assisted the management of patients and collection of samples; YG, YZ, XZ and JB helped data arrangement and analysis; YG, XX, LY and XYoffered constructive suggestion for study design and analytical methods.

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Correspondence to Yidong Zhou or Qiang Sun.

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Zhou, Y., Xu, Y., Wang, C. et al. Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 188, 661–673 (2021). https://doi.org/10.1007/s10549-021-06247-y

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