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Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial

Open access
Jiang, Yi-Zhou, Liu, Yin, Xiao, Yi, Hu, Xin, Jiang, Lin, Zuo, Wen-Jia, Ma, Ding, Ding, Jiahan, Zhu, Xiaoyu, Zou, Jianjun, Verschraegen, Claire, Stover, Daniel G., Kaklamani, Virginia, Wang, Zhong-Hua, Shao, Zhi-Ming·2021·Cell Research

Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, and molecular subtyping may result in improved diagnostic precision and targeted therapies. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we conducted the FUTURE trial (ClinicalTrials.gov identifier: NCT03805399), a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial, to evaluate the efficacy of these targets. Patients with refractory metastatic TNBC were enrolled and stratified by TNBC subtypes and genomic biomarkers, and assigned to one of these seven arms: (A) pyrotinib with capecitabine, (B) androgen receptor inhibitor with CDK4/6 inhibitor, (C) anti PD-1 with nab-paclitaxel, (D) PARP inhibitor included, (E) and (F) anti-VEGFR included, or (G) mTOR inhibitor with nab-paclitaxel. The primary end point was the objective response rate (ORR). We enrolled 69 refractory metastatic TNBC patients with a median of three previous lines of therapy (range, 1–8). Objective response was achieved in 20 (29.0%, 95% confidence interval (CI): 18.7%–41.2%) of the 69 intention-to-treat (ITT) patients. Our results showed that immunotherapy (arm C), in particular, achieved the highest ORR (52.6%, 95% CI: 28.9%–75.6%) in the ITT population. Arm E demonstrated favorable ORR (26.1%, 95% CI: 10.2%–48.4% in the ITT population) but with more high grade (≥ 3) adverse events. Somatic mutations of TOP2A and CD8 immunohistochemical score may have the potential to predict immunotherapy response in the immunomodulatory subtype of TNBC. In conclusion, the phase Ib/II FUTURE trial suggested a new concept for TNBC treatment, demonstrating the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC.

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Metadata

Authors
Jiang, Y.-Z., Liu, Y., Xiao, Y., Hu, X., Jiang, L., Zuo, W.-J., Ma, D., Ding, J., Zhu, X., Zou, J., Verschraegen, C., Stover, D. G., Kaklamani, V., Wang, Z.-H., & Shao, Z.-M.
Venue
Cell Research
Published
2020-07-27
Volume
31
Issue
2
Pages
178-186
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
OpenAlex
W3044428842
Cited by
298
References
51
FWCI
11.36
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial. https://app.cochat.ai/papers/10.1038/s41422-020-0375-9
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Jiang, Y.-Z., Liu, Y., Xiao, Y., Hu, X., Jiang, L., Zuo, W.-J., Ma, D., Ding, J., Zhu, X., Zou, J., Verschraegen, C., Stover, D. G., Kaklamani, V., Wang, Z.-H., & Shao, Z.-M. (2021). Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial. Cell Research. https://doi.org/10.1038/s41422-020-0375-9

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