Theranostics 2019; 9(17):4935-4945. doi:10.7150/thno.35730 This issue Cite

Research Paper

Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer

Shen Zhao*, Xi-Yu Liu*, Xi Jin*, Ding Ma, Yi Xiao, Zhi-Ming Shao, Yi-Zhou Jiang

Department of Breast Surgery, Fudan University Shanghai Cancer Center; Cancer Institute, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, P.R. China
*These authors contributed equally to this work

Citation:
Zhao S, Liu XY, Jin X, Ma D, Xiao Y, Shao ZM, Jiang YZ. Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer. Theranostics 2019; 9(17):4935-4945. doi:10.7150/thno.35730. https://www.thno.org/v09p4935.htm
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Abstract

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Background: Estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancers (triple-positive breast cancers, TPBCs) account for 5% to 10% of all breast cancers. The clinical and molecular features of TPBCs remain elusive. In this study, we aim to analyze the multiomics landscape and responsiveness of TPBCs to trastuzumab.

Methods: We employed five cohorts. The first cohort was from the Surveillance, Epidemiology, and End Results database (n=32,056) and was used to determine the clinical characteristics of TPBC. The second, third and fourth cohorts were from The Cancer Genome Atlas (n=162), GSE2603 (n=37) and GSE2109 (n=30) datasets, respectively, and were used to examine the genomic features and molecular classification of TPBC. The fifth cohort comprised TPBC patients treated at Fudan University Shanghai Cancer Center (FUSCC, n=171) and was used to investigate an immunohistochemistry-defined luminal A-like subgroup of TPBC.

Results: Patients with TPBC had a significantly better prognosis than those with ER-PR-HER2+ breast cancer. Genomic analysis revealed that TPBCs showed a lower TP53 mutation rate (30% vs. 69%, P < 0.001) and lower levels of HER2 mRNA and protein expression than ER-PR-HER2+ breast cancers. More than 40% of TPBCs were classified as the luminal A intrinsic subtype, with an even lower HER2 expression level. Based on the immunohistochemical detection of CDCA8, BCL2 and STC2, we identified a luminal A-like subgroup of TPBCs in the FUSCC cohort (CDCA8-negative, BCL2- and/or STC2-positive). Patients with luminal A-like TPBC had a better prognosis and benefited less from trastuzumab than those with TPBC of other subtypes.

Conclusions: TPBCs consist of clinically and genomically heterogeneous subgroups that may require different therapeutic strategies. The luminal A-like subgroup of TPBCs is associated with a better prognosis and reduced benefit from trastuzumab.

Keywords: triple-positive breast cancer, multiomics, molecular classification, luminal A, trastuzumab


Citation styles

APA
Zhao, S., Liu, X.Y., Jin, X., Ma, D., Xiao, Y., Shao, Z.M., Jiang, Y.Z. (2019). Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer. Theranostics, 9(17), 4935-4945. https://doi.org/10.7150/thno.35730.

ACS
Zhao, S.; Liu, X.Y.; Jin, X.; Ma, D.; Xiao, Y.; Shao, Z.M.; Jiang, Y.Z. Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer. Theranostics 2019, 9 (17), 4935-4945. DOI: 10.7150/thno.35730.

NLM
Zhao S, Liu XY, Jin X, Ma D, Xiao Y, Shao ZM, Jiang YZ. Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer. Theranostics 2019; 9(17):4935-4945. doi:10.7150/thno.35730. https://www.thno.org/v09p4935.htm

CSE
Zhao S, Liu XY, Jin X, Ma D, Xiao Y, Shao ZM, Jiang YZ. 2019. Molecular portraits and trastuzumab responsiveness of estrogen receptor-positive, progesterone receptor-positive, and HER2-positive breast cancer. Theranostics. 9(17):4935-4945.

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