Tags

Type your tag names separated by a space and hit enter

Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer.
Theranostics. 2018; 8(22):6386-6399.T

Abstract

Estrogen receptor-positive, progesterone receptor-negative, and human epidermal growth factor receptor 2 (HER2)-negative (ER+PR-HER2-) breast cancer comprise a special type of breast cancer that constitutes ~10% of all breast cancer patients. ER+PR-HER2- tumor benefits less from endocrine therapy, while its genomic features remain elusive. In this study, we systematically assessed the multiomic landscape and endocrine responsiveness of ER+PR-HER2- breast cancer.

Methods:

This study incorporated five cohorts. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n=130,856) and Molecular Taxonomy of Breast Cancer International Consortium (n=1,055) for analyzing survival outcomes and endocrine responsiveness. The third cohort was from The Cancer Genome Atlas (n=630) for multiomic analysis and endocrine-resistant subgroup exploration. The fourth cohort, from the MD Anderson database (n=92), was employed to assist gene selection. The fifth cohort was a prospective observational cohort from Fudan University Shanghai Cancer Center (n=245) that was utilized to validate the gene-defined subgroup by immunohistochemistry (IHC).

Results:

Clinically, ER+PR-HER2- tumors showed lower endocrine responsiveness than did ER+PR+HER2- tumors. Genomically, copy number loss or promoter methylation of PR genes occurred in 75% of ER+PR-HER2- tumors, collectively explaining PR loss. ER+PR-HER2- tumors had higher TP53 (30.3% vs. 17.0%) and lower PIK3CA mutation rates (25.8% vs. 42.7%) and exhibited more ZNF703 (21.5% vs. 13.6%) and RPS6KB1 (18.5% vs. 7.8%) amplification events than ER+PR+HER2- tumors. Among ER+PR-HER2- tumors, nearly 20% were of the PAM50-defined non-luminal-like subgroup and manifested lower endocrine sensitivity scores and enriched biosynthesis, metabolism and DNA replication pathways. We further identified the non-luminal-like subgroup using three IHC markers, GATA3, CK5, and EGFR. These IHC-defined non-luminal-like (GATA3-negative, CK5-positive and/or EGFR-positive) tumors received limited benefit from adjuvant endocrine therapy.

Conclusion:

ER+PR-HER2- breast cancer consists of clinically and genomically distinct groups that may require different treatment strategies. The non-luminal-like subgroup was associated with reduced benefit from endocrine therapy.

Authors+Show Affiliations

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.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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30613307

Citation

Liu, Xi-Yu, et al. "Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer." Theranostics, vol. 8, no. 22, 2018, pp. 6386-6399.
Liu XY, Ma D, Xu XE, et al. Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer. Theranostics. 2018;8(22):6386-6399.
Liu, X. Y., Ma, D., Xu, X. E., Jin, X., Yu, K. D., Jiang, Y. Z., & Shao, Z. M. (2018). Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer. Theranostics, 8(22), 6386-6399. https://doi.org/10.7150/thno.29164
Liu XY, et al. Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer. Theranostics. 2018;8(22):6386-6399. PubMed PMID: 30613307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomic Landscape and Endocrine-Resistant Subgroup in Estrogen Receptor-Positive, Progesterone Receptor-Negative, and HER2-Negative Breast Cancer. AU - Liu,Xi-Yu, AU - Ma,Ding, AU - Xu,Xiao-En, AU - Jin,Xi, AU - Yu,Ke-Da, AU - Jiang,Yi-Zhou, AU - Shao,Zhi-Ming, Y1 - 2018/12/08/ PY - 2018/08/11/received PY - 2018/11/08/accepted PY - 2019/1/8/entrez PY - 2019/1/8/pubmed PY - 2019/9/3/medline KW - ER+PR-HER2- KW - breast cancer KW - endocrine resistance KW - multiomic KW - non-luminal-like SP - 6386 EP - 6399 JF - Theranostics JO - Theranostics VL - 8 IS - 22 N2 - Estrogen receptor-positive, progesterone receptor-negative, and human epidermal growth factor receptor 2 (HER2)-negative (ER+PR-HER2-) breast cancer comprise a special type of breast cancer that constitutes ~10% of all breast cancer patients. ER+PR-HER2- tumor benefits less from endocrine therapy, while its genomic features remain elusive. In this study, we systematically assessed the multiomic landscape and endocrine responsiveness of ER+PR-HER2- breast cancer. Methods: This study incorporated five cohorts. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n=130,856) and Molecular Taxonomy of Breast Cancer International Consortium (n=1,055) for analyzing survival outcomes and endocrine responsiveness. The third cohort was from The Cancer Genome Atlas (n=630) for multiomic analysis and endocrine-resistant subgroup exploration. The fourth cohort, from the MD Anderson database (n=92), was employed to assist gene selection. The fifth cohort was a prospective observational cohort from Fudan University Shanghai Cancer Center (n=245) that was utilized to validate the gene-defined subgroup by immunohistochemistry (IHC). Results: Clinically, ER+PR-HER2- tumors showed lower endocrine responsiveness than did ER+PR+HER2- tumors. Genomically, copy number loss or promoter methylation of PR genes occurred in 75% of ER+PR-HER2- tumors, collectively explaining PR loss. ER+PR-HER2- tumors had higher TP53 (30.3% vs. 17.0%) and lower PIK3CA mutation rates (25.8% vs. 42.7%) and exhibited more ZNF703 (21.5% vs. 13.6%) and RPS6KB1 (18.5% vs. 7.8%) amplification events than ER+PR+HER2- tumors. Among ER+PR-HER2- tumors, nearly 20% were of the PAM50-defined non-luminal-like subgroup and manifested lower endocrine sensitivity scores and enriched biosynthesis, metabolism and DNA replication pathways. We further identified the non-luminal-like subgroup using three IHC markers, GATA3, CK5, and EGFR. These IHC-defined non-luminal-like (GATA3-negative, CK5-positive and/or EGFR-positive) tumors received limited benefit from adjuvant endocrine therapy. Conclusion: ER+PR-HER2- breast cancer consists of clinically and genomically distinct groups that may require different treatment strategies. The non-luminal-like subgroup was associated with reduced benefit from endocrine therapy. SN - 1838-7640 UR - https://www.unboundmedicine.com/medline/citation/30613307/Genomic_Landscape_and_Endocrine_Resistant_Subgroup_in_Estrogen_Receptor_Positive_Progesterone_Receptor_Negative_and_HER2_Negative_Breast_Cancer_ L2 - https://www.thno.org/v08p6386.htm DB - PRIME DP - Unbound Medicine ER -