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Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.
BMC Med. 2015 Oct 05; 13:254.BM

Abstract

BACKGROUND

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype.

METHODS

Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated.

RESULTS

Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy).

CONCLUSIONS

The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings.

Authors+Show Affiliations

Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, P. R. China. yukeda@163.com.Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, P. R. China.Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, P. R. China.Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, P. R. China. zhimingshao@yahoo.com.

Pub Type(s)

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

Language

eng

PubMed ID

26437901

Citation

Yu, Ke-Da, et al. "Molecular Essence and Endocrine Responsiveness of Estrogen Receptor-negative, Progesterone Receptor-positive, and HER2-negative Breast Cancer." BMC Medicine, vol. 13, 2015, p. 254.
Yu KD, Jiang YZ, Hao S, et al. Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer. BMC Med. 2015;13:254.
Yu, K. D., Jiang, Y. Z., Hao, S., & Shao, Z. M. (2015). Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer. BMC Medicine, 13, 254. https://doi.org/10.1186/s12916-015-0496-z
Yu KD, et al. Molecular Essence and Endocrine Responsiveness of Estrogen Receptor-negative, Progesterone Receptor-positive, and HER2-negative Breast Cancer. BMC Med. 2015 Oct 5;13:254. PubMed PMID: 26437901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer. AU - Yu,Ke-Da, AU - Jiang,Yi-Zhou, AU - Hao,Shuang, AU - Shao,Zhi-Ming, Y1 - 2015/10/05/ PY - 2015/07/28/received PY - 2015/09/18/accepted PY - 2015/10/7/entrez PY - 2015/10/7/pubmed PY - 2016/4/28/medline SP - 254 EP - 254 JF - BMC medicine JO - BMC Med VL - 13 N2 - BACKGROUND: The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. METHODS: Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. RESULTS: Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). CONCLUSIONS: The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings. SN - 1741-7015 UR - https://www.unboundmedicine.com/medline/citation/26437901/Molecular_essence_and_endocrine_responsiveness_of_estrogen_receptor_negative_progesterone_receptor_positive_and_HER2_negative_breast_cancer_ L2 - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0496-z DB - PRIME DP - Unbound Medicine ER -