Clinical Features and Prognosis Analysis of Hormone Receptor-Positive, HER2-Negative Breast Cancer with Differential Expression Levels of Estrogen and Progesterone Receptors: A 10-Year Retrospective Study

Overview

Journal Breast J

Publisher Wiley

Date 2022 Dec 19

PMID 36531979

Authors

Jin Liu

Mingyu Gan

Zijing Lin

Qin Deng

Juan Deng

Bin Zeng

Yanling Shi

Jia Ming

Affiliations

Soon will be listed here.

Abstract

Background: Estrogen and progesterone receptor status can predict breast cancer patient prognosis and treatment sensitivity, but research on low ER and PR levels and expression balance remains limited.

Methods: From January 2010 to October 2016, 283 ER+/PR+/HER2-breast cancer patients who met the inclusion criteria were enrolled and divided into the H group (ER > 10%, = 261) and the group (1% ≤ ER ≤ 10%, = 22). Groups were further divided into the HH group (ER > 10%/PR > 20%, = 201), the HL group (ER > 10%/ER 1% ≤ PR ≤ 20% PR, = 60), the LH group (1% ≤ ER ≤ 10%/PR > 20%, = 5), and the LL group (1% ≤ ER ≤ 10%/1% ≤ PR ≤ 20%, = 17). The LH group was excluded due to its small size, leaving the clinical and prognostic characteristics of 2 large groups and 3 subgroups to be analyzed.

Results: group patients had significantly more stage 2 axillary lymph nodes than H group patients (31.8% vs. 9.2%, = 0.007). Age ( = 0.011), menopause status ( = 0.001), and tumor size ( = 0.024) were significantly different in the HL vs. HH and LL groups. Five-year DFS (94.6% vs. 77.0%, < 0.001) and 5-year OS (97.2% vs. 85.8%, = 0.001) rates significantly differed between HH and HL. No significant differences in 5-year DFS (77.0% vs. 81.9%, = 0.564) or 5-year OS (85.8% vs. 87.8%, = 0.729) rates were observed between HL and LL; the OS rates of HL and LL were similar.

Conclusion: In the group of ER+/PR+/HER2-patients, there was no significant prognostic difference between ER-low positive and ER-high positive groups, but low PR expression was significantly associated with a worse prognosis. The role of ER and PR balance in breast cancer progression and individualized treatment requires further investigation.

Citing Articles

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References

Hilton H, Graham J, Kantimm S, Santucci N, Cloosterman D, Huschtscha L . Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast. Mol Cell Endocrinol. 2012; 361(1-2):191-201. DOI: 10.1016/j.mce.2012.04.010. View

Ellis M, Suman V, Hoog J, Lin L, Snider J, Prat A . Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline.... J Clin Oncol. 2011; 29(17):2342-9. PMC: 3107749. DOI: 10.1200/JCO.2010.31.6950. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

Bardou V, Arpino G, Elledge R, Osborne C, Clark G . Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003; 21(10):1973-9. DOI: 10.1200/JCO.2003.09.099. View

Prat A, Chon U Cheang M, Martin M, Parker J, Carrasco E, Caballero R . Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol. 2012; 31(2):203-9. PMC: 3532392. DOI: 10.1200/JCO.2012.43.4134. View

Tsuboi K, Nagatomo T, Gohno T, Higuchi T, Sasaki S, Fujiki N . Single CpG site methylation controls estrogen receptor gene transcription and correlates with hormone therapy resistance. J Steroid Biochem Mol Biol. 2017; 171:209-217. DOI: 10.1016/j.jsbmb.2017.04.001. View

Yang L, Tseng H, Lin C, Chen L, Chen S, Kuo S . Survival benefit of tamoxifen in estrogen receptor-negative and progesterone receptor-positive low grade breast cancer patients. J Breast Cancer. 2012; 15(3):288-95. PMC: 3468782. DOI: 10.4048/jbc.2012.15.3.288. View

Creighton C, Osborne C, van de Vijver M, Foekens J, Klijn J, Horlings H . Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat. 2008; 114(2):287-99. PMC: 2635926. DOI: 10.1007/s10549-008-0017-2. View

Harvey J, Clark G, Osborne C, Allred D . Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999; 17(5):1474-81. DOI: 10.1200/JCO.1999.17.5.1474. View

10.

Fan Y, Ding X, Xu B, Ma F, Yuan P, Wang J . Prognostic Significance of Single Progesterone Receptor Positivity: A Comparison Study of Estrogen Receptor Negative/Progesterone Receptor Positive/Her2 Negative Primary Breast Cancer With Triple Negative Breast Cancer. Medicine (Baltimore). 2015; 94(46):e2066. PMC: 4652828. DOI: 10.1097/MD.0000000000002066. View

11.

Rhodes A, Jasani B . The oestrogen receptor-negative/progesterone receptor-positive breast tumour: a biological entity or a technical artefact?. J Clin Pathol. 2008; 62(1):95-6. DOI: 10.1136/jcp.2008.060723. View

12.

Hudis C, Barlow W, Costantino J, Gray R, Pritchard K, Chapman J . Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007; 25(15):2127-32. DOI: 10.1200/JCO.2006.10.3523. View

13.

Osborne C, Yochmowitz M, Knight 3rd W, McGuire W . The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer. 1980; 46(12 Suppl):2884-8. DOI: 10.1002/1097-0142(19801215)46:12+<2884::aid-cncr2820461429>3.0.co;2-u. View

14.

Rakha E, El-Sayed M, Green A, Paish E, Powe D, Gee J . Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol. 2007; 25(30):4772-8. DOI: 10.1200/JCO.2007.12.2747. View

15.

Allison K, Hammond M, Dowsett M, McKernin S, Carey L, Fitzgibbons P . Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol. 2020; 38(12):1346-1366. DOI: 10.1200/JCO.19.02309. View

16.

Kunc M, Biernat W, Senkus-Konefka E . Estrogen receptor-negative progesterone receptor-positive breast cancer - "Nobody's land" or just an artifact?. Cancer Treat Rev. 2018; 67:78-87. DOI: 10.1016/j.ctrv.2018.05.005. View

17.

Yi M, Huo L, Koenig K, Mittendorf E, Meric-Bernstam F, Kuerer H . Which threshold for ER positivity? a retrospective study based on 9639 patients. Ann Oncol. 2014; 25(5):1004-11. PMC: 3999801. DOI: 10.1093/annonc/mdu053. View

18.

Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua M, Pruneri G . Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse. Ann Oncol. 2012; 24(3):661-8. DOI: 10.1093/annonc/mds430. View

19.

Cui X, Schiff R, Arpino G, Osborne C, Lee A . Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005; 23(30):7721-35. DOI: 10.1200/JCO.2005.09.004. View

20.

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View