The Prognostic Value and Immune Microenvironment Association of AR in HER2+ Nonmetastatic Breast Cancer

Overview

Journal NPJ Breast Cancer

Date 2023 Apr 21

PMID 37085500

Authors

Danyang Zhou

Mei Li

Mohamed Hussein Yasin

Qianyi Lu

Jia Fu

Kuikui Jiang

Ruoxi Hong

Shusen Wang

Fei Xu

Affiliations

Soon will be listed here.

Abstract

This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.

Citing Articles

Biomarkers derived from CmP signal network in triple negative breast cancers.

Sanchez N, Harvey C, Vincent D, Croft J, Zhang J Transl Breast Cancer Res. 2024; 4:21.

PMID: 38751477 PMC: 11093088. DOI: 10.21037/tbcr-23-30.

References

Papakonstantinou A, Matikas A, Bengtsson N, Malmstrom P, Hedayati E, Steger G . Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial. Cancer. 2019; 126(6):1175-1182. DOI: 10.1002/cncr.32653. View

Takada M, Toi M . Neoadjuvant treatment for HER2-positive breast cancer. Chin Clin Oncol. 2020; 9(3):32. DOI: 10.21037/cco-20-123. View

Wang X, Bi X, Huang Z, Huang J, Xia W, Shi W . The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer. Endocr Relat Cancer. 2020; 27(4):199-208. DOI: 10.1530/ERC-19-0315. View

Bonnefoi H, MacGrogan G, Poncet C, Iggo R, Pommeret F, Grellety T . Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes. Br J Cancer. 2019; 120(9):913-921. PMC: 6734658. DOI: 10.1038/s41416-019-0420-y. View

Yarden Y, Sliwkowski M . Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001; 2(2):127-37. DOI: 10.1038/35052073. View

Bozovic-Spasojevic I, Zardavas D, Brohee S, Ameye L, Fumagalli D, Ades F . The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data. Clin Cancer Res. 2017; 23(11):2702-2712. DOI: 10.1158/1078-0432.CCR-16-0979. View

Chia K, OBrien M, Brown M, Lim E . Targeting the androgen receptor in breast cancer. Curr Oncol Rep. 2015; 17(2):4. DOI: 10.1007/s11912-014-0427-8. View

Giuliano A, Connolly J, Edge S, Mittendorf E, Rugo H, Solin L . Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(4):290-303. DOI: 10.3322/caac.21393. View

Bense R, Sotiriou C, Piccart-Gebhart M, Haanen J, van Vugt M, de Vries E . Relevance of Tumor-Infiltrating Immune Cell Composition and Functionality for Disease Outcome in Breast Cancer. J Natl Cancer Inst. 2016; 109(1). PMC: 6284248. DOI: 10.1093/jnci/djw192. View

10.

Anestis A, Zoi I, Papavassiliou A, Karamouzis M . Androgen Receptor in Breast Cancer-Clinical and Preclinical Research Insights. Molecules. 2020; 25(2). PMC: 7024330. DOI: 10.3390/molecules25020358. View

11.

Venema C, Bense R, Steenbruggen T, Nienhuis H, Qiu S, van Kruchten M . Consideration of breast cancer subtype in targeting the androgen receptor. Pharmacol Ther. 2019; 200:135-147. DOI: 10.1016/j.pharmthera.2019.05.005. View

12.

Yuan Y, Lee J, Yost S, Frankel P, Ruel C, Egelston C . A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer. Oncologist. 2020; 26(2):99-e217. PMC: 7873338. DOI: 10.1002/onco.13583. View

13.

van Rooijen J, Qiu S, Timmer-Bosscha H, van der Vegt B, Boers J, Schroder C . Androgen receptor expression inversely correlates with immune cell infiltration in human epidermal growth factor receptor 2-positive breast cancer. Eur J Cancer. 2018; 103:52-60. DOI: 10.1016/j.ejca.2018.08.001. View

14.

Ricciardelli C, Bianco-Miotto T, Jindal S, Butler L, Leung S, McNeil C . The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome. Clin Cancer Res. 2018; 24(10):2328-2341. DOI: 10.1158/1078-0432.CCR-17-1199. View

15.

Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G . The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2014; 26(2):259-71. PMC: 6267863. DOI: 10.1093/annonc/mdu450. View

16.

Venema C, Mammatas L, Schroder C, van Kruchten M, Apollonio G, Glaudemans A . Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies. J Nucl Med. 2017; 58(12):1906-1912. DOI: 10.2967/jnumed.117.193649. View

17.

Byrne A, Savas P, Sant S, Li R, Virassamy B, Luen S . Tissue-resident memory T cells in breast cancer control and immunotherapy responses. Nat Rev Clin Oncol. 2020; 17(6):341-348. DOI: 10.1038/s41571-020-0333-y. View

18.

Sugie T . Immunotherapy for metastatic breast cancer. Chin Clin Oncol. 2018; 7(3):28. DOI: 10.21037/cco.2018.05.05. View

19.

Guiu S, Mollevi C, Charon-Barra C, Boissiere F, Crapez E, Chartron E . Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers. Br J Cancer. 2018; 119(1):76-79. PMC: 6035246. DOI: 10.1038/s41416-018-0142-6. View

20.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View