Estrogen Receptor and Claudin-6 Might Play Vital Roles for Long-Term Prognosis in Patients With Luminal A Breast Cancer Who Underwent Neoadjuvant Chemotherapy

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jul 18

PMID 35847894

Authors

Yushi Liu

Ye Kang

Jianyi Li

Yang Zhang

Shi Jia

Qiang Sun

Yan Ma

Jing Zhang

Zhenrong Wang

Yanan Cao

Yang Shen

Affiliations

Soon will be listed here.

Abstract

Purpose: It is well-known that the pathological complete response (pCR) rate in patients with luminal A cancer (LAC) is lower than those of other subtypes of breast cancer. The phenotype of cancer often alters after neoadjuvant chemotherapy (NAC) which may be related to hypoxia, and the latter might induce the drift of the estrogen receptor (ER). The phenotype drift in local advanced LAC after NAC might influence the long-term prognosis.

Methods: The oxygen concentration of cancer tissues during NAC was recorded and analyzed (n = 43). The expression of ER and claudin-6 was detected in pre- and post-NAC specimens.

Results: NAC might induce the cycling intracanceral hypoxia, and the pattern was related to NAC response. The median follow-up time was 61 months. Most of the patients (67%) with stable or increased ER and claudin-6 expression exhibited perfect prognosis (DFS = 100%, 61 months). About 20% of patients with decreased claudin-6 would undergo the poor prognosis (DFS = 22.2%, 61 months). The contrasting prognosis (100% vs. 22.2%) had nothing to do with the response of NAC in the above patients. Only 13% patients had stable claudin-6 and decreased ER, whose prognosis might relate to the response of NAC.

Conclusion: NAC might induce cycling intracanceral hypoxia to promote the phenotype drift in local advanced LAC, and the changes in ER and claudin-6 after NAC would determine the long-term prognosis.

References

Li X, Warren S, Pelekanou V, Wali V, Cesano A, Liu M . Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial. J Immunother Cancer. 2019; 7(1):88. PMC: 6457012. DOI: 10.1186/s40425-019-0563-7. View

Rausch L, Netzer N, Hoegel J, Pramsohler S . The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue. Front Oncol. 2017; 7:211. PMC: 5622311. DOI: 10.3389/fonc.2017.00211. View

Weinmann M, Jendrossek V, Guner D, Goecke B, Belka C . Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. FASEB J. 2004; 18(15):1906-8. DOI: 10.1096/fj.04-1918fje. View

Li J, Zhang Y, Zhang W, Gao Y, Jia S, Guo J . Contrast enhanced computed tomography is indicative for angiogenesis pattern and display prognostic significance in breast cancer. BMC Cancer. 2014; 14:672. PMC: 4176577. DOI: 10.1186/1471-2407-14-672. View

Shrivastav S, Bal A, Singh G, Joshi K . Tumor Angiogenesis in Breast Cancer: Pericytes and Maturation Does Not Correlate With Lymph Node Metastasis and Molecular Subtypes. Clin Breast Cancer. 2015; 16(2):131-8. DOI: 10.1016/j.clbc.2015.09.002. View

Kim S, Sohn J, Koo J, Park S, Park H, Park B . Molecular subtypes and tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Oncology. 2011; 79(5-6):324-30. DOI: 10.1159/000322192. View

Song J, Chen C, Yuan J, Sun S . Progress in the clinical detection of heterogeneity in breast cancer. Cancer Med. 2016; 5(12):3475-3488. PMC: 5224851. DOI: 10.1002/cam4.943. View

Kong X, Moran M, Zhang N, Haffty B, Yang Q . Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients. Eur J Cancer. 2011; 47(14):2084-90. DOI: 10.1016/j.ejca.2011.06.014. View

Yafang L, Qiong W, Yue R, XiaoMing X, Lina Y, Mingzi Z . Role of Estrogen Receptor-α in the Regulation of Claudin-6 Expression in Breast Cancer Cells. J Breast Cancer. 2011; 14(1):20-7. PMC: 3148509. DOI: 10.4048/jbc.2011.14.1.20. View

10.

Xie L, Li X, Wang Q, Zhou J, Shen J, Luo L . Effects of core needle biopsy and subsequent neoadjuvant chemotherapy on molecular alterations and outcome in breast cancer. Onco Targets Ther. 2018; 11:677-685. PMC: 5798570. DOI: 10.2147/OTT.S145715. View

11.

Galli G, Bregni G, Cavalieri S, Porcu L, Baili P, Hade A . Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer. Breast Care (Basel). 2018; 12(6):391-394. PMC: 5803695. DOI: 10.1159/000479582. View

12.

Bonnefoi H, Litiere S, Piccart M, MacGrogan G, Fumoleau P, Brain E . Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014; 25(6):1128-36. PMC: 4037859. DOI: 10.1093/annonc/mdu118. View

13.

Ding N, Liu C, Hu C, Yuan J, Liao W, Xiao Z . Prognostic Factors for Luminal B-like Breast Cancer. Curr Med Sci. 2019; 39(3):396-402. DOI: 10.1007/s11596-019-2049-8. View

14.

Soleymani Abyaneh H, Gupta N, Alshareef A, Gopal K, Lavasanifar A, Lai R . Hypoxia Induces the Acquisition of Cancer Stem-like Phenotype Via Upregulation and Activation of Signal Transducer and Activator of Transcription-3 (STAT3) in MDA-MB-231, a Triple Negative Breast Cancer Cell Line. Cancer Microenviron. 2018; 11(2-3):141-152. PMC: 6250616. DOI: 10.1007/s12307-018-0218-0. View

15.

Bustreo S, Osella-Abate S, Cassoni P, Donadio M, Airoldi M, Pedani F . Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat. 2016; 157(2):363-371. PMC: 4875067. DOI: 10.1007/s10549-016-3817-9. View

16.

Khokher S, Qureshi M, Chaudhry N . Comparison of WHO and RECIST criteria for evaluation of clinical response to chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev. 2012; 13(7):3213-8. DOI: 10.7314/apjcp.2012.13.7.3213. View

17.

Ando Y, Ta H, Yen D, Lee S, Raola S, Shen K . A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments. Sci Rep. 2017; 7(1):15233. PMC: 5680268. DOI: 10.1038/s41598-017-15583-3. View

18.

Bonin S, Pracella D, Barbazza R, Dotti I, Boffo S, Stanta G . PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement. Dis Markers. 2019; 2019:7832376. PMC: 6875411. DOI: 10.1155/2019/7832376. View

19.

Menendez J, Mehmi I, Papadimitropoulou A, Steen T, Cuyas E, Verdura S . Fatty Acid Synthase Is a Key Enabler for Endocrine Resistance in Heregulin-Overexpressing Luminal B-Like Breast Cancer. Int J Mol Sci. 2020; 21(20). PMC: 7588883. DOI: 10.3390/ijms21207661. View

20.

Fluegen G, Avivar-Valderas A, Wang Y, Padgen M, Williams J, Nobre A . Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nat Cell Biol. 2017; 19(2):120-132. PMC: 5342902. DOI: 10.1038/ncb3465. View