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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2020

01-08-2020 | Metastasis | Preclinical study

High FOXA1 protein expression might predict late recurrence in patients with estrogen-positive and HER2-negative breast cancer

Authors: Yoshiya Horimoto, Noriko Sasahara, Ritsuko Sasaki, May Thinzar Hlaing, Asumi Sakaguchi, Harumi Saeki, Atsushi Arakawa, Takanori Himuro, Mitsue Saito

Published in: Breast Cancer Research and Treatment | Issue 1/2020

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Abstract

Background

Multi-gene expression assays have been developed with the aim of predicting late recurrence in patients with estrogen receptor (ER)-positive breast cancer. However, establishment of alternative markers based on immunohistochemistry is also important for achieving practical use. Based on our previous study, forkhead box A1 (FOXA1) protein was tested as a potentially useful predictive marker for late recurrence.

Methods

117 patients with ER-positive HER2-negative invasive breast cancer who developed distant metastasis following curative surgery were retrospectively investigated. We also evaluated responsiveness to endocrine therapy according to FOXA1 expression. Furthermore, publicly available mRNA microarray data were analyzed to examine patterns of metastasis according to FOXA1 mRNA expression, employing the Kaplan–Meier plotter.

Results

High expression of FOXA1 was an independent factor predicting long disease-free survival (DFS), along with small tumor size (p = 0.010 and 0.016, respectively). Discrimination of DFS was improved by combining these two factors, i.e., patients with FOXA1-high small tumors had the longest DFS while those with FOXA1-low large tumors had the shortest DFS. Moreover, we revealed that risk of distant metastasis started to increase after the completion of adjuvant endocrine therapy in patients with FOXA1-high tumors.

Conclusion

Among patients who developed distant metastasis, those with FOXA1-high tumors had significantly longer DFS. We believe our data to raise the possibility of FOXA1 being a useful predictive marker for late recurrence and to provide new insights into the biology of FOXA1-high breast cancers.
Appendix
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Literature
1.
2.
Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J et al (2016) Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 375:209–219CrossRef
3.
Mamounas EP, Bandos H, Lembersky BC, Jeong J-H, Geyer CE, Rastogi P et al (2019) Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20:88–99CrossRef
4.
Burstein HJ, Lacchetti C, Anderson H, Buchholz TA, Davidson NE, Gelmon KA et al (2019) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol 37:423–438CrossRef
5.
Cuzick J (2019) Predicting late recurrence in ER-positive breast cancer. Nat Rev Clin Oncol 16:406–408CrossRef
6.
Foldi J, O’Meara T, Marczyk M, Sanft T, Silber A, Pusztai L (2019) Defining risk of late recurrence in early-stage estrogen receptor-positive breast cancer: clinical versus molecular tools. J Clin Oncol 37:1365–1369CrossRef
7.
Yamashita H, Ogiya A, Shien T, Horimoto Y, Masuda N, Inao T et al (2016) Clinicopathological factors predicting early and late distant recurrence in estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer 23:830–843CrossRef
8.
Filipits M, Nielsen TO, Rudas M, Greil R, Stöger H, Jakesz R et al (2014) The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res 20:1298–1305CrossRef
9.
Sestak I, Dowsett M, Zabaglo L, Lopez-Knowles E, Ferree S, Cowens JW et al (2013) Factors predicting late recurrence for estrogen receptor-positive breast cancer. J Natl Cancer Inst 105:1504–1511CrossRef
10.
Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B et al (2013) Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol 14:1067–1076CrossRef
11.
Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM et al (2013) Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. J Natl Cancer Inst 105:1036–1042CrossRef
12.
Filipits M, Dubsky P, Rudas M, Greil R, Balic M, Bago-Horvath Z et al (2019) Prediction of distant recurrence using endopredict among women with ER+, HER2− node-positive and node-negative breast cancer treated with endocrine therapy only. Clin Cancer Res 25:3865–3872CrossRef
13.
Buus R, Yeo B, Brentnall AR, Klintman M, Cheang MCU, Khabra K et al (2018) Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer. Breast Cancer Res 20:103–103CrossRef
14.
Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, Vickery T et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167CrossRef
15.
Jerevall PL, Ma XJ, Li H, Salunga R, Kesty NC, Erlander MG et al (2011) Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer 104:1762–1769CrossRef
16.
Jansen MPHM, Sieuwerts AM, Look MP, Ritstier K, Gelder MEM, Staveren IL et al (2007) HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study. J Clin Oncol. 25:662–668CrossRef
17.
Jerevall P-L, Brock J, Palazzo J, Wieczorek T, Misialek M, Guidi AJ et al (2019) Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score. Breast Cancer Res Treat 173:375–383CrossRef
18.
An X, Xu F, Luo R, Zheng Q, Lu J, Yang Y et al (2018) The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer. BMC Cancer 18:331CrossRef
19.
Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ et al (2005) Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 122:33–43CrossRef
20.
Ademuyiwa FO, Thorat MA, Jain RK, Nakshatri H, Badve S (2009) Expression of Forkhead-box protein A1, a marker of luminal A type breast cancer, parallels low Oncotype DX 21-gene recurrence scores. Mod Pathol 23:270CrossRef
21.
Wolf I, Bose S, Williamson EA, Miller CW, Karlan BY, Koeffler HP (2007) FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer. Int J Cancer 120:1013–1022CrossRef
22.
Thorat MA, Marchio C, Morimiya A, Savage K, Nakshatri H, Reis-Filho JS et al (2008) Forkhead box A1 expression in breast cancer is associated with luminal subtype and good prognosis. J Clin Pathol 61:327–332CrossRef
23.
Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO, Perou CM et al (2007) FOXA1 expression in breast cancer—correlation with luminal subtype A and survival. Clin Cancer Res 13:4415–4421CrossRef
24.
Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS (2010) FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet 43:27CrossRef
25.
Horimoto Y, Arakawa A, Harada-Shoji N, Sonoue H, Yoshida Y, Himuro T et al (2015) Low FOXA1 expression predicts good response to neo-adjuvant chemotherapy resulting in good outcomes for luminal HER2-negative breast cancer cases. Br J Cancer 112:345–351CrossRef
26.
Himuro T, Horimoto Y, Arakawa A, Matsuoka J, Tokuda E, Tanabe M et al (2016) Activated caspase 3 expression in remnant disease after neoadjuvant chemotherapy may predict outcomes of breast cancer patients. Ann Surg Oncol. 2016:1–7
27.
Mihály Z, Kormos M, Lánczky A, Dank M, Budczies J, Szász MA et al (2013) A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer. Breast Cancer Res Treat 140:219–232CrossRef
28.
Kennecke H, Olivotto I, Speers C, Norris B, Chia S, Bryce C et al (2006) Late risk of relapse and mortality among postmenopausal women with estrogen responsive early breast cancer after 5 years of tamoxifen. Ann Oncol 18:45–51CrossRef
29.
30.
Ogba N, Manning NG, Bliesner BS, Ambler SK, Haughian JM, Pinto MP et al (2014) Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells. Breast Cancer Res 16:489CrossRef
31.
Sansone P, Savini C, Kurelac I, Chang Q, Amato LB, Strillacci A et al (2017) Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci USA 114:E9066–E9075CrossRef
32.
Bianchini G, Pusztai L, Karn T, Iwamoto T, Rody A, Kelly CM et al (2013) Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers. Breast Cancer Res 15:R86CrossRef
33.
Bense RD, Qiu S-Q, de Vries EGE, Schröder CP, Fehrmann RSN (2018) Considering the biology of late recurrences in selecting patients for extended endocrine therapy in breast cancer. Cancer Treat Rev 70:118–126CrossRef
34.
Zhang Y, Schroeder BE, Jerevall P-L, Ly A, Nolan H, Schnabel CA et al (2017) A novel breast cancer index for prediction of distant recurrence in HR+ early-stage breast cancer with one to three positive nodes. Clin Cancer Res 23:7217–7224CrossRef
35.
Buus R, Sestak I, Kronenwett R, Denkert C, Dubsky P, Krappmann K et al (2016) Comparison of EndoPredict and EPclin with oncotype DX recurrence score for prediction of risk of distant recurrence after endocrine therapy. J Natl Cancer Inst 108:149CrossRef
Metadata
Title
High FOXA1 protein expression might predict late recurrence in patients with estrogen-positive and HER2-negative breast cancer
Authors
Yoshiya Horimoto
Noriko Sasahara
Ritsuko Sasaki
May Thinzar Hlaing
Asumi Sakaguchi
Harumi Saeki
Atsushi Arakawa
Takanori Himuro
Mitsue Saito
Publication date
01-08-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05751-x

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