Development of recurrence risk score using 95‑gene classifier and its application to formalin‑fixed paraffin‑embedded tissues in ER‑positive, HER2‑negative and node‑negative breast cancer

Naoi,Yasuto; Saito,Yuria; Kishi,Kazuki; Shimoda,Masafumi; Kagara,Naofumi; Miyake,Tomohiro; Tanei,Tomonori; Shimazu,Kenzo; Kim,Seung Jin; Noguchi,Shinzaburo

doi:10.3892/or.2019.7358

Development of recurrence risk score using 95‑gene classifier and its application to formalin‑fixed paraffin‑embedded tissues in ER‑positive, HER2‑negative and node‑negative breast cancer

Authors:
- Yasuto Naoi
- Yuria Saito
- Kazuki Kishi
- Masafumi Shimoda
- Naofumi Kagara
- Tomohiro Miyake
- Tomonori Tanei
- Kenzo Shimazu
- Seung Jin Kim
- Shinzaburo Noguchi
View Affiliations

Affiliations: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Sysmex Corporation, Kobe, Hyogo 651‑0073, Japan
Published online on: October 7, 2019 https://doi.org/10.3892/or.2019.7358
Pages: 2680-2685

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

We previously developed a 95‑gene classifier (95GC) to classify ER‑positive/HER2‑negative/node‑negative (ER+/HER2‑/N0) breast cancer as high‑ and low‑risk. The present study aimed to devise a 95GC recurrence score (95GCRS) to estimate recurrence risk more precisely and, although the 95GC was originally developed using fresh‑frozen (FF) tissues, this was applied to formalin‑fixed paraffin‑embedded (FFPE) tissues. 95GCRS was calculated using between‑group analysis and denominated as a value from 0 to 100. Correlation of 95GCRS with distant recurrence rate and response to neoadjuvant chemotherapy (NAC) was evaluated in 257 patients with ER+/HER2−/N0 breast cancer treated with adjuvant hormonal therapy at Osaka University Hospital and in 425 patients with ER+ breast cancer treated with NAC at Osaka University Hospital and the University of Texas MD Anderson Cancer Center (GSE25066 dataset). Correlation of 95GCRS between FF and FFPE tissues was evaluated in paired tissues from 56 ER+/HER2‑/N0 breast cancer types obtained from patients without NAC treatment. Distant recurrence rates were remarkably low in patients with 95GCRS ≤50 and increased proportionally in patients with 95GCRS >50. Pathological complete response (pCR) rates to NAC were increased in proportion to 95GCRS, indicating a greater sensitivity of breast cancers with high 95GCRS to chemotherapy. 95GCRS was highly correlated (R=0.92) between FF and FFPE tissues, and the concordance rate (94.6%) of high‑ and low‑risk groups was also considerably high. Overall, the present study developed a 95GCRS that correlated with distant recurrence rate and pCR rate to NAC. The 95GC was applicable to FFPE tissues with a high concordance rate in FF tissues.

View Figures

View References

1	Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 351:2817–2826. 2004. View Article : Google Scholar : PubMed/NCBI
2	Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, et al: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 24:3726–3734. 2006. View Article : Google Scholar : PubMed/NCBI
3	van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 415:530–536. 2002. View Article : Google Scholar : PubMed/NCBI
4	van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, et al: A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 347:1999–2009. 2002. View Article : Google Scholar : PubMed/NCBI
5	Naoi Y, Kishi K, Tsunashima R, Shimazu K, Shimomura A, Maruyama N, Shimoda M, Kagara N, Baba Y, Kim SJ and Noguchi S: Comparison of efficacy of 95-gene and 21-gene classifier (Oncotype DX) for prediction of recurrence in ER-positive and node-negative breast cancer patients. Breast Cancer Res Treat. 140:299–306. 2013. View Article : Google Scholar : PubMed/NCBI
6	Habel LA, Shak S, Jacobs MK, Capra A, Alexander C, Pho M, Baker J, Walker M, Watson D, Hackett J, et al: A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 8:R252006. View Article : Google Scholar : PubMed/NCBI
7	Kim C, Tang G, Pogue-Geile KL, Costantino JP, Baehner FL, Baker J, Cronin MT, Watson D, Shak S, Bohn OL, et al: Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer. J Clin Oncol. 29:4160–4167. 2011. View Article : Google Scholar : PubMed/NCBI
8	Nishio M, Naoi Y, Tsunashima R, Nakauchi C, Kagara N, Shimoda M, Shimomura A, Maruyama N, Shimazu K, Kim SJ and Noguchi S: 72-gene classifier for predicting prognosis of estrogen receptor-positive and node-negative breast cancer patients using formalin-fixed, paraffin-embedded tumor tissues. Clin Breast Cancer. 14:e73–e80. 2014. View Article : Google Scholar : PubMed/NCBI
9	Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, et al: A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 305:1873–1881. 2011. View Article : Google Scholar : PubMed/NCBI
10	Naoi Y, Kishi K, Tanei T, Tsunashima R, Tominaga N, Baba Y, Kim SJ, Taguchi T, Tamaki Y and Noguchi S: Development of 95-gene classifier as a powerful predictor of recurrences in node-negative and ER-positive breast cancer patients. Breast Cancer Res Treat. 128:633–641. 2011. View Article : Google Scholar : PubMed/NCBI
11	Sota Y, Naoi Y, Tsunashima R, Kagara N, Shimazu K, Maruyama N, Shimomura A, Shimoda M, Kishi K, Baba Y, et al: Construction of novel immune-related signature for prediction of pathological complete response to neoadjuvant chemotherapy in human breast cancer. Ann Oncol. 25:100–106. 2013. View Article : Google Scholar
12	Tsunashima R, Naoi Y, Kagara N, Shimoda M, Shimomura A, Maruyama N, Shimazu K, Kim SJ and Noguchi S: Construction of multi-gene classifier for prediction of response to and prognosis after neoadjuvant chemotherapy for estrogen receptor positive breast cancers. Cancer Lett. 365:166–173. 2015. View Article : Google Scholar : PubMed/NCBI
13	D'Alfonso TM, van Laar RK, Vahdat LT, Hussain W, Flinchum R, Brown N, John LS and Shin SJ: BreastPRS is a gene expression assay that stratifies intermediate-risk Oncotype DX patients into high- or low-risk for disease recurrence. Breast Cancer Res Treat. 139:705–715. 2013. View Article : Google Scholar : PubMed/NCBI
14	Musella V, Callari M, Di Buduo E, Scuro M, Dugo M, Miodini P, Bianchini G, Paolini B, Gianni L, Daidone MG and Cappelletti V: Use of formalin-fixed paraffin-embedded samples for gene expression studies in breast cancer patients. PLoS One. 10:e01231942015. View Article : Google Scholar : PubMed/NCBI
15	Tsunashima R, Naoi Y, Kishi K, Baba Y, Shimomura A, Maruyama N, Nakayama T, Shimazu K, Kim SJ, Tamaki Y and Noguchi S: Estrogen receptor positive breast cancer identified by 95-gene classifier as at high risk for relapse shows better response to neoadjuvant chemotherapy. Cancer Lett. 324:42–47. 2012. View Article : Google Scholar : PubMed/NCBI
16	Pease AM, Riba LA, Gruner RA, Tung NM and James TA: Oncotype DX^® recurrence score as a predictor of response to neoadjuvant chemotherapy. Ann Surg Oncol. 26:366–371. 2019. View Article : Google Scholar : PubMed/NCBI
17	Bear HD, Wan W, Robidoux A, Rubin P, Limentani S, White RL Jr, Granfortuna J, Hopkins JO, Oldham D, Rodriguez A and Sing AP: Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial. J Surg Oncol. 115:917–923. 2017. View Article : Google Scholar : PubMed/NCBI
18	Chang JC, Makris A, Gutierrez MC, Hilsenbeck SG, Hackett JR, Jeong J, Liu ML, Baker J, Clark-Langone K, Baehner FL, et al: Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat. 108:233–240. 2008. View Article : Google Scholar : PubMed/NCBI
19	Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J, Mariani G, Rodriguez J, Carcangiu M, Watson D, et al: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 23:7265–7277. 2005. View Article : Google Scholar : PubMed/NCBI
20	Whitworth P, Stork-Sloots L, de Snoo FA, Richards P, Rotkis M, Beatty J, Mislowsky A, Pellicane JV, Nguyen B, Lee L, et al: Chemosensitivity predicted by BluePrint 80-gene functional subtype and MammaPrint in the prospective neoadjuvant breast registry symphony trial (NBRST). Ann Surg Oncol. 21:3261–3267. 2004. View Article : Google Scholar