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Published in: Breast Cancer 5/2020

01-09-2020 | Breast Cancer | Original Article

Prediction of Oncotype DX recurrence score using deep multi-layer perceptrons in estrogen receptor-positive, HER2-negative breast cancer

Authors: Aline Baltres, Zeina Al Masry, Ryad Zemouri, Severine Valmary-Degano, Laurent Arnould, Noureddine Zerhouni, Christine Devalland

Published in: Breast Cancer | Issue 5/2020

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Abstract

Oncotype DX (ODX) is a multi-gene expression signature designed for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients to predict the recurrence score (RS) and chemotherapy (CT) benefit. The aim of our study is to develop a prediction tool for the three RS’s categories based on deep multi-layer perceptrons (DMLP) and using only the morphoimmunohistological variables. We performed a retrospective cohort of 320 patients who underwent ODX testing from three French hospitals. Clinico-pathological characteristics were recorded. We built a supervised machine learning classification model using Matlab software with 152 cases for the training and 168 cases for the testing. Three classifiers were used to learn the three risk categories of the ODX, namely the low, intermediate, and high risk. Experimental results provide the area under the curve (AUC), respectively, for the three risk categories: 0.63 [95% confidence interval: (0.5446, 0.7154), p < 0.001], 0.59 [95% confidence interval: (0.5031, 0.6769), p < 0.001], 0.75 [95% confidence interval: (0.6184, 0.8816), p < 0.001]. Concordance rate between actual RS and predicted RS ranged from 53 to 56% for each class between DMLP and ODX. The concordance rate of low and intermediate combined risk group was 85%.
We developed a predictive machine learning model that could help to define patient’s RS. Moreover, we integrated histopathological data and DMLP results to select tumor for ODX testing. Thus, this process allows more relevant use of histopathological data, and optimizes and enhances this information.
Literature
1.
go back to reference Walsh S, de Jong EEC, van Timmeren JE, et al. Decision Support Systems in Oncology. JCO Clin Cancer Inform. 2019;3:1–9.CrossRef Walsh S, de Jong EEC, van Timmeren JE, et al. Decision Support Systems in Oncology. JCO Clin Cancer Inform. 2019;3:1–9.CrossRef
4.
go back to reference Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v8–30.CrossRef Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v8–30.CrossRef
5.
go back to reference Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRef Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRef
6.
go back to reference Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci. 2001;98:10869–74.CrossRef Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci. 2001;98:10869–74.CrossRef
7.
go back to reference Sotiriou C, Neo S-Y, McShane LM, Korn EL, Long PM, Jazaeri A, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci. 2003;100:10393–8.CrossRef Sotiriou C, Neo S-Y, McShane LM, Korn EL, Long PM, Jazaeri A, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci. 2003;100:10393–8.CrossRef
8.
go back to reference Paik S, Shak S, Tang G, et al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer. N Engl J Med. 2004;351:2817–26.CrossRef Paik S, Shak S, Tang G, et al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer. N Engl J Med. 2004;351:2817–26.CrossRef
9.
go back to reference Paik S, Tang G, Shak S, et al. Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor-Positive Breast Cancer. J Clin Oncol. 2006;24:3726–34.CrossRef Paik S, Tang G, Shak S, et al. Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor-Positive Breast Cancer. J Clin Oncol. 2006;24:3726–34.CrossRef
10.
go back to reference Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, estrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55–65.CrossRef Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, estrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55–65.CrossRef
11.
go back to reference Sparano JA, Gray RJ, Makower DF, et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2015;373:2005–144.CrossRef Sparano JA, Gray RJ, Makower DF, et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2015;373:2005–144.CrossRef
12.
go back to reference Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111–21.CrossRef Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111–21.CrossRef
13.
go back to reference Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34:1134–50.CrossRef Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34:1134–50.CrossRef
14.
go back to reference Gradishar WJ, Anderson BO, Balassanian R, et al. NCCN guidelines insights: breast cancer, version 1.2017. J Natl Compr Cancer Netw JNCCN. 2017;15:433–51.CrossRef Gradishar WJ, Anderson BO, Balassanian R, et al. NCCN guidelines insights: breast cancer, version 1.2017. J Natl Compr Cancer Netw JNCCN. 2017;15:433–51.CrossRef
16.
go back to reference Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26:1533–46.CrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26:1533–46.CrossRef
17.
go back to reference Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. Updates to the AJCC Breast TNM Staging System. The 8th Edition. CA Cancer J Clin. 2017;67:290–303.CrossRef Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. Updates to the AJCC Breast TNM Staging System. The 8th Edition. CA Cancer J Clin. 2017;67:290–303.CrossRef
18.
go back to reference Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, et al. Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol. 2013;26:658–64.CrossRef Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, et al. Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol. 2013;26:658–64.CrossRef
19.
go back to reference Hou Y, Tozbikian G, Zynger DL, Li Z. using the modified Magee equation to identify patients unlikely to benefit from the 21-Gene recurrence score assay (Oncotype DX Assay). Am J Clin Pathol. 2017;147:541–8.CrossRef Hou Y, Tozbikian G, Zynger DL, Li Z. using the modified Magee equation to identify patients unlikely to benefit from the 21-Gene recurrence score assay (Oncotype DX Assay). Am J Clin Pathol. 2017;147:541–8.CrossRef
20.
go back to reference Harowicz MR, Robinson TJ, Dinan MA, Saha A, Marks JR, Marcom PK, et al. Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset. Breast Cancer Res Treat. 2017;162:1–10.CrossRef Harowicz MR, Robinson TJ, Dinan MA, Saha A, Marks JR, Marcom PK, et al. Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset. Breast Cancer Res Treat. 2017;162:1–10.CrossRef
21.
go back to reference Sughayer M, Alaaraj R, Alsughayer A. Applying new Magee equations for predicting the Oncotype Dx recurrence score. Breast Cancer. 2018;25:597–604.CrossRef Sughayer M, Alaaraj R, Alsughayer A. Applying new Magee equations for predicting the Oncotype Dx recurrence score. Breast Cancer. 2018;25:597–604.CrossRef
22.
go back to reference Yeo B, Zabaglo L, Hills M, Dodson A, Smith I, Dowsett M. Clinical utility of the IHC4+C score in estrogen receptor-positive early breast cancer: a prospective decision impact study. Br J Cancer. 2015;113:390–5.CrossRef Yeo B, Zabaglo L, Hills M, Dodson A, Smith I, Dowsett M. Clinical utility of the IHC4+C score in estrogen receptor-positive early breast cancer: a prospective decision impact study. Br J Cancer. 2015;113:390–5.CrossRef
23.
go back to reference Flanagan MB, Dabbs DJ, Brufsky AM, Beriwal S, Bhargava R. Histopathologic variables predict Oncotype DXTM Recurrence Score. Mod Pathol. 2008;21:1255–61.CrossRef Flanagan MB, Dabbs DJ, Brufsky AM, Beriwal S, Bhargava R. Histopathologic variables predict Oncotype DXTM Recurrence Score. Mod Pathol. 2008;21:1255–61.CrossRef
24.
go back to reference Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. Routine pathologic parameters can predict Oncotype DXTM recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat. 2012;131:413–24.CrossRef Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. Routine pathologic parameters can predict Oncotype DXTM recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat. 2012;131:413–24.CrossRef
25.
go back to reference Tang P, Wang J, Hicks DG, et al. A lower allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-Gene assay in breast cancer. Cancer Invest. 2010;28:978–82.CrossRef Tang P, Wang J, Hicks DG, et al. A lower allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-Gene assay in breast cancer. Cancer Invest. 2010;28:978–82.CrossRef
26.
go back to reference Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: american society of clinical oncology/college of american pathologists clinical practice guideline focused update. J Clin Oncol. 2018;36:2105–22.CrossRef Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: american society of clinical oncology/college of american pathologists clinical practice guideline focused update. J Clin Oncol. 2018;36:2105–22.CrossRef
27.
go back to reference Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259–71.CrossRef Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259–71.CrossRef
28.
go back to reference Zemouri R, Omri N, Morello B, Devalland C, Arnould L, Zerhouni N, et al. Constructive deep neural network for breast cancer diagnosis. IFAC-Pap. 2018;51:98–103.CrossRef Zemouri R, Omri N, Morello B, Devalland C, Arnould L, Zerhouni N, et al. Constructive deep neural network for breast cancer diagnosis. IFAC-Pap. 2018;51:98–103.CrossRef
29.
go back to reference Zemouri R, Omri N, Devalland C, Arnould L, Morello B, Zerhouni N, et al. Breast cancer diagnosis based on joint variable selection and Constructive Deep Neural Network. 2018 IEEE 4th Middle East Conf. Tunis: Biomed. Eng. MECBME. IEEE; 2018. p. 159–164. Zemouri R, Omri N, Devalland C, Arnould L, Morello B, Zerhouni N, et al. Breast cancer diagnosis based on joint variable selection and Constructive Deep Neural Network. 2018 IEEE 4th Middle East Conf. Tunis: Biomed. Eng. MECBME. IEEE; 2018. p. 159–164.
31.
go back to reference van der Maaten L, Hinton G. Visualizing data using t-SNE. J Mach Learn Res. 2008;9:2579–605. van der Maaten L, Hinton G. Visualizing data using t-SNE. J Mach Learn Res. 2008;9:2579–605.
32.
go back to reference Khoury T, Huang X, Chen X, Wang D, Liu S, Opyrchal M. Comprehensive histologic scoring to maximize the predictability of pathology-generated equation of breast cancer oncotype DX Recurrence Score. Appl Immunohistochem Mol Morphol. 2016;24:703–11.CrossRef Khoury T, Huang X, Chen X, Wang D, Liu S, Opyrchal M. Comprehensive histologic scoring to maximize the predictability of pathology-generated equation of breast cancer oncotype DX Recurrence Score. Appl Immunohistochem Mol Morphol. 2016;24:703–11.CrossRef
33.
go back to reference Turner BM, Skinner KA, Tang P, Jackson MC, Soukiazian N, Shayne M, et al. Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score. Mod Pathol. 2015;28:921–31.CrossRef Turner BM, Skinner KA, Tang P, Jackson MC, Soukiazian N, Shayne M, et al. Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score. Mod Pathol. 2015;28:921–31.CrossRef
34.
go back to reference Acs G, Esposito NN, Kiluk J, Loftus L, Laronga C. A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas. Mod Pathol. 2012;25:556–66.CrossRef Acs G, Esposito NN, Kiluk J, Loftus L, Laronga C. A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas. Mod Pathol. 2012;25:556–66.CrossRef
35.
go back to reference Kim I, Choi HJ, Ryu JM, Lee SK, Yu JH, Kim SW, et al. A predictive model for high/low risk group according to oncotype DX recurrence score using machine learning. Eur J Surg Oncol. 2019;45:134–40.CrossRef Kim I, Choi HJ, Ryu JM, Lee SK, Yu JH, Kim SW, et al. A predictive model for high/low risk group according to oncotype DX recurrence score using machine learning. Eur J Surg Oncol. 2019;45:134–40.CrossRef
36.
go back to reference Bhargava R, Clark BZ, Dabbs DJ. Breast cancers with Magee equation score of less than 18, or 18–25 and Mitosis score of 1, do not require Oncotype DX testing. Am J Clin Pathol. 2019;151:316–23.CrossRef Bhargava R, Clark BZ, Dabbs DJ. Breast cancers with Magee equation score of less than 18, or 18–25 and Mitosis score of 1, do not require Oncotype DX testing. Am J Clin Pathol. 2019;151:316–23.CrossRef
37.
go back to reference Singh K, He X, Kalife ET, Ehdaivand S, Wang Y, Sung CJ. Relationship of histologic grade and histologic subtype with oncotype Dx recurrence score; retrospective review of 863 breast cancer oncotype Dx results. Breast Cancer Res Treat. 2018;168:29–34.CrossRef Singh K, He X, Kalife ET, Ehdaivand S, Wang Y, Sung CJ. Relationship of histologic grade and histologic subtype with oncotype Dx recurrence score; retrospective review of 863 breast cancer oncotype Dx results. Breast Cancer Res Treat. 2018;168:29–34.CrossRef
38.
go back to reference Penault-Llorca F, Radosevic-Robin N. Ki67 assessment in breast cancer: an update. Pathology (Phila). 2017;49:166–71. Penault-Llorca F, Radosevic-Robin N. Ki67 assessment in breast cancer: an update. Pathology (Phila). 2017;49:166–71.
39.
go back to reference Dumay A, Feugeas J-P, Wittmer E, et al. Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer. 2013;132:1227–311.CrossRef Dumay A, Feugeas J-P, Wittmer E, et al. Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer. 2013;132:1227–311.CrossRef
40.
go back to reference Lee SK, Bae SY, Lee JH, Lee H-C, Yi H, Kil WH, et al. Distinguishing low-risk luminal a breast cancer subtypes with Ki-67 and p53 is more predictive of long-term survival. PLoS ONE. 2015;10:e0124658.CrossRef Lee SK, Bae SY, Lee JH, Lee H-C, Yi H, Kil WH, et al. Distinguishing low-risk luminal a breast cancer subtypes with Ki-67 and p53 is more predictive of long-term survival. PLoS ONE. 2015;10:e0124658.CrossRef
41.
go back to reference Millar EKA, Graham PH, McNeil CM, et al. Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53. Br J Cancer. 2011;105:272–80.CrossRef Millar EKA, Graham PH, McNeil CM, et al. Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53. Br J Cancer. 2011;105:272–80.CrossRef
42.
go back to reference Feeley LP, Mulligan AM, Pinnaduwage D, Bull SB, Andrulis IL. Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information. Mod Pathol. 2014;27:554–61.CrossRef Feeley LP, Mulligan AM, Pinnaduwage D, Bull SB, Andrulis IL. Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information. Mod Pathol. 2014;27:554–61.CrossRef
43.
go back to reference Litjens G, Kooi T, Bejnordi BE, Setio AA, Ciompi F, Ghafoorian M, et al. A survey on deep learning in medical image analysis. Med Image Anal. 2017;42:60–88.CrossRef Litjens G, Kooi T, Bejnordi BE, Setio AA, Ciompi F, Ghafoorian M, et al. A survey on deep learning in medical image analysis. Med Image Anal. 2017;42:60–88.CrossRef
44.
go back to reference Khan A, Sohail A, Zahoora U, Qureshi AS (2019) A Survey of the Recent Architectures of Deep Convolutional Neural Networks, preprint arXiv: 1901.06032 Khan A, Sohail A, Zahoora U, Qureshi AS (2019) A Survey of the Recent Architectures of Deep Convolutional Neural Networks, preprint arXiv: 1901.06032
45.
go back to reference Khan A, Sohail A, Ali A (2018) A New Channel Boosted Convolutional Neural Network using Transfer Learning, preprint arXiv: 1804.08528 Khan A, Sohail A, Ali A (2018) A New Channel Boosted Convolutional Neural Network using Transfer Learning, preprint arXiv: 1804.08528
46.
go back to reference Zemouri R, Zerhouni N, Racoceanu D. Deep learning in the biomedical applications: recent and future status. Appl Sci. 2019;9:1526.CrossRef Zemouri R, Zerhouni N, Racoceanu D. Deep learning in the biomedical applications: recent and future status. Appl Sci. 2019;9:1526.CrossRef
Metadata
Title
Prediction of Oncotype DX recurrence score using deep multi-layer perceptrons in estrogen receptor-positive, HER2-negative breast cancer
Authors
Aline Baltres
Zeina Al Masry
Ryad Zemouri
Severine Valmary-Degano
Laurent Arnould
Noureddine Zerhouni
Christine Devalland
Publication date
01-09-2020
Publisher
Springer Japan
Published in
Breast Cancer / Issue 5/2020
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-020-01100-4

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