Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2017

Open Access 01-05-2017 | Preclinical study

Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data

Authors: Amila Orucevic, John L. Bell, Alison P. McNabb, Robert E. Heidel

Published in: Breast Cancer Research and Treatment | Issue 1/2017

Login to get access

Abstract

Purpose

Oncotype DX (ODX) recurrence score (RS) breast cancer (BC) assay is costly, and performed in only ~1/3 of estrogen receptor (ER)-positive BC patients in the USA. We have now developed a user-friendly nomogram surrogate prediction model for ODX based on a large dataset from the National Cancer Data Base (NCDB) to assist in selecting patients for which further ODX testing may not be necessary and as a surrogate for patients for which ODX testing is not affordable or available.

Methods

Six clinicopathologic variables of 27,719 ODX-tested ER+/HER2−/lymph node-negative patients with 6–50 mm tumor size captured by the NCDB from 2010 to 2012 were assessed with logistic regression to predict high-risk or low-risk ODXRS test results with TAILORx-trial and commercial cut-off values; 12,763 ODX-tested patients in 2013 were used for external validation. The predictive accuracy of the regression model was yielded using a Receiver Operator Characteristic analysis. Model fit was analyzed by plotting the predicted probabilities against the actual probabilities. A user-friendly calculator version of nomograms is available online at the University of Tennessee Medical Center website (Knoxville, TN).

Results

Grade and progesterone receptor status were the highest predictors of both low-risk and high-risk ODXRS, followed by age, tumor size, histologic tumor type and lymph-vascular invasion (C-indexes-.0.85 vs. 0.88 for TAILORx-trial vs. commercial cut-off values, respectively).

Conclusion

This is the first study of this scale showing confidently that clinicopathologic variables can be used for prediction of low-risk or high-risk ODXRS using our nomogram models. These novel nomograms will be useful tools to help physicians and patients decide whether further ODX testing is necessary and are excellent surrogates for patients for which ODX testing is not affordable or available.
Appendix
Available only for authorised users
Literature
1.
go back to reference Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826. doi:10.1056/NEJMoa041588 CrossRefPubMed Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826. doi:10.​1056/​NEJMoa041588 CrossRefPubMed
2.
go back to reference Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734. doi:10.1200/jco.2005.04.7985 CrossRefPubMed Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734. doi:10.​1200/​jco.​2005.​04.​7985 CrossRefPubMed
3.
go back to reference Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, Van Poznak C, Bast RC, Hayes DF (2016) 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 34(10):1134–1150. doi:10.1200/jco.2015.65.2289 CrossRefPubMedPubMedCentral Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, Van Poznak C, Bast RC, Hayes DF (2016) 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 34(10):1134–1150. doi:10.​1200/​jco.​2015.​65.​2289 CrossRefPubMedPubMedCentral
4.
go back to reference Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz M, Goldstein LJ, Hudis CA, Isakoff SJ, Marcom PK, Mayer IA, McCormick B, Moran M, Patel SA, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Smith KL, Smith ML, Soliman H, Somlo G, Telli M, Ward JH, Shead DA, Kumar R (2015) Breast cancer, version 1.2016. J Natl Compr Canc Netw 13(12):1475–1485PubMed Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz M, Goldstein LJ, Hudis CA, Isakoff SJ, Marcom PK, Mayer IA, McCormick B, Moran M, Patel SA, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Smith KL, Smith ML, Soliman H, Somlo G, Telli M, Ward JH, Shead DA, Kumar R (2015) Breast cancer, version 1.2016. J Natl Compr Canc Netw 13(12):1475–1485PubMed
5.
go back to reference Henry NL, Somerfield MR, Abramson VG, Allison KH, Anders CK, Chingos DT, Hurria A, Openshaw TH, Krop IE (2016) Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations. J Clin Oncol 34(19):2303–2311. doi:10.1200/jco.2015.65.8609 CrossRefPubMed Henry NL, Somerfield MR, Abramson VG, Allison KH, Anders CK, Chingos DT, Hurria A, Openshaw TH, Krop IE (2016) Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations. J Clin Oncol 34(19):2303–2311. doi:10.​1200/​jco.​2015.​65.​8609 CrossRefPubMed
6.
go back to reference Orucevic A, Heidel RE, Bell JL (2016) Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: lessons learned from the 2010 to 2012 National Cancer Data Base analysis. Breast Cancer Res Treat 157(3):427–435. doi:10.1007/s10549-016-3833-9 CrossRefPubMedPubMedCentral Orucevic A, Heidel RE, Bell JL (2016) Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: lessons learned from the 2010 to 2012 National Cancer Data Base analysis. Breast Cancer Res Treat 157(3):427–435. doi:10.​1007/​s10549-016-3833-9 CrossRefPubMedPubMedCentral
7.
go back to reference Albanell J, Svedman C, Gligorov J, Holt SD, Bertelli G, Blohmer JU, Rouzier R, Lluch A, Eiermann W (2016) Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer. Eur J Cancer (Oxf Eng 1990) 66:104–113. doi:10.1016/j.ejca.2016.06.027 CrossRef Albanell J, Svedman C, Gligorov J, Holt SD, Bertelli G, Blohmer JU, Rouzier R, Lluch A, Eiermann W (2016) Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer. Eur J Cancer (Oxf Eng 1990) 66:104–113. doi:10.​1016/​j.​ejca.​2016.​06.​027 CrossRef
8.
go back to reference Roberts MC, Weinberger M, Dusetzina SB, Dinan MA, Reeder-Hayes KE, Carey LA, Troester MA, Wheeler SB (2016) Racial variation in the uptake of oncotype DX testing for early-stage breast cancer. J Clin Oncol 34(2):130–138. doi:10.1200/jco.2015.63.2489 CrossRefPubMed Roberts MC, Weinberger M, Dusetzina SB, Dinan MA, Reeder-Hayes KE, Carey LA, Troester MA, Wheeler SB (2016) Racial variation in the uptake of oncotype DX testing for early-stage breast cancer. J Clin Oncol 34(2):130–138. doi:10.​1200/​jco.​2015.​63.​2489 CrossRefPubMed
10.
go back to reference Lund MJ, Mosunjac M, Davis KM, Gabram-Mendola S, Rizzo M, Bumpers HL, Hearn S, Zelnak A, Styblo T, O’Regan RM (2012) 21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome. Cancer 118(3):788–796. doi:10.1002/cncr.26180 CrossRefPubMed Lund MJ, Mosunjac M, Davis KM, Gabram-Mendola S, Rizzo M, Bumpers HL, Hearn S, Zelnak A, Styblo T, O’Regan RM (2012) 21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome. Cancer 118(3):788–796. doi:10.​1002/​cncr.​26180 CrossRefPubMed
13.
go back to reference Ingoldsby H, Webber M, Wall D, Scarrott C, Newell J, Callagy G (2013) Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis. Breast (Edinb Scotl) 22(5):879–886. doi:10.1016/j.breast.2013.04.008 CrossRef Ingoldsby H, Webber M, Wall D, Scarrott C, Newell J, Callagy G (2013) Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis. Breast (Edinb Scotl) 22(5):879–886. doi:10.​1016/​j.​breast.​2013.​04.​008 CrossRef
14.
15.
go back to reference Kim HS, Umbricht CB, Illei PB, Cimino-Mathews A, Cho S, Chowdhury N, Figueroa-Magalhaes MC, Pesce C, Jeter SC, Mylander C, Rosman M, Tafra L, Turner BM, Hicks DG, Jensen TA, Miller DV, Armstrong DK, Connolly RM, Fetting JH, Miller RS, Park BH, Stearns V, Visvanathan K, Wolff AC, Cope L (2016) Optimizing the use of gene expression profiling in early-stage breast cancer. J Clin Oncol 34(36):4390–4397CrossRefPubMed Kim HS, Umbricht CB, Illei PB, Cimino-Mathews A, Cho S, Chowdhury N, Figueroa-Magalhaes MC, Pesce C, Jeter SC, Mylander C, Rosman M, Tafra L, Turner BM, Hicks DG, Jensen TA, Miller DV, Armstrong DK, Connolly RM, Fetting JH, Miller RS, Park BH, Stearns V, Visvanathan K, Wolff AC, Cope L (2016) Optimizing the use of gene expression profiling in early-stage breast cancer. J Clin Oncol 34(36):4390–4397CrossRefPubMed
18.
go back to reference Cadoo KA, Fornier MN, Morris PG (2013) Biological subtypes of breast cancer: current concepts and implications for recurrence patterns. Quart J Nucl Med Mol Imaging 57(4):312–321 Cadoo KA, Fornier MN, Morris PG (2013) Biological subtypes of breast cancer: current concepts and implications for recurrence patterns. Quart J Nucl Med Mol Imaging 57(4):312–321
21.
go back to reference Harrell F (2015) Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis, 2nd edn. Springer, New YorkCrossRef Harrell F (2015) Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis, 2nd edn. Springer, New YorkCrossRef
24.
go back to reference Tang P, Wang J, Hicks DG, Wang X, Schiffhauer L, McMahon L, Yang Q, Shayne M, Huston A, Skinner KA, Griggs J, Lyman G (2010) A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer. Cancer Invest 28(9):978–982. doi:10.3109/07357907.2010.496754 CrossRefPubMed Tang P, Wang J, Hicks DG, Wang X, Schiffhauer L, McMahon L, Yang Q, Shayne M, Huston A, Skinner KA, Griggs J, Lyman G (2010) A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer. Cancer Invest 28(9):978–982. doi:10.​3109/​07357907.​2010.​496754 CrossRefPubMed
25.
go back to reference Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM (2012) Routine pathologic parameters can predict Oncotype DX recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat 131(2):413–424. doi:10.1007/s10549-011-1416-3 CrossRefPubMed Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM (2012) Routine pathologic parameters can predict Oncotype DX recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat 131(2):413–424. doi:10.​1007/​s10549-011-1416-3 CrossRefPubMed
27.
go back to reference Turner BM, Skinner KA, Tang P, Jackson MC, Soukiazian N, Shayne M, Huston A, Ling M, Hicks DG (2015) Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score. Mod Pathol 28(7):921–931. doi:10.1038/modpathol.2015.50 CrossRefPubMed Turner BM, Skinner KA, Tang P, Jackson MC, Soukiazian N, Shayne M, Huston A, Ling M, Hicks DG (2015) Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score. Mod Pathol 28(7):921–931. doi:10.​1038/​modpathol.​2015.​50 CrossRefPubMed
28.
go back to reference Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014. doi:10.1056/NEJMoa1510764 CrossRefPubMedPubMedCentral Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373(21):2005–2014. doi:10.​1056/​NEJMoa1510764 CrossRefPubMedPubMedCentral
29.
go back to reference AJCC (2016) AJCC cancer staging manual, 8th edn. Springer, Chicago AJCC (2016) AJCC cancer staging manual, 8th edn. Springer, Chicago
30.
go back to reference Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219CrossRefPubMed Galea MH, Blamey RW, Elston CE, Ellis IO (1992) The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22(3):207–219CrossRefPubMed
31.
go back to reference Todd JH, Dowle C, Williams MR, Elston CW, Ellis IO, Hinton CP, Blamey RW, Haybittle JL (1987) Confirmation of a prognostic index in primary breast cancer. Br J Cancer 56(4):489–492CrossRefPubMedPubMedCentral Todd JH, Dowle C, Williams MR, Elston CW, Ellis IO, Hinton CP, Blamey RW, Haybittle JL (1987) Confirmation of a prognostic index in primary breast cancer. Br J Cancer 56(4):489–492CrossRefPubMedPubMedCentral
32.
go back to reference Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ, Panel M (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of Oncology 22(8):1736–1747. doi:10.1093/annonc/mdr304 CrossRefPubMedPubMedCentral Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ, Panel M (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of Oncology 22(8):1736–1747. doi:10.​1093/​annonc/​mdr304 CrossRefPubMedPubMedCentral
33.
go back to reference Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795. doi:10.1200/JCO.2009.25.6529 CrossRefPubMedPubMedCentral Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795. doi:10.​1200/​JCO.​2009.​25.​6529 CrossRefPubMedPubMedCentral
Metadata
Title
Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data
Authors
Amila Orucevic
John L. Bell
Alison P. McNabb
Robert E. Heidel
Publication date
01-05-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4170-3

Other articles of this Issue 1/2017

Breast Cancer Research and Treatment 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine