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Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age

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Abstract

Purpose

The use of the Oncotype DX recurrence score (RS) to predict chemotherapy benefit in patients with hormone receptor-positive/HER2 negative (HR+/HER2-) breast cancer has recently expanded to include postmenopausal patients with N1 disease. RS availability is limited in resource-poor settings, however, prompting the development of statistical models that predict RS using clinicopathologic features. We sought to assess the performance of our supervised machine learning model in a cohort of patients > 50 years of age with N1 disease.

Methods

We identified patients > 50 years of age with pT1-2N1 HR+/HER2- breast cancer and applied the statistical model previously developed in a node-negative cohort, which uses age, pathologic tumor size, histology, progesterone receptor expression, lymphovascular invasion, and tumor grade to predict RS. We measured the model’s ability to predict RS risk category (low: RS ≤ 25; high: RS > 25).

Results

Our cohort included 401 patients, 60.6% of whom had macrometastases, with a median of 1 positive node. The majority of patients had a low-risk observed RS (85.8%). For predicting RS category, the model had specificity of 97.3%, sensitivity of 31.8%, a negative predictive value of 87.9%, and a positive predictive value of 70.0%.

Conclusion

Our model, developed in a cohort of node-negative patients, was highly specific for identifying cN1 patients > 50 years of age with a low RS who could safely avoid chemotherapy. The use of this model for identifying patients in whom genomic testing is unnecessary would help decrease the cost burden in resource-poor settings as reliance on RS for adjuvant treatment recommendations increases.

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Data availability

The datasets generated and/or analyzed during the study are available from the corresponding author on reasonable request.

References

  1. Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826. https://doi.org/10.1056/NEJMoa041588

    Article  CAS  PubMed  Google Scholar 

  2. Paik S, Tang G, Shak S et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734. https://doi.org/10.1200/JCO.2005.04.7985

    Article  CAS  PubMed  Google Scholar 

  3. Sparano JA, Gray RJ, Makower DF et al (2018) Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 379:111–121. https://doi.org/10.1056/NEJMoa1804710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lund MJ, Mosunjac M, Davis KM et al (2012) 21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome. Cancer 118:788–796. https://doi.org/10.1002/CNCR.26180

    Article  PubMed  Google Scholar 

  5. Guth AA, Fineberg S, Fei K et al (2013) Utilization of oncotype DX in an inner city population: race or place? Int J Breast Cancer 2013:1–3. https://doi.org/10.1155/2013/653805

    Article  Google Scholar 

  6. Cress RD, Chen YS, Morris CR et al (2016) Underutilization of gene expression profiling for early-stage breast cancer in California. Cancer Causes Control 27:721–727. https://doi.org/10.1007/S10552-016-0743-4/TABLES/3

    Article  PubMed  PubMed Central  Google Scholar 

  7. Press DJ, Ibraheem A, Dolan ME et al (2018) Racial disparities in omission of oncotype DX but no racial disparities in chemotherapy receipt following completed oncotype DX test results. Breast Cancer Res Treat 168:207–220. https://doi.org/10.1007/s10549-017-4587-8

    Article  PubMed  Google Scholar 

  8. Kozick Z, Hashmi A, Dove J et al (2018) Disparities in compliance with the oncotype DX breast cancer test in the United States: a national cancer data base assessment. Am J Surg 215:686–692. https://doi.org/10.1016/J.AMJSURG.2017.05.008

    Article  PubMed  Google Scholar 

  9. Roberts MC, Kurian AW, Petkov VI (2019) Uptake of the 21-gene assay among women with node-positive, hormone receptor-positive breast cancer. J Natl Compr Canc Netw 17:662–668. https://doi.org/10.6004/JNCCN.2018.7266

    Article  CAS  PubMed  Google Scholar 

  10. Choi JDW, Hughes TMD, Marx G et al (2022) The utility of the oncotype DX test for breast cancer patients in an Australian multidisciplinary setting. Breast J 2022:1–7. https://doi.org/10.1155/2022/1199245

    Article  CAS  Google Scholar 

  11. Pawloski KR, Gonen M, Wen HY et al (2022) Supervised machine learning model to predict oncotype DX risk category in patients over age 50. Breast Cancer Res Treat 191:423–430. https://doi.org/10.1007/S10549-021-06443-W

    Article  CAS  PubMed  Google Scholar 

  12. Kalinsky K, Barlow WE, Gralow JR et al (2021) 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med 385:2336–2347. https://doi.org/10.1056/NEJMOA2108873/SUPPL_FILE/NEJMOA2108873_DATA-SHARING.PDF

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ha R, Chang P, Mutasa S et al (2019) Convolutional neural network using a breast MRI tumor dataset can predict oncotype Dx recurrence score. J Magn Reson Imaging 49:518–524. https://doi.org/10.1002/JMRI.26244

    Article  PubMed  Google Scholar 

  14. Flanagan MB, Dabbs DJ, Brufsky AM et al (2008) Histopathologic variables predict oncotype DXTM recurrence score. Mod Pathol 21:1255–1261. https://doi.org/10.1038/modpathol.2008.54

    Article  CAS  PubMed  Google Scholar 

  15. Auerbach J, Kim M, Fineberg S (2010) Can features evaluated in the routine pathologic assessment of lymph node-negative estrogen receptor-positive stage I or II invasive breast cancer be used to predict the oncotype DX recurrence score? Arch Pathol Lab Med 134:1697–1701. https://doi.org/10.5858/2009-0439-OAR.1

    Article  PubMed  Google Scholar 

  16. Allison KH, Kandalaft PL, Sitlani CM et al (2012) 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 131:413–424. https://doi.org/10.1007/S10549-011-1416-3/TABLES/5

    Article  CAS  PubMed  Google Scholar 

  17. Mattes MD, Mann JM, Ashamalla H, Tejwani A (2013) Routine histopathologic characteristics can predict oncotype DXTM recurrence score in subsets of breast cancer patients. Cancer Investig 31:604–606. https://doi.org/10.3109/07357907.2013.849725

    Article  CAS  Google Scholar 

  18. Gage MM, Rosman M, Mylander WC et al (2015) A validated model for identifying patients unlikely to benefit from the 21-gene recurrence score assay. Clin Breast Cancer 15:467–472. https://doi.org/10.1016/J.CLBC.2015.04.006

    Article  PubMed  PubMed Central  Google Scholar 

  19. Turner BM, Skinner KA, Tang P et al (2015) Use of modified Magee equations and histologic criteria to predict the oncotype DX recurrence score. Mod Pathol 28:921–931. https://doi.org/10.1038/MODPATHOL.2015.50

    Article  PubMed  Google Scholar 

  20. Eaton AA, Pesce CE, Murphy JO et al (2017) Estimating the oncotype DX score: validation of an inexpensive estimation tool. Breast Cancer Res Treat 161:435–441. https://doi.org/10.1007/S10549-016-4069-4/TABLES/3

    Article  CAS  PubMed  Google Scholar 

  21. Orucevic A, Bell JL, King M et al (2019) Nomogram update based on TAILORx clinical trial results—oncotype DX breast cancer recurrence score can be predicted using clinicopathologic data. Breast 46:116–125. https://doi.org/10.1016/J.BREAST.2019.05.006

    Article  PubMed  Google Scholar 

  22. Lee SB, Kim J, Sohn G et al (2019) A nomogram for predicting the oncotype DX recurrence score in women with T1–3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2 (HER2)-negative breast cancer. Cancer Res Treat 51:1073. https://doi.org/10.4143/CRT.2018.357

    Article  CAS  PubMed  Google Scholar 

  23. Yoo SH, Kim TY, Kim M et al (2020) Development of a nomogram to predict the recurrence score of 21-gene prediction assay in hormone receptor-positive early breast cancer. Clin Breast Cancer 20:98-107.e1. https://doi.org/10.1016/J.CLBC.2019.07.010

    Article  CAS  PubMed  Google Scholar 

  24. Batra A, Nixon NA, Roldan-Urgoiti G et al (2021) Developing a clinical-pathologic model to predict genomic risk of recurrence in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative, node negative breast cancer. Cancer Treat Res Commun 28:100401. https://doi.org/10.1016/J.CTARC.2021.100401

    Article  PubMed  Google Scholar 

  25. Marazzi F, Barone R, Masiello V et al (2020) Oncotype DX predictive nomogram for recurrence score output: the novel system ADAPTED01 based on quantitative immunochemistry analysis. Clin Breast Cancer 20:e600–e611. https://doi.org/10.1016/J.CLBC.2020.04.012

    Article  CAS  PubMed  Google Scholar 

  26. Acs G, Esposito NN, Kiluk J et al (2011) 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. Modern Pathol 25:556–566. https://doi.org/10.1038/modpathol.2011.194

    Article  CAS  Google Scholar 

  27. Kalinsky KM, Barlow WE, Gralow JR et al (2022) Abstract GS2-07: Updated results from a phase 3 randomized clinical trial in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) ≤ 25 randomized to endocrine therapy (ET) +/- chemotherapy (CT): SWOG S1007 (RxPONDER). Can Res 82:GS2-07. https://doi.org/10.1158/1538-7445.SABCS21-GS2-07

    Article  Google Scholar 

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Funding

This work was supported in part by NIH/NCI Cancer Center Support Grant No. P30CA008748 to Memorial Sloan Kettering Cancer Center. Editorial support in preparing this manuscript was provided by Hannah Rice, BA, ELS.

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Correspondence to Mahmoud El-Tamer.

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Conflict of interest

Dr. Monica Morrow has received honoraria from Exact Sciences and Roche. All other authors have no conflict of interest disclosures to report.

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This study was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board.

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Informed consent for this study was waived by the Memorial Sloan Kettering Cancer Center Institutional Review Board.

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Williams, A.D., Pawloski, K.R., Wen, H.Y. et al. Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age. Breast Cancer Res Treat 196, 565–570 (2022). https://doi.org/10.1007/s10549-022-06763-5

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