Logistic regression analysis of the recurrence score (RS) as a categorical variable using standard thresholds for high-risk definition according to menopausal status
FM: Conceptualization, Formal analysis, Writing—original draft, Supervision. SN: Conceptualization, Writing—original draft. G Motta: Conceptualization, Data curation, Writing—review & editing, Supervision. MVS: Resources. C Carnaghi: Resources. MP: Data curation. CG: Data curation. G Corsaro: Data curation. C Conti: Writing—review & editing. LM: Writing—review & editing. GP: Writing—review & editing. SM: Investigation, Resources. GMV: Investigation, Resources. G Magro: Investigation, Resources. G Catanuto: Resources, Writing—review & editing. G Castiglione: Resources, Writing—review & editing. FC: Resources, Writing—review & editing. AR: Investigation, Resources. MC: Conceptualization, Resources. PV: Conceptualization, Resources, Supervision, Writing—review & editing. All the authors read and approved the final version of the manuscript.
Conflicts of interest
Antonio Rizzo and Stefano Marletta who are the Guest Editors of Exploration of Targeted Anti-tumor Therapy had no involvement in the decision-making or the review process of this manuscript. The other authors declare that they have no conflicts of interest related to the present work.
Ethical approval
The study was conducted in accordance with the 2013 Declaration of Helsinki and Good Clinical Practice. No ethics approval is required for this study as this is a retrospective collection of data from a standard database for quality assurance assessment and not an observational study.
Consent to participate
Informed consent was obtained from all individual participants included in the study. Patients consent to sharing data belonging to this database upon admission. Patients also signed written informed consent before Oncotype DX testing.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Bottosso M, Miglietta F, Vernaci GM, Giarratano T, Dieci MV, Guarneri V, et al. Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2– Breast Cancer.Clin Cancer Res. 2024;30:2884–94. [DOI] [PubMed] [PMC]
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.N Engl J Med. 2015;373:2005–14. [DOI] [PubMed] [PMC]
Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial.J Natl Cancer Inst. 2001;93:684–90. [DOI] [PubMed]
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.N Engl J Med. 2004;351:2817–26. [DOI] [PubMed]
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.N Engl J Med. 2018;379:111–21. [DOI] [PubMed] [PMC]
Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.N Engl J Med. 2021;385:2336–47. [DOI] [PubMed] [PMC]
Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. 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. 2012;131:413–24. [DOI] [PubMed]
Zhang S, Fitzsimmons KC, Hurvitz SA. Oncotype DX Recurrence Score in premenopausal women.Ther Adv Med Oncol. 2022;14:17588359221081077. [DOI] [PubMed] [PMC]
Gentile D, Martorana F, Karakatsanis A, Caruso F, Caruso M, Castiglione G, et al. Predictors of mastectomy in breast cancer patients with complete remission of primary tumor after neoadjuvant therapy: A retrospective study.Eur J Surg Oncol. 2024;50:108732. [DOI] [PubMed]
Catanuto G, Gentile D, Martorana F, Tomatis M, Ponti A, Marotti L, et al.; EUSOMA Working Group. Clinico-pathological features predicting indication to mastectomy in breast cancer patients achieving complete response after neoadjuvant therapy: A retrospective analysis of the EUSOMA database.Eur J Surg Oncol. 2025;51:109643. [DOI] [PubMed]
Syed YY. Oncotype DX Breast Recurrence Score®: A Review of its Use in Early-Stage Breast Cancer.Mol Diagn Ther. 2020;24:621–32. [DOI] [PubMed]
Venetis K, Pescia C, Cursano G, Frascarelli C, Mane E, De Camilli E, et al. The Evolving Role of Genomic Testing in Early Breast Cancer: Implications for Diagnosis, Prognosis, and Therapy.Int J Mol Sci. 2024;25:5717. [DOI] [PubMed] [PMC]
Piccart MJ, Kalinsky K, Gray R, Barlow WE, Poncet C, Cardoso F, et al. Gene expression signatures for tailoring adjuvant chemotherapy of luminal breast cancer: stronger evidence, greater trust.Ann Oncol. 2021;32:1077–82. [DOI] [PubMed]
Alkushi A, Omair A, Arabi H, Masuadi E, Abualkhair O. Predictability of 21-Gene Recurrence Score Assay by Using Pathological and Immunohistochemical Parameters in Breast Cancer.Breast Cancer (Auckl). 2020;14:1178223420977848. [DOI] [PubMed] [PMC]
Lashen A, Toss MS, Fadhil W, Oni G, Madhusudan S, Rakha E. Evaluation oncotype DX® 21-gene recurrence score and clinicopathological parameters: a single institutional experience.Histopathology. 2023;82:755–66. [DOI] [PubMed]
Ma SJ, Gill J, Yendamuri K, Chatterjee U, Waldman O, Dunne-Jaffe C, et al. Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer.BMC Cancer. 2023;23:330. [DOI] [PubMed] [PMC]
Yamaguchi K, Matsunuma R, Hayami R, Tsuneizumi M. Comparison of the Modified Immunohistochemical Marker Score and 21-Gene Recurrence Score Assay in Patients with Estrogen Receptor-Positive Breast Cancer.Oncology. 2022;100:155–62. [DOI] [PubMed]
Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer.J Clin Oncol. 2011;29:4273–8. [DOI] [PubMed]
Carr DN, Vera N, Sun W, Lee MC, Hoover S, Fulp W, et al. Menopausal status does not predict Oncotype DX recurrence score.J Surg Res. 2015;198:27–33. [DOI] [PubMed]
Berton Giachetti PPM, Carnevale Schianca A, Trapani D, Marra A, Toss A, Marchiò C, et al. Current controversies in the use of Oncotype DX in early breast cancer.Cancer Treat Rev. 2025;135:102887. [DOI] [PubMed]
Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S, et al. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update.J Clin Oncol. 2022;40:1816–37. [DOI] [PubMed]
Licata L, De Sanctis R, Vingiani A, Cosentini D, Iorfida M, Caremoli ER, et al. Real-world use of multigene signatures in early breast cancer: differences to clinical trials.Breast Cancer Res Treat. 2024;205:39–48. [DOI] [PubMed] [PMC]
Huang JL, Kizy S, Marmor S, Altman A, Blaes A, Beckwith H, et al. Tumor grade and progesterone receptor status predict 21-gene recurrence score in early stage invasive breast carcinoma.Breast Cancer Res Treat. 2018;172:671–7. [DOI] [PubMed]
Sparano JA, Crager MR, Tang G, Gray RJ, Stemmer SM, Shak S. Development and Validation of a Tool Integrating the 21-Gene Recurrence Score and Clinical-Pathological Features to Individualize Prognosis and Prediction of Chemotherapy Benefit in Early Breast Cancer.J Clin Oncol. 2021;39:557–64. [DOI] [PubMed] [PMC]
Probert J, Dodwell D, Broggio J, Charman J, Dowsett M, Kerr A, et al. Ki67 and breast cancer mortality in women with invasive breast cancer.JNCI Cancer Spectr. 2023;7:pkad054. [DOI] [PubMed] [PMC]
Patel R, Hovstadius M, Kier MW, Moshier EL, Zimmerman BS, Cascetta K, et al. Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.Cancer. 2022;128:3602–9. [DOI] [PubMed] [PMC]
Crager M, Wijayawardana SR, Gruver AM, Blacklock A, Russell C, Baehner FL, et al. Population-based estimate for the correlation of the Oncotype Dx Breast Recurrence Score® result and Ki-67 IHC MIB-1 pharmDx in HR+, HER2–, node-positive early breast cancer.Breast Cancer Res. 2022;24:74. [DOI] [PubMed] [PMC]
Gluz O, Nitz UA, Christgen M, Kates RE, Shak S, Clemens M, et al. West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment.J Clin Oncol. 2016;34:2341–9. [DOI] [PubMed]
Selmani Z, Molimard C, Overs A, Bazan F, Chaigneau L, Dobi E, et al. Low correlation between Ki67 assessed by qRT-PCR in Oncotype Dx score and Ki67 assessed by Immunohistochemistry.Sci Rep. 2022;12:3617. [DOI] [PubMed] [PMC]
Sotome K, Maeda H, Yanagisawa T, Harada Y, Mae Y, Ogiso M, et al. Recurrence score-predicted value derived from estrogen receptor, tumor-infiltrating lymphocytes, progesterone receptor, and Ki-67 may substitute for the Oncotype DX recurrence score in estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– breast cancer.Ann Diagn Pathol. 2025;74:152410. [DOI] [PubMed]
Kraus JA, Dabbs DJ, Beriwal S, Bhargava R. Semi-quantitative immunohistochemical assay versus oncotype DX® qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study.Mod Pathol. 2012;25:869–76. [DOI] [PubMed]
Sechrist H, Glasgow A, Bomeisl P, Gilmore H, Harbhajanka A. Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.Hum Pathol. 2020;104:54–65. [DOI] [PubMed]
Haynes BP, Schuster G, Buus R, Alataki A, Ginsburg O, Quang LH, et al. Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer.Breast Cancer Res Treat. 2021;190:295–305. [DOI] [PubMed] [PMC]
Haynes BP, Ginsburg O, Gao Q, Folkerd E, Afentakis M, Buus R, et al. Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer.NPJ Breast Cancer. 2019;5:42. [DOI] [PubMed] [PMC]
Haynes BP, Viale G, Galimberti V, Rotmensz N, Gibelli B, A’Hern R, et al. Expression of key oestrogen-regulated genes differs substantially across the menstrual cycle in oestrogen receptor-positive primary breast cancer.Breast Cancer Res Treat. 2013;138:157–65. [DOI] [PubMed]
Li Z, Wei H, Li S, Wu P, Mao X. The Role of Progesterone Receptors in Breast Cancer.Drug Des Devel Ther. 2022;16:305–14. [DOI] [PubMed] [PMC]
Lashen AG, Toss MS, Mongan NP, Green AR, Rakha EA. The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up.Cancer. 2023;129:1183–94. [DOI] [PubMed]
Chaudhary LN, Jawa Z, Szabo A, Visotcky A, Chitambar CR. Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score.Hematol Oncol Stem Cell Ther. 2016;9:48–54. [DOI] [PubMed]
Kalinsky K, Barlow WE, Pathak HB, Gralow JR, Albain KS, Hayes DF, et al. Correlation of serum anti-Müllerian hormone (AMH) levels on identification of premenopausal patients (pts) with hormone receptor positive (HR+), HER2-negative, node-positive breast cancer most likely to benefit from adjuvant chemotherapy in SWOG S1007 (RxPONDER).J Clin Oncol. 2024;42:505. [DOI]
