SpringerLink
Log in

Relationship of histologic grade and histologic subtype with oncotype Dx recurrence score; retrospective review of 863 breast cancer oncotype Dx results

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Oncotype Dx (ODx) is a multigene assay that is prognostic and predictive in estrogen receptor (ER) positive early breast cancer. ODx recurrence score (RS) is reported to be histologic grade dependent. Relationship of RS with breast cancer histologic subtypes is unknown. This study was designed to assess the relationship of histologic subtype with RS. Histologic grade dependence of RS was also investigated.

Methods

Results of consecutive ODx tests (1/2007–7/2016) from two institutions were reviewed. Histologic subtypes (in: Lakhani et al., WHO classification, IARC Press, Lyon, 2012), combined Nottingham histologic grade, age and tumor size were recorded from pathology reports. Univariate and multivariate analysis was performed to investigate the relationship between RS and ODx risk categories and histologic subtypes, grade, age and tumor size.

Results

RS was grade dependent. RS of grade 1 and grade 2 tumors were significantly lower than grade 3 tumors. There was no high-risk grade 1 tumor. In favorable histologic subtypes there was no high-risk tumor. Mean RS of grade 1 lobular tumors was significantly higher than grade 1 ductal tumors. Using newer ODx cut-offs, 5 grade 1 tumors were reclassified as high risk (RS > 25) and grade 3 lobular tumors showed significantly higher rate of reclassification as high-risk than grade 3 ductal tumors. In a multivariate analysis, only grade showed a significant positive correlation with RS. Adding dichotomous histologic subty** (favorable vs. non-favorable) to grade further improved correlation with RS.

Conclusions

The Oncotype Dx result is impacted by histologic grade and histologic subtype. Tumors with favorable histologic subtypes and histologic grade 1 tumors do not have high-risk RS. High RS in a grade 1 tumor or in a tumor with favorable histology is unusual that warrants further investigation. Invasive lobular carcinomas rarely show high-risk RS. Histologic grade and histologic subtype should be considered while ordering ODx testing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G (1989) Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study. N Engl J Med 320(8):485–490. https://doi.org/10.1056/NEJM198902233200803

    Article  CAS  PubMed  Google Scholar 

  2. Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL, Bryant J, Dimitrov NV, Abramson N, Atkins JN, Shibata H, Deschenes L, Margolese RG (1997) Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 89(22):1673–1682

    Article  CAS  PubMed  Google Scholar 

  3. Fisher B, Dignam J, Tan-Chiu E, Anderson S, Fisher ER, Wittliff JL, Wolmark N (2001) Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. J Natl Cancer Inst 93(2):112–120

    Article  CAS  PubMed  Google Scholar 

  4. Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ, Hortobagyi GN (2017) Breast cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67(4):290–303. https://doi.org/10.3322/caac.21393

    Article  PubMed  Google Scholar 

  5. 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. https://doi.org/10.1056/NEJMoa041588

    Article  CAS  PubMed  Google Scholar 

  6. ​Sparano JA, Paik S (2008) Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol 26(5):721–728. https://doi.org/10.1200/JCO.2007.15.1068

    Article  PubMed  Google Scholar 

  7. 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. https://doi.org/10.1056/NEJMoa1510764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Geradts J, Bean SM, Bentley RC, Barry WT (2010) The oncotype DX recurrence score is correlated with a composite index including routinely reported pathobiologic features. Cancer Investig 28(9):969–977. https://doi.org/10.3109/07357907.2010.512600

    Article  Google Scholar 

  9. 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. https://doi.org/10.1007/s10549-011-1416-3

    Article  CAS  PubMed  Google Scholar 

  10. 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 22(5):879–886. https://doi.org/10.1016/j.breast.2013.04.008

    Article  PubMed  Google Scholar 

  11. Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, Bhargava R (2013) Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol 26(5):658–664. https://doi.org/10.1038/modpathol.2013.36

    Article  PubMed  PubMed Central  Google Scholar 

  12. Harowicz MR, Robinson TJ, Dinan MA, Saha A, Marks JR, Marcom PK, Mazurowski MA (2017) Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset. Breast Cancer Res Treat 162(1):1–10. https://doi.org/10.1007/s10549-016-4093-4

    Article  PubMed  Google Scholar 

  13. Orucevic A, Bell JL, McNabb AP, Heidel RE (2017) Oncotype DX breast cancer recurrence score can be predicted with a novel nomogram using clinicopathologic data. Breast Cancer Res Treat 163(1):51–61. https://doi.org/10.1007/s10549-017-4170-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cotter MB, Dakin A, Maguire A, Walshe JM, Kennedy MJ, Dunne B, Riain CO, Quinn CM (2017) Comparison of oncotype DX(R) recurrence score(R) with other risk assessment tools including the Nottingham Prognostic Index in the identification of patients with low-risk invasive breast cancer. Virchows Arch. https://doi.org/10.1007/s00428-017-2184-1

    PubMed  Google Scholar 

  15. Flanagan MB, Dabbs DJ, Brufsky AM, Beriwal S, Bhargava R (2008) Histopathologic variables predict Oncotype DX recurrence score. Mod Pathol 21(10):1255–1261. https://doi.org/10.1038/modpathol.2008.54

    Article  CAS  PubMed  Google Scholar 

  16. http://www.cap.org/web/oracle/webcenter/portalapp/pagehierarchy/cancer_protocol_templates.jspx?_adf.ctrl-state=v1sjxfnbj_4&_afrLoop=26724739344904#!. Accessed 19 Nov 2017

  17. Kelly CM, Krishnamurthy S, Bianchini G, Litton JK, Gonzalez-Angulo AM, Hortobagyi GN, Pusztai L (2010) Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor-positive, HER2-normal, grade II, lymph node-negative breast cancers. Cancer 116(22):5161–5167. https://doi.org/10.1002/cncr.25269

    Article  PubMed  Google Scholar 

  18. Conlon N, Ross DS, Howard J, Catalano JP, Dickler MN, Tan LK (2015) Is there a role for oncotype Dx testing in invasive lobular carcinoma? Breast J 21(5):514–519. https://doi.org/10.1111/tbj.12445

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tsai ML, Lillemoe TJ, Finkelstein MJ, Money JE, Susnik B, Grimm E, Kang SH, Swenson KK (2016) Utility of oncotype DX risk assessment in patients with invasive lobular carcinoma. Clin Breast Cancer 16(1):45–50. https://doi.org/10.1016/j.clbc.2015.08.001

    Article  PubMed  Google Scholar 

  20. Felts JL, Zhu J, Han B, Smith SJ, Truica CI (2017) An analysis of oncotype DX recurrence scores and clinicopathologic characteristics in invasive lobular breast cancer. Breast J. https://doi.org/10.1111/tbj.12751

    Google Scholar 

  21. Kizy S, Huang JL, Marmor S, Tuttle TM, Hui JYC (2017) Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-017-4355-9

    PubMed  Google Scholar 

  22. Kalife ET, Sung CJ, Singh K (2016) To oncotype or not: knowledge of histologic grade and subtype may help. Arch Pathol Lab Med 140(11):1184–1185. https://doi.org/10.5858/arpa.2016-0195-LE

    Article  PubMed  Google Scholar 

  23. Bomeisl PE, Thompson CL, Harris LN, Gilmore HL (2015) Comparison of oncotype DX recurrence score by histologic types of breast carcinoma. Arch Pathol Lab Med 139(12):1546–1549. https://doi.org/10.5858/arpa.2014-0557-OA

    Article  PubMed  Google Scholar 

  24. Hou Y, Zynger DL, Li X, Li Z (2017) Comparison of oncotype DX with modified magee equation recurrence scores in low-grade invasive carcinoma of breast. Am J Clin Pathol 148(2):167–172. https://doi.org/10.1093/ajcp/aqx059

    Article  PubMed  Google Scholar 

  25. Gwin K, Pinto M, Tavassoli FA (2009) Complementary value of the Ki-67 proliferation index to the oncotype DX recurrence score. Int J Surg Pathol 17(4):303–310. https://doi.org/10.1177/1066896909340274

    Article  CAS  PubMed  Google Scholar 

  26. Acs G, Esposito NN, Kiluk J, Loftus L, Laronga C (2012) 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 25(4):556–566. https://doi.org/10.1038/modpathol.2011.194

    Article  CAS  PubMed  Google Scholar 

  27. Lakhani S, Ellis I, Schnitt S et al (2012) WHO classification of tumours of the breast, 4th edn. IARC Press, Lyon

    Google Scholar 

  28. Yang YL, Liu BB, Zhang X, Fu L (2016) Invasive micropapillary carcinoma of the breast: an update. Arch Pathol Lab Med 140(8):799–805. https://doi.org/10.5858/arpa.2016-0040-RA

    Article  PubMed  Google Scholar 

  29. Liu F, Yang M, Li Z, Guo X, Lin Y, Lang R, Shen B, Pringle G, Zhang X, Fu L (2015) Invasive micropapillary mucinous carcinoma of the breast is associated with poor prognosis. Breast Cancer Res Treat 151(2):443–451. https://doi.org/10.1007/s10549-015-3413-4

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI, 02903, USA

    Kamaljeet Singh, Elizabeth T. Kalife, Shahrzad Ehdaivand & C. James Sung

  2. Rhode Island Hospital, Providence, RI, 02903, USA

    **n He

  3. Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI, 02903, USA

    Yihong Wang

Authors
  1. Kamaljeet Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. **n He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth T. Kalife
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahrzad Ehdaivand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yihong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. James Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kamaljeet Singh.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, K., He, X., Kalife, E.T. et al. 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 168, 29–34 (2018). https://doi.org/10.1007/s10549-017-4619-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4619-4

Keywords

Search

Navigation