Who could benefit from having the Oncotype DX® test?

The Oncotype DX Breast Recurrence Score® test was developed to help guide chemotherapy treatment decisions based on the prediction of chemotherapy benefit. By revealing tumour biology beyond clinical-pathological features (tumour grade, tumour size and age of patient), the test provides an additional piece of information about the treatment benefit of chemotherapy for patients who have HR+, HER2- early-stage breast cancer. The Oncotype DX® test can help directing chemotherapy to those patients who will benefit.1-5

Predictive factors help guide treatment decisions 1-2,4,6,12-14

Predictive markers can inform treatment decisions by proving specific information about a given treatment benefit. This adds additional information and avoids extrapolation from prognostic factors.6 Predictive markers such as ER and HER2 status identify patients responding to hormonal treatment and trastuzumab, respectively. The Recurrence Score® result informs whether a tumour is likely to respond to chemotherapy. The NSABP B-20 and SWOG 8814 studies established the predictive value of the Recurrence Score® result. There is further evidence for the Oncotype DX® test from the prospective phase III TAILORx and RxPONDER studies.

TAILORx refined the estimates of chemotherapy benefit for node-negative disease, identifying two groups of patients:1-3,5,7-11

  1. Those with Recurrence Score® results 0-25 who do not benefit from the addition of chemotherapy to endocrine therapy.
  2. Those with Recurrence Score results 26-100 who are most likely to derive increasing benefit from the addition of chemotherapy to endocrine therapy.

RxPONDER clearly identified the majority of node-positive (1-3 positive nodes) postmenopausal patients who can be spared chemotherapy:4,5

  1. Postmenopausal women with 1-3 positive nodes and Recurrence Score® results 0-25 can avoid adjuvant chemotherapy regardless of clinical pathological features
  2. Premenopausal women with 1-3 positive nodes and Recurrence Score results 0-25
  3. significantly benefit from chemotherapy

Predictive markers can inform treatment decisions 1-2,4,6,12-14




The Oncotype DX® test identifies two groups of node-negative patients based on prediction of chemotherapy benefit 1-3,7-11




* HR+, HER2-, node-negative, early-stage, invasive breast cancer
a do not benefit from the addition of chemotherapy to endocrine therapy
b significantly benefit from the addition of chemotherapy to endocrine therapy



Clinical pathological features provide prognostic information only 2,5,15-20

In clinical practice, treatment decisions are often made based on prognostic factors such as tumour size and grade2. However, clinical-pathological features are prognostic and several studies have demonstrated that they cannot predict the Recurrence Score® results.2,16-20

Clinical-pathological characteristics do not predict the Recurrence Score® results in TAILORx2


a Patients with unknown values were excluded from the analysis
b Low clinical risk:
tumour size ≤3 cm and Grade 1;
tumour size ≤2 cm and Grade 2;
tumour size ≤1 cm and Grade 3
High clinical risk: all other cases with known values for grade and tumour size

Clinical-pathological features alone cannot predict the Recurrence Score® results in clinical practice16

b Low clinical risk:
N0, T ≤3 cm and Grade 1
N0, T ≤2 cm and Grade 2
N0, T ≤1 cm and Grade 3
N1, T ≤2 cm and Grade 1
High clinical risk: all other cases

The benefit of having the Recurrence Score result can help improve confidence in treatment decisions. It has been shown that relying on clinical-pathological factors alone is associated with a high level of uncertainty amongst clinicians when making treatment decisions. Testing with the Oncotype DX® assay provides greater confidence to clinicians in their treatment recommendations as reflected in a recent case study.17

The Recurrence Score® result adds confidence to treatment decisions compared to using clinical-pathological features alone17


The Oncotype DX® test can be used to reduce the risk of over- and undertreatment with chemotherapy 2,18

The value of the Oncotype DX® test for HR+, HER2-, node-negative, early-stage breast cancer patients is demonstrated by data from the TAILORx trial showing that the Oncotype DX® test aids in the identification of patients who are at risk of over- or undertreatment when clinical pathologic factors alone are used to guide treatment decisions.2,18 Numerous world-wide decision-impact studies confirm this potential for the test to reduce the risk of over- or undertreatment with chemotherapy.2,18-21

The Oncotype DX® test reduces the risk of over- and undertreatment2,18


a Low clinical risk: tumour size ≤3 cm and Grade 1; tumour size ≤2 cm and Grade 2; tumour size ≤1 cm and Grade 3
High clinical risk: all other cases with known values for grade and tumour size
b Assuming that adjuvant chemotherapy would have been prescribed or not based on clinical risk.

Decision-impact studies support the potential to reduce over- and undertreatment 2,19-21


a Percentage of patients initially recommended CT-HT based on all clinical-pathological parameters and de-escalated to HT alone based on the RS® result
b Percentage of patients initially recommended HT based on clinical-pathological parameters and escalated to CT-HT based on the RS® result
c Patients with unknown values were excluded from the analysis

International guidelines and health technology assessment bodies provide recommendations on whom to test22-26

International guidelines (NCCN, St. Gallen, ASCO)22-24 and health technology assessment (HTA) bodies (IQWIG, NICE)25-26 recognise the Oncotype DX® test for its value in clinical decision-making. Furthermore, they provide guidance on whom to test. The NCCN guidelines recommend to strongly consider all pre- and postmenopausal N0 patients with a tumour size >0.5cm for testing as well as all postmenopausal N1 (1-3 positive nodes) patients22, whereas the German HTA body IQWIG recommends testing all N0 patients when there is treatment uncertainty based on clinical risk assessment25:


a As voted by a clear majority of the St Gallen International Expert Consensus panel
b ©NICE DG34 2018 Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. Available from www.nice.org.uk/guidance/dg34. All rights reserved. Subject to Notice of rights NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

ABBREVIATIONS
ASCO: American Society of Clinical Oncology
IQWIG: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen
NICE: The National Institute for Health and Care Excellence
NCCN: National Comprehensive Cancer Network
HTA: Health Technology Assessment
CT: chemotherapy
ER: estrogen receptor
ET: endocrine therapy
HER2–: human epidermal growth factor receptor 2 negative
HR+: hormone receptor positive
HT: hormone therapy
N0: node-negative
NSABP: National Surgical Adjuvant Breast and Bowel Project
PR: progesterone receptor
RS: Recurrence Score® result
SEER: Surveillance, Epidemiology and End Results program
TAILORx: Trial Assigning IndividuaLized Options for Treatment (Rx)
RxPONDER: Rx for Positive Node, Endocrine Responsive Breast Cancer
REFERENCES
  1. Paik et al. J Clin Oncol. 2006.
  2. Sparano et al. N Engl J Med. 2018.
  3. Geyer et al. npj Breast Cancer. 2018.
  4. Albain et al. Lancet Oncol. 2010.
  5. Kalinsky et al. SABCS 2020.
  6. Allison et al. Mod Pathol. 2021.
  7. Hortobagyi et al. SABCS. 2018.
  8. Sparano et al. N Engl J Med. 2015.
  9. Petkov et al. npj Breast Cancer. 2016.
  10. Stemmer et al. npj Breast Cancer. 2017.
  11. Blohmer et al. ESMO 2017.
  12. Rastelli and Crispino, Tumouri. 2008.
  13. Viale et al. J Natl Cancer Inst. 2008.
  14. Perez et al. Cancer Treat Rev. 2017.
  15. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Peto R, et al. Lancet. 2012.
  16. Walter et al. Geburtshilfe Frauenheilkd. 2020.
  17. Licata et al. ESMO 2020. 187P.
  18. Barni et al. ESMO 2018. Poster 194P.
  19. McSorley et al. J Clin Oncol 38: 2020 (suppl; abstr 540).
  20. Curtit et al. Breast. 2019.
  21. Thill, EBCC 2020 poster 367.
  22. NCCN Guidelines Insights: Breast Cancer, Version 3.2021.
  23. Burstein et al. Ann Oncol. 2021.
  24. Andre et al. J Clin Oncol. 2019.
  25. IQWIG Press Release, September 2018.
  26. NICE Diagnostics Guidance DG34 December 2018. accessed December 2018.
  27. Battisti et al. St Gallen international conference 2019 P007
Making cancer care smarter.™