Node-Negative

The clinical validity and utility of the Oncotype DX Breast Recurrence Score^® test in patients with HR+, HER2-, node-negative, early-stage, invasive breast cancer have been established through extensive clinical research in over 85,000 patients.^1-3,5,7

Only the Oncotype DX Breast Recurrence Score test is clinically validated for prediction of chemotherapy benefit^2,5

The Oncotype DX Breast Recurrence Score test is clinically validated as prognostic of distant recurrence for node-negative, HR+ early-stage breast cancer patients¹
The Oncotype DX test is clinically validated to predict chemotherapy benefit in the 2-arm randomised clinical trial NSABP B-20^2,5,7 (interaction between Recurrence Score result and benefit from chemotherapy p=0.014⁵).
The practice-changing TAILORx study, a prospective randomised clinical trial, was confirmatory of former findings, enabling a more precise threshold for CT benefit.^3,7,8

Oncotype DX clinical evidence in node-negative patients - prediction of chemotherapy benefit makes the Oncotype DX Breast Recurrence Score test unique.

Clinical evidence from the TAILORx and NSABP B-20 studies established that the Oncotype DX^® test can identify two groups of patients: those who can be spared chemotherapy and those who will significantly benefit from it.^3,5

Oncotype DX clinical evidence in node-negative patients - TAILORx and NSABP B-20 studies - who may be spared chemotherapy and who may substantially benefit from it.

Patients with Recurrence Score results 0–25 do not benefit from the addition of chemotherapy to endocrine therapy^2,3,5

Patients with Recurrence Score results 26-100 significantly benefit from the addition of chemotherapy to endocrine therapy^2,5

The NSABP B-20 trial established that patients with Recurrence Score results 0-10 do not benefit from the addition of CT to ET and that patients with a Recurrence Score result 26-100 do benefit from the addition of CT⁵. TAILORx was designed to determine whether endocrine therapy is non-inferior to chemotherapy plus endocrine therapy in patients with Recurrence Score results 11-25.^3,5,8

Oncotype DX clinical evidence in node-negative patients - TAILORx landmark practice-changing trial - patients with Recurrence Score results 11-25.

TAILORx met its primary and secondary endpoints: patients with Recurrence Score results 11-25 treated with chemoendocrine therapy had similar rates of clinical events to patients receiving endocrine therapy alone.³

TAILORx confirmed that patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy³

Oncotype DX clinical evidence in node-negative patients - TAILORx distant recurrence-free interval and overall survival.

Prospectively planned analysis in TAILORx established that clinical pathological features and clinical risk, as assessed by tumour size and grade according to modified Adjuvant!Online, add prognostic value to estimate the clinical outcome of patients receiving endocrine therapy alone; however, clinical risk was not associated with response to chemotherapy.^3,19

There were further new exploratory analyses aimed at identifying any subgroups of patients who may benefit from chemotherapy. The Recurrence Score result and patient age, in combination, may modify treatment response: patients ≤50 years and with Recurrence Score results 16-25 may benefit from chemotherapy, as detailed in the table below.^3,19

References

Paik et al. N Engl J Med. 2004.
Paik et al. J Clin Oncol. 2006.
Sparano et al. N Engl J Med. 2018.
Ballman et al. J Clin Oncol. 2015.
Geyer et al. npj Breast Cancer 2018.
Hortobagyi et al. SABCS. 2018.
Sparano and Paik. J Clin Oncol. 2008.
Sparano et al. N Engl J Med. 2015.
Stemmer et al. NPJ Breast Cancer. 2017.
Blohmer et al. ESMO. 2017.
Petkov et al. NPJ Breast Cancer. 2016.
Genomic Health. Data on File. 2019.
IQWiG. Press release. 2018.
Andre et al. J Clin Oncol. 2019.
NCCN Guidelines. 2018. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer V3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 15, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
NICE. 2018. © NICE 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.
Cardoso et al. Ann Oncol. 2019.
Burnstein et al. Ann Oncol. 2019.
Sparano et al. N Engl J Med. 2019.

Patients from TAILORx are comparable to those treated in clinical practice during the same period reported in the SEER registry.^3,6,8,11

Age distribution vs Tumour size vs Tumour grade graph.

Real-world evidence is consistent with clinical studies. It confirms that the Oncotype DX^® test consistently identifies a minority of patients (~20% overall) with Recurrence Score results 26-100 who derive increasing benefit from chemotherapy.^2,5,7

Analysis of the real-world SEER study cohort (including >70,000 patients) further supported the evidence that the Oncotype DX Breast Recurrence Score result predicts CT benefit.⁶

9-year Breast Cancer Specific Survival (BCSS) was >97% without chemotherapy*, regardless of nodal status⁶

The Oncotype DX Breast Recurrence Score test identifies the vast majority of women who will not benefit from the addition of chemotherapy to endocrine therapy and the important minority of women for whom chemotherapy may be life-saving.^2-3,5,8

The Oncotype DX test has been studied in over 96,000 node-negative and node-positive breast cancer patients in over 79 clinical studies and registries.^1-6,9

There is a consistent and large body of evidence across prospective randomised clinical trials, validation studies, and real-world registries.^1-6,9

The Oncotype DX test is validated in double-arm randomised clinical trials to identify patients who will benefit from the addition of chemotherapy to endocrine therapy.^2,3,5

Find out more about the difference between prognostic and predictive biomarkers

The Oncotype DX test identifies patients who will benefit from the addition of chemotherapy to endocrine therapy, providing additional information compared to clinical pathological features.^2-4,19

Only the Oncotype DX Breast Recurrence Score test is incorporated in the four major clinical practice guidelines and recommended by two major EU health technology assessment bodies.^13-18

The first clinical validation of the Oncotype DX Breast Recurrence Score^® test, the NSABP B-14 study, demonstrated that the Recurrence Score result quantifies the risk of distant recurrence in node-negative patients. It showed that the 10-year rate of distant recurrence is significantly lower for patients with low Recurrence Score results compared to patients with higher Recurrence Score results.

This study determined that the Oncotype DX Breast Recurrence Score^® test predicts the likelihood of chemotherapy benefit for node-negative patients: a low Recurrence Score result predicted little to no benefit from the addition of chemotherapy to endocrine therapy, while a high Recurrence Score result predicted a larger benefit from chemotherapy.

The first prospective outcomes study providing Level 1A evidence for a multigene assay, TAILORx established that, overall, patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy and may be effectively treated with hormonal therapy alone.

Abbreviations

BCSS = breast cancer specific survival

CI=confidence interval

CT=chemotherapy

ET=endocrine therapy

HER2–=human epidermal growth factor receptor 2 negative

HR+=hormone receptor positive

HR=hazard ratio

N0=node-negative

NSABP = National Surgical Adjuvant Breast and Bowel Project

RS=Recurrence Score result

SEER=Surveillance, Epidemiology and End Results program

TAILORx=Trial Assigning IndividuaLized Options for Treatment (Rx)

References

Paik et al. N Engl J Med. 2004.
Paik et al. J Clin Oncol. 2006.
Sparano et al. N Engl J Med. 2018.
Ballman et al. J Clin Oncol. 2015.
Geyer et al. npj Breast Cancer 2018.
Hortobagyi et al. SABCS. 2018.
Sparano and Paik. J Clin Oncol. 2008.
Sparano et al. N Engl J Med. 2015.
Stemmer et al. NPJ Breast Cancer. 2017.
Blohmer et al. ESMO. 2017.
Petkov et al. NPJ Breast Cancer. 2016.
Genomic Health. Data on File. 2019.
IQWiG. Press release. 2018.
Andre et al. J Clin Oncol. 2019.
NCCN Guidelines. 2018. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer V3.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 15, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
NICE. 2018. © NICE 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.
Cardoso et al. Ann Oncol. 2019.
Burnstein et al. Ann Oncol. 2019.
Sparano et al. N Engl J Med. 2019.

Node-Positive

The Recurrence Score^® result has been proven to be predictive of chemotherapy benefit for HR+, HER2-, node-positive postmenopausal patients in the retrospective SWOG-8814 study.¹ The prospective randomised trial RxPONDER including more than 5,000 patients was designed to refine chemotherapy benefit estimates for HR+, HER2- patients with Recurrence Score results 0-25 and 1 to 3 positive nodes.³ Initial results of the RxPONDER study have been described as practice-changing.²

The majority of N1 postmenopausal patients may be spared chemotherapy based on Recurrence Score^® results 0-25, independent of clinical pathological parameters³
N1 premenopausal patients with Recurrence Score results 0-25 have a 2.9% benefit from chemotherapy in terms of distant recurrence as first site at 5 years³

The retrospective analysis of the SWOG-8814 trial, in which HR+, node-positive, postmenopausal patients were randomised to chemoendocrine therapy vs endocrine therapy alone, established that the Recurrence Score result is predictive of chemotherapy benefit in node-positive patients¹, consistent with the findings in the node-negative setting in the NSABP B-20 clinical trial.^4-5

RxPONDER (SWOG S1007) is a prospective, randomised trial to determine the effect of chemotherapy in patients with hormone receptor-positive (HR+), HER2-negative breast cancer with 1-3 positive axillary lymph nodes. For this purpose, eligible patients with Recurrence Score^® (RS^®) results 0-25 were randomised to adjuvant chemotherapy followed by endocrine therapy or to endocrine therapy alone.³

The Oncotype DX Breast Recurrence Score test identifies the vast majority of women who may not receive a benefit from chemotherapy and can ultimately be spared chemotherapy.¹

Oncotype DX is the only test that has been clinically validated to predict chemotherapy benefit and that can thus be used to distinguish patients who will benefit from chemotherapy from those who may be spared chemotherapy.^1,4-5

Find out more about the difference between prognostic and predictive biomarkers

The Oncotype DX test has been studied in over 96,000 breast cancer patients in over 79 clinical and registry studies.^{1-2,4-9,11-12}

The Oncotype DX test is validated in double-arm randomised clinical trials to identify patients who will benefit from the addition of chemotherapy to endocrine therapy.^2,3,5

Find out more about the difference between prognostic and predictive biomarkers

There is a consistent and large body of evidence across randomised, prospective and retrospective studies and real-world evidence.^{1-2,4-9,11-12}

Only the Oncotype DX Breast Recurrence Score test is incorporated in the four major clinical practice guidelines and recommended by two major EU health technology assessment bodies.^13-18

Abbreviations

CET=chemo-endocrine therapy
CI=confidence interval
CT=chemotherapy
DDFS=distant-disease free survival
ER= Endocrine therapy
HER2–=human epidermal growth factor receptor 2 negative
HR+=hormone receptor positive
N+=node-positive
N0=node-negative
N1mi=lymph node micrometastases
N1=1–3 positive nodes
RS=Recurrence Score result
RxPONDER=Rx for Positive Node, Endocrine Responsive Breast Cancer
TAILORx=Trial Assigning IndividuaLized Options for Treatment (Rx)

References

Albain et al Lancet Oncol. 2010.
SWOG. Press release. 2020
Kalinsky et al. SABCS 2020 GS3-00.
Paik et al J Clin Oncol 2006.
Geyer et al. NJP Breast Cancer. 2018.
Stemmer et al NPJ Breast Cancer. 2017.
Hortobagyi et al. SABCS. 2018.
Nitz et al. Breast Cancer Res Treat. 2017.
Paik et al. N Engl J Med. 2004.
Sparano et al. N Engl J Med. 2018.
Dowsett et al. J Clin Oncol. 2010.
Petkov et al. NPJ Breast Cancer. 2016.
IQWiG. Press release. 2018.
Andre et al. J Clin Oncol. 2019.
NCCN Guidelines. 2018.
NICE. 2018.
Burstein et al. Ann Oncol. 2019.
Cardoso et al. Annals of Oncology. 2019.

Have questions about Oncotype DX^®?

Doctor sitting with patient having a discussion.

Clinical evidence

TAILORx confirmed that patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy3​

References

Abbreviations

References

SWOG-8814 study​

References

RxPONDER trial​

References

Abbreviations

References

TAILORx confirmed that patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy³

SWOG-8814 study

RxPONDER trial