Node-Negative
Prediction of chemotherapy benefit makes the Oncotype DX Breast Recurrence Score test unique
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.
- The Oncotype DX Breast Recurrence Score® test was validated as prognostic of distant recurrence for node-negative, HR+ early stage breast cancer patients1
- The Oncotype DX test was uniquely validated to predict chemotherapy benefit in the 2-arm randomized clinical trial NSABP B-202,5,7 (interaction between Recurrence Score result and benefit from chemotherapy p=0.0145).
- The practice-changing TAILORx prospective randomized clinical trial refined former findings, enabling a more precise threshold for CT benefit.3,7,8
Report Based on TAILORx Results
The Oncotype DX Breast Recurrence Score report has been updated to reflect the TAILORx trial results.
Establishing prediction of chemotherapy benefit with precision
Clinical evidence from the TAILORx and NSABP B-20 studies established that the Oncotype DX test can precisely identify two groups of patients: those who can be spared chemotherapy and those who will substantially benefit from it.3,5
TAILORx landmark practice-changing trial
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. The TAILORx trial was designed to determine whether ET was non-inferior to CT+ET in patients with Recurrence Score results 11-25.3,8
TAILORx proved that patients with Recurrence Score results 11-25 do not benefit from chemotherapy
The TAILORx study met its primary and secondary endoints: patients with Recurrence Score results 11-25 treated with chemoendocrine therapy had similar rates of clinical events to patients receiving endocrine therapy alone in non-inferiority design invasive disease-free survival (primary endpoint), distant recurrence-free interval and overall survival.3,8
TAILORx's pre-planned analysis established that clinical risk, as assessed by tumour size and grade according to modified Adjuvant!Online, added prognostic value to estimate the clinical outcome of patients receiving endocrine therapy alone; however, it was not associated with response to chemotherapy.3,19
Further exploratory analyses aimed at identifying factors predicting response to chemotherapy. In addition to the Recurrence Score result, age is the only factor that was found to have a correlation with 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.
Communiqué de presse . 2018. - Andre et al. J Clin Oncol. 2019.
NCCN Guidelines . 2018.NICE . 2018.- Cardoso et al. Ann Oncol. 2019.
- Burnstein et al. Ann Oncol. 2019.
- Sparano et al. N Engl J Med. 2019.
Real World Evidence
Real-world evidence is consistent with clinical studies. It confirms that the Oncotype DX test consistently identifies a minority of patients (15-20%) with Recurrence Score results 26-100 who derive substantial benefit from chemotherapy.
Are patients enrolled in the TAILORx study representative of clinical practice?
Patients from the TAILORx study are comparable to those treated in clinical practice during the same period reported in the SEER registry.3,8,11
Why choose the Oncotype DX Breast Recurrence Score Test?
The Oncotype DX Breast Recurrence Score test identifies the vast majority of patients who will not benefit from the addition of chemotherapy to endocrine therapy and the important minority of patients for whom chemotherapy may be life-saving.2-6
- The Oncotype DX test has been studied in over 96,000 breast cancer patients in over 79 clinical and registry studies.
- There is a consistent and large body of evidence across prospective randomised clinical trials, validation studies, and real-world registries.
- The Oncotype DX test has been prospectively studied in the patient population most commonly seen in clinical practice.
- The Oncotype DX is the only test validated in double-arm randomised clinical trials to identify patients responding to chemotherapy. Find out more about the difference between prognostic and predictive
- The Oncotype DX test is uniquely superior to prognostic-only parameters to identify patients who will benefit from the addition of chemotherapy to endocrine therapy.
- The Oncotype DX Breast Recurrence Score test is incorporated into the four major international guidelines
Key Study Details
NSABP B-14 Study1
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 scores.
NSABP B-20 Study2,5,7
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 score predicted a larger benefit from chemotherapy.
TAILORx Study3,8,19
The first prospective outcomes study providing Level 1A evidence for a multigene assay, the TAILORx Trial confirmed that, overall, patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy and may be effectively and safely treated with hormonal therapy alone.
Abbreviations
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
RS, Recurrence Score result
SEER, Surveillance, Epidemiology and End Results program
TAILORx, Trial Assigning IndividuaLized Options for Treatment (Rx)
CT, chemotherapy
ET, endocrine therapy
HER2–, human epidermal growth factor receptor 2 negative
HR+, hormone receptor positive
HR, hazard ratio
N0, node-negative
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.NICE . 2018.- Cardoso et al. Ann Oncol. 2019.
- Burnstein et al. Ann Oncol. 2019.
- Sparano et al. N Engl J Med. 2019.
Node-Positive
Oncotype DX® test in node-positive patients
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 he 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.3-5
- The majority of N1 postmenopausal patients may be spared chemotherapy based on Recurrence Score® results 0-25, independent of clinical pathological parameters3-5
- N1 premenopausal patients with Recurrence Score results 0-25 have a modest 2.4% benefit from chemotherapy in terms of distant recurrence-free interval at 5 years4
SWOG-8814 study
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.6-7
SWOG-8814 study
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.6-7
The Recurrence Score® result was a predictive factor of chemotherapy benefit for disease-free survival (P interaction = 0.029), overall survival and breast cancer-specific survival in the first five years.1
References
- Albain et al Lancet Oncol. 2010.
- Kalinsky et al. N Eng J Med. 2021.
- SWOG. Press release. 2020
- Kalinsky et al. SABCS. 2021 GS2•07.
- Paik et al J Clin Oncol 2006.
- Geyer et al. npj Breast Cancer. 2018.
- Kalinsky et al. SABCS. 2020 GS3-00.
- Sparano et al. N Engl J Med. 2018.
- Battisti et al. St Gallen International conference 2019, P007.
- Thill et al. EBCC 2020. Poster 367.
- Cognetti et al. npj Breast. 2021.
- McSorley et al. J Clin Oncol. 38 : 2020(suppl ; abstr 540).
- Curtit et al. Breast. 2019.
- Stemmer et al NPJ Breast Cancer. 2017.
- Hortobagyi et al. SABCS. 2018.
RxPONDER trial
RxPONDER (SWOG S1007) is an ongoing 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, including micrometastases.2,4 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.2,4
RxPONDER trial
RxPONDER (SWOG S1007) is an ongoing 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, including micrometastases.3-5 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.3-5RxPONDER study design: node-positive (1-3 nodes) patients with Recurrence Score results 0–25 were randomised to endocrine therapy alone or chemoendocrine therapy3-5
At a prespecified interim analysis in September 2020, the Data Safety Monitoring Committee advised the study investigators to report the available findings of the clinical trial. Results were presented at the San Antonio Breast Cancer Symposium in 2020 and 2021 as well as published in The New England Journal of Medicine in December 2021.3-5 A total of 5,018 patients were included in the analysis with a 6.1-year median follow up in the latest report.
Postmenopausal patients
Stratified by menopausal status, 5-year distant recurrence-free interval (DRFI) was similar for postmenopausal patients treated with endocrine therapy with or without chemotherapy (hazard ratio 1.12; 95% CI 0.82 to 1.52; p=.49).4 The lack of benefit from chemotherapy was observed regardless of clinicopathological factors such as patient age, tumour grade, tumour size, number of positive nodes, type of surgery, or Recurrence Score group (RS results 0-13 vs results 14-25).3-5 No significant difference in invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) or overall survival (OS) was observed.3-5
Based on this interim analysis, the authors concluded that the majority of N1 postmenopausal patients do not benefit from adjuvant chemotherapy, independent of clinical pathological parameters and thus can likely forgo adjuvant chemotherapy based on Recurrence Score® results 0-25.3-5
N1 postmenopausal patients with RS® results 0-25 did not benefit from the addition of chemotherapy to endocrine therapy on any endpoint reported4
Premenopausal patients
For premenopausal patients, 5-year distant recurrence-free interval (DRFI) differed significantly by treatment (chemotherapy hazard ratio 0.64; 95% CI 0.43 to 0.95; p=.026),4 with a 2.4% absolute difference in rate of distant recurrence-free interval. The benefit of chemotherapy was observed regardless of clinicopathological factors such as patient age, tumour grade, tumour size, number of positive nodes and type of surgery. Chemotherapy benefit by Recurrence Score group (RS 0-13 and RS 14-25) was 2.3% and 2.8%, respectively.4
Based on this interim analysis, the authors suggested that premenopausal patients with N1 breast cancer and Recurrence Score results 0-25 have a modest benefit from adjuvant chemotherapy.3-5
N1 premenopausal patients with RS® results 0-25 have a modest benefit from the addition of chemotherapy with a 2.4% benefit in terms of 5-year distant recurrence-free interval3-5
References
- Albain et al Lancet Oncol. 2010.
- Kalinsky et al. N Eng J Med. 2021.
- SWOG. Press release. 2020
- Kalinsky et al. SABCS. 2021 GS2•07.
- Paik et al J Clin Oncol 2006.
- Geyer et al. npj Breast Cancer. 2018.
- Kalinsky et al. SABCS. 2020 GS3-00.
- Sparano et al. N Engl J Med. 2018.
- Battisti et al. St Gallen International conference 2019, P007.
- Thill et al. EBCC 2020. Poster 367.
- Cognetti et al. npj Breast. 2021.
- McSorley et al. J Clin Oncol. 38 : 2020(suppl ; abstr 540).
- Curtit et al. Breast. 2019.
- Stemmer et al NPJ Breast Cancer. 2017.
- Hortobagyi et al. SABCS. 2018.
Updated RxPONDER results
Professor Catherine Kelly from the Trinity St James Cancer Institute in Dublin presents in the RxPONDER results.
Why choose the Oncotype DX Breast Recurrence Score Test?
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.1,6-7 Find out more about the difference between prognostic and predictive tests
- The Oncotype DX test has been studied in over 96,000 breast cancer patients in over 79 clinical and registry studies.1-14
- There is a consistent and large body of evidence across randomised, prospective and retrospective studies and real-world evidence.1-14
- The Oncotype DX Breast Recurrence Score test is incorporated in the four major international guidelines and recommended as the “preferred” test by NCCN®
. In addition, it is recommended by two major European health technology assessment bodies.15-20
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)
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.
- Kalinsky et al. SABCS. 2021 GS2-07.
- Kalinsky. N Eng J Med. 2021.
- Paik et al. J Clin Oncol. 2006.
- Geyer et al. NPJ 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 . 2021.NICE . 2018.- Burstein et al. Ann Oncol. 2019.
- Cardoso et al. Annals of Oncology. 2019.
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