Clinical significance of the 21‐gene signature (Oncotype DX) in hormone receptor‐positive early stage primary breast cancer in the Japanese population

Abstract

BACKGROUND:The 21-gene signature has been intensively studied and incorporated into major guidelines for treatment decision in early breast caner. However, it remains to be examined whether this system is applicable to Asian populations. METHODS: The authors collected 325 tumor tissues from estrogen receptor (ER)-positive primary breast cancer patients who had undergone surgery and were treated with tamoxifen between 1992 and 1998. The tissues were analyzed for the 21-gene signature, and the patients were classified into groups of low, intermediate, or high risk based on the Recurrence Score. RESULTS: A total of 280 patients were eligible, with adequate reverse transcription polymerase chain reaction profiles for the Recurrence Score. Of those, 200 and 80 patients had lymph nodenegative and lymph node-positive disease, respectively. The proportions of lymph node-negative patients categorized as being at low, intermediate, or high risk were 48%, 20%, and 33%, respectively. In lymph node-negative patients, the Kaplan-Meier estimates of the distant recurrence rate at 10 years were 3.3% (95% confidence interval [95% CI], 1.1-10.0%), 0%, and 24.8% (95% CI, 15.7-37.8%) for those in the low-risk, intermediate-risk, and high-risk groups, respectively. The risk of distant recurrence in the low-risk group was significantly lower than that in the highrisk group when the entire Kaplan-Meier plots were compared (P < .001, log-rank test). There was a significant difference for overall survival between the low-risk and the high-risk groups (P ¼ .008, log-rank test). CONCLUSIONS: This is the first report to show that the 21-gene signature has value in providing prognostic information in Asian populations with ER-positive, lymph node-negative breast cancer. Cancer 2010;116:3112-8.

Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis

“…The methodological quality of the 12 included studies [76][77][78][79][80][81][82][83][84][85][86][87][88] is summarised in Figure 3 (further details are provided in Appendix 7). Generally, only three studies (four citations) performed well, receiving a positive assessment for at least 17 out of 21 methodological quality items.…”

“…a, one paper is included for both OncotypeDX and IHC4 as it contains data relating to both tests; b, from the systematic reviews of Marchionni et al 33 and Smartt. 81 Mamounas et al Although 9 of the 12 studies used a retrospective study design, [79][80][81][82][83][84][85][86][87][88] other potential sources of bias were generally related to the following domains: sample of patients (inadequate description of diagnostic criteria, clinical/demographic characteristics not fully described and not including all eligible patients with tumour samples in the study), follow-up of patients, prognostic variables (not fully defined) and interventions subsequent to inclusion in the study (interventions were not described or standardised, thus precluding an unbiased assessment of the prognostic ability of the test). 30 The assessment of study quality was further hampered by poor reporting of the following methodological items: whether or not sample of patients was representative and assembled at an early point in the course of their disease, whether or not outcomes were fully defined, objective and unbiased and whether or not appropriate statistical analyses were undertaken (continuous predictor variables analysed appropriately and statistical adjustment made for all prognostic factors).…”

“…Toi et al 87 examined the prognostic ability of OncotypeDX in 200 ER+, LN-Japanese patients. They showed that patients categorised as low risk had a significantly lower risk of distant recurrence than patients in the high-risk category (p < 0.001, log-rank test LN-breast cancer.…”

Did Oncotype DX® Recurrence Score Accurately Predict the Risk of Recurrence in Breast Cancer? A 10 Year Period Study in a Single Institution

“…In the past decade, multiple studies have shown that the utilization of 21-gene RS test in clinical practice is frequently responsible for changing adjuvant treatment decisions, with one metaanalysis demonstrating that 21-gene RS changed the clinicalpathological adjuvant chemotherapy treatment recommendation in 33.4% of patients [1]. 21-gene RS has been validated in a number of clinical studies, including the National Surgical Adjuvant Breast Program (NSABP) B-14 and B-20 trials [2,3], in addition to a number of other studies that have investigated its prognostic utility [4][5][6][7][8].…”

To Type or to Print? Oncotype DX and MammaPrint Tests for Breast Cancer

“…8 Since then, multiple studies worldwide have validated the prognostic capability of this assay. 9-10 A subsequent study explored utilization of Oncotype DX categorical scores for prediction of additive benefit of chemotherapy to hormonal therapy.…”