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Apr 26, 2017 09:23AM
Apr 26, 2017 10:34AM
I agree with those above who indicated that the Standard Risk Ranges for the OncotypeDX test for invasive disease remain unchanged as of this date.
I note that the National Comprehensive Cancer Network (NCCN) guidelines for Breast Cancer (Version 2.2017) include the Oncotype test for invasive disease in certain cases in the treatment algorithm for hormone receptor-positive, HER2-negative disease shown in Chart BINV-6 (pdf page 17). The latest version is dated April 6, 2017 and reflects the original Standard Risk Ranges.
I have posted my layperson views on this issue many times, and reproduce text from other posts for those who may be concerned.
The standard risk category ranges for the OncotypeDX test for invasive disease (in node-negative or node-positive disease) based on various validation studies in these groups, are and have always been as follows:
Low-risk: Recurrence Score < 18 (i.e., 0 to 17)
Intermediate-risk: Recurrence Score 18 to 30
High-risk: Recurrence Score ≥ 31 (i.e., 31 to 100)
For links to numerous scientific publications setting forth these standard ranges, see this post:
A Recurrence Score of 24 is squarely in the middle of the standard intermediate range of 18 to 30:
It is possible that the confusion is based on certain investigational ranges being used in on-going clinical trials. In this regard, the prospective TAILORx trial in node-negative (N0) patients and the prospective RxPONDER trial in certain node-positive patients are using different investigational ranges, but they are still in progress.
In 2008, Sparano and Paik commented on various considerations in the selection of these investigational ranges:
Sparano and Paik (2008), "Development of the 21-Gene Assay and Its Application in Clinical Practice and Clinical Trials"
"The RS ranges used in TAILORx are different from those originally defined as low- (< 18), intermediate- (18-30), and high- (≥ 31) risk. The range was adjusted to minimize the potential for undertreatment in both the high-risk group and the randomized group. When the NSABP B-20 data were analyzed using the RS ranges used in TAILORx, the treatment effect of chemotherapy was similar to the original analysis, and the risk of recurrence was 5% or less with tamoxifen alone in the low and midrange RS groups (Table 4). Although a trend favoring the addition of chemotherapy becomes evident at an RS of approximately 11 when the risk of relapse is analyzed in a linear fashion, the 95% CIs completely overlap in the 11 to 25 RS range (Fig 6). An RS of 11 is associated with a risk of both local and distant relapse of approximately 10%, a threshold that has been typically used for recommending adjuvant chemotherapy."
Figure 6 illustrates the overlap of confidence intervals (dotted lines) quite clearly:
This 2015 publication regarding TAILORx trial in node-negative ("N0") patients also provided some explanation for the investigational ranges:
Sparano (2015), Prospective Validation of a 21-Gene Expression Assay in Breast Cancer"
Main Page: http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article
Free PDF: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510764
"To minimize the potential for undertreatment of the participants enrolled in our trial, the recurrence-score ranges used in our study differed from those that were originally defined as low (≤10 in our study vs. <18 in the original definition), intermediate (11 to 25 vs. 18 to 30), and high (≥26 vs. ≥31). The recurrence-score strata derived for the trial were based on prior studies that indicated that the risk of recurrence of breast cancer at a distant site at 10 years after diagnosis and a 5-year course of tamoxifen could be as high as 10% among patients with a score of 11 (point estimate, 7%; 95% confidence interval [CI], 5 to 10) and up to 20% among those with a score of 25 (point estimate, 16%; 95% CI, 13 to 20), indicating a risk that was substantial enough for a recommendation of adjuvant chemotherapy in patients with a score of 11 or higher."
In my layperson's understanding, the revised ranges selected for the purposes of the trial are "investigational" until demonstrated otherwise. Sparano (2015) reported the interim 5-year results in node-negative ("N0") patients with Recurrence Scores of 0 to 10 who all received endocrine therapy alone. These results showed that the test is quite robust in this sub-set of "low risk RS" patients (N0, RS 0 to 10). However, these results (for RS 0 to 10 only) did not operate to change the standard ranges. This is because they do not speak to outcomes for those with other scores (11 and above). We are still awaiting TAILORx trial results in its slightly differently defined investigational "intermediate" risk (RS 11 to 25) and investigational "high" risk (RS 26 and above) groups, so the standard ranges are still in effect (<18; 18 to 30; ≥31).
The on-going RxPONDER trial is still evaluating whether adjuvant chemotherapy is beneficial in patients with hormone receptor-positive, HER2-negative breast cancer with 1-3 positive lymph nodes and a Recurrence Score of 25 or less.
Of course, the investigational ranges reflect considerations of the magnitude of the recurrence risk associated with particular Recurrence Scores, and patients may wish to discuss this with their MOs.
Stage IA IDC, 9/2013 BMX. Right: IDC (1.5 mm, grade 2) with DCIS (5+ cm), 0/4 nodes, pN0. Left: DCIS (5+ cm), 0/1 node, pN0(i+).