Oncotype scores for ILC

John, thanks for providing this abstract. I paid $5000 for the Oncotype DX test (result 22, no chemo). Looks like I didn't need to! My MO recommended it to me and was obviously unaware of its lack of efficacy with ILC patients. I'm pleased and surprised to see a 5 year 100% survival rate for those with PILC in the analysis. My impression of it has been that it's more aggressive than classic ILC. Great to see this.

What works for me - and might work for others but perhaps not - is hypnosis. I cannot tell you how paralyzed I was from anxiety I was before my cancer diagnosis, and after it, wow. I found a website hypnosis downloads.com or something like that and it is a Scottish based company of psychologists that have downloads hypnotherapy for all sorts of things - even cancer issues. I bought some of them and thank goodness they worked for me. I am sure there are other good ones out there, these worked for me. I guess it just trained my brain or broke my habit of worrying. I still get anxious and I still worry but I can control it and guide myself away from it now. It is really very nice. Not perfect but nice.

Since mine was 25 and i had chemo i will always wonder if it did any good. The neuropathy and messed up metabilism stayed on. On the flip side if it recurs i will know i had done everything i could

Meow13....same here. I was also wondering about having only one oncotype score. Which tumor did it apply to?

@momand2kids

Where do you know of survival rates specific to ILC???

I don't know which tumor my oncodx applies to, it could be both were 34. I was extremely disappointed in the lack of detail in my oncodx report. For $4000 I would think they give more information. On the other hand, my pathology report after the mx was extremely detailed. I felt so much better reading it and knowing the care taken to understand the extent and type of cancer I was dealing with.

John, as always, thank you for your contributions. In case we have not asked or made note, I hope your wife is doing well.

My only regret is that they mention 5 years. What about 10? 15? is this too new to hope for 20??
I will be starting year 11 in April and am having small melt-downs periodically, wondering what that means.

Meow

at the time, under 18 was considered low risk, 19-30 considered intermediate and over 30 high risk. I was unwilling to take the risk in the gray area---- I did just 4 rounds of chemo-- Mass General and Dana Farber both supported this decision. I wish I could have skipped it, but I knew I would not rest easy if I did. I think it is a good example of having to make a decision based on the information we have at the time-- and do the best we can. I am not sure now, if someone had my dx, that chemo would be indicated--maybe more of the 10 years on AI (I did 5). As my onc says, it is more an art than a science and every case is slightly different.

I definitely had permanent side effects from AI. I would be very careful deciding to go past 5 years. You do need estrogen for health. Very tricky to know what is best for your overall health.

I was diagnosed at 64, and had an ODX score of 16. My MO said the benefits of chemo—so long as I accepted AI therapy—were way too minimal compared to the risks. Granted, ILC might be a bit more aggressive, but I would listen to your MO. You could ask for a Mammaprint or Prosigna test (both of which have only two possible results—high risk or low risk) if you or your insurer would pay for it. Over on another thread, one person with an ODX of 20 scored “high risk” on Prosigna, whereas another whose ODX was 23 scored “low risk” on Mammaprint.

I was told the same as momand2kids, under 18 is low risk, above 30 will be high risk.

Hi, Sandy,

8 years ago I was told 0-11 was a range, not 0-10, seems there has been some confusion.....

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 category ranges.

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)

Here are links to numerous publications from the scientific medical literature, including the principal validation studies featured in the Oncotype reports, referring to these standard ranges:

(1) Paik et al. (2004), "A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer"

http://www.nejm.org/doi/full/10.1056/NEJMoa041588#...

"Cutoff points were prespecified to classify patients into the following categories: low risk (recurrence score, less than 18), intermediate risk (recurrence score, 18 or higher but less than 31), and high risk (recurrence score, 31 or higher). The cutoff points were chosen on the basis of the results of NSABP trial B-20." (See Assay Methods, Gene Selection, and Recurrence-Score Algorithm, paragraph 3)

(2) Paik et al. (2006), "Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer"

http://jco.ascopubs.org/content/24/23/3726.full.pdf

"The cutoff points that were prespecified before the performance of the validation study of the RS,(15) which categorized patients into low-risk (RS < 18), intermediate-risk (RS ≥ 18 and < 31), and high-risk (RS ≥ 31) groups, were also prespecified in this study."

(3) Sparano and Paik (2008), "Development of the 21-Gene Assay and Its Application in Clinical Practice and Clinical Trials", J Clin Oncol 26:721-728.

http://jco.ascopubs.org/content/26/5/721

Excerpted from Figure 1:

Low risk: RS < 18

Intermediate risk: RS ≥ 18 and < 31

High risk: RS ≥ 31

(4) Albain et al. (2010), "Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial":

http://dx.doi.org/10.1016/S1470-2045(09)70314-6

A pdf copy is available here (scroll down to view or download by clicking blue button at upper right): Research Gate PDF

"Although analyses used recurrence score as a continuous variable, secondary analyses used the clinical recurrence score categories of low (<18), intermediate (18–30), and high (≥31)."

(5) Mamounas et al. (2010), "Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20":

http://jco.ascopubs.org/content/28/10/1677.long

"The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30)." (See Abstract, Subsection Results)

"The cutoff points for the RS were those that were prespecified before the performance of the validation study of the RS,5 which categorized patients into low RS (< 18), intermediate RS (18-30), and high RS (≥ 31) groups." (See Study Design and Endpoints, paragraph 4)

"The cutoff points were prespecified before the performance of the validation study of the RS,5 which categorized patients into low RS (RS < 18), intermediate RS (18 to 30), and high RS (≥ 31) groups, which were also prespecified in this study." (See Appendix, paragraph 4)

(6) Chen et al. (2013), "Evaluating Use Characteristics for the OncotypeDx 21-Gene Recurrence Score and Concordance With Chemotherapy Use in Early-Stage Breast Cancer":

http://jop.ascopubs.org/content/9/4/182.full

"RS documentation and results were abstracted via programmatic query of the iKM EHR system. RSs were segmented into low (<18), intermediate (18-30), and high (≥ 31) risk groups." (See Methods, paragraph 5)

(7) Sparano et al. (2015), "Prospective Validation of a 21-Gene Expression Assay in Breast Cancer":

http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article

This is the recent TAILORx trial publication. The study report compares the investigational ranges being tested to the "originally defined" standard ranges:

"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)." (see Study Protocol, paragraph 3)

(8) Stemmer et al. (2015), Abstract # 1963, "First prospective outcome data in 930 patients with more than 5 year median follow up in whom treatment decisions in clinical practice have been made incorporating the 21-Gene Recurrence Score":

http://www.ejcancer.com/article/S0959-8049(16)30911-X/abstract

Describing a prospective study period of 2004-2010, in which treatment decisions in clinical practice were made incorporating the 21-Gene Recurrence Score, it is stated in Results (line 4):

"Distribution of Recurrence Score risk groups (<18, 18–30, ≥31). . ."

All of the above are all consistent with the following standard risk ranges: <18, 18–30, ≥31.

References (7) and (8) above were published in late 2015.

Some of 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 my layperson's understanding, the revised ranges selected for the purposes of the trial are "investigational" until demonstrated otherwise. Reference (7) above (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 subset of standard "Low risk RS" patients. 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 for the 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.

There is one trial, "WGS PlanB" from a German group that used Recurrence Score of 0 to 11 as an investigational risk category:

Three-year data has been reported in a full-length peer-reviewed publication:

Gluz (2016): http://ascopubs.org/doi/full/10.1200/JCO.2015.63.5383

Five-year data has been reported in an abstract (no longer freely available) and meeting announcement:

EBCC-10 release: http://www.ecco-org.eu/Global/News/EBCC/EBCC10-PR/2016/03/Five-year-results-identifies-early-breast-cancer-patients-who-can-be-spared-chemo

Specifically, "Low risk" for the purposes of the WGS trial was defined as RS of 0 to 11. (Compare: TAILORx was 0 to 10). The results for those scoring 0 to 11 were generally consistent with those for the TAILORx "Low Risk" cohort (RS 0 to 10, all node-negative), indicating that the test is relatively robust in this subset of standard "Low risk" patients, although the WGS study is smaller, and included pN0 and pN1 patients. However, because all patients scoring 12 or above received chemotherapy, the results for these cohorts do not speak to the question of who may forego chemotherapy.

In conclusion, there are now a variety of publications from prospective trials designed to assess certain investigational ranges. Some reports indicate that the test is particularly robust in certain subsets of patients (RS of 0 to 10 or 0 to 11) falling within the Standard low risk range (RS of 0 to 17), yet the results did not operate to redefine risk categories. Additional observational studies are available that used ranges that mimic aspects of the TAILORx investigational ranges, while others use 0 to 25 versus 26 or above. While the findings are informative to a certain extent, in view of the nature of the published results, the standard risk category ranges remain in place.

As additional results become available in the future, the standard ranges may or may not change.

Of course, the investigational ranges reflect concerns regarding the potential for undertreatment (in the context of a clinical trial with randomization to chemotherapy), and considerations regarding the magnitude of the recurrence risk associated with particular Recurrence Scores, so patients may wish to discuss this with their MOs.

BarredOwl

Very good news indeed, yhendrix. You will probably be advised to go straight to radiation and then long-term anti-estrogen therapy.