Intermediate Oncotype

Kessa619

Hi, everyone. My Oncotype is 18. My MO originally said he would do chemo if he were me. Fast forward a few weeks and he is ambivalent, suggesting that chemo is not effective for luminal A-type tumors. This doesn't seem like news and his indecision has thrown me for a loop. To make matters worse, Adjuvant Online has been offline for months. I do not know how to make this important decision. I know others have done so. What were the important factors to you? Anyone's doctor had compelling opinions? Does anyone know where the TailorDx study might be going?

Thanks!

keepthefaith

Kessa, intermediate is hard. I was a 21. You may want to seek another opinion. You may also want to ask for a mamma-print test. The TailorDx study results won't be out for the intermediates for quite some time. Do you have a family history? Had the BRCA test? Any other health issues? Good luck with your decision. It's not an easy one. Bottom line, do what you feel is best for you. I'm sure others will chime in.

Hopeful82014

Kessa, 18 is the very low side of the intermediate range, as I'm sure you know. My MO told me that, depending on patient specifics, she was comfortable with using under 25 as the cut off for encouraging chemo. She's very involved in oncology research, so I think she knows more than she's letting on, frankly.

Since you are node negative, stage 1A and ER+, you have a lot in your favor if you choose not to do chemo (assuming you do endocrine therapy and any recommended radiation).

Your MO may have been reading up on the issue and found information that changed his thinking on this issue.

I'd ask for a good long, honest discussion with him about the issue. Don't hesitate to seek a 2nd opinion if you need it to feel comfortable.

It's a big decision, it affects YOUR body (for better or worse) and YOU need to have the info you need to get to a decision you can live with. (That's much easier said than done, I do realize.)

Kessa619

thank you for your responses, keepthefaith and Hopeful. I always get a little lift from the support on these boards. I did have the Mammaprint, which came back low risk. My MO does not put much stock in Mammaprint. He just feels more comfortable with Oncotype. I just had a BMX so no radiation. No family history or genetic mutations. I am relatively young and otherwise healthy so I feel optimistic that I would weather four rounds of TC, but you never know.

Anyway, intermediate is hard. Thanks for sharing your thoughts.

Manu14

Kessa, I'm 20 years older than you but otherwise a similar profile except I was Grade 1. When my Oncotype score of 18 came back, my surgeon and MO immediately said no chemo was needed and didn't even act like it was a discussion issue. They said that if the score was in the 20s, it would be a harder choice. I hope you can come to a decision that feels right for you.

ShetlandPony

I would ask how your young age and the grade 2 play into the decision. Is your ki67 high or low, and if high would chemo make sense?

A second opinion might help you feel better. My first onc would change his mind about things and it drove me crazy. It made me feel like he didn't really know enough.

ChiSandy

According to the OncotypeDX website, 0-18 is “low” risk, 19-30 “intermediate” and anything over 30 is “high.” So 18 isn’t low end of intermediate, but right on the border of “low.” The research on Luminal-A tumors being less responsive to chemo is newer than the first results from the TailoRx trial. That trial is still ongoing as concerns “low-risk” women whose scores are 11-18, and those results may be released sooner than those for “intermediate” scores.

But if I were in my 40s (or even 50s) and healthier than I am (i.e., no drug allergies, no asthma, normal BP), I might have considered at least some chemo with a score of 18--or even my own score of 16. A 1-2% long-term survival benefit from adding chemo is much less meaningful at 65 than at 43.

Kessa619

I think if it were not for the risk of second malignancy, I would do chemo. I have read that the risk of developing leukemia is .5%...that starts to make a 1-2% potential benefit seem even less significant.

My ki-67 was 7% and mitotic rate was 1. The other two factors drove my grade. My tubule formation was 3 out of 3. If only I knew what that really meant. It doesn't get the same attention as ki-67.

With all the "favorable characteristics" of my BC, I also cannot figure out what contributed to my Oncotype score.

BarredOwl

Hi ChiSandy:

Please note that the information regarding low, intermediate and high risk categories provided on some informational web sites (even some from GenomicHealth**) is not consistent with the standard ranges for risk categories that are set forth in the scientific literature, including publications relied upon as validating the Oncotype test for invasive disease.

Thus, my understanding is consistent with Hopeful's that a Recurrence Score ("RS") of 18 is considered to be in the "intermediate risk" category, and is the lowest score possible score in the intermediate category, using the standard published ranges for the Oncotype test for invasive disease.

In this regard, please find various publications, all setting forth standard ranges of <18, 18–30, ≥31.

Low Risk: RS = 0 to 17 (<18)

Intermediate Risk: RS = 18 to 30 (18-30)

High Risk: RS = 31 to 100 (≥ 31)

Some may recognize author Sparano as the Principal Investigator for the TailorX trial.

(1A) 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)

(1B) 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."

(2) 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

(PatientAccess option available)

Excerpted from Figure 1:

Low risk: RS < 18

Intermediate risk: RS ≥ 18 and < 31

High risk: RS ≥ 31

(3) 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

"There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0·97; HR 1·02, 0·54–1·93), but an improvement in disease-free survival for those with a high recurrence score (score ≥31; log-rank p=0·033; HR 0·59, 0·35–1·01), after adjustment for number of positive nodes." (See Findings)

(4) 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)

(5) 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)

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

http://www.nejm.org/doi/full/10.1056/NEJMoa1510764...

This is the recent TailorX report. The study report compares the new ranges being tested to the "originally defined" 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)

(7) Stemmer et al. (2015), Abstract number 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.europeancancercongress.org/Scientific-P...

Abstract 1963 is from the 2015 European Cancer Congress, describing a prospective study period of 2004 -2010, in which treatment decisions in clinical practice were made incorporating the 21-Gene Recurrence Score. Please see the Results, where it states: "Distribution of Recurrence Score risk groups (<18, 18–30, ≥31). . ."

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

References (6) and (7) above were published in late 2015.

As more research accumulates in the future, the standard ranges may or may not change.

I am a layperson with no medical training. All patients should consult their medical oncologist for current, expert case-specific advice and an affirmative statement regarding the risk category (low, intermediate, high) of their Oncotype Recurrence Score.

BarredOwl

[Edit: ** I have emailed GenomicHealth twice about the ranges provided on one of their patient-focused web sites. To date, I have received no response, and the information remains unchanged. Today, I used a customer service link on the professional site to raise the issue a third time.]

[Update: GenomicHealth has updated their patient-focused website to reflect the standard ranges (<18, 18–30, ≥31).]

[Edit: The text above has been revised to add Reference (1B), Paik (2006), the second major validation study done in a subset of patients from the NASBP B-20 trial.]

[Edit: Added link to free pdf version of Albain (2010)]

Moderators

Hello All,

Here is our most recent information on Oncotype DX test: Oncotype DX Test.

And here is an update on the TAILORx study in Research News: Research Confirms Oncotype DX Test Score Between 0 and 10 Means Women Can Skip Chemotherapy, as well as a blog from Brian Wojciechowski, M.D. about it here: What My Patients Are Asking: What Do the TAILORx Trial Results Mean For Me?

We hope that this helpful!

______________________________________________________________________________

The Oncotype DX test is a genomic test that analyzes the activity of a group of genes that can affect how a cancer is likely to behave and respond to treatment. The Oncotype DX is used in two ways:

• to help doctors figure out a woman's risk of early-stage, estrogen-receptor-positive breast cancer coming back (recurrence), as well as how likely she is to benefit from chemotherapy after breast cancer surgery
• to help doctors figure out a woman's risk of DCIS (ductal carcinoma in situ) coming back (recurrence) and/or the risk of a new invasive cancer developing in the same breast, as well as how likely she is to benefit from radiation therapy after DCIS surgery

The Oncotype DX test is the only one of the four genomic tests for breast cancer (MammaPrint, Mammostrat, and Prosigna are the others) with results that have been validated with much vigorous research.

While the results of the studies on the MammaPrint, Mammostrat, and Prosigna tests are promising, these three tests aren't widely used to help make treatment decisions. Right now, the Oncotype DX test is the only genomic test for early-stage breast cancer that is included in the National Comprehensive Cancer Center Network (NCCN) and the American Society of Clinical Oncology (ASCO) treatment guidelines. Because the Oncotype DX test for DCIS is relatively new, it's not yet included in the ASCO or NCCN DCIS treatment guidelines.

The NCCN is an alliance of the world's leading cancer centers. These NCCN centers collaborate on research, guidelines, and education to improve the care of people diagnosed with cancer. ASCO is a national organization of oncologists and other cancer care providers. ASCO guidelines give doctors recommendations for treatments that are supported by much credible research and experience.

Because strong results are available and the Oncotype DX test is included in the NCCN and ASCO treatment guidelines, it is the only genomic breast cancer test widely used to make treatment decisions.

The results of the Oncotype DX test, combined with other features of the cancer, can help you make a more informed decision about whether or not to have chemotherapy to treat early-stage hormone-receptor-positive breast cancer or radiation therapy to treat DCIS.

Who is eligible for the Oncotype DX test?

You may be a candidate for the Oncotype DX test if:

• you've recently been diagnosed with stage I or II invasive breast cancer
• the cancer is estrogen-receptor-positive
• there is no cancer in your lymph nodes (lymph node-negative breast cancer)
• you and your doctor are making decisions about chemotherapy.

Most early-stage (stage I or II), estrogen-receptor-positive breast cancers that haven't spread to the lymph nodes are considered to be at low risk for recurrence. After surgery, hormonal therapies such as an aromatase inhibitor or tamoxifen are prescribed to reduce the risk that the cancer will come back in the future. Whether or not chemotherapy is also necessary has been an area of uncertainty for patients and their doctors.

If you've been diagnosed with early-stage, estrogen-receptor-positive breast cancer, the Oncotype DX test can help you and your doctor make a more informed decision about whether or not you need chemotherapy. (Some research also suggests the test may help postmenopausal women with estrogen-receptor-positive breast cancer that has spread to the lymph nodes make chemotherapy decisions. Talk to your doctor if you are in this group.)

You also may be a candidate for the Oncotype DX test if:

• you've recently been diagnosed with DCIS
• you're having lumpectomy to remove the DCIS

DCIS is the most common form of non-invasive breast cancer. DCIS usually is treated by surgically removing the cancer (lumpectomy in most cases). After surgery, hormonal therapy may be recommended if the DCIS is hormone-receptor-positive. Radiation therapy may be recommended for some women. Doctors aren't always sure which women will benefit from radiation therapy.

If you've been diagnosed with DCIS, the Oncotype DX test can help you and your doctor make a more informed decision about whether or not you need radiation therapy.

How does Oncotype DX work?

The Oncotype DX genomic test analyzes the activity of 21 genes that can influence how likely a cancer is to grow and respond to treatment.

Looking at these 21 genes can provide specific information on:

• the likelihood that the breast cancer will return
• whether you're likely to benefit from chemotherapy if you're being treated for early-stage invasive breast cancer
• whether you're likely to benefit from radiation therapy if you're being treated for DCIS

So, the Oncotype DX test is both a prognostic test, since it provides more information about how likely (or unlikely) the breast cancer is to come back, and a predictive test, since it predicts the likelihood of benefit from chemotherapy or radiation therapy treatment. Studies have shown that Oncotype DX is useful for both purposes.

Oncotype DX test results assign a Recurrence Score — a number between 0 and 100 — to the early-stage breast cancer or DCIS. You and your doctor can use the following ranges to interpret your results for early-stage invasive cancer:

• Recurrence Score lower than 18: The cancer has a low risk of recurrence. The benefit of chemotherapy for is likely to be small and will not outweigh the risks of side effects.
• Recurrence Score of 18 up to and including 30: The cancer has an intermediate risk of recurrence. It's unclear whether the benefits of chemotherapy outweigh the risks of side effects.
• Recurrence Score greater than or equal to 31: The cancer has a high risk of recurrence, and the benefits of chemotherapy are likely to be greater than the risks of side effects.

You and your doctor can use the following ranges to interpret your results for DCIS:

• Recurrence Score lower than 39: The DCIS has a low risk of recurrence. The benefit of radiation therapy is likely to be small and will not outweigh the risks of side effects.
• Recurrence Score between 39 and 54: The DCIS has an intermediate risk of recurrence. It's unclear whether the benefits of radiation therapy outweigh the risks of side effects.
• Recurrence Score greater than 54: The DCIS has a high risk of recurrence, and the benefits of radiation therapy are likely to be greater than the risks of side effects.

You and your doctor will consider the Recurrence Score in combination with other factors, such as the size and grade of the cancer, the number of hormone receptors the cancer cells have (many versus few), and your age. Together you can make a decision about whether or not you should have chemotherapy or radiation therapy.

How is Oncotype DX different from the MammaPrint test, the Mammostrat test, and the Prosigna assay?

You may have heard about three other tests that analyze breast cancer genes to predict recurrence:

• the MammaPrint test
• the Mammostrat test
• the Prosigna assay

While all four tests analyze genes to help estimate the risk a cancer will come back, there are differences:

• The Oncotype DX test is used to estimate a woman's risk of recurrence of early-stage, hormone-receptor-positive breast cancer, as well as how likely she is to benefit from chemotherapy after breast cancer surgery. The Oncotype DX test also is used to estimate a woman's recurrence risk of DCIS (ductal carcinoma in situ) and/or the risk of a new invasive cancer developing in the same breast, as well as how likely she is to benefit from radiation therapy after DCIS surgery. The Oncotype DX test analyzes the activity of 21 genes and then calculates a recurrence score number between 0 and 100; the higher the score, the greater the risk of recurrence.
  
  Of these four tests, the Oncotype DX test has the most thorough data supporting its use to make treatment decisions. It is also the only one of these four tests that is included in the NCCN and ASCO treatment guidelines. Because of this stronger research, the Oncotype DX test is the only one of these tests right now that is widely used to make treatment decisions.
• The MammaPrint test analyzes 70 genes to see how active they are and then calculates either a high-risk or a low-risk recurrence score. Research suggests the MammaPrint test eventually may be widely used to make treatment decisions based on the recurrence risk of early-stage hormone-receptor-positive or hormone-receptor-negative disease. While the research done on the MammaPrint test so far is promising, more research is needed before the test is widely used to make treatment decisions. The MammaPrint test isn't included in the NCCN and ASCO treatment guidelines.
• The Mammostrat test measures the levels of five genes in breast cancer cells. These measurements are used to calculate a risk index score. Women are assigned to a risk category (high, moderate, or low) based on their risk index score. Research suggests the Mammostrat test eventually may be widely used to make treatment decisions based on the recurrence risk of early-stage hormone-receptor-positive disease. While the research done on the Mammostrat test so far is promising, more research is needed. The Mammostrat test isn't included in the NCCN and ASCO treatment guidelines.
• The Prosigna assay analyzes the activity of 58 genes and calculates a risk of recurrence score (low, intermediate, or high). Research suggests the Prosigna assay eventually may be used more frequently to make treatment decisions based on the risk of distant recurrence (cancer coming back in a part of the body away from the breast) within 10 years of diagnosis of early-stage hormone-receptor positive disease with up to three positive lymph nodes after 5 years of hormonal therapy treatment in postmenopausal women. While research done so far on the Prosigna test is promising, more research is needed before the test is widely used to make treatment decisions. The Prosigna test isn't included in the NCCN and ASCO treatment guidelines.

All four tests can be done on a sample of preserved tissue that was removed from the breast during the original biopsy or surgery.

Insurance coverage and financial assistance

The Medicare program and several other major insurance companies have agreed to cover the Oncotype DX test. According to Genomic Health, about 90% of insured people in the U.S. are members of a plan that covers the test. If you discover that your plan does not cover the Oncotype DX test, talk to your doctor: he or she may be able to work with your insurance company to get coverage. If you have a low Recurrence Score and you and your doctor decide you do not need to have chemotherapy or radiation, your insurance company can save much more than the cost of the test.

Genomic Health also has started the Genomic Access Program to assist you with verifying insurance coverage and obtaining reimbursement. If you do not have or cannot secure insurance coverage, the Genomic Access Program still may be able to help. Various forms of financial assistance and payment plans are available for people facing financial hardships or those who are uninsured or underinsured. The Oncotype DX test costs about $4,000. For insurance- and payment-related questions, call 1-866-ONCOTYPE (1-866-662-6897).

ChiSandy

BarredOwl, thanks for the clarification.