Does Oncotype Score/ Risk% assume radiation?

slp1

This test was validated with the B-14 trial where patients receiving lumpectomy plus XRT were then assigned placebo or Tamoxifen. Genomic Health customer service told me it does not assume radiation. The word radiation appears nowhere on the Oncotype report. Is it baked into the data? Some evidence suggests that your Onco risk % is doubled if you don't take the Tamoxifen, but what if you do neither Tamoxifen or Radiation, does the test mean anything? Does the assessed biology mean anything?

123JustMe

Great question!

besa

The oncotype dx score does not take radiation treatment into account. As you have said it does assume tamoxifen treatment. Tamoxifen reduces your distal recurrence rate by a little less than 50% so you can calculate your distal recurrence rate without tamoxifen.

The oncotype dx test you are looking at the risk of metastatic disease (distal recurrence.)

The assessed biology (ER, PR status, Ki67 among other things) is "baked into" the oncotype dx test score. It is taken onto account. (The final oncotype test result is calculated by pluging the numerical results of individual real time PCR tests into a formula (model) to give the final oncotype dx score. The individual real time PCR test results measure the kinds and amounts of specific mRNA the bc cells are making .)

BarredOwl

My understanding is that the OncotypeDX test for invasive disease has been validated in node-negative patients using the B-14 and B-20 trials. According to this reference, these trials also included mastectomy alone (no radiation):

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

"Patients in both trials had lumpectomy plus axillary node dissection or modified radical mastectomy as their surgical procedure. All lumpectomy-treated patients were required per protocol to receive standard breast irradiation. However, chest wall irradiation after mastectomy was not allowed per protocol. Similarly, regional nodal irradiation was not allowed, irrespective of surgical procedure. As a result, there were two types of initial locoregional (LR) treatment in the two trials: lumpectomy plus breast irradiation (L + XRT) or mastectomy."

For certain node-negative patients with a Recurrence Score of 0 to 10, prospective validation from the TailorX trial is also available:

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

Additional studies have included certain node-positive patients.

Since we are just laypersons and have no information about your situation, please be sure to discuss all your questions and confirm your thinking with your Medical Oncologist.

BarredOwl

besa

Thank you BarredOwl - You have done a better job of explaining this - what groups of patients the test is validated for.

slp1

Thanks all for responding. These questions are for an 84 year old family member. She had a 7mm IDC, lymph node negative, with an Onco of 6. Our medical Oncologist indicated that 'both are in there' meaning the Onco test in fact has information about distant and local recurrence*. The MO seemed comfortable with a 'lumpectomy alone' option. The problem with that option is it's hard to find true numbers because it's never been a standard option. The B-14 trial did not have a lumpectomy alone arm, all were admitted with lumpectomy plus radiation. So it seems there is a baseline of local control in the results. When the study uses the reference 'Tamoxifen alone' it is only to systemic therapy. BUT, we live in an age where these tumors are being ranked and classified, and suddenly it seems the three arms of 'breast conserving therapy' might be separated for some patients, where before they were always linked. So most of the studies and language in fact do assume more rather than less. We asked our radiation oncologist what the recurrence rate would be with only surgery and she seemed baffled 'I don't know', and by guidelines eliminated radiation because of her age, but then advocated the pill. And was shocked when told the MO thought 'lumpectomy alone' was Ok.. The medical oncologist on the other hand seemed completely confident in what he was seeing, that this was a low risk tumor, and that watch and wait was sufficient. But even after seeing the medical oncologist and asking him directly if he was assuming radiation, "I wouldn't assume that either way" I'm having some doubts because the validation studies do not have lumpectomy alone arms. Without hormone therapy he said her risk would be a little less than 10% long term and 7-8% over 5 years. Are those acceptable risks for someone that age? Thanks, this is a wonderful board.

*This is a study arguing the Onco test does contain info on local recurrence.

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.full

BarredOwl

Hi:

Another question might be how well are 84-yr olds represented in these studies? For example, TailorX only included women 18 to 75 yrs old. Sometimes, the data is just not there for unique or unusual presentations, which can be frustrating and worrying.

I note that while the J Clin Oncol paper does discuss loco-regional recurrence (LRR), the conclusion emphasized in the discussion is with respect to tamoxifen-treated patients, and it characterizes the result regarding loco-regional recurrence as "hypothesis generating" (see paragraph 1 of the Discussion). Again, those receiving BCT in this study, also received radiation. I do not know whether other studies speak to this or not.

A risk/benefit analysis is a very personalized assessment. Traditional clinico-pathologic features are weighed (e.g., margin sizes, grade, age), co-morbidities, risk factors, life expectancy, and patient preference. The risk/benefit analysis is a very personal one, and patients will often come to different conclusions under similar circumstances, because of their different personal risk tolerances. For example, one person may want to reduce risk as much as possible no matter what, while another may feel the benefit (risk reduction) achieved does not significantly outweigh the risks (of serious side effects).

Because you/your relative are unsure, and because the case is somewhat specialized due to her age, I would recommend that you seek a second opinion. As part of that process, you will receive additional expert input and discussion of the magnitude of the estimated risks of local and distant recurrence and the potential benefits and risks of radiation and/or endocrine therapy. You can ask about the import of studies (outside of the Oncotype context) that did look at breast conserving treatment with or without radiation and studies of endocrine therapy, and whether they might inform decision-making (or not).

BarredOwl

doxie

I'm guessing that two different types of studies and findings at play here and your MO is aware of these.

There is a recent research paper stating that over a certain age, radiation is not necessary with lumpectomy. I think it is noted on bc.org somewhere and it is relatively recent. Since I was well below that age, and 3.5 years past radiation, I didn't pay attention to details, but certainly 84 is above the lowest threshold. Neither TailorX nor research findings validating the Oncotype scores would include this inquiry or finding as it wasn't on the radar at the initiation of these trials.

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