Oncotype DX gray area for woman under 50

I had four rounds of TC. It was totally doable and I had very few side effects. I worked during chemo only taking off the day of on Friday and Monday. I was never sick but did get a UTI and was hospitized for precaution for a few days.

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JNKK, I got a 22 at age 49. Talk about grey... I decided against chemo. I actually haven't had an in-depth conversation with my MO about it since TAILORx came out—we played phone tag the day after and I made the decision quickly in order to start radiation within 8 weeks of my surgery. But his message supported my decision as did another MO. I second-guess a little, but most of the time I'm pretty comfortable with the decision even though it feels like I have less flexibility to screw around with the Tamoxifin now...

My wife, age 49, just went through this decision based on an Onco score of 23. She had a lumpectomy with a 6mm IDC, Grade 1 (mitotic score of 1), ER+ (90%), HER2 -, no lymph node involvement and 12% ki67. One bad factor is that she is basically PR - (5%). First, based on an Onco score of 23, recurrence risk should be around 15% assuming Tamoxifen is taken. This is represented on the graph on page 1. The graph on page 2 is supposed to show the potential benefit of chemo. In my wife's case, we were told the potential benefit was approximately 3%. We have a primary MO who comes highly recommended. We also went for a second opinion with one of the top MO's at the Moffitt Cancer Center, a NCCN cancer center. Both of our MO's recommended against chemo, based on my wife's total profile. I posted this information in another thread, but will summarize my experience with both MO's here.

Primary MO

We had a detailed discussion of the Oncotype score (23) and the underlying studies that go along with the graphs on page 1 and 2 of the Oncotype Report, as well as the 2018 TailorX study, and how this all fits in with my wife's individual tumor characteristics and other factors (such as age). His bottom line recommendation is against chemo, as he believes the long-term risks of chemo outweigh the negligible benefits (~2% benefit) that could be achieved with respect to recurrence risk.

At first, I was pretty focused on the graph on page 2 of the report, which is intended to show the potential benefit with chemo. With a score of 23, it appears there is a potential to have a reduction of approximately 4%. But on the same page is a bar graph that shows the absolute benefit and, with respect to the intermediate range, the average is shown as a negative benefit (but up to a 4% positive benefit if you took the confidence intervals into account). In the published study, it states that "Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit," and that the benefit from chemo was "less clear" for scores in the 18-30 range. The report did note that tumors with aggressive features, such as high grade, low/no ER and higher proliferation index tended to respond better to chemo.

The 2018 TailorX study has shown that, for the age group 50 and below, there was no perceived benefit from chemo if the recurrence score was less than 15. However, there is "some benefit" if you have a recurrence score of 16-25 in this age group. If you are over the age 50, there is no perceived benefit from chemo if the recurrence score is 25 or less. The MO pointed out that there is no quantification of the "some benefit" amount that could be achieved based on the age subgroup of 50 or under. This is actually discussed in the study itself. First, the study concludes that there was no perceived benefit of chemo with a recurrence score between 11-25, without resorting to a subgroup analysis. The study was not designed to then look at subgroups within the total population and see if different subgroups can benefit from chemo. However, on page 15 of the supplemental materials, it is explained that while no subgroup interaction analysis was planned, they did look at the data to consider whether it suggests that some subgroups within the 11-25 score range might still benefit from chemo. The report states that "Because of the smaller numbers, it is very difficult to establish non-inferiority in individual subgroups, and they generally do not provide adequate power for establishing superiority of chemotherapy, so these analysis should be primarily viewed as descriptive and exploratory." Thus, the MO explained that the statement that there could be some benefit is observational only, and not backed up with proven statistics. Thus, it is necessary to look at other data points in making a recommendation on chemo.

The recommendation against chemo was based on the following factors. First, my wife's age is almost 49.5 years. Because she is closer to the arbitrary age 50 cutoff (where the study says over 50 and recurrence score of 25 or less can safely skip chemo), he felt that there could be more potential benefit with a younger patient in the 50 and below subgroup. Also, there are no aggressive characteristics of the tumor, except for the low PR (5%). He believes the recurrence score is higher than one might expect because of the low PR. Because the pathology suggests there are no fast growing or dividing cells, and the tumor was small (6mm), he would have to give a strong dose of chemo treatment to achieve a potential benefit (and again, he ballparks at about 2%). So he was effectively comparing the potential long term risks of chemo against an approximate 2% recurrence benefit (and the 2% benefit could actually be zero, as a recurrence score of 23 has the Tam and Chemo lines intersecting within the confidence intervals).

Second Opinion

The second MO explained that the 15% recurrence risk that is generally associated with a 23 score was not necessarily the percentage that we should focus on. This is because the 23 score does not take into account tumor size or grade (as examples). He was able to go to the Oncotype Recurrence Score Clinical Calculator (presumably for oncologists) and look at a subgroup analysis. By using the 23 recurrence score, 6mm tumor size, grade 1, and AI hormone therapy, he said the risk percentage we should focus on is 5%, which is what the score was recalculated as with the additional tumor characteristics factored in. If my wife took Tamoxifen instead of an AI, the percentage went up one point. We also discussed the 2018 TailorX study and how to weigh the fact that the study shows that the population tested, which had recurrence scores between 11-25, did not benefit from chemo compared to the observational statement that some 50 and younger with a recurrence score greater than 15 "could" benefit from chemo. He thought, again based on my wife's entire profile, that the study supported the no chemo decision. Both he and my primary MO calculated, at best, a 2-3% reduction which is statistically insignificant.

I will say that there was one point of divergence. My primary MO thought he would have to use a strong chemo regimen to try and obtain a benefit, given the small tumor size and low grade. A stronger chemo regimen has more long term risk, which he was focused on. The second MO said he would recommend an easier chemo regimen, where the long term risks (e.g., for leukemia or heart damage) was significantly less. However, even with a softer chemo plan, the absolute benefit was still 2-3%. So while there was some divergence on the path to the recommendation, the ultimate recommendations were consistent against chemo.

It was a hard decision, because at some level it felt like either decision was the wrong decision. But we felt like we had very experienced professionals providing a consensus recommendation and, therefore, decided to forgo chemo. Like others above, I would suggest talking with your MO and asking for their professional recommendation, rather than saying it's up to you. Understand the risks of both decisions and, if possible, obtain a second recommendation. You could also ask if the hospital your MO practices has a tumor board and have your case presented for recommendation.

I wish you the best as you navigate this, unfortunately, tricky question when the Oncotype score is in the intermediate zone. I do think we could have received a different recommendation if my wife was younger (not close to the age 50 cutoff in TailorX), had a higher grade or a larger tumor size.

I'm not sure if your oncotype score would change, but my wife had a significant change in her PR percentage from core biopsy to surgical pathology. On the biopsy, she was strongly PR positive at 97%. On the surgical pathology, she was PR weak at only 5%. Both of the MO's we consulted indicated that her tumor likely had different "pockets" (I don't recall the word that was used) and that the surgical pathology was done on the whole tumor, rather than a discrete section. The low PR seems to have increased her oncotype score, compared to the result if the 97% PR from the biopsy was the actual result.

JNKK, idc 1cm grade 1 both er and pr positive no nodes, chemo really? How old are you?

JNKK,

I was just barely 41 when I was diagnosed and scored a 20 on the test.  I was told no on chemo by my Oncologist and refused to agree until I took the Mammaprint test as a second opinion and it said 'low risk'.   Only then did I say no chemo.  I would suggest you look into the mammaprint.  It's great for intermediate scores like ours.  

I have a similar diagnosis to you, am 42, scored a 19 on the Onco, and was told that I didn’t need chemo by my BS at a university hospital, a BC oncologist at Cleveland Clinic and my MO. Oh and I also saw an Integrative Onc and she agreed as well. I did have a partial mastectomy with lumpectomy with clear >4 mm margins.

JNKK, could be your age is why they recommend chemo, but still grade 1 suggests chemo might not be as effective. You could ask for oncodx or mammoprint test.

TomMorrow, thank you for posting the background to your, your wife's, and her doctors thinking. It is very close to what my decision-making process was in much the same situation although my PR was higher.

JNKK, if you can possibly talk to someone outside MD Anderson, it might help. I do think there can be a tendency for doctors in the same organizations to not have completely fresh eyes. But definitely agree, find someone you can get along with and trust! I wouldn't necessarily pick my MO as a friend, but I know he's excellent and I think I can talk honestly with him.

One more vote for MammaPrint. I honestly think they should switch from Oncotype Dx to MammaPrint, as the latter gives binary results. You are either high risk or low risk, no "grey areas" or sliding scale based on age. Ugh. If a test is to give info for treatment decisions, it should always be black and white.

TomMorrow, thanks for your input...hope your wife's radiation goes well. It's always helpful to hear what other MO's are recommending.

Hi JNKK, my recurrence rate is 17 and I'm also 43. I actually just got home from seeing my primary MO. After reviewing my surgical path report she thinks no chemo because I am highly ER+/PR+. If I do choose chemo, which she supports if I want to do to avoid "what if" and to gain the small extra %, then her regimen would be TC for 4 rounds. She said that I could do the Mammaprint if I want, but know that insurance may not pay for the test.

Did your MO state why he strongly recommended chemo (certain characteristics, etc)?

I asked my oncologist why they used the Oncotype test and she said they have more history on the test. The vast majority of oncologists where I live used Oncotype. My BC/BS insurance paid the $5k for the test and Gemomic labs who conducts the testing said if they didn’t pay they would bill you on a sliding scale.

I’m wondering why insurance companies pay for the Oncotype test but not for Mammaprint. Either way it’s a barometer on your particular tumor. Insurance companies save a lot of money if they don’t have to pay for chemo so you would think they would more than willing to pay for the test.

Had BC not paid for mine I would have still had it done. I dodged chemo because my score was 11. I have an 8% chance of a recurrence.

Diane

Thanks to those of you who brought up the Mammaprint option and your experiences with it. I was hesitant to go for it while I was at my appointment with my MO last week because they were unsure of costs, but I've since called Agendia and they told me the most I would pay is $500 for both Mammaprint and Blueprint (like Lisey said). Am going to go ahead and have my MO have the tests done as long as we're okay with waiting for the results before my next treatment needs to start. I've always disliked how the Oncotype test was done with my core biopsy sample. Plus I came across a Q&A about Ki67 on Johns Hopkins "Ask an Expert" site and JHU's breast center reply stated that "starting in 2018, it will be a requirement to measure it because there are going to be major changes in the AJCC staging process for determining the stage of breast cancer". That makes it sound like there is some value in this test result. And since my Ki67 is considered high, but everything else is intermediate/low-ish (even my primary MO said that was a discrepancy between my Oncotype score and Ki67), it would be helpful to get one more test done to see if it sways high or low risk.