Log in to post a reply
Jul 18, 2018 02:54PM
Jul 18, 2018 03:01PM
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.
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).
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.