Chemo or No Chemo: OncoDX 30 : RS and % Benefit confusion

LongHappyLife

Hello All,

I am 59 years old living in India, i was diagnosed with breast cancer in my left breast around 6 week back, and i had a Mastectomy 5 weeks back.

I had both my ovaries removed around 12 years back (no cancer was found but i just had fibroids)

Details of tumour:
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Left Breast

Grade 2: Score of 6

Single Focus of invasive carcinoma

Maximum invasive size of tumour: 18 * 18* 1Ams 5 mm

DCIS is present

EIC Negative

Architecture pattern: Solid

Nuclear grade: Intermediate

Necrosis: Present

LCIS absent

ER: SP1 Positive (8/8) ; Allred's score; % of cells with nuclear positivity: > 95%; Onco DX 11.5 ER: positive

Average intensity of straining: Moderate

Internal Control and strain as expected

External control: Present

PR: (1E2) Positive (4/8) ; Allred's score ; % of cells with nuclear positivity: <15%: OncoDX: PR negative 4.7

Her2Neu (By IHC) (4g5 ) Equivocal: Fish 2 Advised: ERBB2 by situ hybridization : Final impression negative

Category Group 5

Ki-67 (MIB-1) - 12-15%

Left Mastectomy

Invasive Ductal Carcinoma; Grade 2

pT1c N0 (sn)

Three Sentinal Lymph Nodes free of tumor (0/3)

Onco DN: RS: 30

Distant recurrence 9 years with TAM Alone: 19%

Group average absolute chemo benefit > 15%

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I have consulted my MO and he is suggesting chemo and then hormone blockers for 5 but i am very scared of chemo and not able to understand the basis of onco DX scores.

My dilemma is that before the Tailor X trial 18-30 was moderate risk, Tailor X proved 18-25 for women above 50 have negligible benefit of chemo, but sadly they did not do the split test for the range 26-30.

Now 26 - 100 data is perhaps taken from the older (NSABP) B20 trial where for the 18-30 range sample data size was only 134 people and the till 8 years the data almost showed no benefit (just in the last 2 years of the graphs there is some benefit of chemo which appears).

Even then i am pretty sure if the Tailor X trial included 26-30 for hormone and chemo groups results would not vary from less than 1% benefit of chemo to > 15% benefit from 25 to 26 or 30 RS score.

I am very confused if i should get chemo or not, Are there any other trials which look at people from 26-30 RS..

How do i figure out what i should do? (chemo or no chemo)

Should i ask my MO to run RSPC scores (will it benefit in my case)?

All help is very highly appreciated, i am so glad i found this site... Thanks!!

Beesie

You've got the issues perfectly nailed. The purpose of the TAILORx trial was to determine where in the intermediate range a benefit from chemo kicked in. But then they made the decision to redefine the intermediate range. So they ran this massive years long trial, and never actually answered the question that they set out to answer. Instead, those with Oncotype scores above 25 must rely on an older very small study that appears to be invalidated by the TAILORx results (if you were to extrapolate the results).

The decision you are struggling with is a common problem for those over age 50 who fall at the lower end of the newly defined high range.

It sounds like you've done a lot of researching on this. Have you seen this chart from the appendix of the TAILORx study? This shows the TAILORx results for all scores, and of course, the Hormone Therapy Only line stops at Oncotype 25. What I've done is drawn in a line that extrapolates HT Only over the higher scores - that's the red line with arrows. It might not be exact because it's impossible to know the exact curve of the line, but it has to be pretty close. I've also added in the yellow line to highlight a 30 score. Based on this, it appears that at a 30 score, the recurrence risk for HT Only would be about 12% - and it certainly doesn't look like it would be anywhere near 19%.

What TAILORx did determine was that with a 30 score, the recurrence risk with chemo and hormone therapy is approx. 8%. To my understanding, based on treatment models and what my oncologist told me, chemo generally provides about a 25% risk reduction. So working backwards, this 8% risk with chemo + hormone therapy would increase to 11% with hormone therapy alone. And that's pretty close to the 12% figure that I extrapolated on the chart.

The treatment models I referred to are PREDICT and CancerMath. Have you seen them? From a bit of playing around, I believe that these models will calculate your recurrence risk with hormone therapy alone to be in the same range as the TAILORx extrapolations.

https://breast.predict.nhs.uk/tool

http://www.lifemath.net/cancer/breastcancer/therapy/

So there are four different calculations/extrapolations that put your risk at less than the 19%, and all seem to fall fairly close together. If you believe these calculations over the older data you received with your Oncotype score, the question then is whether it is worth it to you to take chemo to reduce an 11%-12% risk down to 8%, the 8% risk (assuming both chemo + HT) being the one TAILORx figure that you actually know for your Oncotype 30 score. Since this is metastatic recurrence risk and not local recurrence risk, many would consider that to be a meaningful risk reduction, making chemo worthwhile. But for some, it would not be enough to warrant chemo. Only you can decide if that's enough of a risk reduction benefit for you.

As for the RSPC, I suspect it might not change your risk figure by much. The biggest changes in recurrence risk tend to happen using this model in situations where the pathology or patient age is far off the Oncotype average. In your case, I believe that both your tumor size and grade are very close to average. Not sure on the age. But you never know so it's worth asking your oncologist to run the RSPC model if he is willing to.

It's a tough decision - you are right in the gray zone. TAILORx made the decision easy for those over 50 with a 25 or lower score, but it made the decision even more difficult than it was before for those with 26 - 30 scores.

Hope this helps!

Sugar77

LongHappyLife - I'm in exactly the same boat. I also got a score of 30 last week. Beesie's post is super helpful. My Distant recurrence 9 years with TAM Alone: 19% & Group average absolute chemo benefit > 15% were the exact same as you. I was told the absolute Chemo benefit is misleading because that's an average for the entire High Risk group (26-100). I'm pretty sure our benefit would be less. That said, I'm leaning toward doing it. My onc is recommending four rounds of TC. I did that same regimen 1 years ago and was scared to do it. However, it wasn't that bad. Sure, I'd love to avoid it but I don't want any regrets. I'm hanging on to the feeling I had before when I finished and knew I'd done what I could. I should mention my cancer this timeis something completely new and different so my treatment before was successful. I wish you all the best in making your decision. Keep us posted and feel free to reach out to me at any time.

MinusTwo

LongHappy - for me, a lot of my decision would be based on how the HER2 comes out after the FISh test. If you are HER2 positive, I don't think chemo would be in question. If you are equivocal, you'll still have a hard decision.

Sugar77

LongHappyLife - I'm in exactly the same boat. I also got a score of 30 last week. Beesie's post is super helpful. My Distant recurrence 9 years with TAM Alone: 19% & Group average absolute chemo benefit > 15% were the exact same as you. I was told the absolute Chemo benefit is misleading because that's an average for the entire High Risk group (26-100). I'm pretty sure our benefit would be less. That said, I'm leaning toward doing it. My onc is recommending four rounds of TC. I did that same regimen 10 years ago and was scared to do it. However, it wasn't that bad. Sure, I'd love to avoid it but I don't want any regrets. I'm hanging on to the feeling I had before when I finished and knew I'd done what I could. I should mention my cancer this timeis something completely new and different so my treatment before was successful. I wish you all the best in making your decision. Keep us posted and feel free to reach out to me at any time.

LongHappyLife

@Beesie this is such an accurate, elaborate and amazing input you have given.. I feel like hugging you right now..

I fully agree with you on the risk reduction method you used with tailor X which gives an approx 4% reduction (12-8%) which is inline with the two models you pointed out and the 25% risk reduction your MO said..

I guess i should trust these over the old onco data which is surely skewed (as proven in 12-25 range by tailor X) and has a very wide range..

I just wonder if we can consider the extrapolation of the 12-25 Tailor X curves (age > 50) for chemo and chemo + hormonal the difference will not be even 4% in that case (may be 1-3%).

So it will be safe to assume a reduction of 3-5% for chemo..

I have an appointment with my doctor for RSPC tomorrow but at this point i feel it will be more or less obsolete..

Now the decision to take is 3-5% absolute reduction in metastatic recurrence vs side effects of chemo..

I am very scared of chemo mentally, but i still need to research into the detailed side effects and treatment options (cycles, frequency, type). While consulting oncologists every one told me different options but i did not pay much attention to it yet as i was focusing more on onco output.. But now is the time to dig deep into chemo and figure out if i should take it for a 3-5% benefit..

What is your opinion on side effects and treatment options?

I am also waiting on the result of my BRACA test (not sure if it changes anything in my situation)..

Again thank you so much for such an amazing reply.. really appreciate it..

LongHappyLife

MinusTwo: Her2 is Negative after Fish, but still as per what i understand it does not eliminate chemo..Had it been positive then chemo was sure-shot but right now it is Gray.. which is perhaps more confusing..

LongHappyLife

@Sugar77 our tumors are exactly the same scores and my result came out at the same time as well.. How big was your tumour?

Can you tell me what kind of short term and long term side effects of chemo did you experience? I am very scared of the side effects..

Do you agree with mine and beesie's discussion wrt. risk reduction, and you do agree will you still go for chemo for a 1-4% approx reduction of absolute risk?

Sugar77

LongHappyLife - I just sent you a private message that answers your questions. I trust my oncologist and he said it's my choice whether I want to do the chemo and if I say no, he won't think I'm crazy but if I wanted him to decide, he'd say to do it. I really value and respect his opinion. I never want to look back and have regrets even if the absolute benefit isn't as high as the higher risk scores. If I do it again, I'm even considering working through it this time.

Beesie

LongHappyLife,

Looking at the TAILORx chart, you can see that the 'hormone therapy only' line is starting to curve upwards more sharply at around a 20 score. Based on this, I wouldn't expect the line to flatten out at a 26 score; I would expect it to continue to move upwards at around the same angle and that's what I tried to reflect in the line I added in. Of course my line could be off, but I wouldn't expect the angle of the line to change drastically, just maybe shift a bit in one direction or the other. So while my line suggests a 12% recurrence risk for an Oncotype 30 score taking hormone therapy alone, I'd guess that the range is maybe 11% to 13%. What we do know from the TAILORx study is that with chemo and hormone therapy, the recurrence risk for an Oncotype 30 score is 8%. So I think it's fair to assume that the benefit from chemo will therefore more likely be 3% - 5% rather than 1% - 3%.

What do PREDICT and CancerMath show as being the benefit of chemo when you input your information?

I've spent lots of time digging through the TAILORx results (I'm a research junkie) but since I've never had chemo, I can't offer any advice about the different chemo regimens or the side effects.

Good luck with your decision. And please let us know what your Oncologist says tomorrow. It will be interesting to get his perspective if you share any of this with him. Some doctors are open to this type of discussion but others go by the book and won't question the Oncotype report.

Speaking of which, here is a copy of a chart that used to be on the Oncotype U.S. website, explaining the TAILORx results and how the study showed the benefit of chemo to be less than 1% for those with intermediate scores. This graphic now been removed from their site - probably because it also shows that for scores of 20 to 25, the hormone therapy only recurrence rate from TAILORx is about 5 points lower that what had been found in NSABP B-20 (the scale of the top and bottom charts are different). And this of course begs the question as to what the recurrence risk really would be for scores above 25 if TAILORx had included a hormone therapy only arm.

LongHappyLife

Beesie, Not able to understand the difference between Figure S8 and Figure S10 in the Tailor X (may be S10 just has the additional data for 26-100 people who were given chemo and hormone.

Strangely supposively the same graph looks very different on my onco dx report

But when we look at the s10 graph the increase of the gradient of recurrence score becomes more evident (still not sure if s8 and s 10 are the same graphs with some chemo endocrine data added for 26-100

I did run both PREDICT and CancerMath and they showed scores between 3-4% approx although they did not have the option to add my PR score so may be their accuracy might be off by a few % points.. i did read that the next version of predict will have PR but they don't have it as of now..

(Not allowed to upload images so sent a private message with corresponding images)

Beesie

CancerMath allows you to enter PR but doesn't include Ki-67. PREDICT uses Ki-67 but not PR. In the end both models generally provide fairly similar results. It's good to see that consistency in your case, and that it's consistent as well with the extrapolations of the TAILORx study. Although the info you are getting is different from what your Oncotype report said, at least you have several sources that are all providing the same information and the same approximate chemo benefit.

Here are the S8 and S10 charts from the TAILORx appendix (I believe that people are not allowed to post images until they've been members for a certain number of days) :

It does appear that the Hormone Therapy line is curving up much more in S10 but in fact the data is the same in the two charts. It's just the different scale on the horizontal axis that is causing this optical illusion. In both charts, at an 11 score, the HT line looks to be at about 3.5% risk, with an upper limit of ~4.5%. At a 25 score, the HT line looks to be at about 7%, with an upper limit of ~12%.

The chart you received in your Oncotype report does appear to be somewhat different than the same data mapped in S8. One difference is that vertical axis scale on your chart is 0% - 40% instead of 0% - 25% in S8. But the other difference is that on your chart, at a 25 score, the upper limit 95% CI lines come together, at ~15% recurrence risk, for both the HT line and the Chemo+HT line, whereas clearly those lines remain apart, and both are lower, in S8. I notice that there is a reference number at the top of the chart next to the word 'TAILORx'. Does that provide any explanation? I wonder if they are blending together TAILORx and NSABP B-20 for some of the data.

walkingmydestiny

Thanks Beesie great info. I feel little better. I am also waiting on my oncotype score hopefully on the 10th I will know.

my stats are stage 1A pT1c N0 (sn) ER strong dye 90% positive, PR strong dye 90%positive and HER2 negative clear margins and nodes. tumor sz 1.5 idc and mix... so far i have had a lumpectomy and sentinel on ....

I am trying not to stress about having a high score as the thought of chemo sickens me!

lilrpet

Hey everyone

I just want to say thank you so much! This is my first post but i have been reading on here for a while... since i was diagnosed in March this year after finding a lump the month before. It has been such a fast and crazy time, with COVID too, and while there are so many things that I have learned already, I decided to post here as this has really been one of the toughest decisions and this thread helped me feel better about how hard it was to decide about my post surgical treatment options.

I ended up having an Oncotype of 28 at age 53 after having had bilateral mastectomy with reconstruction (on April 3rd) with a great pathology report and as hoped for...not needing radiation, I guess i was surprised and disappointed to be in the gray area that is recommended chemo after just missing the low risk cut off... i also did some fancy ruler work on the graphs and used the other calculators i found (same ones posted previously on here)... and yet still i agonized at how hard it felt to make any decision I felt sure about. In the end, I have started the TC.This particular discussion helps me to feel clearer about why i had such a struggle with a decision whether to start chemo, which i did on May 25th...taking it one step at a time and giving myself the option to change my mind thanks to my MO who is very understanding and supportive of choice.

It is hard to know what is making sense, statistics in the end are just numbers cuz when something happens its 100%, when it doesnt its 0% so with it all being so theoretical, i was driving myself kind of crazy trying to figure out where to turn in the gray area. For now I guess i will see how it goes. This has been a whirlwind, and every day i am still trying not to get lost in the nightmare of becoming overwhelmed.

Blessings sisters,

I thank all of you for being on here....

Honestly, the gray area kinda sucks....

Cowgirl13

Congratulations on having had your first chemo. Even before I knew I had to had chemo and rads, I wanted to throw the book at it because if I hadn't ,I would have felt terrible and forever wished I had followed the stronger line of treatment. It was 11 years ago today when I was diagnosed and I'm still here.