Oncotype score and estrogen inhibitors

jessie123

I just got my oncotype score of 19 --- which means no chemo. However, please tell me if I'm interpreting this correctly. The paperwork from the onco people indicate that the score is based on the presumption that the patient will take an aromatase inhibitor or tamoxifen. If that is true what happens if I can't tolerate the drugs? If you don't take or stop the drugs does it mean that you should have taken the chemo? They are looking at our risk of reoccurrence with and without chemo, but including estrogen blocking drugs. Right???

Salamandra

Hey jessie123,

That is such a good question and I hope someone can come fill us in. Has your doctor given you any info? I'll try to remember to ask my MO next time.

Statistics show that as many as 50% of women are noncompliant with their endocrine treatment. A lot of the medical profession wants to assume that that's due to the fault of the women. But that seems bogus to me. 5-15% sure, maybe that's individual women not sticking to something. But 30-50%, that's because of intolerable side effects as far as I'm concerned. And of course, none of us know going on how our body will tolerate the therapy.

jessie123

OK - got my sheet out --- there are 3 large results boxes: The first says Recurrence score result -- 19

The second box says -- Distant recurrence - risk at 9 years - with AL or TAM alone -- 6%

The third box says - Absolute Chemotherapy Benefit - <1%

So the recurrence rate is with the drugs -- it doesn't tell what the recurrence rate is without the drugs, but I'm willing to bet it's considerably higher since don't they say the drugs reduce recurrence by 40 or more percent? So is taking chemo based on taking or not taking the drugs. Would the chemo benefit be higher if you have decided not to take Tamox or ALS. My brain is so tired of trying to understand everything.

TwoHobbies

Jessiie it does assume you are taking tamoxifen. These drugs are the preferred treatment for HR+ cancer so no one would recommend chemo instead. It just asseses benefits of adding chemo.

I think I have heard drugs reduce the risk by 50 percent or so as opposed to no drugs.

Spookiesmom

Do keep in mind, even if you do chemo, and the AIs, that doesn’t totally eliminate the risk of recurrence.

SpecialK

The OncotypeDx RS assumes you will take anti-hormonal drugs - either Tamoxifen (or one of the three aromatase inhibitors - and incorporates that into the score. The general thought is that in the absence of these meds your score roughly doubles. See BarredOwl’s post on Nov 19 in the link below:

https://community.breastcancer.org/forum/96/topics/849708?page=1#post_4847322

bcincolorado

I had onco of 17 and did not chemo. I took Tamoxifen for 5 years faithfully. Then on Letrezole. Just finishing with that one since another test showed it won't benefit me to stay on it at this point. Recurrence risk does not ever go to zero with cancer unfortunately. My oncologist said they refuse to tell people they are "cancer free" and just say they are NED---no evidence of disease at that time those labs are drawn. They will never release me and follow me forever.

jessie123

SpecialK ---- wow - that was very good information --- I wrote down how to find that page again so that I can take my time to read some of the links provided. Maybe you can answer this --- are there also long term recurrence statistics on taking Chemo instead of taking the pills or comparing the two individually? If they are similar maybe we should be given a choice ---- not that we need anymore choices with this disease.

SpecialK

You’re welcome. There is not a great deal of information regarding survival with taking anti-hormonal, or not, because studies that use no meds as a control would be unethical. The stats come from the time before the meds existed. It is known that Tamoxifen reduces recurrence by about half - as posted by others above - so it makes sense that the RS roughly doubles without it. The best available way to estimate benefit of individual therapies is probably to use one of the calculators - Cancermath, or Predict. I will link them both below. For the Cancermath/Lifemath be sure to include your age at diagnosis. Most receive a 3rd gen chemo regimen, you would have to try different ones to see if they changed the result. I prefer the pictogram as the graph illustration. For the Predict tool be sure to use tumor size in millimeters (multiply cm x 10 - I had a 2.6cm tumor, so 26mm) since this is a British site

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

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

jessie123

Salamandra --- I don't think many doctors even explain how important the pills are or if they do they need to remind patients often of the survival statistics. We are so stressed in the beginning --- there is too much information to process. I have two friends on the pills and they have no side effects at all. However, I don't know how they will affect me and if chemo alone has the same long term prognosis it may be something to consider.

Spookiesmom --- I know - that is a horrible thought. It's hard to get that in my mind -- I hope that I can go into denial after my radiation is over. I am so sorry for your recurrence --- I saw your post a couple of days ago and it saddened me. Have you told Spookie all about it --- I tell my two everything --- they are really good listeners and they don't get mad at me for repeating myself.

jessie123

Thanks specialK -- I'll let you know how my tests come out. Must do it in the morning when my mind is sharper.

AliceBastable

Keep in mind that the lifetime risk for ANY woman to develop breast cancer is 12%. So any percentage below that for recurrence puts us ahead of the general population.

Ingerp

SpecialK thanks for the calculator/predictor links. I've used them before but not for several years. The Predict reinforces what my breast surgeon told me about AIs as well as what I've read several women post--that the AI has a bigger impact on improving 10-year survival than chemo or Herceptin. I wish that information were more widely known when women are evaluating whether or not to put up with the SEs.

P.S. I'm assuming the AI numbers were based on five years of treatment? Is it possible the effect would be greater if they included seven or ten years of treatment?

SummerAngel

AliceBastable, it's true that an average woman's risk is 12%, but that risk is for breast cancer as a whole - any stage. The Oncotype risk is for a distant recurrence, which is very different.

jessie123, it's interesting that your score was 19 but the risk with AIs or Tamoxifen is 6%. My score was 9 but I had the same risk listed.

SpecialK

ingerp - I’m not sure whether these calculators could include longer term use of anti-hormonals yet as longer term use use has been studied but not adopted universally. The Breast Cancer Index test, done on original tumor material, is a genomics test like OncotypeDx or Mammaprint, that specifically looks at whether there is benefit of continuing on anti-hormonal medication past 5 years, as well as recurrence risk. I had that test at the 5 year mark and while my recurrence risk was high, my drug benefit was low - not a great combo - happens for about 10% of those tested. I continued taking letrozole until the 7 year point and just recently discontinued.There is also a newer calculator that is looking at post 5 year risk:

https://www.breastcancer.org/research-news/online-tool-predicts-hr-pos-recurrence-risk

Beesie

Jessie, I just happened to be digging through the research on Tamoxifen and the AIs and then I saw your post. It appears that most studies put the reduction in metastatic risk (and therefore mortality) from Tamoxifen at approx. 30%; the AIs provide about a 20% additional benefit.

This would suggest that if your risk of metastatic recurrence is 6% with Tamoxifen or an AI, your risk would be approx. 8% if you do not take endocrine therapy.

"The decrease in recurrence risk for ER-positive breast cancer after tamoxifen treatment was accompanied by reductions in breast cancer deaths and in deaths overall. Throughout the 15 years since the beginning of treatment, the yearly rate of breast cancer deaths among patients with ER-positive breast cancer was about one-third lower among women who had received tamoxifen than among women who had not. Deaths from any cause were also substantially reduced in women who took tamoxifen."

Long-Term Data from 20 Trials Confirm Tamoxifen's Long-Lasting Benefit

jessie123

Summer angel --- I think it's because you had some node involvement and also I'm post menopausal vs you are premenopausal. The oncotype also provided a higher score if I had had micromets and one through three positive nodes. If that had been the case my oncoscore would be 16%. If I had had 4 or more nodes positive my score would have 52%. I wish that I had been born 50 years later so that maybe I could get "for sure" answers rather than "maybe" answers.

jessie123

Beesie -- oh I see what you mean. My risk without Al's or Tamoxifen would be 30% higher than 6% - which is 8%. These statistics can be confusing because I was basing it on 30% of 100 which would be about a 32%. So people who haven't had the estimated risk calculated have no way to base their increased risk without drugs. One thing that still confuses me is the statement " death from any cause was substantially reduced in women who took tamoxifen. What on earth does that mean ---- I am missing something with that statement.

Beesie

Jessie,

AIs and Tamoxifen come with side effects, some of which can be very serious and on rare occasions, can even lead to death (uterine cancer, DVT/PE, heart issues, etc.). The line "Deaths from any cause were also substantially reduced in women who took Tamoxifen" means that the survival benefits from Tamoxifen outweighed those risks, and overall survival was significantly better.

One other thing. Lots of people quote a general "50% reduction in risk" as being the benefit ofTamoxifen and the AIs. To my understanding, the 50% figure refers specially to the reduction in risk related to a localized (in the breast area) recurrence. Based the report I linked above, the reduction in risk specifically for distant (metastatic) recurrence is approx. 30%.

dtad

Bessie...is that really true??? I cannot believe how misleading the 50 percent reduction is if that statement is true!! Any more feedback?

Ingerp

Thanks <as always> SpecialK. My risk group was intermediate for Grade 3, low for Grade 2 (I really don't remember what it was this time around!). I'm only four months in--I figure by the time I hit the five-year mark the diagnostics/predictors will be even better. That said, my SEs have not been bad. I started shortly after I turned 61, so in my head I'll stay on the AI through my 60s. Going off it will be a 70th birthday present to myself. :-)

For any interested, here's a direct link to the calculator:

https://www.cts5-calculator.com/

Beesie

dtat,

Yup, we see "50% reduction in risk" for Tamoxifen and the AIs all the time. Is it correct? It depends.

There have been many studies on Tamoxifen that have looked at it's impact on the development of a recurrence after a breast cancer diagnosis, or the development of a contralateral breast cancer in women who have previously been diagnosed, or an invasive breast cancer in women who have had DCIS, or an invasive breast cancer in women who are high risk. Most of these studies have found a risk reduction benefit after 5 years of Tamoxifen is in the range of 40% to 50%. I believe that this is where the oft-quoted "Tamoxifen reduces risk by 50%" comes from and for the most part, when looking at all recurrences (localized + metastatic) or the development of an invasive cancer, the 50% risk reduction figure is in the ballpark (although 45% would probably be more accurate).

The problem is that this generalized, rounded 50% risk reduction figure is also used when discussing the risk of a metastatic recurrence, or the risk of mortality. The Tamoxifen studies that have looked specifically at that, or that have separated out metastatic recurrences from localized recurrences, do not support a 50% reduction in risk figure. Specifically for metastatic recurrence and mortality, a 30% or one third reduction appears to be is more accurate. This is what I referred to in my earlier post, and this is what is relevant to the Oncotype recurrence score.

The "50% reduction in risk" figure is thrown around this board a lot by women posting here, sometimes in the wrong context (i.e. referring to metastatic recurrence) but hopefully this isn't what we are hearing from our doctors when they are giving us information about the metastatic risk reduction benefits of endocrine therapy. I know that my MO quoted a benefit closer to 30% (slightly lower, I think).

One last comment. The reason I've referred to Tamoxifen studies is because Tamox was on the market first, and there are many studies that compare Tamoxifen to a placebo. By the time the AIs came around, Tamoxifen was well established, and most the AIs studies didn't have a placebo arm but instead compared the AI benefit to the Tamoxifen benefit. On average, I believe that AIs have approx. 10% - 20% better risk reduction benefits. In other words, if Tamox reduces the risk of a metastatic recurrence by 30%, it would be about 33%-35% for an AI.

Information on some of the many Tamoxifen studies can be found here: https://www.rxlist.com/nolvadex-drug.htm#clinpharm

Salamandra

Beesie, I appreciate your posts so much! And as an expat, the maple leaf warms my heart every time

I wish they would replace mandatory high school geometry or trig classes with statistics. A short unit mixed in with algebra or whatever is not enough. And at the very least it should be required at colleges that have general education requirements. Statistics are everywhere now. Taking an actual class is on my to do list - whatever I know is hobbled together on my own and I wish it were better.

I hadn't realized about the 30% tamoxifen benefit for distant metastasis. I'm struggling with some pretty debilitating tamoxifen side effects, and that is helpful to keep in mind.

jessie123

Bessie --- so did I understand it correctly? My risk with Al's is 6% and if I refuse the drug my risk will be 8%. (30% increase in risk). I'm going to try the drugs - and they will probably be fine. However, if my risk just increases to 8% if I discontinue them because of SE's I won't be horrified.

Salamandra -- you are so right, but the need for statistics classes includes the doctors. My brother in law is an Oncologist and I remember him going back to a local college to take statistic classes to better understand the studies. I don't think they learn that in medical school.

Beesie

Jessie, yes, you understood correctly, although I did the math on the 30% from the wrong direction so your risk without AIs might be a little bit higher.

If endocrine therapy reduces distant recurrence risk by 30%, and your reduced risk is 6%, it means that your risk without endocrine therapy is 8.6%. (6 is a 30% reduction of 8.6)

Of course this is my calculation based on the studies I've noted above. You should talk to your Oncologist.

You might alsowant to input your stats into PREDICT to see how much % benefit this model says you get from taking an AI. https://breast.predict.nhs.uk/tool

jessie123

Thanks -- I just took the test. My score at the 10 yr survival option is 71% surgery only and 74% with meds. So you are so right -- it is only a small percentage advantage with the meds. Think of the women who have very bad side effects from the drugs, but are afraid to stop because they think the benefit is so much greater than it is. One thing I found interesting --- On the test I lowered my age by 8 years -- nothing else was changed and my 10 yr survival increased to 81% without and 84% with meds. Wonder why it's different. I already have osteoporosis in my hips so these drugs may do me more harm than good when considering the need for prolia or fosamax. (the osteoporosis was caused by very high doses of lupron for fibroids when I was in my 30's)

Beesie

Jessie, if you look at the bottom of the survival stat chart on the PREDICT website, you'll notice a line that says "If death from breast cancer were excluded, X% will survive at least 10 years". That's what causes the higher survival when you lower your age - it's fewer deaths from other causes.

To calculate 'breast cancer caused deaths', subtract your figures (the 71% and the 74%) from this number that's below the chart. I'm guessing the number on the bottom of your chart is probably something like 80%. At 80%, it would mean that 9% will die from breast cancer with no additional therapy, versus 6% with AIs.

dtad

All I can say is wow! 30 percent is NOT 50 percent! I'm one who refused anti hormone therapy from the start but for those suffering debilitating side effects this should make a difference! Also keep in mind that weight loss and exercise has ben shown to lower recurrence rates by 40-50 percent!

Beesie

dtad, whether this should make a difference for those suffering debilitating side effects depends entirely on the specifics of their situation. A 30% relative risk reduction - when we are talking about the risk of mets (and therefore, the likelihood of long-term survival) - can still be quite significant.

Someone has a risk of mets of 6% with endocrine therapy who has significant quality of life side effects from the endocrine therapy might be okay with stopping the therapy and living with a somewhat higher risk in the range of 8-9% (as Jessie's numbers seem to show both from applying the 30% estimate to her Oncotype score, and from her PREDICT estimate). Others, even at this risk level, might be uncomfortable adding this extra level of risk.

Many if not most diagnoses do however present a higher risk. For someone who has a risk of mets of 15% with endocrine therapy, not taking Tamox or the AI would increase the risk to 21.5% - the 30% here represents a 6.5 point reduction in risk. That seems pretty significant to me.

The other consideration is local recurrence (in the breast area) and the risk of a new primary breast cancer. Tamoxifen and the AIs significantly reduce these risks, and this is not incorporated into the Oncotype score. For those who've had a BMX, these risks generally are quite low, unless they had close surgical margins or are high risk due to a BRCA genetic mutation (or something similar). But for those who've had a lumpectomy or a single MX and who still have one or two breasts with all their breast tissue, these risks could be significant.

• A local recurrence can be quite treatable or it could develop into a much more serious diagnosis that the original cancer. Tamox and the AIs can cut this risk by about 45%. So if someone's risk is 10% after surgery and rads, endocrine therapy can reduce the risk to 5.5%. A 20% risk will be reduced to 11%. And so on.
• Similarly, for all of us who've been diagnosed with BC one time, the risk to diagnosed with BC again - a new primary, unrelated to the original diagnosis - is about double that of the average woman (if not higher). Here again, the diagnosis might be low risk or it could be high risk - it won't necessarily be the same as the first diagnosis. Tamox and the AIs reduce the risk of a new primary, in either breast, by about 45%, with the proviso that the benefit only covers the period that you take these drugs plus a few extra years while the effect remains in your system, whereas this higher risk to be diagnosed with breast cancer remains over your lifetime.

.

So yes, for some women, the risk reduction benefits of endocrine therapy might be relatively low. But for many if not most women, the risk reduction benefits can be quite significant when you consider the specifics of their diagnoses and evaluate all their breast cancer risk including distant recurrence, local recurrence and new primary.

cassiecanada

Hi Dtad-

our stats are similar- i start

partial radiation on april 23 and then femara-

( i am 63). I have been a road bike warrior

for years and given the joint and bone

issues on femara, i cant imagine

giving up my one and only hardcore

passion to reduce, in my case, mets by 3%

( down from 6%)...i told my oncologist

i may opt out. I wonder what you or anybody

out there would choose:

a) femara opt out and take the 6 % met

recurrence risk

b) take femara to reduce risk to 3 % (mets)just to see if its as bad as

doctor and others have said it will be.

then ditch if it becomes intolerable.

i just wonder about other peoples threshold

cassiecanada

hey dtad...

what was your reason for med op out.

was it femara? I sm 63... i wonder

if you are post menopausal as well... cos i

think thats a variable given that estrogen

lower etc ( vs pre menopsusal)

i cant tske tamoxifen vos clotting history.

i actually see you are @ 5 years out from lumpectomy with no meds.... thats great