Meaning of low Oncotype Dx score

I had a low oncotype, well, borderline, and my oncologist explained it to me this way:

(1) Since my ER/PR is so positive, Tamoxifen is more likely to work on the cells than chemo is. She said if we did chemo BEFORE surgery on my type of tumor, it would only shrink it about 10% of the time.

(2) Chances are, given the negative lymph node status, that the surgery has already taken care of getting rid of the cancer. Why subject yourself to the toxicity of chemo when it's so much overkill and will upset your immune system and healthy cells when you have no cancer cells to fight off anyway?

(3) You have to weigh the benefits of chemo with the risks of chemo, which aren't small. So say, the Oncotype shows a 5% benefit for chemo...you have to weigh that against the 5% chance of chemo leaving you with a long-term health issue.

Those were the cons...but in my case there were also some pros, including a prior breast surgery that might have caused the cancer to get into my bloodstream, so I did, in the end, opt to do chemo.

Hope that helps.

Jen

Hello there.  I feel your pain and confusion.  When I was first diagnosed at 47, I was told for sure I would need Chemo because of my age.  After they did a lumpectomy and found out none of my lymph nodes were affected and there was not any vascular contamination, I was told by the top Oncologist at Scripps in San Diego CA to have a Oncotype test done.  It came back a "6" which is considered low risk.  What I was told is that they test the cells for genetics and the "likelyhood" that the cancer would reoccur and mine had a 6% chance of returning.  The test said that chemo would do more harm than good.  They look at size, PR/ER pos/HER Neg, lymphnode involvement, rate of growth along with genetic markers that can tell them how agressive the cancer is.  I chose to have a complete hysterectomy to suppress 90% of my estrogen, radiation, and Femara.  I have since gone of Femara because of the side effects and feel much better.  I hope this helps?

Susie has explained it well. Chemo works best on aggressive tumors with rapidly dividing cells. In fact it attacks ALL rapidly dividing cells, which is why your blood counts go down and you lose your hair--those cells divide rapidly also, and the chemo doesn't know a hair-growing cell from a cancer cell.

The oncotype test is a more detailed assessment of the nature of a tumor than the observations the lab technician includes in your path report. While no test is infallible, the oncotype test is highly reliable. And there is also quite a bit of research indicating that chemo is relativley ineffective on "indolent" (slow growing) tumors, and it does involve some substantial risks. If you forego chemo now and have ithe cancer come back, you will of course use it later. But if you use it now and have a recurrence, you can't use the same regimen again because it would be too toxic.

All treatments of cancer have their drawbacks, so it's a matter of trying to identify the treatment plan that will work best for you and do the least harm. You're doing the right thing by asking guestions, and the answers should help you make the best decision you can make.

My mom and grandmother had  BC. My mom lost her life to it.  It was because of them and so many of our other sisters before us who have died with this terrible disease, that we have been blessed with this technology to understand our cancer down to the moelcular level and make decisions about treatment.  Those before us did not have that luxury.  My score was just past the high risk mark.  It was a no brainer to have chemo.  My niece recently has gone through all this.  Her oncotype score was low.  She does not need it.  She can thank her grandmother and great grandmother for what they went through to now have this edge to know what treatment is best. it is each persons responsiblity to educate herself and research as said before.  And thank those who went before us.  If you don't need chemo, thank a previous sister who helped along the way to learn this.

Chasinghope,

You situation got me wondering - and since it's a horribly crappy day here and I've got nothing much better to do today, I decided to try and find an explaination.

First of all, although your oncologist told you that the oncotype "doesn't access or account for the grade" of your tumor, I'm not so sure that's true. Yes, grade is not directly taken into account when determinining the recurrence score (RS). However, Oncotype is based on examining 21 genes. There are 5 control/reference genes and the other 16 are cancer related with 5 of those 16 genes specific to cell proliferation - so almost a third of the cancer related genes being looked at are about proliferation. Proliferation is how rapidly the cells divide and high grade tumors divide rapidly.  The mitotic count is one of the determinations made by a pathologist when assigning histologic tumor grade and the mitotic count is a measure of cell proliferation.  So, although the Oncotype test doesn't directly take someone's predetermined  tumor grade into consideration when calculating a recurrence score,  the genes associated with one of the 3 components of the Nottingham Grading System, which is the most commonly used system to determine tumor grade, is weighted heavily by Oncotype.  

Now on to what got me interested - having a very low RS yet a grade 3 tumor. Everything I've ever read suggests that grade DOES correlates closely with the oncotype recurrence score. So in other words, those with grade 1 are most likely to have a low RS and those with grade 3 are most likely to have a high RS with grade 2 most likely to have a intermediate range RS. Obviously there are some, like yours, that don't correlate well.  So, in having had a pathologist assign a grade 3 to your tumor, it would be reasonable to expect that your RS would NOT be in the low range. Since it was in the low range, the question then becomes why the discrepancy?

Here's something interesting I found -

http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today%2Fcover_stories%2F0307brcancer.html&_state=maximized&_pageLabel=cntvwr

"Collaborating with pathologists at West Virginia University, Dr. Bloom blindly assessed tissue blocks from 28 patients who had previously had Oncotype DX performed. "All 14 tumors that had a low recurrence score had high expression of PR and low expression of KI67 and did not overexpress HER2," Dr. Bloom relates. "So if you want to find people with a low recurrence score, it appears that you could do that with three immunostains. Those also correlate very tightly with tumor grade, AND LOW-GRADE tumors almost always fall into the low-recurrence category." 

Dr. Bloom calls the four tumors with a high recurrence score "more interesting." One had 3+ expression of HER2 while a second did not express HER2 but had a proliferation index of greater than 50 percent. "In the other two cases IHC data would have predicted a low recurrence score," Dr. Bloom says. Both expressed PR and had a low proliferation index. His initial conclusion was that IHC found all tumors with a low recurrence score but may have missed two with high recurrence scores.

However, detailed analysis of the two discrepant tumors showed something more intriguing. A key factor in both tissue blocks was a cavity from the patient's previous needle core biopsy. "So the block contained tumor, but also adjacent to the tumor itself we could see the needle track with inflammatory tissue including macrophages," Dr. Bloom says. "IN THE BIOPSY TRACT THERE WAS GRANULATION TISSUE PROLIFERATING LIKE CRAZY. SO LOTS OF CELL WERE EXPRESSING KI67, BUT THEY WERE NOT TUMOR CELLS." Dr. Bloom also notes that a minor component in the recurrence score is CD68 expression, a macrophage marker. "We saw numerous CD68-positive macrophages in the tumor block," he says, "but no tumor cells expressing CD68." Taken together, he believes these findings can explain the discrepancies between the recurrence score and IHC results. Both patients with discrepant results elected to receive chemotherapy, he told CAP TODAY, "even though without this test they would have received only hormonal therapy. There is no doubt in my mind that both of these patients were significantly overtreated."

So here this Dr. Bloom has offered some insight into how a Oncotype tested tumor might erroneously appear to have a high RS  (due to seemingly high proliferation) because there was granulating tissue present in the specimen which was rapidly dividing (as granulating tissue normally does). In these 2 cases, Oncotype gave a high recurrence score which was apparently  inaccurate and if looked at closely enough, the reason becomes apparent.  Although your situation would be the polor opposite of these 2 cases described,  there's still got to be an explaination for yours just as there was with these two.

So the take home message of my rainy day story is this -

When there is an obvious discrepancy between expectations based on tumor characteristics and oncotype results and things don't jive, then something is amiss somewhere and it should be investigated further.   If I were you, I would definately get another pathology opinion (or maybe even two) to confirm that it's really a high grade tumor before consenting to chemo. If it happens that the Oncotype is correct, then the most likely explaination as to why RS is low is because the tumor is not high grade.  If I had to choose between believing the Oncotype score or believing the assigned grade, I would believe the Oncotype score. Histological grading is subject to a degree of interobservor variabilty - meaning that it's entirely dependent on how a particular pathologist calls it and that another might see it differently. Errors are inevitable when things are subjective. Oncotyping, while still subject to occassional errors as noted by Dr.Bloom is far more reliable, non-subjective and reproducible.  

MarieKelly has given an excellent explanation of the meaning and significance of Oncotype Recurrence Scores and their relationship to tumor grade and IHC for hormone receptors.  That paper out of WVU is a terrific find.  Their observation probably does explain some of the discrepancies; and it also highlights the importance of taking all the evidence into account -- not just focusing on one particular result.

otter

Oh my Lord,

 Ladies, thank you for looking into it and so throughly. I already had the chemo though. My doctor said chemo no matter what because of the grade 3. (That was her opinion and she encouraged me to seek a second opinion. I was to beat up and in shock. This hospital is one of the best in the country. I went with her expertise. I did though put up a fight for my score, while undergoing chemo and she conceaded. Something she said to me stuck with me though. She said "The reason why I didn't want to order your OncotypeDX score is that I thought it would be high because of the grade 3 tumor, and that would scare you even more." When it came back a 6% distant reoccurance she only said to me that she was surprised but it was good news? So, now I'm wondering if I should pursue it. I like her, I think she's been a great onc.....I hate this whole process, pretty scary to think I might have had the wrong course of treatment. I think I need  a PHD to understand all this stuff??? Again, thank you, I'm determined to try to understand it all on this rainy night. Thank you MarieKelly, Otter and swim , thank you everyone for caring enough to look into this and share with me what you've gone through, this whole experience is a miserable one. THANK THE GODDESS ABOVE FOR THIS SITE & all the amazing, kick ass women on it !!!

My Oncotype score is 3; the oncologist said she had never seen a score so low. I'm not sure what that means for treatment. I'm definitely getting radiation, but don't know if AIs are worth it. She threw a lot of numbers at me, but I was too stunned to take them in. I have an appointment with my primary MO tomorrow, so we'll see what he says. If possible I'm going to skip the AIs if they only shrink my risk to 5% or lower.

Cuddyclothes do you have a copy of your Oncotype report? The numbers are on the report. I have been told that without hormonal treatment risk doubles, but don't know how that works with a score as low as yours! Low scores are often are a result partly of high estrogen sensitivity but you must have other factors. But in any case the Oncotype score is based on the assumption you will be doing Tamoxifen (at the time of the creation of the test this was standard I think).

I don't think aromatase inhibitors are that bad. I have written elsewhere that it helped me to start with 1/4 to ramp up, to consider early side effects as temporary while my body adapted, and to work 45 minutes each day to help joints. Many of us don't have bad side effects at all. But with your low score, who knows.

In any case, those numbers are important!!

cuddy my oncotype was 3 also. I initially refused HT but my onc was adamant and said not taking it puts a lot of faith in that one number. I did two years of T and have been on Femara for seven months. The joint issues are really getting me down and I'm tempted to quit. I probably won't though. Too chicken.

Windingshores - my ki67 was 22%. I called the hospital's pathology department in the past month or so and the chief pathologist was gracious enough to take a second look at my slides and he too said grade 2. So yeah - the variations are unsettling.

Cudding - I would be very interested in knowing what your onc thought about not taking HT.

Actually WS - That is good to hear about the healing tissue. I had tissue removed the size of my palm in my excisional biopsy. I'm going with that!

Happy Thanksgiving!

Yeah - that's what my onc said too re: scary family history. I stopped femara yesterday. I feel better already. I'll talk to my gyn this week about starting Tamoxifen again even though I had a lot of uterine issues with it. If she is ok with it I'll stay on it for the rest of the time. To me those SE were easier to deal with than the joint issues.

Now that I've finished with radiation, I'm going to set up appointments with my MO, and I have one with my PCP in two weeks. I'll see the RO in a month.

All these initials...it's like using twitter and writing "OMG IAWYC IMO!"

Translation: "Oh my god I am with you completely in my opinion!"

farmerlucy

You are right about that! I'm going to go back to Diagnosis boards and read through my results again, plus the EXTENSIVE notes my friend took during our meetings with my various doctors.