Luminal A vs. Luminal B stage 1 BC
Comments
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Hi Lisey... do you know where on my oncotype it says I am a or b.. Onco said A but I was confused because of 25% ki 67
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Lisey, you need to look at the difference between your probable recurrence risk both with and without chemo, as well as your Oncotype score. There may be a minimal difference. Some women have a low intermediate score but would derive little benefit from chemo.
I'm sure your MO will go over all of this in detail at your next appointment. If not, ask lots of questions. -
Hi WarriorWoman:
"Are you saying that hormonal treatment decisions should be based on the lab path reports and Oncotype should be used only for chemo decisions? Does anyone know?"
Short Answer:
I am saying that in the general case, hormone receptor status for the purpose of deciding to initiate endocrine therapy should be based on the IHC results from pathology. Over time, as more data is accrued about the single-gene scores, this may change.
Detailed Discussion:
Keep in mind that one should have hormone receptor-positive, HER2-negative disease as assessed by pathology to be "eligible" for the Oncotype test for invasive disease.
The Oncotype test determines levels of mRNAs produced from 16 different test genes and 5 control genes ("21-gene test"), and computes a multi-gene Recurrence Score based on the combined mRNA expression data or gene expression profile. In addition, the individual single-gene scores, reflecting gene expression (mRNA levels) from the ER, PR and HER2 genes are reported.
The main and by far the best validated output of Oncotype testing for invasive disease is the multi-gene Recurrence Score ("RS") and its use for the purpose of informing decisions about the addition of chemotherapy to endocrine therapy.
As of this date, the single-gene ER, PR, and HER2 scores have limited application, and relatively much poorer validation than the central output of Recurrence Score. Thus, the single-gene ER, PR and HER2 scores should not be relied upon in the general case for deciding about initiating endocrine therapy or HER2-targeted therapy. In specialized cases, the single-gene scores may be relied upon; however, in such specialized cases, I think that a second opinion would be warranted.
ER and PR scores: The single-gene ER and PR scores can be confusing to clinicians. See for example, the Discussion in this 2012 paper:
http://www.nature.com/modpathol/journal/v25/n6/ful...
"The additional reporting of qRT-PCR ER and PR results on oncotype report confuses clinicians and unnecessarily creates doubt about validated immunohistochemistry assays."
--- The large clinical studies that evaluated the benefits of endocrine therapy used pathological methods (IHC) for determining hormone receptor-positivity.
The Oncotype Sample Report for node-negative (N0) disease includes a (cryptic) citation to a single study (Kim, J. Clin. Oncol. 2011) that is said to show a correlation between higher single-gene ER scores and clinical benefit of tamoxifen. HOWEVER, it notes that the degree of tamoxifen benefit is already accounted for in the recurrence risk estimates. Specifically, under "Clinical Experience" the Sample Report states:
"For ER+ breast cancer, the magnitude of tamoxifen benefit increases as the ER score increases from 6.5 to [greater than or equal to] 12.5. Please note: The Average Risk of Distant Recurrence reported on Page 1 based on the Recurrence Score Result was determined in patients who received 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER score."---
HER 2 score: The pathological methods of IHC and ISH (e.g., FISH) are currently the preferred validated methods for determining HER2 status. While the Oncotype report includes a "quantitative single-gene report for HER2", the FDA has expressed concerns about false-negative results with this test, raising the possibility of under-treatment (failure to provide trastuzumab). Again, there might be specialized cases where it is appropriate to consider the individual oncotype HER2 score, but such a specialized case likely warrants a second opinion.
Chemotherapy Decision (Adding chemotherapy to endocrine therapy):
Again, keep in mind that one should have hormone receptor-positive, HER2 negative disease as assessed by pathology to be "eligible" for the Oncotype test for invasive disease. For the purpose of deciding to add chemotherapy, the estimated average risk of distant recurrence (10-year risk) associated with a particular Recurrence Score for node-negative patients were determined in patients who received 5 years of tamoxifen and are thus based on the assumption of receipt of five-years of endocrine therapy. If one declines endocrine therapy, the risk of distant recurrence would be significantly higher than shown on the report. I have explained this in more detail here:
https://community.breastcancer.org/forum/96/topics/844898?page=1#post_4729613
I am a layperson with no medical training. Please confirm all information above with your team.
This is a highly specialized and rapidly evolving area. Patients should always obtain copies of their Oncotype report and pathology reports from all biopsies and surgeries, including all ER, PR and HER2 status information based on standard pathological methods, and should discuss individual Oncotype test results (Recurrence Score and single-gene scores) in light of ER, PR and HER2 status as determined by pathological methods with their medical oncologist to ensure active consideration of all test results and identification of any special circumstances, and the receipt of accurate, current, case-specific expert professional advice.
BarredOwl
[Later Edit: The citation of "Kim, J. Clin. Oncol. 2011" is not uniquely identifying, but may correspond to this article:
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Just edited the post above to correct grammar and added some text. New text sandwiched by ---dashes---.
BarredOwl
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JoJo,
What I was told yesterday is that while I am indeed Luminal A (because with both IHC and the Oncotype I show as ER+/PR+), they now use an oncotype score in the middle range (18-30) and basically use the ki-67 test as the deciding factor for chemo or not.
The study I posted about 3 posts above shows that a higher ki-67 for Luminal A's mean they really should be treated more like Luminal B's and in the results aspect Luminal A's with higher ki-67 scores have the same mortality rates as Bs would. Previous to this, it was believed Luminal A's have better odds than Luminal B's ... but this study says that's only the case with low scoring As on the ki.
So you most likely are still a Luminal A, but have you had your Ki tested? It should be in your Oncotype hopefully. I had a oncotype of 20 and a Ki of 30-35% and they are saying definitely chemo, even though I'm stage 1A.
Barred Owl- in reading your post my Oncotype RS score is 13% (with Tamoxifen) which to me is pretty damn high for a Luminal A. -
Hi Lisey:
Did your medical oncologist tell you that with a low intermediate Oncotype score, it is their practice to decide the question of chemotherapy based on Ki-67?
With an intermediate score, the Oncotype website mentions the following (exemplary?) factors to consider:
It appears that a number of NCI-designated cancer centers, such as Dana Farber, no longer test for Ki-67. It seems there are some methodological concerns about reproducibility of the determination (e.g., "interobserver variability").
The literature in the Ki-67 area and in the Luminal A vs Luminal B area is extensive and complex. Members should be cautious about basing treatment decisions on a single report. In this regard, I believe that the paper you cited and quoted from above was published in 2010, and as such, might not reflect the most current thinking in the area. There might be conflicting studies (earlier or later) or subsequent studies that alter the picture and understanding. This is the Japanese study you cited I think:
"Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer", published 2010
https://www.spandidos-publications.com/etm/1/5/747
If your thinking about treatment decisions is influenced by something you read in the scientific literature, always be sure to discuss the publication and specific information with your Medical Oncologist, to ensure proper interpretation and understanding of the information, as well as to confirm its currency and applicability to your specific case, including whether there are any potentially conflicting studies.
Please be sure to discuss what the estimated potential risk reduction benefit of chemotherapy would be with your team to gain an understanding of about how much that 13% might potentially be reduced by the addition of chemotherapy. To arrive at a decision, the magnitude of the estimated benefit must then be weighed against the incidence of serious adverse effects, in light of your personal risk tolerance. You may also wish to inquire with your MO whether the MammaPrint test may be helpful in your case or not.
BarredOwl
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thank you Lisey .. My ki of 25 was in the initial pathology.. I do not see it on my oncotype report.. My score was 1
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how high was your er/or Lisey? My er was 70-80 and pr was 80
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JOJO,. how high was my what?
I have and ER+ of 98%, a PR+ of %5 and HER2- = 0; ki67 is 30-35% and my Oncotype said 13% chance of recurrance with ER inhibitors. I think I will ask for the mammaprint as well,
I'm debating getting the extender removed too, so there's that. -
BarredOwl - You have been helpful countless times and I thank you. I'm stuck on this and I feel like my treatment is a guessing game. I had the Oncotype test because one pathology report score my ER at 90% and the other at 70%. But then the Oncotype said ER negative and with an ER score of 5.4 and 6.5 needed to be positive. It states, "The specimen must be ER positive by RT-PCR or IHC for the Recurrence Score Clinical Experience to apply". I've assumed my risk of recurrence is significantly higher than what is reported in the test results.
My brain hurts.
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Hi WarriorWoman:
Luckily, you were ER positive by IHC (which is what pathologists use), so the Recurrence Score Clinical Experience should apply according to that explanatory note.
BarredOwl
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I can’t find ki67 anywhere in either my path or OncotypeDX reports.
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ChiSandy - Ki67% not explicitly reported on Oncotype report, though it is one factor used to calculate the Recurrence Score. Sometimes it is done during biopsy and/or surgical pathology. General disagrement whether 3 pathologists could come up with the same statistically same answer (accuracy).
BarredOwl I had a huge discrepancy between ER IHC and Oncotype ER. My MO said Oncotype ER trumps IHC. Could you elaborate on what you just said as what my MO said may be in disagreement with what you said, if I'm reading you right.
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hi Lisey ... Er/pr... I read low or and high ki match...mine is wierd because I have high or and high ki ..
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hi Quinn cat... Hmmmm maybe my ki 67 of 25 is a high estimate ... My scores are odd... High pr and high ki
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Lisey - my stats similar to yours. PR >90, PR 5, my Ki was 29.1%. Oncotype 19, negative sentinel node so no chemo.
Turns out I did in fact have a positive node and Mammaprint done. High risk. Chemo.
SMH
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Hi QuinnCat:
I was speaking in the general case, not the specific case. Whether the single-gene ER score should be utilized appears to be fact-specific, which is why above I recommended discussing the single-gene scores and IHC findings with your MO to be sure any special circumstances are identified.
For example, the GenomicHealth website states the single-gene ER score can:
- Provide additional information for clinical decision making for a patient whose ER protein expression is borderline positive by IHC or reported as uncertain
I have no additional information on the scenarios described in that bullet, which represent more specialized cases or how one would be advised in such a case today.
On the other hand, in general, based on the advice that others here have received in the past year, differences in the degree of positivity by IHC versus single-gene score should not be too concerning. This is also consistent with the 2012 paper I cited, indicating that IHC is the more sensitive method of determining ER status.
I am not sure what your specific results were, or what an expert medical oncologist would say to you today about your specific IHC results and single-gene ER score (versus the advice you received in 2011). However, today, in the case of a very significant discrepancy in ER status as determined by IHC versus single-gene ER score, a second opinion may be in order, including an expert pathology review of ER status, possibly with re-testing of ER status by IHC, and if possible, consideration of whether the block or slides provided for Oncotype testing were sufficiently representative (including whether tumor heterogeneity or sampling error may be in play).
BarredOwl
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FarmerJo, what type of Chemo are they recommending? I'm meeting for the first time with my Onc on Tuesday. Also, have you been on the flat threads as well? I'm STRONGLY considering removing these evil TE's and just going flat.
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kayb, but oncodx takes ki-67 into its equations or am I wrong?
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I am repeatedly told by my MOs that ki-67 is unreliable and places are either not using it or considering abandoning its use. At the same time, I see so many articles that examine the correlation between ki-67 and recurrence. It's enough to make me crazy. If ki-67 is not on your path report(s) it's because your hospital doesn't use it.
BarredOwl - Thank you for all your helpful imput.
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Meow13:
Yes, Ki-67 is one of the 16 test genes whose mRNA expression levels are used to generate the multigene Recurrence Score. It is one of several proliferation-associated genes tested: Ki-67, STK15, Survivin, Cyclin B1, and MYBL2. For the complete list of genes whose expression is measured, scroll to the bottom of this page:
BarredOwl
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BarredOwl - I need a ladder to get to my Oncoscore to tell you my ER score (which means moving my car and it's late!). It was about 1/4 or less the distance from the cutoff for doesn't count to the end of the scale (i.e. on the low side). The IHC was 90% for ER from the biopsy. By my estimation, they are in total disagreement. PR was 5% on IHC and positive on the Oncotype, but barely, so seems they did agree. It has always been a conundrum to me. I also had a 4 month wait between biopsy and surgery.
I do not know the term "single gene score???"
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Hi, Luminal B here. [waving]
Question for anyone that can answer: My path report says K1-67 is ">20%, unfavorable" but it doesn't tell me the exact number. My Mammaprint has a notation that my tumor cell percentage is 40%. Are these the same thing?
Thanks.
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Hi QuinnCat:
Because the Oncotype Recurrence Score is based on measurements of mRNA levels from multiple genes, it is often referred to as the "multigene" Recurrence Score. In contrast, the individual measurements, for example of the level of mRNA measured from one single gene like ER, are "single gene" scores.
The section of the sample report with ER, PR and HER2 scores is entitled "Quantitative Single Gene Report", reproduced in part here:
Your memory from five years ago of where your score fell in the range (indicated by the upside-down triangle "▼") might not be reliable. However, from other posts, it appears that you received endocrine therapy plus chemotherapy (the latter based on a "High risk" Recurrence Score)? Receipt of endocrine therapy would be consistent with your IHC results at least (90% ER positive). In any event, the initiation of endocrine therapy would suggest that your MO considered you to be "hormone receptor-positive" overall (whatever the Oncotype single gene ER score was).
In addition, your positive PR status (by both IHC and Oncotype single gene PR score) may independently warrant endocrine therapy, per the Introduction of the article cited by Lisey earlier in the thread:
http://advances.sciencemag.org/content/2/6/e1501924
"Clinically, PR expression is assessed as a biomarker of functional ER activity even in the absence of detectable ER expression. Hence, women with ER−PR+ tumors receive adjuvant antiestrogenic hormone therapy (4,5)."
BarredOwl
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BarredOwl - ok, got all of my information together and this is what I've never understood other than my MO says oncotypeDX report trumps IHC.
Initial biopsy ER+ IHC 95% PR+ IHC 1-2% (concurred via slide with Surgeon's pathologist)
Quantitative Single Gene Report from Oncotest:
ER 9.0 positive PR 5.7 positive Her2 7.9 Negative
Ok - question is about the discrepancy between ER IHC 95% and ER 9.0
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Hi QuinnCat:
Whether determined by biopsy or from surgical pathology, there does not appear to be a meaningful discrepancy between your IHC results and the Oncotype single gene scores for ER and PR. By both methods, you are deemed ER+ PR+.
===> Ok - question is about the discrepancy between ER IHC 95% and ER 9.0
Here is the ER scale from the sample node-negative report, with a triangle (▲) added below the range to mark where your ER score of 9.0 falls (well within the positive green zone):
▲
(1) An ER score of greater than or equal to 6.5 units is "ER positive" by Oncotype.
(2) Your ER score of 9.0 is clearly positive, and well above the cut-off value of 6.5.
IHC versus Oncotype use completely different analytical methods and sample cells in a different way. They measure different molecules: ER protein versus mRNA. The numerical outputs are reported in different "units" and cannot be directly compared: percent positive cells versus score in unit values. These methodological differences can lead to apparently differing degrees of positivity, which is very confusing for patients.
(3) In your case, you are clearly "ER positive" by both methods.
Lastly, I am wondering if your MO actually said "Oncotype trumps pathology" in reference to the multigene Recurrence Score. This short-hand has been quoted many times by members here. Indeed, the well-validated Recurrence Score is generally more informative than and "trumps" standard pathological factors such as tumor size, grade, etc.
BarredOwl
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kayb - yes needle biopsy
BarredOwl - she may indeed have been referring the total oncoscore trumping the "whole" biopsy pathology - though either spelled "chemo." (I feel so sorry for those that fall in the gray area, in that respect.) It was good that I dug up my paperwork because at 95% ER, I won't feel so bad if she tells me I'll be on Exemestane another 5 years. What really got me a high score of 39 was my very high Ki67 at 60% and low PR - which ultimately brings us back to that darn Luminal B and what is going on to make it that much more aggressive than Luminal A.
I will find some solace that the hormone blocker has something to work on if my IHC has any meaning at all. No need to suffer for nothin! -
kayb - yes I agree that the biopsy sample might just not be representative of the whole tumor, but if IHC and PCR do not have to agree, maybe it is representative? My bottom line question, can the bulk of my tumor, or let's say all of my tumor be 95% IHC and the oncoscore (which I believe is from multiple samples) also be what it is, somewhat middling. If the tests are truly not correlative, than why can't both test results be accurate, rather than wondering if my biopsy is not representative? And if they are not correlative, than what is the point of IHC (assuming oncoscoring single-gene test is better) or via versa, if IHC is deemed better. If either test is only meant to be positive or negative and they arrive at that final point (both positive) with a number of varying degrees rather and a "yes" or a "no," what is the point of handing out a number?
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QuinnCat, you and I have similar Dx's er%95 and pr less than 1%. I don't know the significance of getting 2 tumors one ILC and one IDC, I got an oncodx 34, don't know what sample they took. My pathology was certain the tumors were 2 separate occurances. My mo said 2 tumors really no different than 1 he want to do an aggressive chemo on me. I always felt that chemo was not going to help, kind of feel funny going against wishes of top oncologist in Seattle. But it is almost 5 years and I did AI as long as I could. I don't regret my decision nor do I think I will blame myself if it comes back.
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Meow-i actually commend you for skipping chemo. Really, the science says it would give me only 9% out of a 27% deficit and I have permenant issues from chemo. I was grade 3, maybe explaining my 5 extra points
. My Mammo finding cancer was 10/9/2011, but due to genetic testing, holidays, didnt have surgery til 1/2012, otherwise we are in the same timeframe too. We are bothalso living in the PNW too. I went to grad school at UW too :You've quit the AI?
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