Interesting Oncotype DX news from Asco meeting

voraciousreader

Breast Cancer Recurrence Score Cannot Be Predicted by Traditional
Clinicopathologic Measures

• An analysis of 2,097 patients from Clalit Health Services and 484 patients from
  Maccabi Health Services in Tel Aviv, Israel who
  received the Oncotype DX breast cancer tests
  between January 2008 and June 2010 concluded that the RS result
  cannot be predicted by traditional clinicopathologic measures, such as patient
  age, tumor grade, and tumor size.  The study, "Evaluation of recurrence score
  and traditional clinicopathologic assessments in a large ER-positive, lymph
  node-negative patient cohort" (Abstract #632) will be presented on Monday, June 6.

Additional Breast Cancer Studies Expand Understanding of Tumor
Biology

• Based on published data comparing the relative efficacy of aromatase
  inhibitors and tamoxifen in reducing the risk of distant recurrence, researchers
  concluded that an individual patient's Recurrence Score and Recurrence
  Score-Clinical-Pathologic (RSPC) distant recurrence risk assessment can be used
  to determine distant recurrence risk for early-stage breast cancer patients
  receiving treatment with an aromatase inhibitor.  The study, "Using the 21-gene
  Recurrence Score (RS) and the recently developed Recurrence
  Score-Pathology-Clinical (RSPC) to assess recurrence risk in patients with
  node-negative, ER-positive early-stage breast cancer receiving aromatase
  inhibitor treatment alone" (Abstract #592) will be presented on Monday, June 6.
  
• Initial data from the prospective, multicenter West German Study
  Group (WSG) Plan B trial examined the relationship between tumor grade and
  the tumor immunohistochemistry biomarker, Ki-67, the invasion markers uPA
  (urokinase-type plasminogen activator) and its inhibitor PAI-1, and the Oncotype DX Recurrence Score. Results
  from a preliminary analysis of 1,795 patients showed that there were only weak
  correlations between all the markers and the Recurrence Score. These results
  reinforce the conclusion that the Recurrence Score result cannot be predicted by
  other clinicopathologic measures. The study, "Prospective comparison of
  recurrence score, uPA/PAI-1, central grade and molecular classification in early
  breast cancer: Interim results from the WSG-Plan B trial" (Abstract #10594) will
  be presented on Monday, June 6.
  
• Results from an analysis of 5,644 early-stage breast cancer patients from a
  large US-based oncology group practice concluded that younger patients and
  patients who had better performance status and higher grade tumors were more
  likely to receive the Oncotype DX test.  The study,
  "Evaluating utilization characteristics for the Oncotype DX recurrence score in
  early-stage breast cancer" (Abstract #625) will be presented on Monday, June 6.
  
• Finally, an analysis of 1,543 early-stage breast cancer patients from a
  large US-based oncology group practice demonstrated a strong association between
  RS values and adjuvant chemotherapy administration.  This study, "Evaluation of
  relation between Oncotype
  DX recurrence score and
  adjuvant chemotherapy administration" (Abstract #e11105) will be published
  online in conjunction with the 2011 Annual Meeting and citable to the
  Journal of Clinical Oncology as a supplement, but will not be
  presented at the meeting

voraciousreader

The role of Ki-67 proliferation index vis-à-vis Oncotype DX. Print this page Sub-category:ER+ Category:Breast Cancer - HER2/ER Meeting:2011 ASCO Annual Meeting Session Type and Session Title:This abstract will not be presented at the 2011 ASCO Annual Meeting but has been published in conjunction with the meeting. Abstract No:e11055 Citation:J Clin Oncol 29: 2011 (suppl; abstr e11055) Author(s):S. Sahebjam, R. Aloyz, D. Pilavdzic, M. Brisson, C. Ferrario, N. Bouganim, V. Cohen, W. H. Miller Jr., L. C. Panasci Abstract:Background: Most newly diagnosed patients with invasive breast cancer have node negative disease. A key question in management of these patients is the risk/benefit ratio of adjuvant chemotherapy. Several microarray tests have been developed and are currently used to help identifying the patients who will benefit from adjuvant chemotherapy. Ki 67 proliferation index is less expensive and has been used as a prognostic and predictive factor in node positive breast cancer and neoadjuvant setting. Methods: Forty five cases of T1-2 N0 M0 (ER positive, HER2/neu negative) breast cancer were reviewed. Oncotype Dx results were available for all patients. Tumor specimens were stained for Ki 67. Results: The median of Ki 67 index was 17 (range 2-90). The median Oncotype recurrence score was 17 (range 7-60). There was a strong linear correlation between Ki67 index and Oncotype recurrence score (correlation coefficient= 0.74, P value= 0.000). This correlation was stronger in tumors with Ki 67 proliferation index of ≥ 25. Patients were divided to low risk, intermediate risk and high risk group based on expression of Ki 67. All patients in low Ki 67 group (Ki 67 of ≤ 10) had recurrence score of low or intermediate. Most patients (92%) in high Ki 67 group (Ki 67 ≥ 25) had oncotype recurrence score of high or intermediate. Furthermore, neither semi-quantitative immunohistologic expression of ER and HER2, nor nuclear grade had a significant impact on the correlation between Ki67 index and Oncotype recurrence score. Conclusions: Ki 67 proliferation index is a major but not the sole determinant of Oncotype Dx score. Immunologic expression of ER and HER-2 do not significantly impact this correlation. Ki 67 proliferation index can be used to identify patients with a high probability of having increased Oncotype Dx score and requiring adjuvant chemotherapy.

Maybe484

Very interesting.  My Ki-67 was 20%, but I had a zero score on the Oncotype Dx.  I wonder how much of that low Oncotype score had to do with the fact that my tumor was 100%ER+?

kira1234

Maybe484, My score was 24, and my Ki-67 was 13. I was also 99% Estrogen driven, so makes no sense to me how the scores are decided.

Maybe484

There goes my theory, kira1234.  lol  And actually, the study contradicts my theory too. 

Merilee

The next piece of info to be published should be interesting

coraleliz

My oncotype came back 4 but no Ki-67 was ever run on my tumors from what I can tell. Attatched to my Oncodx report was a "quantitative" ER score. Mine was "10.6 positive" . Positive being 6.5-12.5. All of my pathology reports, biopsies & surgery, have both of my tumors estrogen positive at 99%. I guess I'm reading this 10.6 as being less positive than 99%. I thinking I might have too much faith in Tamoxifen. I guess I just like the sound of 99%, even if I don't understand the methodology.

Lee7

coraleliz

4 is a great low Oncoscore. The paperwork you get doesn't show Ki-67 specifically, but it is used in figuring the score and I believe quite a bit of weight is placed on it. I would say your ER score is too.

DebRox

It's all very confusing. My onco score was 21, but my ki-67 score was 50%. I'm 90% er+.



To be honest, I expected a higher onco score due to my ki-67 score. Makes me wonder if ki-67 is subjective to pathologist.



Looking at my scores, i thought they would qualify eachother. But the high ki score doesn't match the "low intermediate" onco score. Ive wondered if there has been a mistake in pathology.

kira1234

DebRox, I've wondered the same thing about my score. I know my sample got lost somehow in being sent at the time, but it finally got there several weeks later. I've always wondered if it was mine being tested or some one else's.

Anonymous

Hmmm. Very interesting.  My Ki67 was labeled as "high" ( >20% - but did not give me the actual %?) but my oncotype was technically in the "low" range - 15. (I thought it would have been higher because of the Ki67 too)  

Maybe some of us are just an "exception to the rule"?  Or maybe it really can depend on the reading of the pathologist?  Interestingly enough my grade went from 3 based on my biopsy.. and down to grade 2 based on the pathology from my BMX.  And the reading from the 3 different factors (Tubule formation, Mitotic Count, Nuclear Pleomorphism) ...changed quite a bit.. one of them went from a reading of 3 to a 1?  At least with the Oncotype score you get to have your ER/PR status reconfirmed.  So I feel pretty confident that my ER is truly "high" and that Tamoxifen is my best weapon.. for now.  I'm just hoping that 5 years from now...when I am done with the Tamoxifen..that they will have more information on my best options considering I will most likley still be menstruating at age 49. (Be "done" with hormonal therapy vs. Get rid of the ovaries and start on an AI? )  

voraciousreader

Susan....here is a small study from 2009....

Int J Surg Pathol. 2009 Aug;17(4):303-10. Epub  2009 Jul 3.

Complementary value of the Ki-67 proliferation index to the oncotype DX recurrence score.

Gwin K, Pinto M, Tavassoli FA.

Source

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA. katja.gwin@uchospitals.edu

Abstract

Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen receptor-positive breast cancer, which is expressed as the recurrence score (RS). Studies have shown that patients with a high-risk RS will most likely benefit from adjuvant chemotherapy, but there is no proven advantage for patients with a low-risk RS who still face an average recurrence risk of 7%. In this study, the relationship between the RS and the cell cycle-related antigen Ki-67 was assessed in 32 breast carcinomas and evaluated for a potential association. Comparison of the RS with tumor type, grade, and the Ki-67 proliferation index (PI) revealed an overall concordance. However, some tumors with a low RS revealed a surprisingly high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas that recur. Therefore, the authors propose a combined evaluation of the RS and Ki-67 PI to identify tumors with high recurrence potential from the low-risk and intermediate-risk RS groups

voraciousreader

according to Susan Love:

What is Ki-67?

An antigen is a protein that sits on the surface of a cell and stimulates the production of an antibody. Ki-67 is an antibody marker to a tumor antigen that can be found in breast cancer cells.

If your tumor is tested for Ki-67, your pathology report will show a Ki-67 score. High scores-greater than 20%-mean that the cancer cells are growing and dividing at a rapid pace.

  Higher-grade tumors typically have a higher Ki-67 score. However, there is no conclusive evidence that Ki-67 is associated with survival. Some studies have found that it is; others have found that it is not.

Some studies have suggested that there are certain estrogen receptor (ER)-positive tumors with a high Ki-67 score that may not respond as well to tamoxifen or an aromatase inhibitor. However, they do respond well to chemotherapy.

You should not worry if your pathology report does not include information about your tumor's Ki-67 level. Some labs do the test; others do not.

If you had an Oncotype DX test done on your tumor, Ki-67 is one of the 21 genes the test used to predict your breast cancer recurrence risk.

Anonymous

Thanks VR!  I didn't realize that Ki-67 was one of the 21 genes tested in the Oncotype to access my risk.  That actually makes me feel a little better.

voraciousreader

Susan...my medical oncologist refered to the KI-67 test as the "poor man's Oncotype DX."  He places greater importance on the Oncotype DX test than the KI-67.  Good luck to you.  I don't know my KI-67 number.  Not sure if I want to ask.....

DebRox

"However, some tumors with a low RS revealed a surprisingly high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas that recur. Therefore, the authors propose a combined evaluation of the RS and Ki-67 PI to identify tumors with high recurrence potential from the low-risk and intermediate-risk RS groups"

If I read this correctly that sounds like it applies to me.  I had a high Ki-67 - 50%  but a low/int oncotype score of 21.  Does this mean I need to worry about more about recurrence?  That ki-67 probably bumped up my oncotype score.

I too was told by my Onc that Ki-67 is the poor mans oncotype score.  I really thought my onco score would be higher given my Ki-67.  The two numbers did not match.

And then I have been told that Ki-67 is subjective to the pathologist.  And that the Oncotype is more trustworthy.  Who knows!!!!  ITs all a nightmare if you ask me!

voraciousreader

DebRox..I wonder about the utility of the OncotypeDX test for me since I have a rare breast cancer.  In the 2011 NCCN breast cancer treatment guidelines, it was included for the first time for most ER/PR + breast cancers, but wasn't included for tubular and mucinous... Whatever....

I think what the authors of this study were trying to determine was the following....

If you look carefully at your OncotypeDX report, in addition to a Recurrence Score number such as mine, 15, it also states that the 15 gives  a distant recurrence possibility of 10%.  However, if you look carefully at that page, it also gives a range of percentage possibilities from 7% to 12%.  Furthermore, taken as a whole, the ENTIRE low risk Recurrence Score category is a combined 7% distant recurrence risk.  So basically, what these researchers were trying to understand was if, in fact, the women who had high KI-67 scores in the LOW RISK Recurrence Score category are skewing the percentages...That's how I interpret it.....

Anonymous

Ugh.  Sometimes I feel like it's all a crap shoot.  I'm re-reading a book I bought when I was diagnosed back in October.  "The Emperor of all Maladies: The History of Cancer"... it was in a way both comforting to see the advances in treatments/care (getting rid of radical mastectomies, SNB instead of automatic full lymph node dissections, medicine to alleviate chemo SE's, advances in breast reconstruction to name a few) ...but at the same time it really became apparant that most cancers (breast cancer especially) have a LONG way to go to be fully understood because there are so many unknown variables that affect the cause/growth/recurrence.  Discovering estrogen status and HER2 made some great progress, but it's obvious that we still have a long way to go.  And all we can do is go with what the "recommended protocol" is based on current studies.  What's frustrating is that very little , if any of it, is definitive.  So much is left up to the patient to decide and "roll the dice".

And for the record.  I never did like gambling. 

voraciousreader

Susan... You get up in the morning and get out of bed and it's a crapshoot. I always say that it is a good day when you start out vertical! We can all get bogged down with statistics, but at the end of the day we have to all remain hopeful that with each passing day there will be new discoveries.

kira1234

clyn, That is so true about the mid range group. To make it even more frustrating is those that can and want to join the clinical trials are limited. In my case there were two different trials my BS and Onc. would have liked me to be a part of, but I was unable. In the first case they were only taking IDC, and in the second case even though I had a 24 on the Oncotype DX test I have a small tumor with a grade 1, so again no eligible.

NoMoreHL

voraciousreader: What a great statement you just made! I would like to print it, cut it out, and tape it to my bathroom mirror. You will get all the credit, of course! Thank you!

MarieKelly

There's a reason why some have path reports with high Ki-67 but then get an unexpectedly low oncotype score - sloppy pathology work. The Ki-67 stain doesn't specifically identify cancer cells that are dividing/proliferating...it identifies ANY cell that is dividing, some of which might simply be normal tissue that's in the process of healing after a biopsy.

See the following from this article

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 

"...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 track there was granulation tissue proliferating like crazy. So lots of cells 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."

(Dr. Shak says the GH clinical lab pathology group routinely performs manual microdissection in cases that contain biopsy cavities to exclude the contribution of granulation tissue to the recurrence score. Dr. Bloom counters that these two cases are real-world examples in which the microdissection was apparently less than optimal.)..."

voraciousreader

Mariekelly... It is interesting that you posted that controversial finding. I also read it awhile ago. I was hoping that there would be a continued investigation, but I haven't read anything further on this topic. You would have thought that SOMEONE would have been following this up.

MarieKelly

Her's something from 2009 -   Interesting that someone decided NOT to present it at the 2009 ASCO meeting.   But hopefully, pathologists have since then all gotten the message and are dissecting out those biopsy cavities before doing the Ki-67 stain.  I know some tend to think "it's all just a crap shoot", but really it's not. When there's results and eventual outcomes that don't make any sense in the big picture, then there's an explaination - there's ALWAYS an explaination if someone bothers to take a good, hard look for it.  

The critical role of surgical pathology in personalized medicine: The impact of biopsy cavities in breast cancer samples on recurrence risk when assessed by quantitative RT-PCR.

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Sub-category:Molecular Diag. Category:Tumor Biology Meeting:2009 ASCO Annual Meeting Session Type and Session Title:This abstract will not be presented at the 2009 ASCO Annual Meeting but has been published in conjunction with the meeting. Abstract No:e22016 Citation:J Clin Oncol 27, 2009 (suppl; abstr e22016) Author(s):F. L. Baehner, J. Anderson, C. Millward, C. Sangli, C. Quale, D. Cherbavaz, A. Goddard, S. Shak; University of California, San Francisco, San Francisco, CA; Genomic Health, Redwood City, CA Abstract: Background: Tumor gene expression analysis using the Recurrence Score (RS) assay is frequently used in ER+ breast cancer. Manual microdissection is performed in cases where biopsy cavities (BxC) are present in the submitted specimen. The objective of this was to characterize by quantitative RT-PCR the impact of BxC on 21 gene expression profiles and the RS. Methods: 48 (15 well, 18 moderate, and 15 poorly differentiated) breast cancers were evaluated for gene expression differences between whole sections (WS; containing BxC) and enriched tumor (ET; BxC excluded). Standardized quantitative RT-PCR analysis for the 21 Oncotype DX genes was performed; reference normalized gene expression measurements ranged from 0 to 15, where each 1-unit reflects an approximate 2-fold change in RNA. Analyses of individual genes and the RS were performed on the entire sample set and stratified by tumor grade. Correlation analyses used Pearson's R, concordance analysis used Lin's sample concordance and paired t- tests to characterize differences. Results: There were statistically significant differences in reference normalized gene expression between ET and WS in 6 genes: BAG1 (ET-WS: 0.13 units, p=0.0025), CD68 (ET-WS: -0.64 units, p<0.0001), ER (ET-WS: 0.29 units, p=0.0012), GSTM1 (ET-WS: 0.18 units p=0.0025), STK15 (ET-WS: -0.18 units, p=0.0041) and STMY3 (ET-WS: 0.62 units, p<0.0001). Expression of the macrophage marker CD68 was higher and expression of ER was lower in WS containing BxC. The correlation (0.95) and concordance (0.92) were generally high between WS and ET for RS overall however among moderately differentially tumors, there was a statistically significant mean increase in RS for WS of 3.3 units (p = 0.0012) while among poorly differentiated tumors there was a trend toward a statistically significant decrease in RS for WS of 2.2 units (p=0.0569). Conclusions: Histologic identification of invasive carcinoma and exclusion of BxC is essential for precise RS assessment. Inclusion of BxC in breast cancer specimens is associated with significant changes in the expression of individual genes and impacts the RS. Removal of BxC from breast cancer specimens assessed for gene expression levels is warranted.

voraciousreader

MK... Very interesting. Too bad there hasn't been more follow up and surveillance.

Lee7

Thank you so much for continuing to post info as it comes out! The info that a higher Ki67 could be due to healthy cells rapidly dividing makes sense and gives me some more hope since my Ki67 was borderline 20% and my Oncoscore was 20.  

I know I often feel its all a crap shoot ...I continue to struggle with the tx decisions I made, and I hope I did the right thing for me at this point.  I do believe we need to look at indivdual tumors and ask for personalize treatment plans rather than just accept the one size fits all approach or hit it with everything in the book approach.  I hope in the future we can all receive better, more tumor approriate treatment and care.   

Lee 

cookiegal

Great thread...never knew that about the healthy cells along the track.

I kind of figure there is the ki67 part, the ER part, and what remains is a genetic profile of your cancer.

I had a low KI67 and ER + around 85....so I was surprised my Onco score was 22. My oncologist was as well. 

Jojo0529

Hi Susan,

My ki67 was 25, onco 17 and Miotic rate 1. I also had an oopherectomy.