ER+ PR+ then genomic changed to triple negative

phaila

has that happened to anyone else. My new oncologist decided he didn't like my low er pr positive results so he re ran them using genomic health company, the ones who do oncotype Dx. The results came back triple negative. I'm clueless about what to do now:

doxie

Did you get a Oncotype DX score

phaila

yes. That's when they said I was TN instead or er pr low positive as previously diagnosed

BarredOwl

Hi phaila:

Your question is excellent and important.

Elsewhere you said:

". . My estrogen positive is 10-20 %. . ."

"well I tested low pr and er positive after my partial mastectomy, then my oncologist said it didn't seem right so he retested with genomic health the oconottoe company. My results all came back negative. How can you test pisitive then all of a sudden by negative??"

"i was just given a 47 oncontype dx score as a pre treatment test. I had thought and was told all i would need was rads and drugs. Now out of the blue im high possiblerecurrence and triple negative when i was initially diagnosed at er+ pr+"

=> Do you have a copy of your Oncotype report? If not, you should obtain a copy so you can read it.

QUESTION: In your specific case, what is the proper method for determining ER and PR status for the purposes of deciding (a) endocrine therapy; and (b) selecting an appropriate chemotherapy regimen?

In general, is it appropriate to override the results of a validated IHC test with individual oncotype ER score and PR score? In my layperson's view (no medical training), the answer is "no, not in the vast majority of cases."

Even if I were a hypothetically all-knowing trained pathologist and medical oncologist (which no one here is), without access to your pathology slides, or at a minimum complete copies of your all your pathology reports and test results, I would not be able to answer the question in your specific case in an intelligent or informed manner.

(Is your tumor a single, homogenous tumor? What were the specific validated pathology methods used to determine ER and PR status? What are the cut-offs for positivity for those specific tests? What was the source of the tissues used for pathology and for oncotype? Were all tests conducted properly on suitably representative tissue? etcetera)

In addition, unfortunately, no one here has the requisite training or expertise in medical oncology, sufficient familiarity with the relevant scientific literature, detailed knowledge and understanding of the individual oncotype ER and PR score outputs, or the VERY LIMITED AND SPECIFIC (SOMEWHAT) validated uses of individual oncotype ER and PR scores, to be in a position to properly advise you whether their use in your specific case is either PROPER OR IMPROPER.

Having posted some of your details, you may receive input from others about their specific experience. Unfortunately, in this highly specialized, fact-specific, and rapidly evolving area, the anecdotal experience of others may not reflect current practice or apply to your specific case. This is because your specific pathology findings and test outputs may differ in some material way from another person's, and as a layperson (without access to their records or relevant training), you have no way of actually knowing what those differences may be. Analogy is not a reliable method of making such a critical treatment decision.

It is clear that you appreciate the criticality of these questions to your treatment plan. On such important questions, prior to commencing chemotherapy, if you were my sister I would absolutely insist that you seek a second opinion at a center of excellence (e.g., famous teaching hospital) to obtain expert professional advice on your question. The second opinion should include an expert pathologist's review of physical pathology slides and all related written reports, and consultation with a medical oncologist in light of all pathology findings and test results.

Please let us know if you will proceed to seek a second opinion.

BarredOwl

BarredOwl

Once again, I have edited my post multiple times.

BarredOwl

phaila

Thanks Barredowl,

I did just get my ca27-29 result back and it was 35.

The thing is, my Dr was very confident I was stage 1a er pr + and would only need chemo. Chemo only came up IF any nodes were positive. Sentinel and 2 other nodes were removed and negative. Radiologist and oncologist both did my oncodx score without my knowing and both think chemo.

My tumor was 1.4cm and grade 2.

My er+was 10-20% and pr+ <10% very low but still tested positive

Ki67 was <10% low

For the heck of it posted my oncotypedx score. I have no idea how to compare that to surgical pathology er pr report

Vicki

BarredOwl

Hi phaila:

They cannot be compared directly. Do not try this at home.

Usually, the validated pathology methods ("IHC") used to measure Estrogen Receptor protein and Progesterone Receptor protein look at whole cells. Results are reported as percent positive cells in a field of view (i.e., some cells are stained by a "molecular tag" and are seen as "positive for staining," and some cells are not stained). The percentage of cells that do stain is reported.

Oncotype uses a completely different method ("qRT-PCR") to measure mRNA from ground-up cells. It gives a numerical score in "units", where particular unit values falling below a specified positive/negative cut-off of X units are considered "negative" by Oncotype (arrow in the orange range at left).

In general, is it appropriate to override the results of a validated IHC test with individual oncotype ER score and PR score? In my layperson's view (no medical training), the answer is "no, not in the vast majority of cases."

Should these outputs be used to determine ER and PR status in your case or not?

This just brings us back to your main question. To answer it, expert advice is required:

In your specific case, what is the proper method for determining ER and PR status for the purposes of deciding (a) endocrine therapy; and (b) selecting an appropriate chemotherapy regimen?

For the reasons noted in my earlier post, please seek a second opinion.

BarredOwl

BarredOwl

The main and by far the best validated output of Oncotype testing is the Recurrence Score.

The individual oncotype ER, PR, and HER2 scores have very limited application, and relatively much poorer validation than the central output of Recurrence Score. They should not be relied upon in the general case. These individual outputs can be confusing to clinicians as well. This is yet another reason why an expert second opinion should be obtained in the specific case.

BarredOwl

[EDIT: 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."

Again, this is a highly specialized and evolving area, so while this article exemplifies the nature of the problem, it does not answer the question in the specific case or your case.]

Anonymous

You have an interesting case and I'm glad you did the Oncotype. The low ER+ might be a case for chemo on it's own, but combined with a negative result on Oncotype muddles the water more. I would see if you can get a second opinion on the pathology (have it sent to a different lab). But the question becomes, which result will you use for your treatment plan? It's not likely that another pathology report would show a hugely difference. I was curious so I looked into what is considered "negative" and it's an ER+ result <1%. My PR was only 2% on the surgical pathology and it was something like 6.0 score on Oncotype. You mentioned ki-67, which I don't think many oncologists look at anymore. Mine was 25%, which is high, but the mitosis score on the pathology showed 1 (low cell division). My recurrence score was 15 so I chose not to do chemo after getting a second opinion at UCSD breast cancer center.

Get as much information you can and you're doing great by coming here and asking questions. That's what I did right when I was diagnosed. Wishing you the best going forward.

BarredOwl

Hi:

I edited my last post above to add:

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."

Again, this is a highly specialized and evolving area, so while this article exemplifies the nature of the problem, it does not answer the question in the specific case or your case.

BarredOwl

phaila

more results. I'm trying to find a second opinion now. My oncotypedx is 47. But isn't that with their own er pr interpretations? So confusing

BarredOwl

Hi Phaila:

The multigene Recurrence Score is based on 16 test genes and 5 control genes. mRNA expression data from those 21 genes is processed by a computer program (which uses a proprietary algorithm) to compute a multigene "Recurrence Score." A number of studies have assessed the prognostic and predictive value of the multigene "Recurrence Score" for the purpose of aiding in the decision regarding chemotherapy in specific patient groups who were hormone receptor-positive and HER2-negative as assessed by validated pathology tests, and who received adjuvant endocrine therapy. This testing process is called "clinical validation," and is the basis for the use of the "Recurrence Score" in certain patients who resemble the study group.

Whether any individual oncotype ER score, PR score and/or HER2 score (in "units") has any particular prognostic or predictive value for a different purpose in certain patient subsets is a different question and requires separate study for clinical validation. From what I can tell, this has been studied somewhat. The individual scores appear to be a source of confusion among clinicians and patients alike.

For a second opinion, you may wish to consider an NCI-designated cancer center or NCCN member institution, if feasible:

http://www.cancer.gov/research/nci-role/cancer-cen...

http://www.nccn.org/members/network.aspx

BarredOwl

phaila

thanks Barredowl!

I think you should become a doctor;)

BarredOwl

Hi phaila:

Luckily, that boat has sailed, because I think the stress would kill me.

BarredOwl