Tumor Biology Before and After Surgery

SummerAngel · July 2017

I keep seeing posts that tell newbies that they won't know their exact tumor biology until after surgery, because a biopsy is only the initial determination of ER/PR/Grade and that the entire tumor will be re-tested after it is removed. However, I didn't have a re-test (for the right tumor, as the left was excised before it was discovered to contain cancer). The surgical pathology report says, "Biomarker studies were performed for the right breast specimen on the previous core biopsy." That's it, along with a re-print of the initial findings from the biopsy. So I'm wondering if my situation was uncommon or if newbies are being told inaccurate information.

Legomaster225 · July 2017

I did not get new pathology report on my original tumor after my BMX. They just referred to the original biopsy. After chemo there were only "rare" cells that remained so maybe that would make it harder. They did a path work up on the "surprise" tumor in the other breast though. Different makeup on that one.

MTwoman · July 2017

I did get a full pathological report after my mx. And there were some differences.

kira1234 · July 2017

I received a pathology report from my double mastectomy. The pathology report was different from the biopsy report.

ChiSandy · July 2017

I got two path reports—first, from my core biopsy and then the final one after my lumpectomy. The only difference was size of the actual tumor.

SpecialK · July 2017

What type of pathology is performed on post-surgical tissue if often dependent on what is determined at the biopsy. If you have surgery for what is thought to be DCIS based on biopsy, the post-surgical tissue will be looked at carefully to double check for any invasive element because that could potentially change treatment. At my biopsy it was determined that based on the core samples I was strongly ER+ and strongly Her2+, so there wasn't much need to repeat testing for Her2 or hormonal receptors on my post-surgical tissue. I also had Mammaprint testing done on a biopsy core sample so there was a pre-surgical double check of hormonal and Her2. A pathology report was generated after surgery regarding the IDC tumor size in entirety, my bi-lat SNB, the cored nipples since I had skin and nipple sparing surgery, my supposedly prophylactic left breast tissue was checked, which contained surprise ADH and ALH, and the extent of DCIS was noted in addition to the IDC on the cancer side because it had not previously been quantified by size since it was not seen on imaging. For those who are ER+ and have OncotypeDx testing done, a double check of hormonal receptor and Her2 status comes by way of that result. If hormonal receptors have low percentages, or Her2 is equivocal, I think testing for these is sometimes done post-surgically if it has not been tested again on core samples prior to surgery. Generally, if there is potential to find something that changes treatment, repeat testing is done, but I don't think that aspect is routine post-surgically.

SummerAngel · July 2017

SpecialK, so you're saying that those who are posting to newbies that the markers will be checked again post-surgery are incorrect for the most part?

My tumor biopsy tested equivocal for Her2 and was sent for FISH testing, but this test was not performed again after surgery (seeing the price for FISH testing, I can see why). I also had no Oncotype test performed on the tumor.

BarredOwl · July 2017

Hi SummerAngel:

In my case, I had a surgical excisional biopsy on the left. The DCIS in the surgical biopsy was tested for ER and PR status. ER and PR testing was not repeated on the DCIS in the left mastectomy sample (MGH, 2013).

While each biopsy, surgical sample, or re-excision must be assessed by the pathologist and summarized in a written report, the question of retesting appears to be fact-dependent.

The results of ER, PR and HER2 testing on biopsy tissue are generally considered sufficiently accurate for the purpose of prescribing neoadjuvant chemotherapy in, for example, HER2-positive or triple-negative invasive disease. Note that those with pathologic complete responses cannot be retested.

Where neoadjuvant treatment is not received, with invasive disease, re-testing for HER2 status is not always repeated. However, there are situations where guidelines recommend repeat testing on surgically-removed tissues. See for example:

>> Wolff (2013) (ASCO/CAP Guideline Update): "Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update"

>> http://ascopubs.org/doi/pdf/10.1200/jco.2013.50.9984

>> "In summary, if available, perform the first test in the core biopsy specimen in a patient with newly diagnosed breast cancer. If the test result is clearly positive or clearly negative as defined in Table 1, no retesting is needed. If the test is negative and there is apparent histopathologic discordance (Table 2), or if specimen handling has not been in accordance with guideline recommendations, a section of the tumor from the excisional specimen should be tested. If this result is positive, no further testing is needed. However, if the test is negative and there remains significant clinical concern about the result after consultation between the pathologist and the medical oncologist, it may be appropriate to repeat the test in a different block from the patient's tumor. If all three tests are negative, no additional testing is recommended."

The above may not be a comprehensive summary of all situations in which a pathologist may retest.

Here is a link to the 2010 ASCO/CAP guideline for ER and PR testing. If you search the pdf document for the word "repeat" or "biopsy", you can see some of the considerations relevant to the question of repeat testing of either the same sample, a different block, or a different specimen.

>> Hammond (2010)( ASCO/CAP Guideline): "American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer"

>> https://www.asco.org/sites/new-www.asco.org/files/content-files/practice-and-guidelines/documents/2010-JCO-ASCO-CAP-Immunohistochemical-testing.full_.pdf

This may not be a comprehensive summary of all situations in which a pathologist may retest.

While not a "retest" but in fact a new test, I note that if a biopsy shows pure DCIS (tested for ER and PR), but an area of invasive breast cancer is later identified in surgical samples, the invasive breast cancer should be tested for all three ER, PR and HER2 statuses, no matter how small (if feasible).

BarredOwl

[[[EDIT (03 June 2018): Please note this 2018 ASCO Focused Guideline Update for HER2 testing:

Wolff (2018): "Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update"

http://ascopubs.org/doi/pdf/10.1200/JCO.2018.77.8738 ]]]

SummerAngel · July 2017

Thanks, BarredOwl. From what you posted, it seems that another ER/PR test isn't typically called for on the excised tumor, except in certain (rare) situations. This also seems to apply for Her2 testing. One line from the indications for another test caught my eye, though:

"Resection specimen contains high-grade carcinoma that is morphologically distinct from that in the core."

How would they know that the resection specimen contains different cancer if they don't re-test? They wouldn't, of course. So there would need to be a clear indication that a re-test is needed for ER/PR/Her2 to be reassessed.

Legomaster225 · July 2017

Summer Angel, I was just looking at your stats. Did you not have radiation or chemo?

When I had my BMX my clean breast was found to have 9mm IDC/DCIS. I am on tumor board discussions today but right now the plan is no radiation on that side. RO said if I had had just a lumpectomy there would be chemo but since I had a BMX no rads were needed. Just curious as to others treatments. I already did preadjuvent chemo and will be in tamoxifen after rads to my original known cancer side

BarredOwl · July 2017

Hi SummerAngel:

Re: Your question about the situations which may warrant HER2 testing of the surgical resection samples, including when the "Resection specimen contains high-grade carcinoma that is morphologically distinct from that in the core." This is one of the criteria to consider from Table 2 of the 2013 ASCO/CAP Guideline.

The 2013 ASCO/CAP Guideline re HER2 Testing and Pending Focused Update:

Your question reminded me that the home page for the 2013 ASCO/CAP guideline for HER2 testing includes additional materials, including a Data Supplement and additional correspondence and related publications. One such publication discusses Table 2 ("Histopathologic Features Suggestive of Possible HER2 Test Discordance"). Here is a link to the home page:

http://www.asco.org/practice-guidelines/quality-guidelines/guidelines/breast-cancer#/9751

The criterion you quoted, "Resection specimen contains high-grade carcinoma that is morphologically distinct from that in the core," is located the the third section of Table 2 in the 2013 guideline, under the header:

"If the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test must be ordered on the excision specimen if one of the following is observed: [See original for list of five criteria]"

However, it is possible that under current clinical practice, "must" should be "may" with respect to one of the five criteria (the one re grade 3), and perhaps possibly others per this publication:

>> Hammond (August, 2015): "American Society of Clinical Oncology/College of American Pathologists Human Epidermal Growth Factor Receptor 2 Testing Clinical Practice Guideline Upcoming Modifications - Proof That Clinical Practice Guidelines Are Living Documents"

>> http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2015-0074-ED?code=coap-site

BEGIN QUOTE:

"The other issue raised by Rakha et al,[1] and supported by evidence they cite, concerns the need to retest excision samples when a core biopsy is HER2 negative by either IHC or in situ hybridization. The evidence suggests that although this may be useful, it should not be required. In view of the greater clinical experience confirming the high concordance in HER2 testing between core and excisional biopsies, the Update Panel will be updating Table 2 to allow the pathologist and oncologist to exercise clinical judgment and will no longer indicate that grade 3 alone suffices as a criterion for mandatory retesting. The revised language will indicate that ''If the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may [emphasis added] be ordered on the excision specimen.'' Other criteria mentioned in Table 2 as reasons for excision testing will undergo careful scrutiny to see whether other Table 2 revisions are needed.

The Update Panel has communicated these upcoming changes in a reply to the letter to the editor of JCO.[3] It responds to the original correspondence from Rakha et al.[1] Revisions to the figure and table will be incorporated in a focused update of the HER2 Testing Guideline Update to be completed this year and published simultaneously by JCO and the Archives of Pathology & Laboratory Medicine. This will ensure that all the information and evidence is clearly communicated in a widely accessible, peer-reviewed document.

The letter from Rakha et al, the Update Panel's response, and supporting materials will be available on the CAP Web site. We urge pathologists to review them with care and to continue to contribute to this work by providing feedback to the Update Panel. Your guidance is always welcome."

END QUOTE.

In addition to Table 2 matters featured in the quote, Hammond discusses additional matters to be included in a focused update. To my layperson knowledge, no "focused update" of the 2013 guideline has been issued as of this date. However, from this May, 2017 Press Release, it appears that a "focused update" of the HER2 guideline is currently in the works.

The above illustrates how guideline documents are snap shots in time and there may be additional information that affects their application. This is why one should always confirm the currency and applicability of outside documents with one's team.

Your Question:

How would they know when the "Resection specimen contains high-grade carcinoma that is morphologically distinct from that in the core"?

I think that this refers to a visual assessment of physical attributes ("morphology"). Another publication regarding updated United Kingdom (UK) recommendations from 2014 includes some examples of what may be considered "morphologically distinct":

QUOTE >> "If the tumour in the resection specimens is morphologically distinct from that in the core biopsy, for example of a clearly different histological type or histological grade (eg, low grade on the core and high grade on the excision, but not just reflecting minor difference in the mitotic count or proportion of solid areas).[23] A repeat may also be undertaken on concurrent metastatic nodal disease if it is morphologically distinct from the primary breast tumour."

This is exemplary, so there are probably additional "morphological" features that a pathologist would recognize.

BarredOwl

[[[EDIT (03 June 2018): Please note this 2018 ASCO Focused Guideline Update for HER2 testing:

Wolff (2018): "Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update"

http://ascopubs.org/doi/pdf/10.1200/JCO.2018.77.8738

Among other changes, the one proposed above is addressed: "Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria." ]]]

SummerAngel · July 2017

Legomaster, I did not have radiation or chemo, no. I had a BMX and was node-negative with clear margins, so no radiation was necessary (yay!). I was not given chemo due to the low Oncotype score (and negative nodes) on the left-side tumor.

BarredOwl, thanks for the reply. It makes sense that a lot of this would be in the pathologist's hands, as they are the experts.

Legomaster225 · July 2017

Thanks Sumner Angel. That makes sense and is consistent with what my RO says. I'm glad you were able to avoid those treatments.

letsgogolf · July 2017

I have the results from both my biopsy and my lumpectomy. There were 2 results which were slightly different. The pr was 100% on 1 test and 99.89% on the other so that is essentially the same. The Ki67 was 3.3% on the biopsy and 10% on the lumpectomy. I have read that the biopsy damage itself causes the numbers to go up on the Ki67 for later surgery. Some tend to believe that the biopsy result is more accurate because of this but others say that Ki67 testing varies greatly and is not reliable. Use plain text editor

SpecialK · July 2017

summerangel - to answer your question, I think it is totally situational, so the answer is both yes, and no - some will be retested, and some won't. Certainly not all will be.

VLH · August 2017

Reviving a month old post I just noticed, my core needle biopsy showed hormone receptor negative, but HER2 positive results. Against medical advice, I refused targeted (Perjeta Herceptin) & chemotherapy and moved forward with a lumpectomy. The lumpectomy / solid tumor pathology report also showed hormone receptor negative; however, to my dismay, it showed HER2 negative or a triple negative diagnosis.

Was the core needle sample not representative of the entire tumor? Did the tumor morph to triple negative in Lee's than two months? No idea. With the poorer prognosis associated with triple negative cancer, I ended up reluctantly doing AC + T chemo. Are there HER2+ cells migrating through my system? I don't know. My first mammogram and two post-chemo biomarker tests showed nothing worrisome plus a tiny nodule in my lung discovered during a baseline chest CT scan hasn't grown so I'm hopeful that the cancer won't metastasize or recur. Also, nothing disturbing was found during a recent reduction surgery. I personally would want pathology tests every step of the way.

Lyn

Leatherette · August 2017

In my case, the biopsy came back with DCIS only, but there were suspicions since the mammogram that there was something else in there. As the DCIS was 6 cm. it was not easy to get a full core sample with the biopsy. So after the mx pathology, IDC was confirmed, And the ER/PR markers were different.

VLH · August 2017

Interesting, Leatherette. DCIS was found in the margins of my first lumpectomy so I had to have more tissue removed two weeks later.

Lyn

beach2beach · August 2017

Hi,

My biopsy indicated IDC. After Bmx, the pathology was ILC, with dcis/lcis. The size and hormone receptors stayed the same.

stephaniebc · August 2017

i wasn't retested as i had a PCR, but interestingly, i had 2 biopsies leading to 3 different path reports (two of them from the same biopsy but different slides). her2 status was consistent over the three reports but grade wasn't and pr/er % are wildly different.

medicine is not a hard science!

Tumor Biology Before and After Surgery

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