Core Needle HER2+, but Lumpectomy HER- ???

VLH · July 2016

I spoke to my breast surgeon briefly before my second surgery today. DCIS was discovered in the initial pathology report for my IDC lumpectomy so today's surgery hopefully will show clean margins on the second cancer. Via the patient portal & a follow-up conversation with the surgeon's nurse, I'd asked about the pathology report from the first surgery so she brought me a copy. Since my core needle biopsy showed HER2 positive, I was shocked when she said the tumor was HER2 negative. The ER- / PR- status was consistent between the two reports so I guess I'm now triple negative?

My surgery was again running 1 1/2 hours late, she was rushed, I had a nasty headache and was totally caught off guard so I didn't push her on a vague explanation, but I assume the tumor excision pathology is deemed more reliable given that it's presumably a larger sampling of cells, right? I've read that some people have a different HER2 status from their original tumor to a recurrence tumor, but don't recall reading about the status changing from biopsy to lumpectomy less than two months later. The MO and both surgeons were all in favor of neoadjuvant TCHP. Had I not balked, it seems I would have spent six months being subjected to the risks of the two targeted drugs that wouldn't have even been appropriate if I really am triple negative. It's rather shocking to me that such powerful drugs are administered if there is a significant margin for error or am I missing something since most of my research attention has been devoted to the HER2 aspect of my cancer and I'm a relative newcomer to cancer? I think I recall the doctor performing my biopsy said she provided four or five tissue samples. Do they only do the FISH on a single sample, perhaps choosing the block that potentially looks most problematic? How can one trust pathology reports that produce such different results? My surgeon is going on vacation so I think she was cramming people in today. I applaud her wanting to treat anxious patients before she leaves, but find myself with a niggling doubt about being the patient pushed back both times because I ask questions and am, therefore, probably perceived as high maintenance.

I hope this makes sense. I was at the hospital at 12:30 p.m. for a 2:30 p.m. procedure, didn't get into surgery until 4:00 p.m., was discharged shortly before 7 p.m. and didn't get home until around 7:45 p.m. As is typical before surgery, I only slept for three hours so I'm toast.

dragonsnake · July 2016

Is it possible that they biopsied DCIS rather than IDC? Several ladies on the boards have different receptor status for IDC and DCIS that is attached to it. It's my understanding that DCIS has to mutate to start breaking through the ducts, and thus it's quite possible that the two have different signatures. It is also my impression that tumors have a variety of cell types, and the receptor status is determined from the number of cells that get stained, indicating a certain receptor type. Thus some cells may have receptors, some may not, and the percentage of the ones that have the receptors determine the receptor status. I do not know how big should be the sample, and how accurate are those measurements, but if the sample is small, then it's harder to work with it, and the results may be inconclusive. Unfortunately, when it comes to cancer, nothing is certain: no imaging technique can give you a conclusive result, biopsy may collect samples from the sites that are far from the tumor, receptor status is determined by counting the stained cells within a limited field of view, pathology may not cut through the right tissue, etc.

gracie22 · July 2016

My question is the same as Dragonsnake's. I have read here that DCIS is sometimes HER2+ even if the IDC ultimately is not, and that the final pathology of the IDC is what determines treatment. No idea how the testing is done, but there have been many others here who have experienced the same thing--change up in final pathology. You will talk further with the surgeon to get more info. Agree that it's scary that they would have had you do the HER2 protocol especially with your existing health concerns. This testing stuff is definitely an art, not always a science. Hope you are recovering well; don't let this throw you--it will be figured out. One thing is for sure--your gut did not fail you on your decision to avoid the recommended neo. If you do eventually opt for further treatment, at least you will know what you are doing. Heal well!

VLH · July 2016

I'll definitely have to come up with a list of questions for my post-operative visit on 8/2. As to possibly testing the DCIS rather than the IDC primary tumor, I find the pathology report quite confusing. The FISH was performed on Block 3E, which the legend (probably not the correct term) shows as: Tumor to include anterior and posterior margin. The DCIS is shown as less than 10% of the mass lesion. Under Final Margins in Situ, it says FOCAL INVOLVEMENT OF ANTERIOR MARGIN 0.3 MM FROM MEDIAL MARGIN. That does make one wonder. The pathology lab performing the surgical study is not the same one that performed the core needle biopsy so I don't know if that pathologist was aware of the earlier HER2 positive finding.

twintwin2 · July 2016

a similar thing happened to me this week. Like you I have to go back in next week to get clear margins on a small dcis. Not entirely sure yet if this is related to my original idc/dcis or not. Anyway, when I was reviewing my pathology report I was shocked to see that my her2 status now read her2+. My core biopsy clearly stated her2-. But I also noticed a note on the report stating that another test was not ordered, that they go by the results from the core biopsy. After calling my nurse navigator she was able to talk to the pathologist. It turns out the her2+ on my post op report was a mistake. It should have been her2- like my biopsy. After researching this a little more, it seems that her2 status is extremely accurate with core biopsy and that post op retesting is not always done. It's a good thing we are on top of things! Going from + to - or vice versa is a big deal! Good on us for picking up on it.

VLH · July 2016

I might suspect a clerical error, TwinTwin2, but the report has the more detailed information HER2/CEP ratio, average number of HER2 signals, etc., that are significantly different from the biopsy report so it isn't just a hand jotted note. The discrepancy makes me question how reliable the testing is, which is alarming given that it's used to dictate chemo / targeted treatments. I'm glad that you were able to clarify your HER2 status.

dragonsnake · July 2016

My pathology report after the first lumpectomy had a clerical error. It mentioned IDC in the body of the text, but stated in the summary that I had DCIS. My surgeon called the lab twice, they looked at the slides two more times, I then sent the slides to the other hospital for a second opinion. Receptor status was determined by using the material from my biopsy, and was not re-tested using the pathology material.

The pathology report should describe techniques that they used to slice, preserve, stain and analyze the tissues. You may want to research the method that they used to determine the HER2 status and see what it involves. You may just post what it says about the method: someone here may know the limitations of the used technique, and explain what's going on with your HER2 status. My HER2 status was never determined because it's not a standard practice for DCIS, but please keep posting, someone out there should know.

BarredOwl · July 2016

Hi VLH:

As you appreciated, if truly HER2-negative, HER2-targeted therapies would not be indicated. On the other hand, if the HER2+ result on biopsy was indeed a true reflection of HER2 status in a part of the tumor, then HER2-targeted treatment should be considered. Please don't hesitate to push for a credible explanation of either why the biopsy may not be reliable or why both the biopsy and surgical testing may be reliable in your specific case.

In the typical case, HER2 testing based on biopsy is seen as suitably reliable for the purpose of neo-adjuvant (pre-surgery) treatment decisions. However, occasionally, there can be technical issues with minimally-invasive biopsy. See for example, this 2012 article. Note that this paper predates the 2013 ASCO/CAP guidelines for HER2 testing, and may not reflect current practice in all aspects:

2012 article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503664/pdf/conc-19-315.pdf

In the 2012 article, see the discussion of potential artifacts and sample processing issues with minimally-invasive biopsy. Smaller tissue volumes from minimally-invasive biopsy might be less representative when heterogeneity is present. "Tumor heterogeneity" means there are different types of cells in the tumor, and can lead to different degrees of HER2 amplification seen between cells in the same tumor.

Note the comment that "[s]urgical excisions have long been the "gold standard" sample-type for the assessment of her2 status," which I take to mean that when available, the large amount of tissue and lack of edge artifacts and the like make surgical samples a preferred test sample. However, that does not mean that one can just automatically disregard the results from a biopsy.

A difference between the results of HER2 testing on minimally-invasive biopsy versus the results of testing on surgical samples might be due to variability in performance of the assays, certain technical limitations with minimally-invasive biopsy, AND/OR due to "tumor heterogeneity." You may wish to ask your MO and pathologist (and have them confer) about the various possibilities, and whether additional expert pathology review and/or further testing could be used to distinguish between the various possibilities and provide some definitive information to clarify the true situation and inform your treatment decisions.

I wonder if your biopsy site was marked, whether that area can be located in the surgical samples, and if appropriate, re-tested to confirm the HER2+ status.

BarredOwl

BarredOwl · July 2016

VLH:

I should add that sometimes HER2 testing is performed by an outside commercial laboratory, the in-house pathologist studies the report, and includes key points on his pathology report. This introduces some risk of error. Please ask for copies of any underlying HER2 test results/reports that may have been used to prepare your pathology report, so you can confirm your name on the original reports and check the original report content. You are entitled to copies of all medical records.

BarredOwl

VLH · July 2016

Thanks so much for the responses. [Edited to note that my carefully spaced columns disappeared. Apparently, this program eliminates the "extra" spaces like Facebook does, but doesn't have a table or column function so I'm using the tilde instead]
The IHC in both cases was equivocal. Here's more about the FISH test:

Surgical Results ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~Core needle biopsy (CNB)
Block 3E ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Block A1
Fixation >6 and <72 hours in 10% buffered formalin ~~~~~ Fixation 10% NBF Duration 6-72 hours
HER2/CEP17 Ratio = 1.43 (<2 considered Negative) ~~~~~ Ratio = 2.90 (Two criteria shown below for Positive)
Avg number HER2 signal / cell = 2.85 ~~~~~~~~~~~~~~~~~ Avg number HER2 signals/nucleus = 7.25
Avg number CEP17 signs/cell = 2.00 ~~~~~~~~~~~~~~~~~ Avg number of CEN-17 signs / nucleus = 2.50
Number of cells counted = 40 ~~~~~~~~~~~~~~~~~~~~~~~ Number of cells counted = 2.90

The surgical report shows HER2/CEP17 ratio <2 is considered Negative / Not amplified. The biopsy report says that a HER2/CENT17 ratio greater than or equal to 2.0 and also an Average HER2 Copy Number / Cell greater than, equal to or less than 4.0 in 10% of Tumor is Positive / Amplified. (That reads oddly since it seems the second number could be anything.) If the HER2/CEN17 ratio were less than 2.0 & Average HER2 copy Number per Cell was greater than or equal to 6.0 in a homogeneous & contiguous population within > 10% of the Invasive Tumor Cells, it would be Positive / Amplified.

I have no idea if it's significant, but noticed that the CNB lab used the HER2 IQFISH pharmDx Kit from Dako while the surgical report mentioned the PathVysion Abbot Molecular FDA-Modified Method - Single Multiplex Probe Stain Procedure. On both reports, the ER and PR receptors are 0% so there is consistency there. The CNB proliferation rate is a scary 90% while the surgical report shows 60%, still far out of range, but less so. I have a follow-up appointment with the surgeon next week. She didn't seem particularly concerned about the discordance (the term I found in my research), but I find it disconcerting. As some of you know from another thread, I have some troubling pre-existing conditions that make me very hesitant to pursue chemotherapy and simply couldn't make myself commit to the recommended six month neoadjuvant TCHP protocol recommended. I would at least like to feel more confident about the information received in making a final decision on adjuvant chemo before getting set up for radiation.

BarredOwl · July 2016

VLH:

I don't know enough to comment on your specific test results. Your surgeon needs to provide you with an explanation of why it is not a concern to your satisfaction. However, the indications for HER2-targeted therapy are within the area of expertise of the medical oncologist, so please also ask your medical oncologist for advice about these results. The pathologist may be involved in trouble-shooting as well. You may also wish to seek a second opinion with pathology review, time permitting (your MO should advise you by when you should commence adjuvant systemic treatments such as chemo and/or HER2-targeted therapies).

BarredOwl

ElaineTherese · July 2016

Sadly, kayb is probably right. HER2+ or triple negative, your medical oncologist (MO) is likely to recommend chemo. Triple negative breast cancer cannot be treated by either targeted therapies like Herceptin or hormonal therapy. At present time, chemo is the only systemic weapon to fight it. Sigh.

VLH · July 2016

Sadly, I know that chemo is the only systemic option. I had hoped that perhaps Herceptin monotherapy might offer some benefit since that drug seems to be more well tolerated than Taxotere, Carboplatin & Perjeta, but a triple negative diagnosis throws even that option out. I feel like I went from a very bad scenario to an even worse one. I'm frustrated that I'd sought a copy of the pathology report on 7/21 and didn't get to see it until the rushed bedside visit before surgery on Wednesday. The surgeon seemed quite cavalier about the reversed finding on HER2 so I'm not very hopeful that I'll get much good information at my post-op visit. With the diabetes, fibromyalgia and psoriasis on my big toe that leaves it constantly tender already, I feel that the nail changes could easily lead to an amputation and that peripheral neuropathy is almost a certainty with chemotherapy. Thanks for the input & moral support, ladies!

dragonsnake · July 2016

VLH, I found this on another thread. It's quite relevant to your case

https://www.sciencedaily.com/releases/2016/07/160728105619.htm

doxie · July 2016

I'm not so sure this article is relevant. Though not clearly stated, this article refers to testing by Genomic Health for ER+ tumors for the Oncotype score. Tumor tissue is ground up for testing. Since VHL is ER-, her tissue will not have been sent for testing.

I've always thought getting a 2nd opinion on the tumor was a good idea. For those of us ER+ , the Oncotype score serves this purpose. Just a thought, you might want to have it sent to another pathology lab unassociated with the current one.

VLH · July 2016

Like Doxie, it's my understanding the Oncotype test is only for HR positive tumors. Since I doubt that I'll do chemo, perhaps an accurate diagnosis isn't that important except for researching statistics. I'd wondered if patients can ask for a second opinion on their pathology testing and if insurance will cover the expense. Does anyone know...must the surgeon submit the order or can a patient initiate the request by contacting another lab?

KBeee · July 2016

VLH, If you do Taxol X 12 instead of Taxotere, your MO can more carefully adjust it if neuropathy develops. You also can request ice booties to help reduce the risk of neuropathy.

Positivepower11 · July 2016

VLH my tumour was biopsied twice by two different hospitals and it was found to be hetrogenious. This was done post operation parts of the tumour were solidily Her2 negative and part was Her2 positive. I was given Taxotere Herceptin Perjeta and AC to cover all possibilities. I understand that hetrogenious tumours are not common but do end up creating these issues.

meg2016 · July 2016

I was HER2+ from my initial pathology. I got a second opinion on my pathology (Dana Farber) and it found it to be HER2-. They did some further lab analysis and decided my tumor is heterogeneous. So it has both. According to my oncologist, this is more common than many people are aware and a single tissue sample often won't show it. This changed my treatment a bit as well. I haven't yet had surgery (and don't know if I will still have tumors left when I do) so not sure how that pathology will come out. But they did go ahead and include Herceptin and Perjeta in my neoadjuvant treatment, it works on the HER2+ part. Now I am getting AC for the rest.

VLH · July 2016

How interesting! Not only am I conflicted with all this cancer stuff, it's possible that my tumor is also indecisive and unable to commit.

BarredOwl · July 2016

VLH:

You need expert assistance from your team. Reading the ASCO/CAP guidelines, makes me think you should engage your medical oncologist and pathologist for advice. Do not hesitate to seek-- or have one of them seek an expert pathology review on your behalf-- as suggested by several of us above.

Johns Hopkins, Dana Farber and other places provide such services:

http://www.breastcancer.org/treatment/second_opinion/where

"A few major medical centers — such as the Cleveland Clinic, Johns Hopkins, and Harvard-affiliated Partners HealthCare — now offer online second opinion services that don't require an in-person visit. A specialist would review all of your test results and other information to compile a report of recommendations about your care, which is then sent to you and/or your current doctor. Because this type of service is so new, insurance companies don't always cover the expense. Some state medical boards don't allow remote second opinions, so you also would need to call the cancer center or check the website to find out whether residents of your state are eligible. If it's impossible for you to travel but you really want a second opinion from a physician at a top-flight institution, this may be a good option for you."

BarredOwl

dragonsnake · July 2016

I cited this study because it showed that tumors could be heterogeneous. It is my understanding that not only Her2 receptor status may vary from site to site, but also the ER/PR. The receptor status is determined statistically, from the percentage of the cells having certain receptors, but the composition may vary depending on which part of the tumor is studied (according to this article).

IMHO, chemo is a trial-and-error business: regarding of the declared receptor status, it may work, or not (if the criterion of it working is cure). In some cases, patients are in a long remission, in some cases- short, some metastasize while on chemo. There is no clear cause-effect connection when it comes to medical treatment. Modern medicine cannot tell with 100% certainty which patient will benefit from a particular kind of chemo drug. So doctors are collecting data, and try correlating certain successful treatment plans with certain tumor characteristics, but it is just a statistics run on a limited number of cases. As I pointed out in many of my previous posts, medical science is all about statistics, probabilities, and statistical correlations, but humans cannot be a subject of statistics because of the complexity of the biochemical, molecular, and physiological processes taking place in our bodies. However, medical science as we know it is still the best tool that we have to fight diseases.

BarredOwl · July 2016

The 2012 link I posted and discussed in more detail above is actually about HER2 testing using validated IHC and ISH methods in biopsy versus surgical samples:

2012 article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503664/pdf/conc-19-315.pdf

Tumor heterogeneity is one possibility, but not the only one. The MO and pathologist should review the case.

I will again recommend to VLH: You may wish to ask your MO and pathologist (and have them confer) about the various possibilities, and whether additional expert pathology review and/or further testing could be used to distinguish between the various possibilities and provide some definitive information to clarify the true situation and inform your treatment decisions.

BarredOwl

dragonsnake · August 2016

I agree with BarredOwl's suggestion that the tissues should be re-tested in another facility, if possible. My experience with second opinion is that the pathologists there reviewed the same slides prepared at my local hospital. Reviewing slides may be helpful, however if would have been great if they would re-test the tissues that did not maker it to the slides. I do not know their protocols, but they may keep some "raw" material, not only the slides.

dragonsnake · August 2016

Great citation, BarredOwl! Thank you.

VLH · August 2016

I've only spoken with the MO once at the initial consultation weeks ago. She was leaving town on vacation and I'd left a message on her nurse's voicemail declining the recommended neoadjuvant treatment. I didn't realize how unreliable the testing can be. Given the potential side effects of the drugs, one would think there would be some redundancies to at least improve the chances of pursuing the best treatment plan.

PositivePower11, Taxotere, Herceptin, Perjeta and AC sounds like a very challenging treatment plan. You've certainly done everything possible to defeat your cancer.

BarredOwl · August 2016

Hi VLH:

Having declined the offer of neoadjuvant treatment should not prevent you from consulting her again in light of new information from surgical pathology and lymph node biopsy (including new HER2 test results that do not agree with a prior test result) and about a different question (adjuvant treatment). Please do not hesitate to contact her office first thing in the morning and to request an appointment as soon as possible to discuss these matters.

If she can't fit you in soon or you didn't mesh well with her, ask to see a different MO (in network).

BarredOwl

VLH · August 2016

Thanks, BarredOwl. I doubt that I'll do chemo / targeted therapy anyway.

BarredOwl · August 2016

Hi VLH:

Even if you think you'll probably decline, there is value in seeking advice from an MO in light of all currently available pathology information.

Because it seems to be either triple-negative and/or ER-PR-HER2+ disease (ER-PR- in either case), in my layperson's understanding (which one should not rely on), endocrine therapy would not seem to be an option for you. However, this is point on which you should obtain case-specific expert advice from an MO familiar with your actual test results.

At the same time, it may be worthwhile to pin down your diagnosis with the help of the MO and pathologist, for current or future use. This information will inform her estimate of your current distant (i.e., metastatic) recurrence risk, in light of your ER PR HER2 status(es) and all other relevant clinical and pathology findings (e.g., histology (ductal, lobular, etc.), tumor size, nodal status, grade, etcetera). The information will also inform the estimate of potential benefit (risk reduction) of any proposed treatment(s). At the same time, please don't hesitate to discuss with the MO each of your concerns about how your various co-morbidities and overall presentation may or may not place you at increased risk of problems from treatment, concerns your about quality of life and impact of treatment, and ask whether there may be certain regimens that could achieve a reasonable balance between potential benefit and risk of issues. Through the consultation, you will receive more information about personal risk / benefit, that will help you make an informed decision about systemic treatments whatever you decide.

Best,

BarredOwl

VLH · August 2016

Great input from both of you! An added challenge for me is that even the shorter 12 week chemo options combined with radiation would push me into a new insurance year and a new maximum out-of-pocket. That "maximum" reference is misleading since it doesn't include medications although I understand that some of the drug companies help with co-pays on chemo or targeted therapy.

I also don't think I'll be able to work during treatment, which would be a big hit financially on top of all the money going out. My coaching job is only a few hours a week, but it definitely helps with the budget. The job requires booking space and marketing well in advance and I can't cancel last minute or come in an hour late if I feel lousy. I am speaking & analyzing performances most of the time so mouth sores and/or chemo brain would be very problematic. I have to lift 35 pounds, which I generally keep close to my chest as much as possible to protect my herniated disc / sacroiliac joint. That would be tough with radiation burns.

I try not to linger overly long on the Pity Pot, but find it ironic that I earned two degrees, accepted a lonely traveling job for nearly five years, moved across the country for educational & job opportunities and worked 50 hour weeks for months in an attempt to escape the financial challenges of my childhood only to find myself mulling over these lifesaving options the week I'm supposed to be retiring with a paid mortgage, nice annuity and tidy savings plan. I feel guilty being a Wendy Whiner when there are those diagnosed who are half my age or a much higher stage at diagnosis so need to suck it up!

gracie22 · August 2016

V, I am also a quality of lifer, so I totally and completely get where you are coming from, BUT I really hope you will do what you think is best in your gut for YOU without clouding the issue with the $$$ stuff. The money is a quality of life issue too, I get it. I wound up being a single mother many years ago despite my carefully laid plans to not be such, and have had to make a lot of difficult concessions over the years including taking work that required many more hours and much more stress than I would have cared to had I been in a situation where I had more $$ to work with. When you are on your own, there is no down time in the survival equation and you carved out a successful life, so please give yourself the credit you deserve for getting here, becoming well educated and a productive, intelligent person. I wanted just a low key job and family, not a "career", but wound up with one because circumstances demanded it if I was going to be able to provide a decent life for my kid and myself. Your motivator was your childhood; mine was providing for a kid, and I understand how strong that identity is, and your desire not to lose more ground dealing with health challenges. You are early stage, it is possible that you will be fine without chemo, but rads are pretty much a given with a lumpectomy, nodes or not. That is the trade off with the lumpy/mast decision for many. I hate that people in this country have to make their medical decisions with a budget in mind, but docs and hospitals will work with you, and there are other sources of funding out there. I don't want you to skip any treatments that you would want to take if money was not an issue. Because this is your life, and if there are treatments that you want to do, you should do them.

Core Needle HER2+, but Lumpectomy HER- ???

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