Is FISH Test mandatory?

sid82

Hello All,

This is my first post in this forum.I am taking care of my mom who is diagnosed with breast cancer and has recently undergone lumpectomy. The drain can is still attached to her body and we have been noticing a drain of 30-40 ml 3 weeks into post surgery. We received the IHC results last week. Her2 score is reported as 2/3 and the interpretation is mentioned as "POSTIVE". The comments did mention that it is advised to go for FISH for confirmation. However, when we met with the doctor yesterday he ruled out FISH test and mentioned the IHC results are conclusive for deciding next steps.

I have been doing a lot of primary research lately. It is mentioned in various forums and help articles that if the Her2 score is 2, then it is considered borderline and we need to be doubly sure if it is really Her2 postive. However, my doctor feels convicted that it is Her2 positive and has been talking about going for chemo once she is totally recovered. The doctor is well renowned and belongs to a respectable medical group. I would like to seek inputs from folks here in this forum on what should my next course of action. Should I go with what the doctor advises and get my mom prepped up for Chemo or should I insist on FISH or retake of IHC? Please advice.

Thanks,

Sid

ElaineTherese

If I were you, I would insist on the FISH. Your Mom has a small lump and no nodal involvement. If she is HER2-, the doctor would order an Oncotype test to see whether or not she needs chemo. So, without the HER2+, it might be the case that your Mom doesn't need chemo and it will just be overkill for her. I had chemo, but I was Stage IIIA, HER2+, and Grade 3.

The doctor may be well-regarded, but if he pushes back on the FISH, there's nothing wrong with seeking a second opinion from someone who will do the FISH. There's no reason your Mom should have to go through chemo if she doesn't have to.

sid82

Thanks Elaine for your valuable inputs. I believe FISH is done on the tumor cells that have been retrieved during surgery. I am not quite sure if they are being stored intact so they can perform FISH. If in the worst case scenario, the sample is no longer available, can FISH still be done using some other means? Appreciate if someone can clairfy.

Truffles1968

I would get a FISH to confirm the Her2+ and think about changing oncologists if he disagrees. I had a Her2- biopsy (IHC 2 - equivocal, FISH Her2-) then surgery pathology was Her2 equivocal by IHC and Her2+ by FISH. My oncologist at Johns Hopkins (a Her2 expert) did not think I was Her2+ based on my low mitosis rate and low Ki67 (5%) and did not want to order the Herceptin/Taxol chemo that they use for Her2+ without being sure. He sent a tumor sample to Mayo and they confirmed Her2-. I then had the Oncotype DX test to see if chemo would be beneficial, it came back as a 7 (no benefit to chemo) and a Her2-.

While waiting for all the tests to come back was stressful, I am glad to have a consensus and not to be overtreated.

besa

Under normal circumstances the tumor that was removed ( or at least a significant portion of it) should be kept stored in the hospitals path department and should be available for additional testing.( When I asked I was told my local hospital stored -I think it was paraffin fixed tumor tissue- for ten years.)

I agree with the above posters. If your current doctor won't order a FISH test I would absolutely seek a 2nd opinion before deciding about chemo. Also I would not want a "redo" of the HER2 immunohistochemisry but would want FISH as the next step. (I wouldn't care how "renowed" the first doctor is supposed to be. )

I think your mom is very lucky to have you advocating for her

BarredOwl

Hi sid82:

I am surprised that HER2 IHC 2+ is said to be positive, but I am just a patient.

Do you know if the testing lab and pathologist who issued the report are following the "ASCO / CAP guidelines for HER2 testing"? (American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing).

I understand that HER2+ mucinous disease is quite uncommon. It is possible that the percent mucinous and accurate assessment of grade may be factors in determining whether "reflex" testing by FISH is indicated.

Given the relatively unusual diagnosis and seeming conflict between the pathologist's remarks and medical oncologist's (MO's) conclusion, plus the MO's treatment recommendation based on the very point of disagreement, I would not not hesitate to seek a second opinion now at an independent institution.

The second opinion should include an expert pathology review of all available pathology slides and all HER2 testing to date (including pathology slides from all biopsies and surgeries (ensure they are sent with tracking)), in order to confirm all pathology findings such as percent mucinous, grade, HER2 test results, etc. I would include a specific request for advice regarding further reflex testing by FISH in light of the expert pathology review, and advice re recommended treatment plan.

If you are in the US, please consider an NCI-designated cancer center if possible, or if not, a large university hospital with comprehensive breast cancer center. Here is a list of NCI-designated cancer centers:

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

Best wishes,

BarredOwl

BarredOwl

Hi:

I am a layperson with no medical training. I would like to clarify the basis for my comments above.

I also do not understand why the interpretation of a HER2 IHC test results would be given as "positive" in the opinion of a professional pathologist, if the sole finding was indeed IHC 2+.

Is it possible that there are additional findings or details in the pathology reports or HER2 test results that we are not aware of, such as differences in HER2 staining between an IDC component versus a mucinous component that led to the interpretation as "positive" ? I have no idea.

With mucinous disease, the question of percent mucinous versus ductal, grade of such components, and HER2 positivity of ductal versus mucinous components, might be considerations. Personally, I have no idea and I would seek expert professional advice on these questions. It is possible that this is not your usual case.

For the reasons noted by kayb, the patient should be clearly apprised of the histopathological and clinical basis for a recommendation of HER2-targeted therapy, and of any related caveats (e.g., if equivocal). HER2 test results should be explained thoroughly and clearly to the satisfaction of the patient. If reflex testing is not ordered, the basis for not ordering reflex testing should be explained thoroughly and clearly. This does not appear to have been done here.

In general, guidelines require reflex testing for an "equivocal" result. However, they are difficult for me to comprehend.

Main Page: http://www.instituteforquality.org/recommendations...

Guideline: http://jco.ascopubs.org/content/31/31/3997.long

ASCO /CAP pdf: http://www.archivesofpathology.org/doi/pdf/10.5858...

The above guidelines are technically complex, and there are refinements reflected in supplemental materials and subsequent publications. Patients reading these must always confirm any information therein and their understanding of same with their expert medical providers, to ensure accurate, current, case-specific expert professional advice.

Under "Key Recommendations for Pathologists", this passage in particular from a section regarding handling of "equivocal" results is of note:

• "Must report a HER2 test result as equivocal and order reflex test on the same specimen (unless the pathologist has concerns about the specimen) using the alternative test if: (a) IHC 2+ equivocal or (b) ISH equivocal using single-probe ISH or dual-probe ISH (Table 1; Figs 1 to 3). This assumes that there is no apparent histopathologic discordance observed by the pathologist (Table 2). Note that there are some rare breast cancers (eg, gland-forming tumors, micropapillary carcinomas) that show IHC 1+ staining that is intense but incomplete (basolateral or U shaped) and that are found to be HER2 amplified. The pathologist should consider also reporting these specimens equivocal and request reflex testing using the alternative test."

What does the quoted sentence in bold text mean? Table 2 does not refer to "equivocal" results, yet Table 2 does provide further guidance in the case of certain histopathologic findings that might be considered "discordant". However, the passage I quoted above is expressly applicable to an "equivocal" finding and refers one to considerations in Table 2.

I do not really understand how this is applied in practice. My lack of understanding of this is why I hesitate to state that reflex FISH testing is always and in every case definitively mandated upon a finding of "equivocal" results (IHC 2+). (Also, per paragraphs 2-4 of this post, there may be some lack of clarity regarding the full content of the pathology report and HER2 test results in this case.)

However, IF Table 2 was indeed applicable to "equivocal results", please note that certain statements relate to percent mucinous and grade.

The grade from surgical pathology has not been provided by the original poster. Moreover, "grade" has been shown in certain studies to be relatively subjective. This is why in certain clinical studies, provision is made for central pathology review to ensure consistent and expert interpretation of grade.

In view of the foregoing, if this were me, I would be inclined to seek answers to the questions above, an expert pathology review, and a second opinion from a Medical Oncologist in light of same regarding the recommendation for HER2-targeted therapy in what may be a specialized case.

Note also the section "Key Points for Clinicians to Discuss With Patients Regarding HER2 Status" regarding what may be considered best practices for patient communication and informed decision-making. The guidelines indicate that patients should be clearly apprised of certain things, because it is necessary to making an informed decision. This is another reason to seek a second opinion.

BarredOwl

carpe_diem

My cancer is also mucinous and tested 2+ (equivocal) on initial HER2 testing. Mucinous carcinoma of the breast very rarely metastasizes, but mine already had before it was discovered in 2011 (despite regular mammograms). The original biopsy was on the tumor in my left lung, which was equivocal and then negative to FISH, as were the original breast cancer (removed 18 months later) and the tumor on my shoulder blade about a year ago. There is a long-running thread on mucinous carcinoma in "Less Common Types of Breast Cancer" and several people have noted that their cancer was HER2 positive. There is a new thread for HER2 + mucinous carcinoma you might look at, but I completely agree that further testing is called for.

It's generally felt that mucinous carcinoma of the breast has a good prognosis. Even in my case, I've lived much longer than expected for de novo Stage IV bc with visceral mets where the typical survival is about 12 months. I don't know whether it's dumb luck, clean living', or some mitigating effect of the variety of cancer cells, but I'm still going strong after five years.

ChiSandy

Mine tested 1+, which is still considered HER2-, but the only reference to type of test I saw in my path report was FISH; didn’t see “IHC” mentioned anywhere. Wonder if there’s been any research concerning use of Herceptin after hormone+ tumors have become resistant to endocrine therapy in women with “equivocal” or even “1+” HER2 results?

sid82

Thanks a lot everyone for your responses. I really appreciate you all taking time to provide your inputs. As suggested by almost everyone here, I am going to persist on the FISH test.

Just to give you some context,we are based in India and the way the pathology reports are reported here may differ. I have given screenshots from the actual IHC report so you have a fair picture. I am still confused if I need to interpret the score given in this report (02/03) as 2+ which refers to equivocal. Does the "% of cells" values have any significance on the doctor making a conclusion around suggesting Chemo as the way forward?

Thanks,

Sid

SummerAngel

Both of my tumors were equivocal ("2+" is how it's listed on my pathology report) with IHC and negative with FISH. The left tumor was scored after excision, but the right was only scored with biopsied tissue and was never re-scored after excision. I would insist upon FISH.

SpecialK

I went to the website for Ventana, the testing method used for this specimen's Her2 status on IHC.  This is an excerpt from the package insert that explains the test scoring.  It appears to me that it is a combination of staining percentage and numerical score - i.e., 2 or greater plus 10% or more of staining, that is making up the positive interpretation.  Here is a copy of the insert:

"Definition of positive and negative results: Breast carcinomas that are considered positive for HER2 protein overexpression must meet a threshold criteria for the intensity and pattern of membrane staining (2+ or greater on a scale of 0 to 3+) and for the percent positive tumor cells (greater than 10%). Staining must localize to the cell membrane. Staining of the cytoplasm may be present, but this staining is not included in the determination of positivity. If heterogenous staining for HER2 protein is present in the tissue, repeat the section based on the score that is present in the most intensely staining area. Following in Photosets B through H are examples of a variety of staining patterns in breast carcinoma with PATHWAY HER-2/neu (4B5)"

I would definitely want a FISH confirmation of Her2 status prior to moving forward with any systemic therapy.

sid82

Hi Everyone,

Finally, some respite. The doctor did recommend for FISH test and the results are expected by mid next week. I am hoping to get all the needed clarity on the next steps post then.

Thanks for all your inputs.

Regards,

Sid

sid82

The FISH test results have come out to be positive . Now she is officially triple positive.

SpecialK

sid - there is an active Triple Positive thread here, lots of good people and info:

https://community.breastcancer.org/forum/80/topics/764183?page=978#idx_29322

ElaineTherese

Sid,

Sorry to say that your Mom will probably have at least Taxol + Herceptin chemo/targeted therapy, if not something more aggressive like Taxotere, Carboplatin, Herceptin, and Perjeta. But, Special K is right -- we have an awesome thread for Triple Positives like your Mom. Stop by and ask anything!