Question about pathology results versus biopsy results
I am newly diagnosed with breast cancer and my pathology report after surgery was a little different from my biopsy report and I want to understand what that means. My surgeon says it doesn't affect any treatment decisions since essentially the pathology confirmed the biopsy results and the chemo decision is still waiting for my oncotype results to come in. That will probably be next week. I am not super hopeful to avoid chemo due to my grade 3 status. But I know my high progesterone might surprise me and save my rear end. We'll see. But in my biopsy results I was 75% estrogen at an intensity varying between two and three and 95% progesterone at an intensity 3. HER-2 results was negative at 1+. Second biopsy opinion put me at 90% estrogen at 2 intensity and 90 percent progesterone at 3 intensity with a HER-2 score of 1+. But after surgery pathology place me at 68% estrogen at a 2 intensity and 95% progesterone at a 3 intensity with HER-2 score of 2+. FISH ended up still placing me at negative but my ratio was actually 2.03. My HER2 was 3.7 and my CEP17 copy number was 2.0. What does that all mean? Plus my surgeon placed me at 2A stage but with the new staging system out in 2018 I should be at 1B (T2N0M0, hormone positive, HER-2 negative). Does that even matter? I am trying to get a handle on all this but it's so hard since it seems new details are coming out daily right now. I am at a nationally recognized and rated cancer center so I do trust my doctors but I have a driving need to understand what is happening with my cancer and why they are choosing the actions they are choosing. Any clarification and especially encouragement will be welcome as I am really struggling with anxiety right now. Thanks so much and good luck to each and every one of us!
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okay a really simplistic way to explain why results can be different. If you slice a tomato and take a center slice, you have a lot of seeds and if you take a slice towards the end you might have less but if someone is only looking at one slice they extrapolate the data based on what’s in front of them. So a biopsy gives you a small tiny piece but surgery gives a larger sample. So my biopsy might give me a part that 99 % of the cells stain estrogen positive but in reality a bigger sample shows that really it’s more like 75 but whether it’s 99 or 75 it’s still enough to say you might benefit from a certain treatment
I don’t know if that helps or not. But it’s matter of having more data collecte can sometimes give them a bigger picture that’s going to differ somewhat from the very small initial sample
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Hey Kay! Your reports show consensus that your tumor is Er+/Pr+/Her2-, with no evidence of cancer in lymph nodes. That's all good news...for having breast cancer. AND, your care is being provided at a nationally recognized cancer center, with up-to-date everything. Also good news! That your tumor is T2/IIA suggests it is between 2-5cm in size. Is that right? As you mentioned surgery, did you elect lumpectomy or mastectomy and were margins clean (should be on Path report)? Tissue sample has been sent to Oncotype who will report back as to the benefits of chemo. A grade 3 cancer tends to be fast-growing, which should be responsive to chemo, and also tends to have a higher Oncotype score, so be prepared for that possibility. As your tumor was Er+, estrogen blocking drugs will also be in your arsenal. Your docs appear to be doing everything by the book and now it is just the 'waiting game', perhaps the hardest step in this process. Once you have all the data and you and your docs have a treatment plan, you'll start to feel purposeful. Believe me, right now is the toughest part of the early process. Reach out all you need to...
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I elected to do a double mastectomy and margins were clean at 8mm. Tumor was 32mm. No LVI or DCIS detected. And I am as prepared as possible for chemo but still hoping that maybe my high progesterone level will surprise me. Not expecting it though but hope can't hurt. My oncologist was hopeful herself. If I needed it I had decided I wasn't going to cold cap and just told myself it'll grow back, etc. But last night I did some more research and found out my hospital has it's own cold cap machine I can rent. If we can afford it I think I might do that. The thought of perhaps saving some of my hair and thus not looking as sick really made me feel better contemplating the possibility so I think that was my answer in order to feel as sane as possible through it all. I was told if I do need chemo it would be 4 sessions three weeks apart so at least I'm done by mid October it looks like. Radiation is off the table thanks to the negative nodes. Do you know anything though about what my FISH score means and the HER and CAP17 ratio?
And I hope I start feeling purposeful soon. This waiting is tough although not as tough as the waiting for my diagnosis. It was a three week process from getting called back from my yearly mammogram (despite the size and my rigorously doing monthly checkups I never caught it because it was buried deep in dense tissue and had some cystic components which probably made it feel like my regular lumpy, fibrocystic breasts) to my biopsy results and I can only describe that time as torturous. This waiting is hard but it's a little better because I know the cancer is out and anything I do at this point will be to try and ensure it stays that way. But you still picture worst case scenarios or at least I do so I'm having multiple moments of fear each day.
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Kay, from your post, you have every reason to be hopeful! I'm not a physician and I would trust your docs to know what is what. I did find the following excerpt from a 2021 Nature article. It sounds like ASCO changed the definition of your tumor (GROUP 2) from a positive to an Her2 negative. This seems to be based on the findings that Group 2 tumors didn't respond differently to Herceptin treatment in Er+ tumors, which suggested that ER was the main driver of tumor growth and not Her2. However, I believe there are now new drugs targeting lo-Her2 expressing tumors. Sounds like a great topic of discussion with your doc when you next meet!
'In 2018, ASCO/CAP published an update to refine the definition of cases showing mismatch between the HER2/CEP17 ratio and HER2 gene copy number, comprising ~4–15% of cases.3 Possible combinations of the ratio and gene copy number were classified into 5 groups (Table 1). Unlike Group 1 and Group 3, Group 2, defined as a HER2/CEP17 ratio ≥2.0 with an average HER2 copy number <4.0 signals per cell with IHC score of 2+, was re-classified from HER2 positive4,19 to HER2 negative.3 This change was based on the lack of substantive evidence for the efficacy of HER2-targeted therapy in such tumours in terms of survival benefit.3,20 These tumours are rare.'
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It might help to understand how the percentages of positivity are determined. When a percentage is given for ER or PR, the way it is arrived at is the pathologist looks at a slide that contains 100 breast cells. They count how many have ER receptors, and how many have PR receptors. If there are 53 receptors for ER, the ER+ percentage is 53%, etc., and likewise for PR. Every slide of 100 cells may have a differing number of receptors, and thus a differing percentage. Unless you have a very low ER+% the degree of positivity, usually the cut-off is 10% or less, the differences will not influence treatment decisions - positive is positive whether it is 50% or 100%. The intensity noted refers to the staining process that helps the pathologist read the slides and determine the number of receptors, and the number refer to how strong the staining is on a particular slide. It is also important to note that breast cancer tumors are not homogenous. Pathological results may depend on where on the tumor the sample is taken from. Generally, if you have any test result that falls into a parameter for treatment - whether it be grade or Oncotype result, Her2 status, or hormonal receptor arrangement - appropriate treatment will be offered. For the Her2 status - it looks like your biopsy and initial surgical pathology used IHC testing to determine positive or negative. Because there was a 2+ IHC result from the surgical pathology it triggered a reflex test with FISH, which is a more sensitive test. IHC is often done initially because it is a more affordable, but still accurate measure. FISH is employed when there is an equivocal result, such as on your surgical sample. This is the scoring rubric, published on Medscape:
- Positive HER2 amplification: FISH ratio is greater than 2.2 or HER2 gene copy is greater than 6.0.
- Equivocal HER2 amplification: FISH ratio of 1.8-2.2 or HER2 gene copy of 4.0-6.0.
- Negative HER2 amplification: FISH ratio is less than 1.8 or HER2 gene copy of less than 4.0.
What are they saying about your ratio on the FISH result? It appears, if I am interpreting your result correctly, that your ratio remains equivocal on FISH, but your other values indicate a negative result. Is that your thought as well?
As far as staging, particularly if it doesn't change treatment decisions, it doesn't matter if they use the old system in which you are classified as 2A, or newer system at 1B. Independently, that difference would not likely dictate any change in treatment decisions. It seems to be pretty arbitrary which hospitals and treatment centers use which staging system. When is your Oncotype result expected? Have your docs said anything so far about the steps forward? You are still in that limbo of knowing some things, but not everything that determines what will happen next - it does make one anxious, right? Once that stuff is nailed down I think you will feel better and more proactive vs reactive. Wishing you the best and hang in there!
Edited to add - I had the same info up in another window of my computer as murfy commented on - the 5 groupings article. For those with a ratio above 2.0, but a copy number below 4, it looks like that correlates with a negative IHC Her2 result. That is a topic to refresh with your docs - if only for your peace of mind. Another point to make - OncotypeDx is only done on Her2- tumors, it is not a test offered for those who are Her2+, however I believe that the testing platform will report Her2 status as well as ER and PR, so that will be another piece of confirmatory info when you get the results.
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Thank you for some clarification in regards to my HER-2 scores. I was thinking you were either positive or negative. Didn't realize there was a group for low-positive that was still considered negative because they wouldn't respond to Herceptin. I've only read a few studies on it this afternoon (because of course I did. Part of my problem) and it seems like it's actually pretty common. About 60% of hormone positive tumors have low HER-2 expression of varying degrees. They seem to be the ones with the higher grades although higher octoscore isn't a given. Also seems that results are mixed in regards to whether they have worse prognoses but some studies actually show them with a better long term prognosis for both in the low and higher octoscore groups. So at this point it seems no one really bothers with them and just let the octoscore dictate if chemo is needed. But there are some promising ADC treatments I think in the works. A couple may be out already and I will definitely mention them to my oncologist next week. It can't hurt. If I'm missing any pertinent information or have something wrong please let me know. I really am trying to understand my tumor's biology despite having no oncology training whatsoever
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Wow, Kay, you've got a really good grasp of the problem! And, it does sound like lo-Her2 offers another potential therapeutic option. Good luck with your doc appt!
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Just want to suggest that it may be difficult to seek treatment for low expressing Her2 outside of a clinical trial. Kadcyla is offered to early stage Her2+ patients who have had neoadjuvent chemo with a taxane and Herceptin/Perjeta and who have residual tumor at the time of surgery. I don't believe I have seen it being offered to patients adjuvently, and especially those who are not receiving specific Her2 directed treatment. The other targeted therapy for low expressing Her2+ patients - the ADC therapy (T-Dxd) mentioned above in your post - is only FDA approved, I believe, for metastatic patients who have used at least two lines of anti Her2 medications. One thing to remember is that outside of a trial for which you must meet enrollment criteria, treatments need to be standard of care for insurance to cover them. Of course you can ask your oncologist, but if they are ruling you Her2- I doubt either of these drugs would be available for you.
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That's good to know so thank you. I'll still ask of course because that's only being thorough but chemo is probably going to be my only option if I qualify for it. And to be quite honest I hope I don't. We'll see if high progesterone wins out over grade for me. I did read though that HER2 low has really great responses to chemo so if I have to get it that will be comforting. Probably because we tend to be higher grades but whatever. Just glad to know chemo tends to do the trick for those little buggers.
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