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HER2 negative but actually a low positive and neratinib

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kaynotrealname
kaynotrealname Member Posts: 422
edited November 2022 in HER2+ (Positive) Breast Cancer

I'm making a list of questions for my oncologist appointment coming up and in looking at posts relative to metformin I came across neratinib. I realize the metformin trial ended up demonstrating that it was not beneficial in lessening recurrence rates. But apparently neratinib trials were because it was approved by the FDA in 2017 I think for HER2+ positive patients diagnosed in early stage. Does anyone know if it also helps HER2 low positive in early stage? If so, what are the side effects?

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  • specialk
    specialk Member Posts: 9,236
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    The vast majority of breast cancer drugs start in trials with metastatic patients, where they are studied for a period of time in that population. After noting efficacy, some of these drugs are then extended to the early stage community, where they are studied again - usually more rapidly because the dosing has already been established - and incorporated into the standard of care for early stage. For some of these drugs there are parameters for use such as hormonal receptor arrangement, Her2 status, tumor size/nodal spread, etc. Neratinib is one of those drugs, initially studied and used for metastatic patients, then offered to Her2+ patients who have had chemo and Herceptin, and possibly Perjeta. I have not seen it used for those who are not classified as Her2+, it is not FDA approved for that type of use, nor could I find any trials doing so. It is possible that the I-Spy trials might have been a fit, but I believe that this is for neoadjuvent design so you can't have had surgery yet. Neratinib is currently prescribed to be used after you have completed a year of Herceptin for those who are early stage. I believe the most common side effect is diarrhea, but through experimentation I think they have found that is anti-D meds are taken simultaneously for those with this SE, and/or the dosage is ramped up slowly, it works out - but some have had to discontinue because it can't be controlled.

  • kaynotrealname
    kaynotrealname Member Posts: 422
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    Thanks so much for that information. So as of right now it would probably not be something I could take advantage of. I'll still ask but keep that in mind.

  • olma61
    olma61 Member Posts: 1,027
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    Enhertu is the big breakthrough drug for HER2 low pts, but I think this is also reserved for metastatic BC at the present time

  • horse2310
    horse2310 Member Posts: 18
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    I can not seem to get a clear answer on this…sorry if its posted on the wrong place….but is everyone that shows equivocal 2 plus on IHC but then tests negative on FISH …..are they considered HER2 low? …..do the FISH results have to have a certain ratio?

    When I research HER2 low it seems that this is what it says…

    Thanks

  • kaynotrealname
    kaynotrealname Member Posts: 422
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    Yes, they are Her+ low. However, in the early stages that is treated as Her negative. Even those with 1+ on a IHC test is Her2 low. It's actually more common to be Her2 low and most hormone positive tumors are than it is to be truly Her2 negative so don't feel weirded out by it.

  • parakeetsrule
    parakeetsrule Member Posts: 605
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    HER2 low being significant is a relatively new concept, so there isn't much info out there yet. I just listened to an Our MBC Life podcast episode about it today if you want more info: https://pca.st/episode/ccda51ee-3e84-4315-ab7e-73bb733ce4ce
  • horse2310
    horse2310 Member Posts: 18
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    So if I was 2+ equivocal on ish and non amplified negative on fish with a ratio of 1.1..then I'm considered her 2 low?.. does this mean I could have a more agressive cancer?.. I was 90% estrogen positive and 70% progesterone positive... And I'm on an astrazole..should I be taking another drug to avoid a recurrence?

    Why does her2 low seem to be talked about in the metastatic setting?

    Thanks

  • maggie15
    maggie15 Member Posts: 1,071
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    Dana-Farber has an article discussing HER2 low in non-metastatic bc. I am having trouble copying the link so the name of the article is below and can be googled.

    Study finds breast cancers with low levels of HER2 protein are not a distinct subtype of the disease

  • horse2310
    horse2310 Member Posts: 18
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    Thank you

  • kaynotrealname
    kaynotrealname Member Posts: 422
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    Maggie's study is an interesting read but essentially it says that being HER2 low in an early diagnosis doesn't really add anything to your diagnosis. Again, most hormone positive tumors are HER2 low. If it makes your tumor a little more aggressive your oncotype score will pick up on it and your oncologist will respond with appropriate treatment. For example I was 2+ yet with a non-amplified Fish score and my oncotype ended up being intermediate. With being under 50 that put me in the recommendation for chemo. Was the higher score because of my low Her2+? Maybe. But there's so much that goes into our body making a tumor who knows. But after chemo, I went straight into endocrine therapy with nothing else added. At some point they may design medications for early breast cancer that can target low HER2+. They do have a medication that can target it in the metastatic setting (Trastuzumab deruxtecan) and that's why you're hearing about it. But it means nothing to us in early stages at the moment and by itself bares no weight in diagnosing a more aggressive tumor.

  • horse2310
    horse2310 Member Posts: 18
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    Thank you that's very interesting.. The thing is I never got an oncotype test... I had stage one grade one ...one centimeter... But I was equivocal on the ISH but then negative on fish..with a 1.1 ratio whatever that means... So everything I'm reading says to me I'm HER 2 low which has me questionable and a little concerned that I may have had some HER 2 in the tumor which would make my risk of recurrence higher... I had lumpectomy radiation and I'm on 5 years of anastrazole

  • kaynotrealname
    kaynotrealname Member Posts: 422
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    With grade 1, it's almost a guarantee that your tumor would have a low oncotype score which is probably why they didn't do one. Plus it was a small tumor. By itself HER2+ low means nothing and studies aren't showing any predictive power in recurrence which is why they aren't given a separate category nor even considered in staging. I wouldn't give your treatment a second thought. Endocrine therapy is the biggest gun of them all in regards to hormone positive tumors anyway and you're on one.

  • horse2310
    horse2310 Member Posts: 18
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    Thank you so much I appreciate your response... I have one of my follow-ups in January and I'll be asking them questions but thanks again.... Our minds can really go to strange places...

  • parakeetsrule
    parakeetsrule Member Posts: 605
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    As others have said, being her2 low at an early stage doesn't mean much and doesn't affect the treatment plan. The reason it's a big deal for metastatic patients is because they discovered that a drug that was only thought to work for her2+ cancer also works for people who are her2 low. That means a ton of people now qualify for it. A new drug is a big deal when you only have a limited number of treatment options. It extends people's lives.

  • horse2310
    horse2310 Member Posts: 18
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    This is making more sense to me now... thank you

  • lindajfrady
    lindajfrady Member Posts: 3
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    I am triple negative AND Her2 low. The doctor told me I have both types of cancer in one little tumor. I'm so special! He is treating it for both types with TCH.

  • lindajfrady
    lindajfrady Member Posts: 3
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    This is not always the case. I am stage 1A, triple negative and Her2 low. My doctor is treating me for both. Oh joy!