Triple positive but no response to 5 cycles of TCHP

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Khanniganslp9
Khanniganslp9 Member Posts: 29
edited July 2016 in HER2+ (Positive) Breast Cancer

Has anyone had NO response to TCHP.

At diagnosis my tumor was estimated to be 2cm by US, mammogram and by physical palpitation. I completed 5 cycles of Neoadjuvent TCHP in April. In May I had an MRI which showed "complete response" or NED. On June I had the mastectomy and the tumor was alive and well and was 5cm with 80% lobular and 20% ductal features. They say lobular tumors can be difficult to see or palpitate and can be completely hidden even on MRI. My pathology report notes no evidence of response to chemo (no tissue necrosis and no scarring of tissue). I am HER2 positive, though my second opinion oncologist says I "barely meet criteria" for HER2 positivity. MyHER2 ICH (sp?) was inconclusive at a level "2", then I was positive for FISH (again, just barely meeting criteria).

Any ideas on what this all means? Am I not really HER2 positive? Do I need more chemo to attack the micrometastasis? If so, what regimen given my unusual profile and the fact that I was already non responsive to TCHP?


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  • JohnSmith
    JohnSmith Member Posts: 651
    edited July 2016

    Sorry you had to join this group.

    It's known that neoadjuvant chemo is not very effective against ILC.
    Source: http://meetinglibrary.asco.org/content/100002-176

    What was your KI67 percentage? Is the Oncotype DX test offered for borderline HER2? If so, get the test done and let us know your score.

    It may be wise to get a second opinion.

    ILC is less common and plagued by numerous challenges. I'd recommend heading over to the ILC section of the forum, here.

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  • BarredOwl
    BarredOwl Member Posts: 2,433
    edited July 2016

    Hi Khanniganslp9:

    When you say: " I was positive for FISH (again, just barely meeting criteria)," I assume the test result was deemed "positive" by the pathologist, and was not "equivocal". Please advise if that is not the case. The comments below assume a "positive" result by FISH and testing in accordance with ASCO/CAP guidelines.

    An IHC of 2 is deemed to be an "equivocal" result, and triggers reflex testing by FISH. If found to be "positive" by FISH, then the disease is deemed "HER2-positive." The Oncotype test for invasive disease is not indicated for HER2-positive disease.

    2013 ASCO/CAP guideline: http://jco.ascopubs.org/content/31/31/3997.full.pdf

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

    "Patients should understand that although most HER2 test results are definitively positive or negative, there are equivocal results that require additional testing using an alternative test or using the same or alternative test on a different portion of the same specimen (different block). Sometimes, the oncologist or pathologist may recommend additional testing using a different type of tumor specimen (eg, surgical excision v core biopsy), if available."

    On the one hand, if positive is positive, it is possible your MO was highlighting a lower degree of positivity as a possible explanation for the poor response to neoadjuvant TCHP (alone or in combination with low grade and/or the large ILC component).

    On the other hand, he could have been voicing a possible concern about the need for an expert review of your HER2 status. In this regard, was your HER2 status determined by core-needle biopsy only, or were the surgical samples re-tested for HER2 status?

    I ask because: 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. This document predates the 2013 ASCO/CAP guidelines for HER2 testing, so it 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 might be less representative when tumor heterogeneity is present. 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.

    I recommend you ask the MO what he intended by that comment about your HER2 status, and request and explanation of what the potential implications are.

    Anyway, a second or third opinion, including expert pathology review and review of the HER2 status determination, and possible confirmatory testing, may be in order.

    BarredOwl

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  • Vildanbt
    Vildanbt Member Posts: 32
    edited July 2016

    Hello

    My mother is also has triple positive invasive micropapillary tumour. She had no response to 2 cycle taxotere cyclophosphamide herceptin and 2 cycle doxorubicin florouracil cyclophosphamide chemo. So we switched to surgery. In the pathology report the tumour was same and had no necrosis.

    After the surgery She got 4 cycle taxol cisplatin herceptin and radiotherapy.

    Some tumours do not respond well chemo. It is more than we we think. But everyone does not take neoadjuvant so diffucult to know real percentage. It does not mean you have bad prognosis.

    May be you have no distant micrometastasis it is only local and removed all the tumour from the body sö you do not need chemo.



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  • ShetlandPony
    ShetlandPony Member Posts: 4,924
    edited July 2016

    Following on BarredOwl's comment about the low grade and the large ILC component: I see your stats say grade 1, which means a slower-growing cancer. Chemo works best on fast-growing cells. What are your ER and PR percentages? Are they high? ILC is generally a very hormone-driven type of bc. If the cancer is grade 1 with high ER and PR, it may be the kind that will respond very well to hormone therapy. Ask your oncs. Perhaps aggressive hormone therapy -- with an aromatase inhibitor and ovarian suppression if you are premenopausal -- would be more appropriate than chemo at this point. Perhaps adding a Her2 drug depending on pathology review and further testing.

    When things get complicated or unusual, I recommend going to a major cancer center for an opinion and for treatment if you can.

    https://www.nccn.org/members/network.aspx


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  • Khanniganslp9
    Khanniganslp9 Member Posts: 29
    edited July 2016

    Thank you for all the responses. This is so helpful to discuss and to clarify what I need to be asking and talking about with my doctors.

    Ki67 and oncotype have not yet been done. Yes, my IHC was equivocal (2) which led to the FISH tests which was in fact positive. It was done on both the core needle biopsy in January as well as on the excised tumor in June. It is my second opinion post-surgery oncologist with UCLA who is questioning my HER2 status and wants to retest both these samples. She also wants to know my Ki67 numbers for each sample. Back in January my pre-surgery 2nd opinion oncologist with City of Hope also wanted to retest HER2, but we decided not to. We are meeting with my primary oncologist tomorrow and will request both oncotype and Ki67 testing, as well as the HER2 retesting on both samples.

    I'm not sure what all of this will tell us, ie, how it will shape what treatment plan will be recommended for right now. I think what is being considered is whether or not I should have a different chemotherapy to attack possible micrometastesis not seen under the microscope. If they can come up with which one they reasonably think will do this, I am leaning toward wanting that. To me it seems like I have started all over, like I have not had chemo at all. In that scenario, of not having had successful chemo, we have taken the tumor out, but we have not blasted my system with a successful chemo regimen to get rid of the micromestatsesis. I am currently on Herceptin every three weeks, for 1 year and the plan was to start hormonal therapy in a few weeks. I think Herceptin is also being reevaluated as far as whether it is in fact medically indicated given my lack of response to TCHP.

    There is also the possibility that the TCHP DID in fact work on some level, but there is no way of really knowing - unless maybe some of these additional tests will tell us something about that, ie whether the growth rate was the same in January vs June, or maybe whether it slowed down? It seems to me it is possible that in January the tumor was even larger, like 10 cm, and that the TCHP shrunk it to the 5cm they excised in June. However, this scenario doesn't match up with the imaging back then which showed it to be 2cm on US and on mammography. It also doesn't match up with the MRI imaging done after chemo but before surgery which showed NED. Either way, the palpable 2cm portion of the larger tumor did change and seemed to go away between February and April. It was palpable when I started chemo, and it got smaller and smaller/ or flatter. At the end we could feel something, but it was no longer round like a grape. I described it as possibly wider, but flat like a pancake. The doctors speculated that it was likely scar tissue. But on excision, nothing was mentioned about scar tissue.

    My ER was 95%, and PR was 5%. I wonder if I am a candidate for an aromatase inhibitor plus ovarian suppression. On diagnosis I was premenopausal, but I have been in a chemically induced menopause since starting chemo, and my period has not yet come back since I stopped. Can it be assumed that my ovaries are still making estrogen even now that I am in chemically induced menopause? About ovarian suppression, do you have any recommendations about oovectomy vs drug supression? I also have a family history (maternal grandmother) of either ovarian cancer or uterine cancer, though we don't know which one it was, as well as breast cancer in the same grandmother. I wonder if it makes more sense to do the oovectomy to address this cancers ER+ status as well as to reduce my chances of ovarian cancer.

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  • BarredOwl
    BarredOwl Member Posts: 2,433
    edited July 2016

    Hi Khannigansip9:

    It sounds like they wish to gather additional information to inform decision-making, which is good.

    Re your last question, please confirm with your team, but NCCN guidelines for breast cancer (Version 2.2016) note:

    "It is not possible to assign menopausal status to women who are receiving an LHRH agonist or antagonist. In women premenopausal at the beginning of adjuvant chemotherapy, amenorrhea is not a reliable indicator of menopausal status as ovarian function may still be intact or resume despite anovulation/amenorrhea after chemotherapy. For these women with therapy-induced amenorrhea, oophorectomy or serial measurement of FSH and/or estradiol are needed to ensure postmenopausal status if the use of aromatase inhibitors is considered as a component of endocrine therapy."

    It would be best to discuss the pros and cons of AI; AI plus ovarian suppression; and oophorectomy plus AI with your expert MO in light of your personal medical and family history, as well as whether you may be a candidate for genetic counseling and possible genetic testing (in case certain results would support bilateral salpingo-oophorectomy).

    For more information about the use of an AI plus ovarian suppression, I have these bookmarked:

    ASCO 2016 Update: http://jco.ascopubs.org/content/early/2016/02/11/JCO.2015.65.9573.full.pdf

    ASCO 2014 Guideline: http://jco.ascopubs.org/content/early/2014/05/20/JCO.2013.54.2258.full.pdf

    SOFT (Francis): http://www.nejm.org/doi/pdf/10.1056/NEJMoa1412379

    Supplementary Appendix to Francis: http://www.nejm.org/doi/suppl/10.1056/NEJMoa1412379/suppl_file/nejmoa1412379_appendix.pdf

    "[R]esults of the planned primary analysis in SOFT comparing adjuvant tamoxifen plus ovarian suppression with tamoxifen alone after a median follow-up of 67 months"

    TEXT/SOFT (Pagani): http://www.nejm.org/doi/pdf/10.1056/NEJMoa1404037

    Supplementary Appendix to Pagani: http://www.nejm.org/doi/suppl/10.1056/NEJMoa1404037/suppl_file/nejmoa1404037_appendix.pdf

    "[P]rimary combined analysis of data from TEXT and SOFT comparing adjuvant exemestane plus ovarian suppression with adjuvant tamoxifen plus ovarian suppression after a median follow-up of 68 months"

    Regan (2016): http://jco.ascopubs.org/content/early/2016/03/31/JCO.2015.64.3171.abstract

    (Full pdf version available for US $2.00 via PatientACCESS option with registration at Copyright Clearance Center)

    BIG 1-98: http://jco.ascopubs.org/content/early/2015/07/24/JCO.2015.60.8133.abstract

    (Full pdf version available for US $2.00 via PatientACCESS option with registration at Copyright Clearance Center)

    ASCO Post Article re BIG 1-98, "Benefit of Adjuvant Letrozole vs Tamoxifen Is Greater in Lobular Than in Ductal Breast Cancer": http://www.ascopost.com/News/31718

    BarredOwl

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  • Khanniganslp9
    Khanniganslp9 Member Posts: 29
    edited July 2016

    thank you for the information and all the links. I will post more after I discuss with my MO tomorrow.

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