BRCA1 mutation & Her2+

sad-hubby
sad-hubby Member Posts: 6
edited May 2015 in Genetic Testing

My wife who is 44+ was diagnosed with BC ER+ & Her2+ locally advanced in lymph nodes. She went through neoadjuvant therapy (chemo + targeted ones) Taxotere + Carboplatin + Herceptine + Purjeta for 6 rounds (3 weeks apart).

The surgery was lumpectomy with several lymph node removal. Pathlogist's report indicated pCR (pathologically complete remission). We were extremely excited and getting ready for last round - 3/6 weeks of radiation. In between she went for genetic testing. We wanted to get it done primarily because we have two daughters.

The genetic result shattered our excitement. The report says - "pathogenic mutation or a variant that is likely pathogenic in the BRCA1 gene".

We thought that BRCA1 cancer is mostly ER- (often triple negative) & Her2-. I thought I would share it this forum to see if there is anybody who had same diagnosis.

Earlier plan was - after completing radiation and year long Herceptine she will take Tamoxifane for next 5 years to prevent recurrence. We read that for BRCA1 cancer (which are often triple negative) Hercpetine & Tamoxifane don't give much benefit. We are waiting for the surgeon to come back (who is out of town currently).

I am very depressed and feel like we are fighting a losing battle. I can't see her suffering any more. At the same time we can't take BRCA1 lightly in view of ovarian cancer and the high possibility of new breast cancer coming back in the other breast.

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  • inks
    inks Member Posts: 746
    edited May 2015

    I don't see any cause for alarm. Yes, a bigger percentage of BRCA1 mutation carriers have triple negative disease and poorer outcomes, but your wife is not triple negative. HER positivity was considered worse in the past but thanks to herceptin and perjeta the outcomes are similar to ER+ . Your wife is ER+ so in her case hormone therapy is effective and if she will remove her ovaries she can be on aromatose inhibitors. My grandmother was ER+ too and is still doing well, and so is her sister, still kicking it 30 years after diagnosis, all BRCA1. There was a study that was not very good but it concluded that BRCA1 responded well for carboplatin. So infact your wife may have a leg up on some HER negative women with BRCA1 mutation since she got carboplatin thanks to being HER+. The only thing that BRCA1 changes is that she will need a double mastectomy and ooporectomy. If she is young oophorectomy and aromatose inhibitor may also increase her disease free survival.

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  • sad-hubby
    sad-hubby Member Posts: 6
    edited May 2015

    Thank you for your reply. I have heard that BRCA cancers are usually triple negative at least most of the time Her2-. We have doubts about false positive results from genetics testing. It was done by Ambry Genetics in Vallejo CA.

    I did lot of research in the internet to find false negative/positive rates but didn't come up with much. I want to be very sure before we take any drastic decision.

    Thanks


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  • inks
    inks Member Posts: 746
    edited May 2015

    If you are worried about the accuracy of the genetic testing see if your wives relatives can get themselves tested too. When I found out about my BRCA mutation I was more worried about my relatives than my 18 month old daughter since I have some relatives close to my age. And as it happened as I was finishing up chemo one of my relatives was diagnosed with stage IIIc ovarian cancer. So try to urge her relatives to get tested too and if some of them are positive for the mutation you can be sure that your wives results are correct. There is no rush with the prophylactic surgeries. It's my personal opinion that it's actually better to wait and have your body bounce back from chemo and radiation, I had my oophorectomy a year after radiation.

    I don't know why you have the idea that BRCA1 has to be triple negative stuck in your head - I know plenty of women who are BRCA1 and ER+.

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  • inks
    inks Member Posts: 746
    edited May 2015

    Here is a table showing wich BRCA1 genes are associated with ER+ cancers

    Table 5. Genetic Modifiers of Breast Cancer Risk

    Putative GeneChromosomeSNPCitationOR (95% CI)Comments
    CI = confidence interval; ER+ = estrogen receptor–positive; ER- = estrogen receptor–negative; OR = odds ratio, SNP = single nucleotide polymorphism.
    EMBP11p11.2rs11249433[191]1.09 (1.02–1.17)BRCA2carriers
    MDM41q32.1rs2290854[192]1.14 (1.09–1.20)BRCA1carriers
    CYP1BI-AS12p22.2rs184577[193]0.85 (0.79–0.91)BRCA2carriers
    CASP82q33D302H variant[194]0.85 (0.76–0.97)BRCA1carriers
    SLC4A/NEKID3p24.1rs4973768[134]1.10 (1.03–1.18)BRCA2carriers
    MAP3K15q11.2rs889312[134]1.10 (1.01–1.19)BRCA2carriers
    FGF10/MRPS305p12rs10941679[134]1.09 (1.01–1.19)BRCA2carriers
    TERT5p15.33rs2736108[195]0.92 (0.88–0.96)BRCA1carriers
    5p15.33rs10069690[195]1.16 (1.11–1.21)BRCA1carriers
    6q22.23rs218341[196]0.89 (0.80–1.00)BRCA1carriers
    6p24rs9348512[193]0.85 (0.80–0.90)BRCA2carriers
    ESR16q25.1rs2046210[191]1.17 (1.11–1.23)BRCA1carriers
    6q25.1rs9397435[191]1.28 (1.18–1.40)BRCA1carriers
    6q25.1rs9397435[191]1.14 (1.01–1.28)BRCA2carriers
    LRRC4C9q31.2rs965686[197]0.95 (0.89–1.01)BRCA2carriers
    ZNF36510q21.1rs10995190[197]0.90 (0.82–0.98)BRCA2carriers
    10q21.2rs16917302[198]0.84 (0.72–0.97)BRCA1carriers, mainly ER+
    10q21.2rs16917302[199]0.75 (0.60–0.86)BRCA2carriers
    FGFR210q26.13rs2981582[134,200]1.30 (1.20–1.40)BRCA2carriers
    10q26.13rs2981582[134,200]1.35 (1.17–1.56)BRCA1carriers, ER+
    10q26.13rs2981582[134,200]0.91 (0.85–0.98)BRCA1carriers, ER-
    LSP111p15.5rs3817198[134]1.14 (1.06–1.23)BRCA2carriers
    PTHLH12p11rs10771399[197]0.87 (0.81–0.94)BRCA1carriers
    RAD5115q15.1rs1801320[201]3.18 (1.39–7.27)BRCA2carriers (CC homozygous only)
    TOX3/TNRC916q12.1rs3803662[134]1.09 (1.03–1.16)BRCA1carriers
    16q12.1rs3803662[134]1.17 (1.07–1.27)BRCA2carriers
    BRCA1-wild type17prs16942[202]0.86 (0.77–0.95)Wild type modifiesBRCA1
    BABAM119p13.11rs8170[203]1.25 (1.18–1.33)BRCA1carriers, triple negative
    19p13.11rs865686[197]0.86 (0.78–0.95)BRCA2carriers
    19p13.11rs67397200[198]1.17 (1.11–1.23)BRCA1carriers, mainly ER-
    GMEB220q13.3rs311499[199]0.72 (0.61–0.85)BRCA2carriers
    FGF13Xq27.1rs619373[193]1.30 (1.16–3.41)BRCA2carriers
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  • inks
    inks Member Posts: 746
    edited May 2015

    Sorry it did not copy and paste correctly. You can find the table here http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page2#_2640_e

    Scroll down about quarter of the way. Is your wives mutation the one associated with ER+?

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  • inks
    inks Member Posts: 746
    edited May 2015

    And from the same source:

    Of breast tumors arising in BRCA1 carriers, 78% were ER-negative; 79% were PR-negative; 90% were HER2-negative; and 69% were triple-negative. These findings were consistent with multiple smaller series.[83,216,221-223] In addition, the proportion of ER-negative tumors significantly decreased as the age at breast cancer diagnosis increased.[220]

    There is considerable, but not complete, overlap between the triple-negative and basal-like subtype cancers, both of which are common in BRCA1-associated breast cancer,[224,225] particularly in women diagnosed before age 50 years.[83-85] A small proportion of BRCA1-related breast cancers are ER-positive, which are associated with later age of onset.[226,227] These ER-positive cancers have clinical behavior features that are "intermediate" between ER-negative BRCA1 cancers and ER-positive sporadic breast cancers, raising the possibility that there may be a unique mechanism by which they develop.

    Therefore about 20% of BRCA1 BC is not triple negative.

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