Her2/ most inherited type of BC?

Hello,

I was reading through some of the old posts and someone had written that this is the most inherited type of BC. Is this true? My mom's onc. nurse told her to tell me to be v. careful cause she said her2 tends to run in families. I am 30 and have already had a baseline mammogram. I would like to know if someone has read any articles relating to this.

Thanks,
Anne

Hi Anne,
From what I learned the other day from my genetics counselor, (sorry guys but we talked about everything) HER2 is an oncogene that everyone carries. At present they don't know why some peoples HER2 goes nuts and causes cancer and others live harmonously with it.
I myself feel that is does, at least in my family.
If it only happens in 30% of breast cancers, my family is at 50-75%. But then again I am no scientist.
Anne, if I find any supporting articles for it being hereditary, I will post them. Good question. Take Care k

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1: Maturitas. 2004 Sep 24;49(1):34-43. Related Articles, Links


Oncogenic pathways in hereditary and sporadic breast cancer.

Kenemans P, Verstraeten RA, Verheijen RH.

Department of Obstetrics and Gynaecology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Kenemans@vumc.nl

Cancer is a genetic disease. Breast cancer tumorigenesis can be described as a multi-step process in which each step is thought to correlate with one or more distinct mutations in major regulatory genes. The question addressed is how far a multi-step progression model for sporadic breast cancer would differ from that for hereditary breast cancer. Hereditary breast cancer is characterized by an inherited susceptibility to breast cancer on basis of an identified germline mutation in one allele of a high penetrance susceptibility gene (such as BRCA1, BRCA2, CHEK 2, TP53 or PTEN). Inactivation of the second allele of these tumour suppressor genes would be an early event in this oncogenic pathway (Knudson's "two-hit" model). Sporadic breast cancers result from a serial stepwise accumulation of acquired and uncorrected mutations in somatic genes, without any germline mutation playing a role. Mutational activation of oncogenes, often coupled with non-mutational inactivation of tumour suppressor genes, is probably an early event in sporadic tumours, followed by more, independent mutations in at least four or five other genes, the chronological order of which is likely less important. Oncogenes that have been reported to play an early role in sporadic breast cancer are MYC, CCND1 (Cyclin D1) and ERBB2 (HER2/neu). In sporadic breast cancer, mutational inactivation of BRCA1/2 is rare, as inactivation requires both gene copies to be mutated or totally deleted. However, non-mutational functional suppression could result from various mechanisms, such as hypermethylation of the BRCA1 promoter or binding of BRCA2 by EMSY. In sporadic breast tumorigenesis, at least three different pathway-specific mechanisms of tumour progression are recognizable, with breast carcinogenesis being different in ductal versus lobular carcinoma, and in well differentiated versus poorly differentiated ductal cancers. Thus, different breast cancer pathways emerge early in the process of carcinogenesis, ultimately leading to clinically different tumour types. As mutations acquired early during tumorigenesis will be present in all later stages, large-scale gene expression profiling using DNA microarray analysis techniques can help to classify breast cancers into clinically relevant subtypes.

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PMID: 15351094 [PubMed - indexed for MEDLINE]

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Feb 10 2005 12:03:04

Hello all,

If anyone has info about inheritability of her2+ cancers I'd love to hear it. Of the inherited bc mutations (BRCA 1 or 2) my sense is that they tend to express as ER+ cancers, which her2+ tends NOT to be. So, this is all a big puzzle.

And it's true that her2 plays a function in many cells. One of the reasons for fears about herceptin and cardiotoxicity is that cells in the heart have-and need--her2...

Best,
Jeff

Thanks Kristen and Jeff,

Unfortunately I had a miscarriage today. I don't know why I am sharing this with you guys but I feel close to people on this site. The doc. thought there might have been some genetic anomaly even though I am 30. Who really knows what our genes are like but probably we are more likely to have faulty ones if we have bc in the family. Thanks for sharing what you know. XOXO Anne

Dear Anne,
I am so sorry to hear of your loss. It just breaks my heart. I know doctors will say that something is probably wrong and the body will take care of it's self, but it still doesn't erase the dreams and the visions of what the little one would look like or grow up to be. God Bless you Anne and hugs to you. K

Oh Anne.

What a sad day. I have no words to help you but only my wishes that you are surrounded by loving attention and tender care.

with a heavy heart,

Jeff

Dear Anne,
We are truly saddened to hear this. I hope brighter days await you and know we are thinking of you.
Stay Strong,
Al and Linda

[kat in the delta]

Kristen (guest) : Now what was that ??? Can you explain if Her2 is or is not inherited and how one can tell ??? That lingo is a bit much for me at this pt. in time. RSVP & please give the site.
thanks, kat

[tousled1]

My understanding is that HER2 breast cancer is not hereditary. That's not to say that if there is a high incidence of HER2 breast cancer iyour family that you won't get it. I thought that the hormone dependent breast cancer was more hereditary.

[penelope]

Ok this is what I have come to understand through my own research and the help of my sister who is a hematologist. She studies blood but is quite knowledgable in genetics.

Brca 1 and 2 are different. BRCA1 is usually estrogen negative
BRCA 2 is usually estrogen positive. This is not to say "always" but more often then not. It is unual to be BRCA1 or 2 and Her2+ as well. Again, sometimes it happens but rarely.
Her2+ is NOT genetic. I researched this at length with my sister as I am the third generation to have BC. So naturally we were worried when I was first diagnosed. I do not have any studies to cite here but I have read it several times. Now I probably carry a genetic predisposition to BC...clearly I am the third generation, but the her2+ apparently was sparodic.

[Lani]

Since 1 in 9 women are at risk for breast cancer and since BRCA1/2 make up a tiny percentage of those with breast cancer(and usually ER- AND 97% Her2---the latter for brca1 at least), the chance of two or three female relatives with breast cancer in one's family is 1 in 84 and 1 in 831. Since her2 testing has only been done regularly within the last decade and only well in most locations within the last 3 years or so (and that is only if you lived in certain developed countries and near higher powered medical centers--ie, they are still debating in France whether to routinely test new breast cancer specimens for her2 and I am entirely unsure if they are doing it in Denmark), who is to say if your relative had her2+ vs her2- breast cancer if it was diagnosed in the past or in a location unlikely to have good testing.

According to Dr. Slamon, her2 breast cancer tends to recur somewhat earlier than her2- breast cancer(but as we all know this is very variable), but more importantly perhaps for differentiating it from her2 - breast cancer, and has been (before herceptin) associated with death within an average of one year from recurrence (vs death within an average of two years from recurrence for her2- breast cancer ) {recurrence defined as distal metastasis, not lymph node metastasis or in breast recurrence}

That said, I have been researching whether therre is such a thing as her2+ breast cancer--and have found a couple of interesting articles.


Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY 10029, USA.
BACKGROUND: The HER2 gene, located on the long arm of chromosome 17, codes for a protein with the characteristics of a growth factor receptor. In a preliminary study, we reported that high levels of tumor HER2 (erbB-2/neu) protein are associated with a family history of breast cancer (that is, one or more female blood relatives with breast cancer). METHODS: We have now collected a larger number of subjects (94) and performed a multivariate analysis of the independent variables family history of breast cancer, tumor estrogen receptor, age, and tumor DNA index. Family history of breast cancer was assessed by questioning the patient, in many cases by telephone. RESULTS: HER2 levels were significantly higher in women with a family history of breast cancer (p = 0.015, two-tailed t-test). The 27 women with family history were predominantly postmenopausal, mean age 61 +/- 2.3 (mean +/- SEM), versus a mean age of 56

[Lani]

+/- 1.7 for the 67 women with no family history. Of the 27 women with a family history of breast cancer, 13 had a first-degree relative (mother or sister) with the disease. The remaining 14 women had other relatives (grandmothers, aunts, cousins, or a niece) with breast cancer. The results of multiple linear regression analysis, with HER2 as the dependent variable, showed that family history of breast cancer was significantly associated with elevated HER2 levels in the tumors (p = 0.0038), after controlling for the effects of age, tumor estrogen receptor, and DNA index. CONCLUSIONS: The association of family history of breast cancer and elevated tumor HER2 protein suggests that postmenopausal familial breast cancer may be associated with altered HER2 expression.

This is in contrast to BRCA 1/2 breast cancer which is a premenopausal disease on the whole.

Could everyone with one or more relative (mother, daughter, sister, grandmother, aunt, etc) please post how many relatives you have with breast cancer and, as best you know, what age they were (at least what decade they were in, or pre or post menopausal)when they got it, how they are/were related to you, whether they are living or dead, whether they died of the disease (or something else), how they were treated (eg. whether surgery, whether radiation therapy, whether chemo, whether antihormonals, whether oophorectomy--ovary removal--, whether herceptin), if they were her2 tested (and as best as you can find out what the results were and whether by IHC or FISH), and, if they died, how long it was between diagnosis and death (as well as whether they were diagnosed with or without metastases and their staging(TNM) if known. T stands for size of tumor and gets a 4 if they were diagnosed with metastases, N is the number of positive lymph nodes, and M is the number of distal mets. Also if you or they were ER+ and/or PR+

This does not seem to be a sexy area for the medical researchers, but I would guess, is a concern for each and every one of you.

Will try to start a roll-call, as I am certain this board holds a treasure-trove of information which might spark the interest of some researcher to settle this question more definitively.

[tousled1]

Lani,

I have a very strong history of breast cancer on both mother and father's side and ovarian cancer on father's side. Due to my family history, my oncologist suggested genetic testing. I had the genetic testing performed and was really surprised that I tested negative for both BRCA1 and 2. My sister also had breast cancer but she was fortunate that her's was HER2 negative.

[Lani]

Am J Clin Pathol. 2003 Dec;120(6):917-27. Links
Her-2/neu gene amplification in familial vs sporadic breast cancer. Impact on the behavior of the disease.

Espinosa AB, et al
Cancer Research Center, Department of Medicine, General Cytometry Service, University of Salamanca, Salamanca, Spain.
We compared the incidence of Her-2/neu amplification in patients with and without a family history of breast cancer and correlated gene status with clinicobiologic and prognostic features in sporadic and familial cases. Of 108 patients, 28.7% had gene amplification. Among 96 cases with family history information available, 28 had an affected first-degree relative. The gene was amplified more frequently in familial than in sporadic cases (13/28 [46%] vs 14/68 [21%]; P = .01). Among familial cases, amplification was associated with adverse clinicobiologic features (poorly differentiated tumors [P = .05], larger tumors [P = .05], more lymph nodes involved [P = .04], and DNA aneuploid [P = .02] and highly proliferative tumors [P = .005]), and the relapse (P = .02) and disease-related death (P = .05) rates were higher than in cases without amplification. Among sporadic cases, amplification was not associated with significantly different disease features, except for a higher incidence of DNA aneuploid tumors (P = .01), percentage of S-phase tumor cells (P = .006), and lower proportion of estrogen (P = .001) and progesterone (P = .002) receptors. Her-2/neu amplification was observed more frequently among patients with a family history of breast cancer, in whom it was associated with adverse clinicobiologic features and a worse clinical outcome.
^^^^^^^^^
They discussed that those with sporadic (non-familial) breast cancer had a much better prognosis than those with familial (defined just as having a relative with breast cancer, since going back and testing those specimens seems to be impossible)

[Jean]

No history of breast cancer in my family I am the first.
My mother had seven sisters none of whom had breast cancer or cancer of any kind.
My mother and her sisters all lived into their 80's.
My mother died of lung cancer (she was a heavy smoker) at age 84.
All her sisters died of old age.

I have two sisters who are older than me and so far (thank God) are
healthy.

On my father's side of the family there is only one sister who is 93 yrs.
old she smokes,drinks, and lives a full life. No cancer of any kind.

My Great Grandmother lived until 102 and died of old age.
My Grandmother lived until 98 yr. old and ran her home until the day she died.
My Father's mother died during the Spannish Flu.

So, my family history was solid and boy was I surprised to be told
I had bc.

Jean

[tousled1]

WOW Jean. You really have a line of longevity in your genes.

[Jean]

But what happened to me? My sisters were shocked when I told them
I had bc. I have always been careful about what I eat etc. No red meat
etc. etc. for years. As a matter of fact my Aunt makes fun of me.
God bless her she is a real devil at 93....Kate I am hoping that my good
genes will help me fight back....and hopefully give this dam monster a run for it's money....

Jean

[AlaskaAngel]

I too am interested in this. Too bad HER testing is so recent and not entirely reliable early on. If it is hereditary there will still be those whose bc behaves differently if they are not only HER2 but with other HERs -- which complicates simple comparisons. I wish they would start testing routinely for more than HER2. I talked with my surgeon last week and he said that at present they are still basically only testing at time of diagnosis for HER2 and ER and PR.

How many relatives with bc? mother, sister, aunt, grandmother, first cousin.

Ages, living or dead, and how many died of bc? Unknown other than that my sister and I were diagnosed in our 50's. Only 1 person of those I have listed died of bc, and that was from mets to the brain. My sister and I and my first cousin are still alive more than 4 years from diagnosis and none of us have had recurrence to date. Incidentally another aunt died of ovarian cancer but to my knowledge did not have bc.

Treatment and testing? I had lumpectomy, SNB, CAF, rads, and hormonal treatment. My sister had lumpectomy and rads and it is unknown if she did hormonal treatment or if she was HER2 positive. My mother had lumpectomy but no rads or other treatment. My grandmother had a unilateral mastectomy and the rest is unknown for her except that she basically died of CHF years later. I do not know what my first cousin has had for treatment or if she is HER2 positive. My testing was IHC+++, T1M0N0 (T1c).

A.A.

[Chelee]

I have NO history of any bc in family on Mothers or Fathers side. (I thought my cancer was from excessive exposure to x-rays from childhood to about age 18) But who really knows?

My Mother had three sisters and one died around 55 yrs old due to complications to other health issues...none related to cancer. But her other two sisters and still alive & doing well. Both sisters are in their 80's & living full lives doing well. My Mother WAS just DX with stage IV lung cancer at age 76...but a heavy smoker for 40 + years. She had two brothers which both have passed but not related to cancer.

So I am the first one DX with cancer, let alone her2. I have cousins my age and older and not a one of them have had cancer of any type. So when I was DX...it blew me out of the water.

Chelee