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

[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

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

[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

[Lani]

I think MD Anderson looks at EGFR in its BRCA+ patients as they seem to often be triple negative and have an increased incidence of EGFR positivity...Also it gives them a possible targetted drug to treat with.

As neither Iressa, Tarceva and Erbitux is officially approved for breast cancer I think they feel testing would not be "clinically relevant" But if you don't test, you don't find out and you don't make progress against the disease.

My two cents.

[MJo]

On my mother's side I had five great aunts who got breast cancer in their 40s --two of my grandfather's sisters and three of my grandmother's sisters. Then it skipped a generation -- nobody from my mother's generation got breast cancer. I'm the only one that I know of with BC from my generation so far. Go figure.

[Jackie]

I have an aunt on my father's side that died of breast cancer about 15 years ago. She was in 50's.My father died of melanoma 27 yrs. ago. He was 48. There is no bc on my mother's side. In fact my grandmother is the only one who had any cancer. It was a very slow growing cancer in her gums. She was in her 90's when this was dx. She didn't die from it, just old age.


I had always been told to look at your mother's side of the family. I was greatly surprised by my dx. I did not have any factors that are listed as risk factors in bc.

[rinaina]

No history of breast cancer or any cancer on either side of my family. I am the only one who has had breast cancer. My mother died of complications from diabetes and congestive heart disease at the age of 74. Her mother, my grandmother lived until she was 87 when she died of a heart attack but she was healthy until then. My dad is 80 and has diabetes that is well under control. His mother lived until she was 86 and also had diabetes. I always was worried about getting diabetes given the strong adult onset history in my family. Never thought about the possibility of getting cancer with no family history yet here I am at the age of 55, relatively healthy except for this years diagnosis of Her2+ breast cancer.

[Kimberly Lewis]

My paternal Aunt informed me after I was diagnosed that my grandmother, great grandmother, and great grandmother's sister all died of breast cancer very young. My grandmother was only 34. I don't know what that means if anything - no other cases reported in my family that I am aware of. I tried to get the genetic couseling but BCBS didn't cover it and I didn't have the $1000. to spend!

[kristen]

Since that post my sister has been dx with BC. She I believe will be er+. She is having her double mast in about a week.
My family history is 13 girl cousins and 4 have/had BC. I am the only one who has been Her2. 2 of us had it at age 41 where the other 2 had it at 53 and 62.
On my paternal side, my cousin (er+) also had BC at 41 and her and I have both been tested and are neg for BRAC's.
My Aunt the mother of the other 2 cousins had ovarian cancer at age 51 and an great aunt who had a mast. sometime in her life, we found out when she passed away at age 90+, back then they didn't talk about it. So if there is any other BC in our family, we don't know about it.
Cancer runs high in our family, 2 uncles have had prostate,1 bone and we have had other frightening diseases in our family: Ataxia is supposed to be very limited and yet 3 of my second cousins have it from 2 different sets of parents, go figure? Genetics is a wide open field and one I find hard at times to follow when you see the toll it takes on your family but finding all the links and so forth are way out of my league.
Kat, sorry I didn't see this post earlier, but i think you got your answer, as of right now, her2 is not hereditary from what they say, but reading all these and looking at my own family history, I gotta think they are missing something or it really does have something to do with envirtomental issues?

[BethSh]

I am 46 years and dx in August of 2006, Her2 pos, IDC with pos lymph nodes, Stage IIA. I am post menapausal. I finished 4 A/C and am currently taking Taxol and Hercepton for 12 weeks.

I tested negative for the BRAC1 and 2 genes.

I have a deep family history going back 3 generations. I am the 4th generation, (at least as far back as I know)

My mother was dx at the age of 36 in 1972. She had a recurrence in her 4th year and passed away 7 years later at 47. Her uncle, was dx with breast cancer at a old age and pass away from it and his mother, my great-grandmother also had breast cancer at a young age, yet lived to be 80 and died from another cause.

Needless to say, I have been wondering about my mother's illnesss, I was young at the time and don't know much. It been over 22 years and my father doesn't recall much. I've thought about inquiring about her records, but don't know what that would solve even if they have them.

I am mindful that my mother lived 11 years, it was not easy, yet I have hope that if our cancers are the same or similiar that with all the new meds, I can beat this or at best enjoy a long life.