HER2 3+

Hi Nicole - You've just received some really scary news and you're terrified - understandable! I was also terrified 3 1/2 years ago when I found out that I was Her2+. Now - take a deep breath. There are many, many Her2+ women here who are going to help you get through this.

Let me give you a quote from an oncologist regarding Her2+ breast cancer that I read in CURE magazine (I'm paraphrasing): 20 years ago we didn't test for this. 10 years ago it was a negative prognosis. Today, I'm actually happy to see my patients test positive because of all the new treatment options.

The good news: your tumor is relatively small and you're a grade 2 (not 3 - the most mutated cells). Your next surgery will give you more info - how many nodes are involved and if all of the cancer is gone. Then you'll form a treatment plan with your oncologist. I did 6 cycles of chemo - taxol/carboplatin/herceptin, then did herceptin every 3 weeks for a year.

New treatments for Her2+ are being tested right now - I participated in a clinical trial for a new drug called Neratinib. And if you're ER/PR +, you'll have even more options.

It's all "doable" - you're at the worst stage of all of this right now. You have enough info to scare yourself silly but no real treatment plan yet. And having to wait two weeks doesn't help. I went from January to April before starting chemo due to needing more surgery than originally planned.

Please feel free to come here any time - there are no stupid questions! You now have a group of Her2+ sisters who are going to be holding your hand all of the way.

Wishing you peace - Sue

Dear Nicole,

I am so sorry that you are having to deal with this news.  Both Sue and Wendyspet are absolutely right - this is the most difficult part because you don't have a lot of information yet.  

By no means is this the "worst" cancer.  You have two attributes that open up treatment options for you.  Because your cancer has estrogen receptors (ER+), you will likely take Tamoxifen for several years followed by an aromatase inhibitor.  The Tamox is in pill form and while not entirely without side effects, it is not a chemotherapy in the traditional sense.  It will render the estrogen in your body unable to "feed" your cancer, which for many, many women is all they need to deprive any remaining cancer cells from causing a recurrence.  This is a great treatment option for you that gives you added benefit towards keeping a recurrence from happening.

Also, you are Her2+, which as Sue said, opens up receiving Herceptin.  Herceptin is given either weekly or every 3 weeks by IV.  Some folks have some bone creakiness, but others (such as me) have no side effects at all.  Herceptin binds with Her2 receptors on any remaining cancer cells rendering them unable to multiply - and targeting them for your immune system to attack them.  You will be on this for a year.

Ask your oncologist about clinical trials.  There is one during Herceptin treatment that utilizes Herceptin, Lapatinib (the next generation Herceptin), or both.  Following Herceptin treatment, there is a Neratinib trial, which is the 3rd generation Herceptin.  It is an oral drug that you can take for a year that targets both Her2 receptors and Her1 and Her4 receptors.  Most of the progress that is being made with vaccine clinical trials are for women with Her2+ breast cancer.  There are multiple clinical trials going on with vaccines.  Look on the National Institutes of Health site to narrow down the clinical trials that are in place for women with your type of cancer (node positive, ER positive, HER2 positive).  You will be amazed and this is the time to become informed about these trials - not after you have already started treatment.

And in the end, there is no substitute for doing your own research.  I have a great oncologist, but even he was not aware of the Neratinib trial - I had to bring it to his attention.  So don't be afraid to research topics, take them to your oncologist and insist.  If he/she doesn't like it, change oncologists.

Unfortunately, you are likely to require chemotherapy.  That scared the bejeebers out of me - my worst nightmare - but I actually handled it rather well and it was not nearly as bad as I imagined it to be.  Your onc will give you TONS of medication to address every possible side effect and that will keep you comfortable.  

Lastly, please think twice before moving forward with further lymph node surgery.  If you must have surgery to get better margins on your tumor, then of course, you need to do that.  But if you having additional surgery solely because you had positive nodes - and you are having more nodes removed - please check the latest research on this and other websites that has determined that removing all the lymph nodes when fewer than 3 are positive does not give you a better prognosis when you are going to have chemotherapy.  In fact the research shows a very slight advantage to survival rates when the nodes are left in.  These are recent findings - within the last six months or so - and many surgeons are still taking out all those nodes - I had 25 taken out.  You run the risk of developing lymphedema when you get multiple nodes removed and you may not have to go through that based on the new research, so just look into it.

I wish you the very best, Nicole.  You have a much better prognosis than you are thinking right now and while none of us can predict the future, you really are fortunate to have many treatment options ahead for you.  Once you get over the initial shock of the misfortune of having cancer (which all of us goes through and it is a tough one, I agree!), you will feel somewhat better that you have these options - I promise.  God bless.  Kelly

Hi all. Nicole, I am sorry you have had to wait and worry. It's one of the worst things. I hope you have good support and can sleep. I wish you well.

I also have a question -- what does the 3+ part of HER2 3+ mean? In April, I had a lump removed, Then I had four rounds of chemo, I finished almost two weeks ago. I will start rad in August, but I am having trouble getting my head around the Herceptin. I am estrogen responsive 99%, Progesterone (SP???)  not responsive 0% and HER2-neu 2.7 -- does anyone know what the 2.7 means and what the implications are of PR 0 and Estrogen 99?

I am having trouble thinking about blood work and the chemo chair every three weeks for the next year (not to mention the possible long and short term side effects and heart ultra sounds) I have to have a really good reason to do Herceptin and so far I can't convince myself it will be worth it.

Those of you on tykerb...did your Oncologist request a (MUGA) heart function test prior to taking it? 

Diagnosed 7 years ago..mast. w reconstruction.  Stable with arimidex for five years then recurred in bones.  Stable on faslodex for 18 months now in spine and adrenal gland (rare).  Going on tykerb and xometa.

going to be 76 hope to make it to at least 80! !  Old in age but young at heart... 

Introduction Surpassing heart disease in 2004, cancer is now the leading killer in the United States. According to the American Cancer Society, more than 1,500 people die each day from cancer and over 16 million people have been diagnosed with cancer since 1990.

In recent years, medical science has taken great strides in understanding and treating cancer.  However, prior to 1997, the majority of treatments such as chemotherapy and radiation, were not based on the underlying biology of cancer growth.  These treatments are also often associated with serious side effects.

Since the discovery of the HER2 gene, researchers from around the world have elucidated that HER2 is a main component of a complex signaling pathway that includes numerous family members, many of which are also involved in the formation of cancer and other diseases.

Cancer Growth and the Genesis of Cancer Cancer begins when the DNA of a normal cell changes, or "mutates", making normal cells grow uncontrollably.

There are two types of mutations:

• Somatic mutations, which are caused by environmental factors such as sunlight or carcinogens; and
• Hereditary cancers, which are harmful mutations passed down from one generation to another.

Each type of mutation eventually "expresses" itself by producing chemical signals within the cell that tell the cell to grow.  The cell then enlarges, divides and reproduces itself, creating two new identical copies of the original.  In normal cells, growth occurs at a steady, regulated rate.  In cancer cells, growth is unregulated and continues as long as the tumor obtains the requisite nourishment it needs from the surrounding environment.

Communication by Signal Transduction Signal transduction is a means by which one cell communicates to another.  The "conversation" between two cells involves a molecular messenger (called a ligand) from the sender and a site (called a receptor) on the membrane surface of the cell receiving the signal.   When the signal is received, it is passed along within the cell in the same way a bucket of water might be passed along a bucket brigade.  In this way, the message is communicated from the outer surface of the cell into the cell's nucleus.  Messages can be healthy or harmful.  For example, some messages might be signals telling the cell to grow (which can lead to cancer) or a growth signal might be used by the immune system to increase the amount of white blood cells needed to fight and infection.  In other cases, signals may cause cells to store materials such as fatty acids, which is healthy in moderation but when uncontrolled, may lead to obesity.  This process is referred to as signal transduction.

Some of the more common signaling pathways involve proteins called receptor tyrosine kinases, which have three components:  

• An extracellular ligand-binding domain receptor that is located outside the cell and receives incoming signals;
• A transmembrane domain that crosses the cell membrane and conveys information from the outside to the inside; and
• An intracellular tyrosine kinase domain that adds a phosphate molecule to tyrosine, a type of protein. This process initiates an internal messaging cascade and is referred to as "phosphorylation."

Introduction to the HER Pathway In oncology, one of the most important tyrosine kinase signaling networks is a group of receptors belonging to the "HER" family, also known as the ErbB signaling network.  The ErbB receptors are named after the Avian erythroblastosis tumor virus, which encodes an aberrant form of the human epidermal growth factor receptor (from which "HER" originates).

The HER family of receptors consists of four main members commonly referred to as HER1/EGFR, HER2, HER3 and HER4.  Each of these receptors is in some way culpable in the development of malignant tumors, although some are more involved than others.  There is a considerable amount of "cross-talk" between the receptors, meaning that activation or inhibition of one can have collateral effects on the others.

Understanding the biological role of the HER family has led to the discovery of other important signaling systems, such as receptors that are distinct from the HER family but have the ability to "quiet" HER-generated tumor-stimulating signals.

One of many important discoveries resulting in an exploration of the HER-based signaling pathways includes the PTEN gene, which appears to be abnormal in as many as 50-60 percent of advanced prostate cancers. PTEN is thought to be a tumor-suppressor gene, and works in complete opposition to the HER genes although it uses the same signaling pathways.  Unlike kinases, which make cells grow, the PTEN gene produces an enzyme called a phosphatase, which halts cell growth.  The PTEN phosphatase regulates growth in a common signal transduction pathway activated by receptor tyrosine kinases.

Identifying the Source of Dysfunction In all cells, some level of growth-signal transduction is normal and is part of the regular growth cycle.  It is the overexpression, or activation, of these signals - or the failure to counterbalance or block those signals - that leads to uncontrollable growth.  In the case of the HER2, for example, overexpression is the result of a genetic alteration that generates multiple copies of a gene that encodes a growth receptor.  Because of the surplus of growth receptor genes in the cell, excessive numbers of growth receptors are created that, when activated, enlarge the number growth signals stimulating the cell, accelerating cell division and tumor growth.

Key Players in the HER Pathway The four members of the HER family are called HER1, HER2, HER3 and HER4.  Each is implicated in the development of cancer although the degree of involvement varies.

A Closer Look at the HER Pathway Players An physical feature of the HER pathway is that the signaling system always involves two receptors in combination, in a formation called a "dimer." Homodimers are combinations of two similar receptor types, such as HER1/HER1 and HER3/HER3.  Heterodimers contain two different receptors, such as HER1/HER2; HER1/HER3; and HER4/HER3.  The various hetero- and homo-dimer pairs affect the signal strength within the cell.  For example, the co-expression of certain pairs (such as HER3/HER2) is more powerful than others such as the HER3/HER- homodimer, which is inactive.  Research is underway to better understand why certain pairings have different effects and how those effects manifest themselves.

HER1/EGFR:  Another abbreviation for the human epidermal growth factor receptor is EGFR, a name that is often used due to the observation of clinical benefits associated with its inhibition.

HER1 overexpression enhances tumor cell motility, adhesion and metastatic potential while normal HER1 signaling disrupts cell cycle control (leading to proliferation) and apoptosis (programmed cell death).

HER2:  Perhaps the best-known member of the HER family, overexpression of the HER2 gene is correlated positively with an especially aggressive form of breast cancer that occurs in approximately 25 percent of all breast tumors.  HER2 also is overexpressed in a variety of other solid tumors and may interact with certain steroid hormone networks, suggesting that it could affect patient response to anti-estrogen therapies.

HER3:  Expression of HER-3, when activated in a conjunction with HER-2, is linked to increased tumor aggressiveness.

HER4:  Some studies have shown a lower expression of HER-4 in breast and prostate tumors relative to normal tissue.

Future of Cancer Therapy and the HER Pathway Having established the HER pathway's role in a variety of solid tumors,  molecular-targeted therapies are a valid and rationale approach to cancer treatment.  Scientists are now utilizing the underlying biological mechanisms involved in cancer growth and metastases to develop clinical strategies to treat patients with cancer.  While researchers continue to study the biological inner-workings of the HER pathway and other pathways involved in cancer, Genentech clinicians and collaborators are using the acquired knowledge to identify new and innovative ways to treat cancer patients.

Since certain receptors in the pathway work together to produce malignancy, one of the clinical strategies being explored today involves the possibility of combining several targeted HER molecules as well as other targeted therapies into a single treatment regimen - based on the biology of disease - that potentially have a synergistic or additive effect on the tumor and could on day lead to cancer becoming a more chronic disease.

This article answered a few of my her2 questions

What is HER2?:

http://breastcancer.about.com/od/diagnosis/p/her2_diagnosis.htm

HER2 is a gene that sends control signals to your cells, telling them to grow, divide, and make repairs. A healthy breast cell has 2 copies of the HER2 gene. Some kinds of breast cancer get started when a breast cell has more than 2 copies of that gene, and those copies start over-producing the HER2 protein. As a result, the affected cells grow and divide much too quickly.

Since HER2 is a gene, is it inherited?: This genetic problem is not inherited from your parents. The most likely cause of this problem is aging, and wear and tear on the body. It is not yet known if environmental factors (pollution, smoke, fumes) are part of the cause of this problem. Positive vs. Negative Test Results: If your breast cancer is tested for HER2 status, the results will be graded as positive or negative. If your results are graded as HER2 positive, that means that your HER2 genes are over-producing the HER2 protein, and that those cells are growing rapidly and creating the cancer. If your results are graded HER2 negative, then the HER2 protein is not causing the cancer.

It seems to me that if herceptin shrinks and destroys the her2 cancer cells then why chemo?

When breast cancer cells overexpress HER2 proteins, they also will increase their production of another type of protein known as a chemokine receptor. The type of chemokine receptor produced by breast cancer cells is called CXCR4, and it is naturally drawn like a biochemical magnet to another type of chemokine receptor that is produced as a matter of routine by the lungs, liver, and the bones. This fatal attraction is why HER2 breast cancer spreads to these other parts of the body so readily - and when breast cancer metastasizes in this way, the consequences are usually dire.

http://www.breastcancerinformationhelp.com/HER2-positive-breast-cancers.html

http://www.youtube.com/watch?v=48VSU4AZ-L0

http://www.youtube.com/watch?v=Gc67CCGShZ8&feature=related

http://www.youtube.com/watch?v=wQED8SJ4BiA&feature=related

simply explains in anamation

All this information is good for newbies with her2+ like myself

After reading all this, and some of your comments, I've decided I'm doing hercepin...

I have not had my f/u appointment post BMX so I may be asking this question prematurely......what does HER2 positive (3+) mean in the case of DCIS??? My MD's nurse called to inform me that my lymph nodes were negative and that there was no invasive cancer, just DCIS like we discovered during the original biopsy. So I asked for a Copt of my path report. When I received it I saw that I am ER positive, PR negative and HER2 positive 3+. I am only familiar with HER2 and invasive cancer. Anyone have experience with HER2 and DCIS???

Eve - not all invasive cancers are HER2+ve - I've had 2 only 1 was HER2. HER2 is not a gene you have like BRCA1 or 2, it is a gene the cancer expresses.

Eve - the invasive component they talk about is when the DCIS has managed to escape the duct even if it is a micro invasion, so when your surgeon said that he meant you were lucky it hadn't escaped. It's very possible your DCIS was not HER2 and it is also possible it was - you'll never know now. It's very possible (as in my case) to have totally different cancers, so it's also possible you did too. Don't beat yourself up for not having an MX last time. I've not gone down that path yet and I may regret it in the future, but at the moment, I don't regret it at all. I hope you make the right decision regarding your treatment - I did see you've decided on hercpetin - good.

(((((((((((((HUGS))))))))))))))))

Sue

Eve - I know you are not keen on having chemo and if you can find someone who will give you herceptin only, great - but please consider chemo - herceptin has been proven to work better in conjunction with chemo. I did a lot of research into it before I had it, and I trust my onc SO much (I have known him for 8 years - he is my DH's onc as well), I didn't hesitate to go with his recommendations.

Sue

ME EITHER!! WOW!!

30% recurrence is about right.  According to 5 year results of BCIRG 006 study (at 5 years, most people that will have recurrences, will have done so by then), women with 4 or more positive nodes had about a 61% disease free survival rate without herceptin (chemo and hormonals only) and a 73% disease free survival rate with chemo, hormonals and herceptin.

 Google BCIRG 006 and look for the PDF - has complete study results.