her2 resistance Lani's Post two cents worth
 

Lani,
you posted on 3/15/06 "my two cents worth--give your oncologoist the following abstract"

You mention that at the San Antonio Breast Cancer Conference, the feeling was that all her2 positive invasive breast cancer should be treated with herceptin.
Dr. Slamon suggested that to decrease cardiotoxicity the tumor's level of topo 11 should be tested.

As mentioned size used to be considered one of the most important prognosticators. I have been having an on going battle with this.
My onc. have advised me that the size of my tumor (mine was 6MM prior to biopsy) was 3MM when lumpectomy was performed. Was small and my grade
which was 1 - was favorable and my cancer could almost be considered
a microinvasion. This did not seem to matter much to me. Micro or otherwise. I have fought with this since day one that my her2neu status
was most important. I am also er positive and I am now taking Arimidex.

My oncs advised against having the Oncotype DX test done - their point
being even if it came back high they would not advise chemo/or/herceptin.
I hope I am understanding your post correctly in that Dr. Slamon's suggestion
is not exclusive for women who have developed metastases. For instance
early stage bc patients - stage 1 - node negative - would the feeling
still apply to have treatment with herceptin?

Were there any discussions regarding treatment of Her2 positive women
to be treated with herceptin without chemo?

The statistics you obtained by Dr. Slamon regarding her2 positive tumors
which receive no systemic treatment are more than twice as likely to recur.
When you mention systemic treatment would Arimidex be considered a
systemic treatment? or is that just chemo/with hercpetin? You mention that no one knows the best way to treat hormone receptor positive her2nue + early breast cancer, (that is me) and I have been rather frantic trying to get the best treatment.
I live just outside New York City and have seen four top onc.
All of which say the same thing. No chemo/No herceptin/ Tumor size
was an important factor in their decision even though I kept insisting
that the her2 positive status was the greater concern. They all agreed
that Arimidex should be taken due to the er positive status,
had lumpectomy followed by radiation. Do you think I could contact Dr. Slamon for an opinon regarding my profile? I would be interested in a specialized institution who will review my case. Can you give me any advise?

Many thanks,
Jean

Wow, that's a lot of questions!
 

It's my birthday and I have houseguests, so I will try to answer all your questions an other day, but just to start...

I have heard of patients (some on this website) who had only her2 +DCIS with microinvasion who recurred as Stage IV. So there is no tumor so small it can be said with certainty that it needs no treatment.

What was your Ki67(sign of how quickly it is proliferating)? If it was low and your Grade was low (old fashioned microscopic appearance based way of telling how specialized vs. proliferative the cells were) those are both signs of a less aggressive tumor.

Targeted Molecular Diagnostics does tests (which Robin P says cost $190 a piece which may help)--also MD Anderson although it won't see patients for second opinions will do pathologic second opinions on your slides.

Dr Slamon said at San Antonio that he felt OncoDx was a waste of money--that it didn't tell you more than a well performed ER, PR, her2 by FISH and Ki67.

If you have the funds and your Ki 67 was high , you might consider the following tests from TMD (learned about them from RobinP):

PTEN--to see if herceptin was even likely to work in you (Rhonda H today listed a clinical trial out of MD Anderson giving combined therapy as a way to make Herceptin more likely to work in those with low PTEN.

pAKT--reportedly predicts whether tumor likely to be antihormonal resistant
(just one paper, not a "slam-dunk")

topo IIa--predicts whether anthracycline would even help (if negative any possible benefit of anthracycline(little or none) less than cardiac risk with herceptin (and probably without)

cox2--to see if something as simple as taking Aleve or Celebrex is likely to help

(other tests like EGFR, IGFR1 not necessary until lapatinib is approved--even if they are positive the drugs to inhibit them Tarceva, Iressa, lapatinib, etc are not approved for adjuvant use in breast cancer)

There are many other things you can do without a prescription from Vitamin D combined with Aleve, flaxseed oil/olive oil/walnuts (I am not the expert), tumeric. The preclinical evidence for these helping is for her2 breast cancer for the second, but not specifically for her2 breast cancer for the first and third.



From what I understand Dr Slamon was not seeing patients in 2005. I believe I read a post from someone who saw Dr. Slamon this year, so that may have changed. His secretary usually referred patients to his colleague Mark Pegram.

The good news--

your tumor was small so hopefully found early so hopefully less likely to have spread

your tumor was grade I so cells not "multiplying like crazy"

your tumor ER+ (you didn't say how much)--Dr. Pegram has published papers regarding the fact that her2+tumors have quantitatively less ER and PR even when their percentages are not that low. Targeted Molecular Diagnostics has a more quantitative way of measuring ER and PR but there is as yet no difference in the way you would be treated clinically based on it

ER+/PR+ tumors are GENERALLY less responsive to chemotherapy, but again the her2+hormonally+ tumors are a group that noone has described yet as an entity ie, they have grouped breast cancer into four types based on multigene arrays 1)triple negative 2)her2+ which are supposedly ER-
3)/4) two groups of ER+ tumors one of which has a better prognosis than the other, but both of which have a better prognosis than 1) and 2)

Most interviews I have read in the past four months state that herceptin is appropriate treatment for all invasive her2+ breast cancer, but if you listen to the audio recording of Dr. Slamon on Breast cancer update, he is not sure than the cardiac risk is worth it for those with a low grade, small tumor without lymphnode metastasis. I believe he is stating this based on the fact that Herceptin is always given with chemo in the adjuvant setting and all chemo (not just anthracyclines) can have some cardiotoxic effects.

He stated that there would have to be some comorbidity (eg 85 year old patient with preexisting heart failure etc) for him to ever consider giving Herceptin without chemo



The knowledge is evolving. There is so much that is not known.

You fail to list your lymph node status, but as you considered OncoDX I assume it was negative. That is also another GOOD SIGN to add to your others!

If you cannot be at peace with the answers you have received so far,perhaps you want to check how Er and PR positive you were on your pathology report, check your Ki67. You will have to decide if you want to spend $600-$800 to find out if herceptin would even be likely to work for you and if anthracyclines would be/would have been necessary or effective, and if something as simple as Aleve might be beneficial.

I will keep an eye out for opinions in the medical literature, conference summaries etc regarding T1aNOMO her2+ breast cancer The problem is that is almost always for ER- cases. One year ago, almost all the literature said only 10% of her2neu cases were ER+, now they say it is more like 45%!! As I said, knowledge is evolving.

Please do read my post regarding the oncologist with breast cancer. I bet she would be understanding of your concerns(not practical as she practices in California) Sometimes oncologists in private practice are less pressured to practice "evidence based medicine"ie, they won't do something unless there has been a clinical trial proving it , than those at academic institutions.


Just thoughts (more than I thought I would have time for!!!)

HAPPY BIRTHDAY!!!.

Your posts are so impressive, clear comprehenisble and informative, obviously the result of considerable reading and reseach, and freely given. 10/10.

The omega three six balance has been shown to impact on HER2.

In wider BC high levels of DHA EPA in breast tissue equated to a 70% risk reduction of lumps being invasive of the top third over the bottom third of subjects which is potentially very impressive.

Why more trials are not done save the obvious human dynamics - not sexy - no real profit - no new drugs discovery glory - unlikley to get a drugs company excited hence no work etc. - potentially helping the health of many millions some how does not seem to get put on the scales, is the question - and the answer is they will not in all likelyhood get done until the subject gets in the concsious of those in Governments funding the health budget - dealing with the social pressures of anger at treatment injustices due to cost pressures - dealing with the economic cost of illness etc.

Keep up your exellent posts.

10/10

RB

MANY answers to many questions
 

Lani,
A big HAPPY BIRTHDAY to you.
Thank you for your speedy response when you are so very busy.
I appreciate your reply so very much.

My Proliferation Index was 40% (I would call this high) would you?
Estrogen Receptor was >90% (also high)
More than 20% tumor cells were actively cycling (in the G1, S, G2 and M phases of the cell cycle),this tumor is considered to have a high index.
Yes, I was node negative.

I am taking Vit. D along with additional vit. I am already taking Aleve
(mostly for the joint pain relief from the Arimidex). Of course I have
enhanced my diet with fish oil, Omega 3 (thanks RB)..olive oil, walnuts,
and organic products as much as possible.

My oncs have said what Dr. Slamon says regarding the cardiac risk is not worth it (since my tumor was small and low grade) but I cannot help but feel so very concerned that all Her2nue cancers are extremely dangerous and fall into a special catagory. My dr. is not and states he would not
consider givering chemo / or / herceptin to me.

Yes Lani, there is a great deal to be learned - I pray it is sooner rather than later. I am now not sure if I made the correct decision regarding Oncotype
test - (once again my onc did not feel that test was worth it) I thought
it would give me some peace of mind if the results were low (my onc thought with my tumor it would be).

Read your post regarding the oncologist with bc. (excellent post).

Lani am I understanding your post correctly when you mentioned that
those who are her2+ have a much higher rate of recurrence (okay understood that) and they are relatively chemo-and hornomal -therapy resistant.
Would you expand on that - I have not heard anything regarding the
her2+ positive being resistant - ex. Arimidex, please explain what that means?

Lani thanks so much again!
Jean

Re omega three six.

From your post diet is part of your strategy. Whilst omega three is widely recognised as benificail at all sorts of levels, it is also important to balance omega three and six intake.

This is still hotly debated territory, but omega six whilst essential is a percusor of many of the inflamatory pathways, and hence it is argued the need to restrict and balance six with threes.

See the posts on this site on omega three , six flaxseed etc.

This can take a little effort to find out how much omega six and three is in various food in general terms. Eg virgin cold pressed olive oil is about 10% omega six, walnuts a lot higher etc, so as a general rule you have to watch how much you take in and add flax etc if you are going to balance the omega threes and sixes.

As usual it is complex and potentially particularly for those on medication. Looking up the NCBI library and using the search engine can be helpful for seeing if any trials of omega three and various medications have been done. It is always best to discuss magor dietary changes with your advisors.

RB

Lani Happy birthday to you! Just want to thank you for such an interesting and informative reply to this post, AND thats when you're in a hurry:)
I also am triple positive and still trying to find and understand as much as I can about this. Thank you again.
Tricia

Lani's Two Cents - Early Stage, No Lymph Nodes
 

I had a 1/2 centimeter tumor, neg. nodes, estrogen/progesterone pos. and Her2++. Diagnosed in late October. Had lumpendectomy in early November. The radiologist had me all set up for radiation, but the oncologist intervened.

I had an Oncotype test and my score was 31. I had a 21% chance of recurrence in 10 years. That was too high for me. I am fighting with my insurance company to pay for Oncotype, otherwise I'm out $3000+. I read a message on the internet in which a Her2++ woman wrote that the oncologist told her not to waste $$ on Oncotype, because Her2 patients will never come in low risk.. I am glad I got the Oncotype, since I was unaware of cheaper tests.

I decided to treat the cancer aggressively, because I was very worried about Her2. I took 3 A/Cs (got too sick to take the 4th). I have had two taxols and three Herceptins. My body tolerates taxol and herceptin better better. I am back at work part-time. Have 2 more taxols to go and will take Herceptin every 3 weeks for 10 months. Will also get radiation for 6 weeks and will probably take arimidex.

So you see, I had a tiny tumor with no lymph node involvement, but I'm treating this aggressively. I'm being treated at Helen Graham Cancer Center in Delaware. My oncologist is known for treating cancer aggressively. I got a second opinion from another oncologist who has been in business 30 years. He agreed with my oncologist about agressive treatment. My surgeon told me he didn't think I would need chemo. Three months later, when I went back for my checkup, he told me he thought I was doing the right thing by treating this aggressively.

I think we are in a time of change. I think nobody is sure what to do with us small tumor, node neg Her2 patients. The oncology nurses told me they thought I was doing the right thing. They said they see women who didn't get chemo come back in five years with mestastic cancer (sorry for spelling). Of course, the nurses see the ones who come back. They don't see those of us who remain cancer free. Still, I am not taking chances.

For someone like me, the the topoII test would have been most useful. I got very sick from A/C -- anemia, respiratory infection, etc. The TopoII test might have spared me the A/C if I didn't have the HER2 that responds to this chemo. On the other hand, you never know how you will respond to chemo until you take it. A/C for me was very difficult. My boss, who also has Her2++ breast cancer, sailed through it and kept Now, she has severe muscle pain from Taxol, and I feel almost normal.

Best of luck to you. It is hard to decide how much risk to take when you are Stage 1. I think to myself that there is an 80% chance that I have no cancer cells in me, yet I'm putting these drugs in my body. However, there's no way of knowing that I don't have cancer cells in me. Do I want to take the risk? For me, the answer is no. Still, when does the risk from the drugs become more dangerous than the risk of recurrence? I don't think doctors can answer that yet. We are the bridge generation. Future patients won't have to go through this. Keep the faith, Mary Jo

Value
 

Stage 1, triple positive... I almost missed this discussion entirely... it is worth a LOT more than 2 cents to me, Lani....

AlaskaAngel