HER-2 Positve BC Doubles Risk of Brain Metastases

[RhondaH]

http://www.docguide.com/news/content...2570D50070D507

Rhonda Hoffman

That scares the SH*T out of me. Since I'm her2neu ++ and er and pr ++

Just another fun thing to look forward too

[Joan]

Her2 twice as likely to get brain mets Yikes!!!!That is very scary information - we Her2 gals seem cursed - guess we all have to be vigilant, watching for symptoms and at the same time enjoy every blessed day.

Joan

[Maryanne]

Would any one know what those symptoms would be?

Maryanne

[TriciaK]

Wow, this is scary! We need to take seriously all the advice we've received on this site about checking for brain mets. Does anyone know what symptoms to watch for? Or how often we should have MRI's or PET's or whatever? What does show brain mets best, by the way? This is one time we need to all nag and cajole each other to be vigilant! Hugs, Tricia

[StephN]

Under INDEX on the HOME page you will find a list of items.

Click on METASTATIC BRAIN TUMOR and you will get a whole host of links to all kinds of articles and sites dealing with brain mets.

As for symptoms, there is a long list and what they are may be caused by different areas of the brain affected.

Numbness in the arm or hand
Seeing "stars" or other sudden vision difficulty
Headaches that are worse in the morning and get better during the day
Balance problems - wobbliness

These are some of the main ones.
As for ME - I had NO symptoms. I Just have an annual screening ever since I became metastatic. Some of you gals who are newer on this board did not go through the whole spate of board members who came up with brain mets earlier this year. Maybe do a search and see what they all had to say.

One thing that shocked me was the comment by one lady who is a 25-year survivor and is active with another support group. There she was in San Antonio and told me that it was news to her that the chemos and Herceptin DO NOT cross the blood-brain barrier! How can she support people when she lacks such BASIC knowledge of the workings of these drugs???
Good thing we had those little brains as ice-breakers so that we could "break the news" to some people!!

[Joe]

While in San Antonio, we had lengthy discussions with Dr. Eric Winer of Dana Farber and a few of the neuro-oncologists from GSK. They recognize the problem and are currently working on it.

Dr. Winer is conducting clinical trials using Tykerb which has shown to pass through the blood brain barrier. They both feel confident that they will achieve considerable success in the near future.

Regards
Joe

[michele u]

Ok, if i got this right they counted only 60 of the 100 women? If thats right and they said 57% of the 60 were Her2 pos. then 43% were Her2 neg, right. Well how the heck did they get "twice as likely to have brain mets from that?" Did i miss something?

Joe, this is why i hope they get the adjuvant Tykerb(lapatinib) trials going. If this drug could PREVENT brain mets from coming in a oral form BRING IT ON!! Are the Glaxo reps seeing this need? I hope they are!!

[kristen]

I for one am curious as to did they go straight to the brain or route through the lungs or bone or liver? This is pretty scary stuff. Is there a longer more indepth report of this study?

I have my noggin scanned every 6 months, but I know a lot who aren't. Will ASCO now change there recommendations of post care for HER2 BC patients to include brain MRI's? Is that the only way the onc's will do them? Or do we still have to get headaches? How long afterwards should we be getting MRI's done? Does anybody have estimates? It said it lets the cancer grow and can get into the brain but I didn't see how long it took?

Any estimates are welcome or personal experiences. thank you. k

[Becky]

Well, I forwarded Rhonda's link to my onco (thank God I switched to him) and he emailed me back saying that he is getting more convinced to at least do one MRI of the brain on all his early stage HER 2 gals instead of just the metastatic patients. He said he will order it for me the next time I have an appt (in about a month).


It is nice to have an intelligent onco who reads not only the data out there but the stuff you send him too and will work with you.

(I think I want to give him one of our brains as an "award of the year" thing).

Best regards

Becky

[kk1]

Michele;

They get the 2x more likely to get brain mets because there were 2x more her2 positive people than would have be expect if the ratio of her2+/her neg had remained the same as that seen in the non metastatic population.

for example:
if you had 60 early stage BC patients you would expect to find 15 of them her2+ (eg.25% ==1/4).

if the her2+ and her2 neg patients all went on to develop brain mets at the same rate then the 1/4 ratio should be maintained. So if you had 60 people with brain mets only 15 of them would be expected to be her2+ but what they found was that 34 of the 60 were Her2+-- eg. there were twice as many as expect if the two populations had the same level of risk.

kk1

[lexigirl]

Boy, I must admit that I was surprised too when I learned on this site that the chemo doesn't go to the brain. When I was first diagnosed I had told my surgeon that I'd been having aches and pains everywhere including my head. I think he tried to pacify me by saying that the chemo was systemic and would penetrate everywhere! My surgeon is fairly renowned here in Northern Calif. and I told my husband it makes me angry that he didn't give me the correct info. I still have head pain off and on and I am scared.

[Joe]

Lexigirl,

"My surgeon is fairly renowned here " why aren't you seeing a clinical oncologist?

Regards
Joe

[lexigirl]

Boy, I am pretty upset that patients aren't given correct info. When I was first being diagnosed with b/c I let my surgeon know that I was feeling aches and pains everywhere. Including headaches I have been having. He told me that the chemo was a systemic drug and would take care of all cancer cells. I really think he was poo-pooing me and it makes me feel sad. My surgeon is really well known here in North. Calif. and it makes me scared because I still have headaches off and on.
Thanks for letting me vent...
Lexi

[lexigirl]

Joe,
You know I do see an Onc. and she makes me a little apprehensive. She doesn't specialize in B/C only and she doesn't know a whole lot about her2. At least that is how I am feeling. We have Kaiser and was told that she was very good. My surgeon is Dr. Bodai and while being really compassionate, I think it was kind of stinky not to get the facts on the whole systemic thing. I know the Dr.s do their best, but I am feeling really scared about my situation. I will always put my trust in the Lord first, but would be reassured if I felt more confident in my Docs.

Thanks Joe,
Lexi

[Rozebud]

How long would it be between the time you'd have a met and the time you'd have symptoms? Kristen, I understand what you mean, I am tempted to lie to get them is most mets show up without symptoms, but I feel it's not right to do. What does everyone else think?


As to the stat, I think you take 57% divided by the number of people who have her2 positive cancer (let's say 22.5% for average sake). So 57/22.5 = 2.5x as high of a risk. Meaning over 1/2 of the people in this small study who have brain mets are her2+ but the general b/c population has less than 1/4 that are her2+. Hope that makes sense.

Its that old chestnut omega three again. IT reaches far and wide it would seem. Here the omega three six issue is reported as impacting on gene expression. I have not looked in any depth at the subject of omega three and the brain but keep seeing mention of the importance of omega three / three six balance to "brain health". The trial is not about cancer, but there are lots of links on this site showing links between omega threes and BC as well.
RB

http://www.ncbi.nlm.nih.gov/entrez/q...576&query_hl=1

1: Asia Pac J Clin Nutr. 2004;13(Suppl):S77.
Related Articles, Links


Influence of dietary omega-3 polyunsaturated fatty acid (PUFA) supply on brain gene expression.

Jayasooriya AP, Weisinger RS, Weisinger HS, Mathai M, Puskas L, Kitajka K, Chen N, Ackland ML, Sinclair AJ.

Department of Food Science, RMIT University, VIC, Australia, 3001.

Background - The functional roles of omega-3 polyunsaturated fatty acids (PUFA) are thought be mediated by the modulation of physico-chemical properties of the cell membrane and eicosanoid metabolism. Recent evidence suggests that omega-3 PUFA might also play a pivotal role in regulation of body functions through the modulation of its genetic apparatus. Objective - To determine the influence of dietary omega-3 PUFA supply on brain gene expression. Design - Female rats were fed with a alpha-linolenic acid (ALA) sufficient (CON) or deficient (DEF) diet throughout gestation and lactation. Three groups of male offspring were studied: (1) pups maintained on CON diet, from mothers on CON diet, CON (n= 4); (2) pups maintained on DEF diet, from mothers on DEF diet, DEF (n=4) (3) pups maintained on CON diet from weaning (3 weeks of age), from mothers on DEF diet, DEF-CON (n=4). Brain gene expression of weanlings and adult offspring were analysed by microarray technique. Confirmation of prominent microarray results was done by RT-PCR. Outcomes - Compared to CON weanlings, a total of 24 known genes and expressed sequence tags (ESTs) were differentially expressed in DEF weanlings. Compared to CON adults, a total of 129 genes and ESTs were differentially expressed in adult DEF offspring; a total of 12 genes and ESTs were differentially expressed in adult DEF-CON animals. Over-expression of the zinc transporter 3 gene was identified as the most prominent change in gene expression due to omega-3 PUFA deficiency. Conclusions - Dietary omega-3 PUFA supply influences the gene expression apparatus of the brain and it may be one of the mechanisms responsible for the physiological actions of the omega-3 PUFA.

PMID: 15294576 [PubMed - in process]

[RobinP]

Wow, let's not jump to conclusions from Dr. Pateerson's extremely small study and say her2+ are more likely to develop brain mets. The study below is it not big enough to be stastically significant with only 6o her2+ study subjects. Anyway, I think her real point is not that her2+ more likely to develop brain mets, but given the treatment of Herceptin , which included most of the group, these study subjects still went on to develop brain mets.

Note, for a better study on the incidence of brain mets in her2+ bc, look at abstract #3020 Breast cancer phenotype associated with apropensity for CNS mets, from the SABC 2005. It suggests er,pr- and high grade is assoc. with brain mets, not her2+. This study was huge with thousands of women, indicating significance!!!!!!!!!!!!!!!!!!!




4086] Does HER2 positive breast cancer have a prelediction to metastasise to the brain?

Paterson C, McIntyre A, Canney PA. Beatson Oncology Centre, Western Infirmary, Glasgow, United Kingdom

Background: There have now been several reports of an increased rate of central nervous system (CNS) relapse in patients with metastatic HER2 positive tumours treated with Trastuzemab. However in one report CNS metastases occurred as frequently in patients with HER2 positive tumours but who had not been exposed to Trastuzemab [1], suggesting that CNS disease in these patients may not just be an effect of better control of systemic metastatic disease leading to longer survival. To investigate this further we have examined the rate of HER2 positivity in a sequential cohort of patients treated for brain metastases from breast cancer.
Material and Methods: Between April 2003 and October 2004 a cohort of 60 patients with a diagnosis of breast cancer who were treated with palliative radiotherapy for brain metastases were identified from the radiotherapy bookings system. A further 9 patients were excluded due other primary tumours. HER2 and ER status were obtained from the patients case records.
Results: 34/60 (57%) patients had HER2 positive breast cancers and 26/60 (43%) were HER2 negative. Of the patients with HER2 positive tumours 14 (41%) had not received Trastuzemab before developing their brain metastases. 13/34 patients (38%) with HER2 positive brain metastases were also ER positive, and 10/26 of patients with HER2 negative tumours (38%) were ER positive.
Discussion: The reported rate of HER2 positivity in the general population of breast cancer patients is between 20% 25%, less than half the rate in this series of patients with brain metastases. In contrast the rate of ER positivity in this group of patients was lower than expected and not related to the HER2 status. These results suggest that the high rate of brain metastases in HER2 positive patients is an intrinsic feature of the disease not just an effect of better control of systemic metastases by Trastuzemab.
1. Lai et al. Cancer. 101(4):810-6, 2004.

Saturday, December 10, 2005 7:00 AM