Brain MRIs for early stage....consensus??

[Rozebud]

Christine/Joe/others:

Given the article posted about brain mets being twice as common (my math in the small study was that it was 2.5x as common) in her2 cancers, should those of us that are "early stage" (so my onc keeps telling me, even though I'm stage 3C) who have never had mets be pushing for brain MRIs in absence of symptoms?

[saleboat]

Hi Rose,

I've wondered the same thing as well. Is there any reason to believe that early treatment of brain mets, before the presentation of symptoms, would be advantageous? If so, then maybe there's an argument for taking a closer look. Otherwise, I'm of the 'ignorance is bliss' school of thought. If I have to go back into treatment eventually, I'd rather not spend my healthy days looking for trouble, if you know what I mean. (I was also staged at 3C)

I'm interested to know what others think on this topic. If catching brain mets early means less-invasive treatment, then maybe there's an argument for proactively scanning women who had early stage disease. Things are never black and white though, are they?

Thanks,
Jen

[Becky]

I was able to have my onco agree to give me a prescription to get a brain MRI when I see him in a month based on the SABCS paper on Her 2 women having 2X the chance of brain mets (even early stage). He said he would recommend a brain MRI yearly to all his HER 2 women that are not metastatic.


It was that easy for me.

Best regards

Becky

PS - I am going to get it done.

[RobinP]

Hi Rozebud,

I actually read almost every abstract from the SABC this year. I do recall one abstract stating that the phenophyte for increased brain mets was high grade tumors and er, pr negative, NOT her2. Having said that, I also read that once you have a her2+ recurrence, then you are more likely to reoccur thereafter in the brain.

I do get yearly MRI, but I was thinking even more frequent MRI would be nice. This is especially true when I just read of a her2+ bc patient would had a clear cat scan only 4 months prior to multiple nodules of brain met. LOL, help us.


3020] Breast cancer phenotype associated with a propensity for central nervous system (CNS) metastases.

Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R. Baylor College of Medicine, Houston, TX

Background: There is anecdotal evidence that the incidence of CNS metastases has increased with the advancement of systemic therapy, such as trastuzumab. However, it is unclear whether either specific tumor biological properties or systemic therapies influence the risk of CNS metastases. Furthermore, the identification of a tumor phenotype with a propensity for CNS metastases would be important for future screening or preventive strategies.
Methods: Using a database of 10782 patients that were diagnosed and treated from 1970 to 1999, 2685 patients were identified who relapsed distantly. Clinical and biological features of these patients were analyzed in two groups: 1) Patients who ever had CNS metastases (14%, n=383) were compared with those who never had CNS metastases (86%, n=2302) and 2) Patients who had CNS metastases as the first site of relapse (39%, n=150) vs. those who had other sites (61%, n=233). Survival after CNS metastasis was calculated using the Kaplan-Meier method and this was correlated with clinical and biological features of the patients.
Results: In the ever versus never analysis, factors associated with CNS metastases were young age (p<0.001), premenopausal status (p=0.008), ER and PR negative tumor (p<0.001), high S-phase (p=0.002), aneuploidy (p=0.02), and altered p53 (p=0.01). ILC was less likely to be associated with CNS metastases (p=0.01). Tumor size and lymph node status were not associated with a relative increase in risk of CNS metastases compared with other sites. Adjuvant systemic therapy also did not alter the relative risk of CNS vs. non-CNS metastases when compared with patients that did not receive therapy. Her2 positivity was not associated with CNS metastases in these patients, all of whom were treated prior to the trastuzumab era (p=0.91), though Her2+ patients were more likely to develop CNS metastases following non-CNS relapse (p=0.04). The biomarker profile of CNS failure as first recurrence did not otherwise differ from those with CNS metastases as subsequent recurrence. In a multivariate analysis of the above factors, ER negativity (OR 2.8, p<0.001), IDC histology (OR 2.5, p=0.02), and young age (p<0.001) were independent factors associated with any CNS metastases. The median survival after CNS metastases was 5.5 months, with 25% of the patients alive at one year and 10% at 2 years. The only factor that significantly influenced survival was Her2 status, with Her2 positive patients having a shorter survival (p=0.02).
Conclusion: Younger patients with hormone receptor negative tumors that are highly proliferative, genomically unstable, and p53 altered are at increased relative risk for CNS metastases. Her2 expression did not increase the relative risk of CNS metastases in the absence of trastuzumab therapy. Adjuvant therapies did not change the patterns of distant recurrence.

Friday, December 9, 2005 5:00 PM

[Rozebud]

Robin - CNS = brain mets? Interesting article. Are there other good ones from SA you'd recommend? There were just too many for me to sift through! (Aren't there like 100?)

Jen - to answer your question, yes, gamma knife is much easier to tolerate on your brain if you have just one or two mets vs. WBR (whole brain radiation). The latter can only be used one time in your life as well. Hopefully Joe or christine will weigh in.

[StephN]

Dear Robin -
At the Symposium there is an area where the posters are blown up and mounted on large boards. Ms. Tham was at hers for discussion and Ginger and I happened to zero in on that one.
As stage IV survivors maintained on Herceptin we asked her if anyone like us was included and she said "no." The time period involved is really Pre-Heceptin and she felt that this would be a separate group that would need its own study. The fact that more of us are able to survive through the other distant mets leaves us open to a higher chance of CNS (Brain) mets.

In other words Ms. Tham felt that not enough patients on Herceptin were included in her large number to make a difference.

She was interested that we stopped to introduce ourselves and take in her study results. She seemed to be more of a statistician than one who deals directly with patients - MHO.

This was a HOT topic.

[RobinP]

Yes, I did realize the study group by Tham was pre-Herceptin days. And it would be interesting to know what had happened if this study had taken Herceptin. I have read an article by Martine Piccart, PI of the HERA trail, that indicated that in the mets. populatioin, those who have been treated with herceptin, should they have a brain mets later, have a better OS survival with a brain mets than those never having had hercetpin. Her conclusion was that herceptin itself helped to make the disease less aggressive in the brain; interesting!

[Joe]

I understand that Dana Farber is doing a study on early intervention of brain mets. but,

Gamma Knife can only treat tumors up to 3 cm. Generally there are very few areas that you cannot Gamma Knife. If the tumor is over 3 cm, the only alternative may be a crainiotomy (sic). If the tumor is in an inoperable area, that is not an option.

In 2004, the HER2 Support Group launched an online campaign to have metastatic stage IV survivors insist on brain MRI's from their doctors. Some even suggested making up non-existant symptoms. We had 10 respondents who were found to have brain mets or lesions. All were treated by either Gamma Knife or WBR. Of these 10, 9 are still alive today.

Although this study was unscientific, I believe it would sway me.

Warmest Regards
Joe

[athena453]

Great question, Rose!

I certainly think there is enough evidence to ask for brain MRI's. I also think Joe's explanation of the available treatments for brain mets does support regular (and frequent) brain MRI's for the purpose of early detection.

Anyone know what their insurance considers reasonable? I'm almost afraid to find out...

[karenann]

In the article, it mentions that one of the factors for cns mets (within this study) is being er/pr-. I have often wondered if cns mets are more prevalent in er/pr- or er/pr+ or if it really doesn't matter. What do all of you think?

Karen

[RobinP]

Well, if there finding was negative hormonal status in most of the bc patients that had a recurrence in the brain , then I believe those stats. My question is if most of her2+ bc are er,pr negative, then why didn't they find more of those study subjects with her2+ disease?

Hey all,

A great thread. First off, if you want a brain MRI I think it's pretty easy to get. Rachel has had a few in the past three months, and not even by choice. Basically, she told her pcp that her regular headaches seemed a little more frequent and given her bc history the doc said "Well, we better do an MRI." So, if you DO feel like you want one, just go to your primary docs and tell them that you have had a steady headache for two weeks, that it's in one place, and that it wakes you up at night. You'll get your scan.

As for predisposing factors (and here I'm referring to RobinP's last post) I think it has been demonstranted that er/pr negativity and history of lung mets are the major factors. But I don't think that it is accepted anymore that most her2 positive women ARE er/pr negative. There have been some recent studies that say it really varies by age (i.e. under 40 her2 positive women have a more standard breakdown of er/pr positive and negative. It's only in over 50, I think, that the hormone negativity increases).

for what it's worth...

Jeff

I'd like to add my experience here in case my situation might help someone to convince their oncologist to give them a brain MRI.

I'm Stage VI now (original diagnosis in 2001) and have been battling various mets over the past few years (liver, lymph nodes, bone). Along with various chemo treatments throughout the years (AC, Taxotere+Herceptin, Navelbine+Herceptin, Carbo+Taxol+Herceptin) I have been receiving Herceptin more or less on a continuous basis for 4 years.

I've been following our discussions on the board, and I recently began asking my oncologist for a routine brain MRI. He felt this was not necessary because I didn't have any symptoms.

I continued to ask for a brain MRI each time I saw him and I finally had a brain MRI done in April 2005 which showed NO brain mets except for a very very tiny nodule formation in the left temporal area of the brain to watch. My oncologist said it was probably nothing. I was reassured and we continued on with my regular treatment.

In Sept 2005 I asked for another brain MRI which my oncologist felt was totally unnecessary, and much too soon, especially since I had no symptoms whatsoever. I brought this up during every appt and he finally agreed and I had another brain MRI done in October 2005.

The results showed 10 brain lesions in various parts of the brain, the largest being 26 cm, 16 cm and 13 cm. Needless to say this was a shock, especially since I was having (and still have) absolutely NO SYMPTOMS.

I have just finished WBR treatment and we will be doing another brain MRI in a few months.

I feel very strongly that we should insist on brain MRIs every 6 months, even without symptoms. I encourage all of you to follow this very closely.

Good luck to all of you.

[RobinP]

This is in response to Jeff' post. If you look at the HERA trail percentage of those with her2+ disease in the New England Journal of Med., overwhelmingly, most her2+ were er, pr negative as opposed to other hormonal receptor sensitivity. This was a large study, so I think this is significant and says something about the strong correlate between er, pr negative and Her2+.

[AlaskaAngel]

Good morning all.

For starters, I am either a definite minority or incorrectly classified by IHC as +++, since I am triple-positive.

I had an appointment this week with an onc this week who specializes in bc and genetics, since I have a significant family history that includes ovarian cancer as well. (I participated in one of the early detection for ovarian cancer clinical trials for 3 years.) The family history includes the aunt who died of ovarian cancer and another aunt who died of bc mets to the brain.

I find it puzzling that the onc thinks I should consider having my ovaries removed (due to the difficulty in detecting ovarian cancer, considering that the risks for that increase with age), but had no recommendations about the identical family history of an aunt with brain mets from bc, considering that I am HER2+++. It would be my thought that brain mets is equally difficult to discern. Thanks to this site we do know that often there are NO symptoms.

In addition I am curious about something else. Right after my third CAF chemo treatment, early one morning I was sitting working at the computer and suddenly lost my eyesight. My eyes were wide open but all I could "see" was nothing although it wasn't black. I felt a fluid wave that started at the base of the head and slowly went up the back of the head and over the top and down the forehead. After about 3 minutes my vision came back. The fluid wave was distinctly different in temperature. I wish I knew what that represented. (?BBB?) Has anyone had a similar experience?

AlaskaAngel

P.S. Then again, what if I had an MRI and there was NOTHING at all in there....

[Montana]

Like Alaska, I'm also triple +++ and am stage 1. I had headaches all summer and onc ordered a brain MRI right away. All was clear but I felt better just knowing that was one area I didn't have to worry about. At the same time, I had a CT scan of pelvis/abdomen and that found cysts on kidney, liver and an adrenal adenoma so these will rescanned in Feb.

[StephN]

I was just postmeno when got the BC diagnosis.
Also found to be hormone neg.
When my mets appeared in liver and bone, I had a brain MRI immediately. My med onc has ordered one annually as he knows what my risk of brain mets was. (I could have had more if I wanted.) The third year turned up the mets.

As I have said many times here, NO symptoms and one tumor was 3 cm. These can grow quite quickly, so there is nothing in my experience that says patients on Herceptin will have less aggressive brain mets. My tumor path is HER+++ and high grade. Once a tumor gets going, they grow quickly, as also happened in my liver where the tumors took over like wildfire in only 3 months.

Vigilance, my dears. Keep on insisting if your docs won't listen to stats and assess risk for you.

[karenann]

Hello everyone,

I wanted to post this question again, because I don't think I was very clear in my previous post. Here goes: I know that Her2+++ breast cancer can be er/pr+ or er/pr-, but what I am trying to find out, is whether or not being Her2+++ and er/pr- makes you more susceptible to brain mets. It appears that (or at least from what I have read and seen on the boards) most women who get brain mets, and are Her2+++ are also er/pr-. Any thoughts on this?

Alaska Angel,

I completed dose dense AC/T in June, 2005 and started herceptin in July. A few days after my second infusion of Herceptin, my left pupil dilated and my vision in that eye became very blurry. I also had pressure on the left side of my face and pain above and behind my left eye. The other symptom I experienced was my left ear became very clogged. This has happened 3 - 4 more times after my herceptin. I have had a brain mri (clear) and I have been seen by a neurologist and had an eye exam. Everyone seems to think I am having ocular migraines. It is really scary when it happens, so I am looking forward to the end of treatment.

Karen

[AlaskaAngel]

Eeeeee.... For me it was like being halfway across a bridge and knowing that the river is high and if you don't get across in time....

Karen, since completing chemo I have been examined yearly by the ophthalmologist and am also told the pressure I have occasionally behind the eyeball is likely ocular migraine. One other problem I had during chemo was that my daily employment requires excellent mind/hand coordination, and for a whole week my brain would not work with my fingers at the computer -- my fingers kept getting tangled up no matter how slowly I worked.

My first thought in answer to your question regarding hormone receptor status is that there probably are more HER2 negatives anyway if most bc patients are hormone receptor negative in the first place.

A.A.