what is your risk of brain metastases and what are they recommending you do about it?

[Lani]

J Clin Oncol. 2006 Nov 13; [Epub ahead of print] Links
Prognostic Significance of Human Epidermal Growth Factor Receptor Positivity for the Development of Brain Metastasis After Newly Diagnosed Breast Cancer.

Gabos Z,
Sinha R,
Hanson J,
Chauhan N,
Hugh J,
Mackey JR,
Abdulkarim B.
Department of Oncology, Cross Cancer Institute and University of Alberta; and the Departments of Radiation Oncology, Statistics and Epidemiology, Laboratory Medicine and Pathology, and Medical Oncology, University of Alberta, Edmonton, Alberta, Canada.
PURPOSE: As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) -overexpressing breast cancer patients is not yet fully defined. We aim to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients. PATIENTS AND METHODS: To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS: Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION: Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.
PMID: 17102066 PubMED

[KellyA]

Lani-

So is this saying that not only do her2+ patients have more brain mets, but that also her2+ er- have a higher rate than her2- er+ ?

Kelly

[Lani]

i just went over the original article--yes her2+ breast cancer patients have a proclivity to metastasize to the brain

Only 30 of the her2+ early breast cancer patients in this study got herceptin as part of a clinical trial, so it was not herceptin which was affecting where the mets presented or didn't present in the majority of cases (some say herceptin is changing the natural history of the disease by preventing most of the liver, bone and lung mets but being unable to prevent the brain mets due to its inability to cross the blood-brain barrier)

Of the her2+ patients who developed brain mets, it seems more were ER- than ER+

Hope this helps!

[KellyA]

One more question, Lani-

The article stated that most brain mets developed after systemic disease had begun- does this mean that they usually develop later in more advanced cases where there were other mets, or do the brain mets present initially as advanced disease?

Kelly

[Lani]

they more often appear as later metastases after other mets have already appeared, but in a minority of cases (look at my other posts on the matter for previous statistics) they have presented as the initial metastases in what was previously localized or regional disease only (in the breast or regional lymph nodes only)

Again, this report by and large reports the behavior of the disease when NOT treated with herceptin.

Previous posts by me review the fact that her2+ patients treated with herceptin are more likely than those not treated with herceptin to present with brain mets as their initial presentation

THIS PAPER had relatively large numbers of her2+patients (around 300) and all but 30 were not treated with herceptin. In such a setting 9% had brain mets.

It is hard to find these kinds of stats in the literature, particular focusing on her2+ patients.

I try to post them not to alarm people, but to put it in perspective as best we can as knowledge increases. ie, so one can have a meaningful discussion regarding prophylactic MRIs and if they are worth it . This paper
repeated time and again that they are not currently doing propylactic MRIs on these patients--but the paper is from Canada and provincial governments have to set local policies for what can and cannot be done

Hope this helps!

[KellyA]

Lani-

Thank you for your help with this. As much as it is not wonderful news, I embrace ANY information that might help me to be as educated and prepared as I can. My dilemma is just what you said- I have an onc. (who I love) that I have been very happy with as far as treatments and care goes. Savannah is a small town, however he came out of MD Anderson and is not only a oncologist, but is a licensed internist and hematologist (although he only practices oncology). I have been very pleased with him to this point and he is very attentive, however he falls into the "no scanning unless symtoms warrant" bunch. I did have scans at diagnosis, which were all clear, but none of my docs would do an MRI, because they felt the chances of mets there before anywhere else would be rare. So I guess now I am in the predicament of weighing all of the risks and deciding how to proceed.

Anyways, I always am interested to read your articles and find them to be very helpful. It is so difficult to find her2 specific information.

Thank you!
Kelly

Thanks for this fascinating and informative abstract. Although initially depressing, we can look on the bright side and find reassurance in knowing that someone is trying to do something about it. This is helpful information. Thanks again.

[bashmaz]

Hi Lani - just a quick thought: if 30 of the her2+ group had Herceptin, and 27 (9%) of the her2+ group developed brain mets, how many of the 30 were in the group of 27?

Just curious,
Marianne

[Soccermom]

Thanks for posting this study ,Lani. I am just beginning to grasp the different nuances of Her2 positivity.

Warmly,Marcia

[Lani]

rereading the article of the 30 patients who received adjuvant herceptin only 1 developed brain mets (3.3% vs 9% in of the group of her2+ patients in general) but the numbers are so small ie, 30 patients, it is not clear that it would truly be significant. It sounds rather reassuring though!

[heblaj01]

The study reported by Lani makes several points clearer.
It is however disappointing that so few Herceptin treated patients were included in the study.
Clinical trials on Herceptin alone did not (to my Knowledge) assess if there is a relation between this drug & increased risk of brain metastases.
The fact that one patient in Germany has been successfully treated for brain tumors with Herceptin (injected in the spine to overcome the blood brain barrier) lands some credibility to the lack of direct toxicity.
But on the other hand some studies of patients taking Herceptin show a greater ocurrence of brain tumors which some commentators have atributed to the extended lifespan enjoyed by these patients who are not protected against these later occuring metastases.
Other unknown possibilities might be found in the case of changing growth factors once resistance to Herceptin develops or when cross talk occurs.

Once again thanks for this article. I retrieved it from the Univ library here. A couple of things ...in the article as well as the abstract under results it says "tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. So I would interpret this to mean that if one is ER+ that is somewhat protective from brain mets. That is very good news for all ER+ persons!

Also, in HER2+ patients (27 total) in 8 patients the brain was the initial site of mets (as Lani said earlier - because the herceptin is frequently stopping other mets) and in 19 pts, the CNS were dxd subsequent to other mets. They go on to say that because of this high-risk population, serial radiologic screening and/or prophylactic cranial irradiation (PCI) in HER-2 metastatic patients are warranted.
Wow, prophylactic cranial irradiation - that is a pretty heavy concept, but 8/27 patients is significant for a first metastasis!

[pattyz]

Nedra,

From all I've learned and read in my four yrs with brain mets, WBRT does not have a great track record of 'success' OR longevity of success when had....but the side effects afterwards are indeed damaging in the long term.

I've seen this talk of 'preventative radiation' (ie: WBRT) before... and it just nauseates me. For so many reasons. I pray it does NOT become sop in the future. Shame on them if it does.

However, I do hope that regular brain MRi's with contrast will become the sop for all Her2+'s. That only makes sense to me from all known risk factors.

As an aside, I am er+ pr- Her2+++ with brain mets.

Hi Patty - I am so sorry you have brain mets, truly. So much for ER+ being "protective", eh? Well I agree, just the concept of someone irradiating my brain prophylactically is upsetting. I think there may be some new drugs on the market, either approved or getting approved, that have molecules small enough to cross the blood/brain barrier, and I think therein lies our collective hope. Also, I don't know what the initials WBRT mean. Could you explain? Thanks
I sincerely wish you all the very best. Words seem so trite in light of what you are facing! Stay strong! Keep positive. Here's a big hug!

Kind regards
Nedra

[pattyz]

Nedra,

WBRT = whole brain radiation therapy.

also just WBR without the T.


I have been responding to the combo of Xeloda/Temodar for my current 8 brain mets for 15 mos... don't know how long I will be able to maintain this good luck run. However, these chemos DO cross the bbb. With varied success or none.

Staying 'positive' helps with quality of life, but has done nothing for survival of the many who have passed on.

Thanks for your kind words, dear. We all just do the best we can, day by day.

[Lani]

(probably more later, but am too tired right now)

1)The authors pointed out time and time again that because of their country of practice, they were not allowed to do screening MRIs. Perhaps out of exasperation they wrote that to try to force the authorities to allow screening MRIs ie, if you don't we may decide we have to TRY prophylactic WBRT and yes, there are lots of articles on how those with brain mets who get WBRT do. I try not to post those, as there are some on this board who have proved them wrong, and as posting those kinds of informations may harm more than they help. If anyone wants these I could post those with a big yellow warning sign and perhaps Joe should make a new category of posts for scary information which only those who WANT to should see.

These articles follow many people who are pre=herceptin and pre- better combinations of Herceptin with chemos so in most cases they are not even
truly relevant or accurate to our times (except in those countries where people still cannot get Herceptin)

more later...

[Becky]

Another reason having a positive progesterone receptor is a good prognostic factor. I wonder what that little bugger does. One day we will know. It just might not be ER+ that is a good thing but being PR+. Not alot of evidence to go on since few are ER neg but PR+.