ASCO abstract: most important to STAY on herceptin once have brain mets!!!

[Lani]

Abstract No:
11507
Citation:
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 11507
Author(s):
B. Nam, K. Lee, T. Kim, J. Ro
Abstract:
Background: Brain metastases (BM) occur in as many as one-third of patients with metastatic breast cancer (MBC). Incidences and prognoses by triple receptor subtypes in BM have not been well delineated. Methods: Retrospectively, prognoses were assessed according to clinical characteristics, triple receptor subtypes, and receipt of trastuzumab therapy by univariate and multivariate analyses. ER/PR/HER2 were tested by IHC with HER2 FISH for IHC 2+ and for all 118 consecutive primary BC. Results: Between 8/2001 and 4/2006, 138 of 805 pts (17.1%) with MBC presented with BM at NCC Korea. More pts with triple negative and HER2+ tumors developed BM (see table). The median age was 47 years. They were single (9%), multiple (80%), or leptomeningeal disease with or without multiple BM (11%). As initial therapy, 104 pts received WBRT, 8, intrathecal therapy (IT), 9, WBRT with IT, and 17 others. Of 56 HER2+ pts, 45 received trastuzumab either before (n=25) or after (n=13), or continuously before and after BM diagnosed (n=7). By 10/2006, 117 pts died with a median survival of 4.5 months. Multivariate analyses indicated age, tumor receptor subtypes, leptomeningeal presentation and number of extracranial disease sites as significant factors. Receipt of trastuzumab therapy after BM was a significant variable for survival in HER2+ diseases (3.8 vs. 13.4 mo, p=0.0000). Pts with triple negative subtype lived shortest compared with other types (p=0.0035). Conclusions: More pts with triple negative and HER2+ disease developed BM. HER2+ disease gained a significant survival benefit by trastuzumab therapy. Supported by NCC Grant 0610240 and 0510520.
Triple receptor status Brain metastasis
N (%) Metastatic breast cancer
N (%) Early breast cancer
N (%) P-value
ER or PR+/HER2- 23/126 (18.2) 254/556 (45.7) 68/118 (57.6) <0.0001
ER or PR+/HER2+ 19/126 (15.0) 73/556 (13.1) 16/118 (13.5)
ER and PR-/HER2+ 37/126 (29.4) 91/556 (16.4) 15/118 (12.7)
ER and PR-/HER2- 47/126 (37.3) 138/556 (24.9) 19/118 (16.1)
Unknown/total 12/138 111/667 0/118

[StephN]

Good info, but I am not sure why. This abstract leaves open several questions in my mind.

1. I ASSUME all these patients had mets in other places. There is a reference to the number of extracranial sites as a factor. It does not say what drugs they were on before, during or after brain mets treatment. Some drugs are felt to make the blood/brain barrier a little flabby and allow some Herceptin penetration.

2. The other main question is whether the use of Herceptin was for keeping the other mets under control so that there are less cancer cells to get into the brain. This is only sensible and does not need a study.

The conclusion that a person with brain mets who has the benefit of Herceptin will live longer is obvious to us on this board. We who participate here are only a small number, but our survival rate seems much higher than the 13.4 months in the study.

[Adriana Mangus]

I believe this is a preliminary results based on a small number of participants.
I agree with Stephanie, did the participants had mets to other organs, where?
How long?

Is the addition of herceptin helpful to the "late" development of Brain mets, regardless of mets to other organs, and if so in average how long did it take to develop brain mets, after the addition of herceptin.

What is clear to me is that herceptin is a clear winner vs bc, what I still do not know is whether regardless of receptors i.e. _ or +, brain mets will follow.

My onc believes (he's the head of Onc Dept, and has traveled extensively to other countries that dispensed herceptin), that no matter what your pathology reports results are, "thanks" to herceptin, brain mets will develop soon or later due to Her2 positive patients longevity. Hard to believe, uh??? What a price to pay to be alive? Does it make sense to you. Still do not want to believe it.

[Lani]

unable to speculate.

138 is not such a small number of patients from a single institution to provide meaningful info

as to what other sites, how many...they state it was a significant factor/variable in their statistical correlation but more details can only follow once
information disseminated

Stay tuned for more info...perhaps someone at ASCO will hear this presentation and comment

[Hopeful]

Adriana,

Your onc certainly is a jolly old soul. It does not make sense to me, and I certainly don't interpret the current statistics that way.

FWIW, I read an article about aromatase production the other day, and was surprised to learn that a good amount of it is actually produced in the brain. That being the case, I would expect more hormone positive patients to develop brain mets, but the stats all show the opposite. So, who knows?

Hopeful

[Lani]

effect, etc

: J Neurooncol. 2007 Jun 8; [Epub ahead of print] Links
Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer.

Bartsch R, Rottenfusser A, Wenzel C, Dieckmann K, Pluschnig U, Altorjai G, Rudas M, Mader RM, Poetter R, Zielinski CC, Steger GG.
Department of Medicine 1 and Cancer Centre, Clinical Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria, guenther.steger@meduniwien.ac.at.
Background: Brain metastases are frequently encountered in Her2 positive advanced breast cancer. It is still not clear, if trastuzumab treatment should be continued following their diagnosis. In this analysis we evaluated if trastuzumab was able to influence time to in-brain progression (TTP) and overall survival (OS). For this reason, we compared patients who continued on trastuzumab with a historical control group. Patients and Methods: Seventeen Her2 positive patients receiving whole brain radiotherapy for brain metastases and continuing on trastuzumab were identified. As historical control group, thirty-six patients treated before 2002 were identified from a breast cancer database. We performed a multivariate analysis (Cox regression) to explore which factors were potentially able to significantly influence TTP and OS. Results: Median TTP was 6 months, range 1-33+ months. Median OS was 7 months, range 1-38 months. Seventeen patients received trastuzumab after WBRT. Factors associated with prolonged TTP were KPS (p = 0.001), and intensified local treatment (p = 0.004). A trend towards longer TTP was observed in patients treated with trastuzumab (p = 0.068). OS was significantly influenced by KPS (p < 0.001), and continued antibody therapy (p = 0.001). Conclusion: Two parameters were significantly associated with prolonged OS: KPS and trastuzumab. While there was a trend towards prolonged TTP in patients with trastuzumab treatment after WBRT, this did not reach statistical significance. It appears therefore reasonable to suggest continuation of antibody therapy in patients with good performance status despite disease spreading to the brain. Concerning activity of trastuzumab in brain metastases themselves, no final conclusion is possible.
PMID: 17557136 [PubMed - as supplied by publisher]

[pattyz]

Crap, I hate to say this aloud for the universe to 'hear'...

In the past 7 and almost 1/2 yrs I've been on Herceptin for a total of 4 months.

Have remained NED in body for 4 yrs. without Herceptin.

"Just" the brain mets recurrances.

I DID get the Herceptin after my first brain mets were treated with SRS, rather than WBR.

And although I am er+ I have been on HS Estratest for three yrs. Small amount of Estrogen/Testosterone for QOL issues.

Plus Melatonin at night (amt up to 10mg now) for past four yrs atleast.

It just makes me wonder........ am I doing something by 'accident' that is helping me stay NED or able to live with my brain mets... after I get my mind in a twist about it all, I need a break of some mindless activity, lol

xoxopatty

[AlaskaAngel]

As I recall, another long-term survivor of brain mets here who has used melatonin as one of her defense mechanisms, is StephN, so I think that is interesting, Pattyz. I did not know you were also using it consistently.

Steph is also one of the most constantly active people I've met, and perhaps that helps too. Are you active too?

I still think that we should be provided with an endocrinologist to sit on each of our tumor boards at diagnosis.

A.A.

[StephN]

Hey A.A. -

I would Just LOVE to see an endocrinologist. Never have.
I know you have some different family history that causes you to see one.

Wanted to rectify something you mentioned in the last post. Regarding Melatonin. I only took that for a short time when I was on Taxotere - mainly to help my sleeping pattern since I had to use the Decadron with that drug and it was so disturbing to my sleep pattern.

Once my sleep pattern normalized, I wanted to try to keep it that way on my own. One reason I tried hard to keep myself from napping during the day. Resting, but not napping.

I know we talked about this supp at some point, but we have covered a lot of bases in our get-togethers.
Maybe a new thread on Melatonin would garner many more viewpoints.

[pattyz]

AA,

Active? What's that?? Not for the past few yrs. And getting less so. Only in spurts.

My 'puttering' is less than even last yr. I get sob and 'woosey' with any 'extra' effort, yet can walk for a couple hrs with rest-stops.

As to the fruits and veggies etc. Did all that before dx. Little red meat. Worked dawn til dusk 7 mos. a yr and hiked nearly daily for the other 5 mos. Many supps, raw nuts, flax blah blah blah........... Now I eat what sounds good at the moment.

Thanks for thinking on this, too..

xoxopatty

[Andrea Barnett Budin]

Adriana, I agree that your jolly old soul of an onc is beyond cynical on his prediction we'll all get brain mets if we live long enough. I will not accept that. Not just out of fear, and as a matter of self-protection, but I don't think they know enough to say such a thing.

Patty Z.'s post re estro/testoster and melatonin 10 is most interesting. I read on this board somewhere that testoster (maybe within a site click) may be a factor for longevity in bc. I went to an endocrinol becz of my incessant hot flashes, endured for 22 yrs, as my mother, who never had bc, but multiple mini strokes and Alzheimer-like condition, w/paralysis. My dghtr suggested endocrin when I said I can't live like this anymore. She paused in front of me, lked at the ground and then asked, Wait. What do you mean by that? I said not ready to jump out a window but edging closer from across the room. Thoughtful alw, Ali said Why don't you see an endocrinol. Not one OB/GYN, oncol ever sugg such a thing. I went, in total desperation. She is fabulous.

Dr. Mata said hot flashes can come w/high bld sgr. I am not diab but have very elevated bld sgr and am now on meds to regulate that. Also -- she found that I had slightly elevated testosterone. That amazed me as I feel like such a girly girl alw, but I am fiesty and proactive and damned determined. So my antenae went up when reading about testost and bc longevity and again when reading Patty Z's post. A link? HORMONES AGAIN.

Now reading about ESTRIOL and Progesterone sublingually for hot flashes somewhere in here the other day my ears alert to MORE on this. Then some one posted re CLONIDINE and hot flashes and I am awonder on that. My head is spinning. Can anyone make sense of all this.

Steph, as alw yr overview is so keen. MELATONIN thread maybe, or Melatonin, Testosterone thread. Plus an Estriol/hot flash/clonidine thread. I made 1 thread, w/much help. And we all know what attention that drew. Threads are key to helping those of us who wander around in here for info.

Any thoughts re any of the above would be greatly appreciated by those of us who can't make sense of it all. Sending happy, healthy energy to our my beloved Soul Sisters... ANDI