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Old 07-27-2006, 08:22 AM   #1
RobinP
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primary bc types associated with increased propensity for brain mets...

Surprise, it's not her2 that includes the phenotypes, that's the good news. But the bad new is that it is young age, hormonal status negative, high proliferation, and altered p53 that increases brain mets. Crap, doesn't this fit the description of many her2+s anyway?

Original Article

Primary breast cancer phenotypes associated with propensity for central nervous system metastases
Yee-Lu Tham, MD, Krystal Sexton, MS, Rita Kramer, MD, Susan Hilsenbeck, PhD, Richard Elledge, MD *http://www3.interscience.wiley.com/g.../10/dagger.gifBreast Care Center, Baylor College of Medicine and Methodist Hospital, Houston, Texas
email: Richard Elledge (relledge@breastcenter.tmc.edu) *Correspondence to Richard Elledge, Breast Care Center, Baylor College of Medicine and The Methodist Hospital, 6550 Fannin, 7th Fl., Houston, TX 77030

http://www3.interscience.wiley.com/g.../10/dagger.gifFax: (713) 798-8884
setDOI("ADOI=10.1002/cncr.22041") Funded by:
http://www3.interscience.wiley.com/g...ry/12/bull.gif Susan G. Komen Multidisciplinary Breast Cancer Fellowship, Medical Oncology Program Project; Grant Number: P01 CA 30195
http://www3.interscience.wiley.com/g...ry/12/bull.gif Dan L. Duncan Center; Grant Number: P20 CA 1033698

Keywords CNS metastases • breast cancer • phenotype • HER-2 Abstract
BACKGROUND.There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk.
METHODS.Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: 1) patients who ever had versus those who never had CNS metastases, and 2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed.
RESULTS.In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl-2, high S-phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER-2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P<.001), IDC histology (OR 2.5, P = .02), and young age (P<.001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER-2 status. HER-2-positive tumors were not more likely to undergo recurrence initially in the CNS (P = .04). The median survival after CNS metastases was 5.5 months and HER-2-positive patients had a shorter survival.
CONCLUSIONS.Younger patients with hormone receptor-negative, highly proliferative, genomically unstable, and p53-altered tumors were at increased relative risk for CNS metastases. HER-2 expression and adjuvant systemic therapies did not increase this risk. Cancer 2006. © 2006 American Cancer Society.
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Old 07-27-2006, 08:42 AM   #2
R.B.
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"Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER-2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02)."

Is this not saying that HER-2 is a subset of the symptom group. So it may not be good news after all but bad news for all equally?.

AND?

Also EGFR is that not HER 1 (I must write them down or print them out as I get them mixed up), and there has been much discussion on cross talk between the HER family - so I suppose as the receptor balance shifted from HER2 to HER1 in drug resistance etc you might expect to see more cases in the HER1,2,3,4 group??.

Please check this out as it if off the top of my head as I have not had time to double check.

If somebody more knowledgeable could comment I would be grateful.

RB
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Old 07-27-2006, 11:48 AM   #3
RobinP
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Thanks for the input Rhonda. I agree with you that her2 seems to be a subset of the her1 group, with her1 being more of a risk factor for brain mets. At the same time, it appears tha her1 had less of a significance than hormonal status and young age, both of the later being most significant risk factors for brain mets.
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Old 07-27-2006, 12:33 PM   #4
R.B.
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Just to clear it up as there seems to be some confusion - R is for a male christian name.

At some point people must have got Rhonda who also posts on diet and I think who is also an RB, and me mixed up.

Its not a problem but just to save confusion.

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Old 07-27-2006, 12:40 PM   #5
RhondaH
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Nope...

I'm a RRH. Sorry.

Rhonda
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Dx 2/1/05, Stage 1, 0 nodes, Grade 3, ER/PR-, HER2+ (3.16 Fish)
2/7/05, Partial Mastectomy
5/18/05 Finished 6 rounds of dose dense TEC (Taxotere, Epirubicin and Cytoxan)
8/1/05 Finished 33 rads
8/18/05 Started Herceptin, every 3 weeks for a year (last one 8/10/06)

2/1/13...8 year Cancerversary and I am "perfect" (at least where cancer is concerned;)


" And in the end, it's not the years in your life that count. It's the life in your years."- Abraham Lincoln
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Old 07-27-2006, 08:48 PM   #6
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I'm actually a Rhonda H. B.----so Sassy is less confusing!


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Last edited by sassy; 08-22-2011 at 08:50 AM..
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Old 07-28-2006, 11:37 AM   #7
Christine MH-UK
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Don't forget the triple negatives

They tend to be younger than other breast cancer patients and have agressive cancers. I think that they are about 15% of cancer patients and therefore about half of hormone-receptive negative cancer patients. I checked and BRCA1 carriers, who tend to be triple negative, do have an increased incidence of brain mets.
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