percentage of us who develop brain mets???

[gqmom]

Hi all,
I have been reading that 30-40% of women with Her2 positive BC develop brain mets. Is this correct?? Is that percentage for all of us or is it for people with more advanced cancer? Is that the personal risk or does it apply to a large group? I'm so confused...the more I read, the more confused I get!!!! I should stay off the computer and just listen to my onco, I guess.

[Becky]

About 30% or so of women who have metastatic (Stage 4) Her2+ disease develop brain mets.

Of Her2+ women who are not Stage 4 initially but become metastatic later, 10% will present in the brain as their first (and perhaps only) site.

[Jackie07]

Found these abstracts while trying to locate the source of those numbers (percentages) cited by Becky:

Breast Cancer Res Treat. 2011 Jun 14. [Epub ahead of print]
Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse.
Harrell JC, Prat A, Parker JS, Fan C, He X, Carey L, Anders C, Ewend M, Perou CM.
Source
Lineberger Comprehensive Cancer Center, University of North Carolina, 450 West Drive, CB7295, Chapel Hill, NC, 27599, USA.
Abstract
The ability to predict metastatic potential could be of great clinical importance, however, it is uncertain if predicting metastasis to specific vital organs is feasible. As a first step in evaluating metastatic predictions, we analyzed multiple primary tumors and metastasis pairs and determined that >90% of 298 gene expression signatures were found to be similarly expressed between matched pairs of tumors and metastases; therefore, primary tumors may be a good predictor of metastatic propensity. Next, using a dataset of >1,000 human breast tumor gene expression microarrays we determined that HER2-enriched subtype tumors aggressively spread to the liver, while basal-like and claudin-low subtypes colonize the brain and lung. Correspondingly, brain and lung metastasis signatures, along with embryonic stem cell, tumor initiating cell, and hypoxia signatures, were also strongly expressed in the basal-like and claudin-low tumors. Interestingly, low "Differentiation Scores," or high expression of the aforementioned signatures, further predicted for brain and lung metastases. In total, these data identify that depending upon the organ of relapse, a combination of gene expression signatures most accurately predicts metastatic behavior.

Am J Pathol. 2011 Jun 24. [Epub ahead of print]
Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2(+) and ErbB-2(-) Primary Breast Tumors.
Sanz-Pamplona R, Aragüés R, Driouch K, MartÃ*n B, Oliva B, Gil M, Boluda S, Fernández PL, MartÃ*nez A, Moreno V, Acebes JJ, Lidereau R, Reyal F, Van de Vijver MJ, Sierra A.
Source
Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), Hospital Llobregat, Barcelona, Spain.
Abstract
The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.

Bull Cancer. 2011 Apr 1;98(4):433-444.
Brain metastasis from breast cancer: Who?, when? and special considerations about the role of technology in neurosurgery.
Dutertre G, Pouit B.
Abstract
Questions about both the place and the role of surgery on brain metastasis from breast cancer are arising more and more frequently in practice due to the increase of brain metastasis in patients suffering from a form of cancer recognized as one of the most recurrent cancers in adults but also one of the most sensitive to general treatments of the systemic disease. With improvements in anaesthesia, in surgical instruments, and in global care, neurosurgery has taken advantage of new techniques such as pre- and even per-operative imagery and also neuronavigation. These techniques enable radical and effective surgical intervention with a high level of safety for the patient, making neurosurgery perfectly competitive with other therapeutic modalities, particularly on functional grounds. As for symptomatic treatments or other anti-metastasis treatments, most situations allow a reflection on the global therapeutic strategy which can be adapted to individual cases depending on the patient's general prognosis. In developing this global therapeutic strategy, surgical treatment is still as relevant as ever.

[Jackie07]

Medscape has an overview of brain mets in general:

http://emedicine.medscape.com/article/1157902-overview

[BonnieR]

ggmom, you don't have to stay off the computer necessarily! But it seems you are new to all of this and it can be scary at first to be reading so much and not knowing how it applies to oneself. And, of course, fearing the worst. That is an understandable reaction. But it is important to try and stay in your lane and concentrate on what is on your immediate horizon. First things first! And keep the faith. We are here to help...

[Lien]

I am still here, and I just had a lumpectomy and radiation therapy. I'm 7,5 years out from diagnosis. Most women who are diagnosed with breastcancer do fine. Herceptin has changed our outlook even more, because now Her2 positive disease is treatable and I believe that the effect is that we have an even better chance than other breastcancer subtypes to survive.

You are getting treatment that is aimed at curing you. Ofcourse there's a small chance that it could come back. We all have to live with that. But anyone can develop any nasty disease.

The only difference is, that you know what it feels like to fear for your life. Others, who haven't had this kind of diagnosis are able to ignore the fact that they are one day going to die.

Treatment is tough and it gets worse before it gets better. But after that, we all learn how to move on to a new normal. You will too. And we are here for you during the whole process.

Hugs

Jacqueline

[Jackie07]

According to this Italian retrospective (2004-2007)study, 5% of Her2-positive breast cancer patients who were initially diagnosed at Stage I-III developed brain mets in a 4.1 year (average) span (while the brain mets incidents of Her2-negative patients was just 1.3%) :


Cancer. 2011 May 1;117(9):1837-46. doi: 10.1002/cncr.25771. Epub 2010 Nov 10.
Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study.

Musolino A, Ciccolallo L, Panebianco M, Fontana E, Zanoni D, Bozzetti C, Michiara M, Silini EM, Ardizzoni A.
Source

Medical Oncology Unit and Cancer Registry of Parma Province, University Hospital of Parma, Parma, Italy. antoninomusolino@hotmail.com

Abstract

BACKGROUND:

A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk.
METHODS:

The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4-year period between 2004 and 2007.
RESULTS:

A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow-up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2-negative patients and HER2-positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2-positive status and trastuzumab treatment, high Ki-67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis.
CONCLUSIONS:

To the authors' knowledge, this is the first population-based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2-positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab-based therapy may lead to an "unmasking" of CNS disease recurrence that would otherwise remain clinically silent before a patient's death.
Copyright © 2010 American Cancer Society.

[Jackie07]

This study done by the Chinese has a good explanation of why Herceptin(Trastuzumab) seems to be linked to higher incidence of brain mets:

PLoS One. 2011;6(6):e21030. Epub 2011 Jun 9.
Trastuzumab in the Adjuvant Treatment of HER2-Positive Early Breast Cancer Patients: A Meta-Analysis of Published Randomized Controlled Trials.

Yin W, Jiang Y, Shen Z, Shao Z, Lu J.
Source

Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

BACKGROUND:

Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors.
METHODS:

Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data.
FINDINGS:

With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.
CONCLUSION:

This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

[Laurel]

That's very interesting, Jackie. Thanks so much for the post. You are so faithful to us posting such insightful comments and links. You rock, Sista. I just want you to know I appreciate all your efforts on our behalf!

[tfabre]

Thanks so much!

[Jean]

gqmom,
Another point to keep in mind. New current stats are on the horizon for us as more early stage and later stage patients have been treated with herceptin which will make those stats change.

Also, more women are being dx. earlier as awarness and newer digital mammos have come on the scene.
Of course we have a long journey yet to walk....
we are seeing more women survive with her2 in recent years and I really believe that we will see impressive stats in the next few years.

Knowledge is power so don't bury your head in the sand but do keep a balance with the information you are reading. It may be reporting old stats.

Best regards,
jean

[hutchibk]

Well stated Jean. You are so right!