The Correlation between HER2+ Status and Brain Metastases in Trastuzumab-treated patients with Metastatic Breast Cancer
SSM 2013-‐14
3
The Correlation between HER-2
Status and Brain Metastases in
Trastuzumab-treated Patients with Metastatic Breast Cancer
Ka-Kiu Claire Fung
Literature Review: Biochemistry/ Molecular Biology Project
Convenor:
Dr J A Smith
Word Count:
3223 words
C a n d i d a t e N u m b e r : 2 0 7 7
Ka-Kiu Claire Fung
Abstract
It is widely known that patients with HER-2-positive advanced breast cancer are at particularly high risk of developing brain metastases, especially if patients have been managed with trastuzumab-based treatments. However, the biologic reason for this is not fully understood.
Currently, there are three hypotheses that explain this. Firstly, the basic biologic role of the HER-2 receptors is considered. Excess HER-2 receptors over-activate the
PI3K/Akt and MAPK pathway, leading to an inhibition of apoptosis and depression of regulatory proteins of the cell cycle respectively. Coupled with other survivalpromoting factors such as the secretion of basement membrane degradative enzymes, the formation of invadopodia to assist in cell migration and the promotion of angiogenesis via VEGF, overexpression of HER-2 leads to a more aggressive, more invasive type of cancer.
Secondly, trastuzumab does not come into contact with brain metastases, as its molecular weight is too large to allow it to cross the blood brain barrier. Lastly, trastuzumab is very effective in prolonging the life of HER-2-positive breast cancer patients. Since brain metastases are considered a late manifestation of the disease, it may be safe to assume that the correlation between trastuzumab and brain metastases is due to the fact that patients merely live long enough for the central nervous system involvement to become apparent.
Currently, the development of treatment targeted to brain metastases from the breast is focusing on drugs that can cross the blood brain barrier, or
3
The Correlation between HER-2
Status and Brain Metastases in
Trastuzumab-treated Patients with Metastatic Breast Cancer
Ka-Kiu Claire Fung
Literature Review: Biochemistry/ Molecular Biology Project
Convenor:
Dr J A Smith
Word Count:
3223 words
C a n d i d a t e N u m b e r : 2 0 7 7
Ka-Kiu Claire Fung
Abstract
It is widely known that patients with HER-2-positive advanced breast cancer are at particularly high risk of developing brain metastases, especially if patients have been managed with trastuzumab-based treatments. However, the biologic reason for this is not fully understood.
Currently, there are three hypotheses that explain this. Firstly, the basic biologic role of the HER-2 receptors is considered. Excess HER-2 receptors over-activate the
PI3K/Akt and MAPK pathway, leading to an inhibition of apoptosis and depression of regulatory proteins of the cell cycle respectively. Coupled with other survivalpromoting factors such as the secretion of basement membrane degradative enzymes, the formation of invadopodia to assist in cell migration and the promotion of angiogenesis via VEGF, overexpression of HER-2 leads to a more aggressive, more invasive type of cancer.
Secondly, trastuzumab does not come into contact with brain metastases, as its molecular weight is too large to allow it to cross the blood brain barrier. Lastly, trastuzumab is very effective in prolonging the life of HER-2-positive breast cancer patients. Since brain metastases are considered a late manifestation of the disease, it may be safe to assume that the correlation between trastuzumab and brain metastases is due to the fact that patients merely live long enough for the central nervous system involvement to become apparent.
Currently, the development of treatment targeted to brain metastases from the breast is focusing on drugs that can cross the blood brain barrier, or