Drug Resistance Mechanism in Breast Cancer Brain Metastases

Running head: RESEARCH PAPER ON BCBM
DRUG RESISTANCE MECHANISM IN BREAST CANCER BRAIN METASTASES
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RESEARCH PAPER ON BCBM1
Introduction:
The paper aims for researching on the topic of drug resistance in HER-2 positive Breast
Cancer Brain Metastases. HER-2 stands for the term Human Epidermal Growth Factor Receptor
2. The HER-2 is a type of receptor tyrosine kinase protein that is present in the normal cell and
can be associated with the control of the growth of the cell. However, in case of some cancer
cells, those HER-2 proteins are expressed in an excessive level, which results in the uncontrolled
growth of those cancer cells. An excessive expression of the HER-2 proteins is the causal factor
for those cancers. In the case of stage IV breast cancer, there is a huge risk of the women
developing metastasis, which can reach to brain. The incidence is known as breast cancer brain
metastasis (BCBM) (Witzel et al.).
There are various challenges that are considered to be in association with the problem of
breast cancer brain metastasis. The disease condition is associated with a very poor prognosis.
One of the treatment procedures used to treat the HER-2 positive BCBM is the use of various
targeted drugs. The drugs have been found to have various harmful side effects on the patients,
such as a damage to the heart, dyspnea, lung disease and various others. The use of those drugs is
very risky in pregnant women, since it may cause the death of the fetus. The drugs are also found
to be ineffective in treating the disease condition sometimes due to the frequent drug resistance
phenomenon that are often found these days. It has also been found from a study that the rate of
metastatic relapse in the central nervous system (CNS) is much higher in the patients who have
been treated with adjuvant trastuzumab. The paper will be focusing on discussing the
significance of all the treatment procedures related to BCBM first. After that, the mechanism of
the drug resistance will be discussed in detail.

RESEARCH PAPER ON BCBM2
Significance of the Drugs and the Other Treatment Therapies:
HER-2 Systematic Therapies:
Trastuzumab is an HER-2 targeted drug and is a human monoclonal antibody in nature. It
is used with chemotherapy sometimes and sometimes it is used completely alone. The drug has
been found to have a considerable efficacy level in treating the Stage-I HER-2 positive breast
cancer. The drug is also used in the patients, who are experiencing a relapse. The drug works by
interfering with various chemical signals that are responsible for the uncontrolled growth of the
cancer cells.
The use of Afatinib drugs has been seen to improve the prognosis event in case of the
HER-2 positive breast cancers. A study has shown the Afatinib drug to be effective while
adapting a treatment approach for HER-2 positive breast cancer. The study was conducted to
examine the efficacy of the drug in the treatment of HER-2 over-expressive breast cancer. The
drug is an inhibitor of pan-HER tyrosine kinase, which fall under the irreversible inhibitor
category (Cortés et al.). It has also been observed that the drug is more effective when
administered with trastuzumab drugs.
Lapatinib is a tyrosine kinase inhibitor drug and thus effective in the inhibition of the
HER-2 receptor, which is a tyrosine kinase protein in nature. It has been found from the studies
that this drug is very effective in the treatment of the HER-2 positive BCBM. The drug is able to
diffuse through the blood-brain barrier effectively and prevents the growth of the cancerous cells
easily, unlike various other treatment procedures, which are unable to cross that barrier to
provide the proper treatment.