Molecular Cloning of BIG3 Gene Associated with Secondary Breast Cancer in the Brain

Running head: DISSERTATION
Introduction
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Author Note

1DISSERTATION
Introduction
Breast cancer refers to the cancer that generally develops in the breast tissue and the
common signs and symptoms of this condition comprise of lump development in the breast,
change in shape of the breast, fluid ejection from the nipple, or scaly red patch on the skin.
Time and again it has been found that major risk factors that are responsible for the
development of breast cancer comprise of reduced physical activity, alcohol consumption,
obesity, hormone replacement therapy, and/or early menstruation age (Neuhouser et al.
2015). Secondary breast cancer, also referred to as metastatic breast cancer refers to stage IV
of the disease where the cancerous cells have spread to sites that are distant from the breast,
farther than the axillary lymph nodes (DeSantis, Ma, Bryan and Jemal 2014). Currently, no
cure has been discovered for secondary breast cancer. It typically occurs more than a few
years after diagnosis of the primary breast cancer, though it is occasionally diagnosed at the
similar time or, seldom, prior to diagnosis of primary breast cancer.
Discussion
Research evidences elaborate on the fact that breast cancer predominantly
metastasizes to the lungs, bone, liver, regional lymph nodes, and the brain, with bone being
one of the most common region (Aceto et al. 2014). Treatment of secondary breast cancer is
dependent on the site of the metastatic tumours and encompasses several means such as,
radiation, surgery, biological therapy, chemotherapy, and hormonal therapy. The brain has
been identified as a unique organ where breast cancer metastasis occurs owing to the fact that
the tumour cells have to cross the blood-brain barrier for development of micrometastasis.
According to Chen and Bourguignon (2014) CD44 is a cell-surface transmembrane
glycoprotein that acts as a hyaluronic acid specific receptor that is responsible for cell
adhesion, which in turn is brought about by binding to particular components of the

2DISSERTATION
extracellular matrix. In addition, CD44 also controls adhesion of the breast cancer cells that
are circulating in the brain, at the secondary site to the endothelium, via the hyaluronate
matrix ligand and/or cytoplasmic attachments. Therefore, the primary aim of treatment is to
regulate and reduce down the spread of cancerous cells to the brain.
Leone and Leone (2015) highlights breast cancer as the common cause of brain
metastases and it is a catastrophic event for patients as it is associated with poor prognosis
and survival of patient. The investigating regarding prognostic factors indicate that tumor
subtypes is a prognostic factor that influences overall survival rate. Another prognostic factor
is the performance status of patients at the time of diagnosis of brain metastases. Some of the
local therapy modalities available for the treatment of brain metastasis include surgical
resection, stereotatic radiosurgery and the whole brain radiation therapy. The advantage of
surgical therapy is that it is associated with improvements in focal deficits and decrease in
intracranial hypertension. In contrast, whole brain radiation therapy plays a role in controlling
macroscopic metastases. However, as brain metastases represent at unmet need in breast
cancer patient, a better understanding of the molecular underpinnings of CNS progression is
needed in future.
According to the "seed and soil" hypothesis particular organs trigger metastases from
one kind of cancer by promoting their proliferation and growth, when compared to other
cancer types. This interaction is generally found to be reciprocal and dynamic, owing to the
capability of the cancer cells to transform the environment where they are present (Liu et al.
2017). Hence, this hypothesis considers tumour embolus as the seed and suggests that the
target organs that are affected by cancer act as the substratum or soil. Secondary breast cancer
in the brain has also been associated with cell-surface sialylation that results in cell–to-cell
interactions. This mechanism is directly responsible for the over-expression of
sialyltransferase in the breast cancer cells that are located in the brain, thereby highlighting