"Breast Cancer is caused by uncontrolled cell division of the abnormal cells"
What Is Breast Cancer?
Although we have developed lots of understanding about the cancer biology and many therapeutic drugs has been discovered for the treatment of cancers.
We can manage few cancers to some extent such as blood cancer and cervical cancer if detected at early stages.
Still we have big challenge for the development of effective and safe drugs for most of the other cancers. The war against cancer is still challenging.
Cancer is caused by uncontrolled cell division of the abnormal cells. Cancer causing agents are called carcinogens such as chemical carcinogenic (nitrobenzene), DNA damaging radiations (UV raditions) and biological carcinogens (alfa toxin, tumor viruses).
Cancer cells grow and proliferate in defiance of normal controls and able to invade the surrounding tissues and colonise in the distant organs (Metastasis).
Normal cells stop cell division when no more cells are required and undergoes programmed cell death (apoptosis) when it face un-repairable DNA damage while cancer cells do not arrest cell division when there is no more cells are required and becomes resistant to undergo apoptosis.
Most of the cancers arises from a single normal cells by experiencing initial mutation and become abnormal further their progeny cells accumulates additional genetic and epigenetic changes which give them additive advantages to become full blown cancerous cells.
"The war against breast cancer is still challenging"
Development of cancer requires gradual mutational accumulation in various genes- different for different cancers. At each step cancer acquires additional changes to counteracting new challenges during their progression.
Stromal cells evolved along with cancer progression to support the tumour growth. Cancer cells starts secrete some soluble factor which stimulates stromal cells to support the tumor growth.
"Breast cancer is the cancer of mammary gland due to uncontrolled cells division of mammary epithelial cells of the lobules or milk duct of the gland"
Breast is a mammary gland which is mainly meant for the lactation for baby feeding. Breast is glandular fatty connective tissues consist of lobules and ducts.
The basic unit of the mammary gland is alveoli which is lined by milk secreting cuboidal cells and surrounded by myoepithelial cells and these alveoli joined to form lobules which open into the nipple to drain the milk via lactiferous duct.
At puberty when the level of steroid hormones gets increased induced the division of epithelial cells of lobules and ducts.
Fatty connective tissues surround lobules and ducts, protect and give shape to breast.
Oestrogens are among most important hormone to which breast tissues respond under the influence of estrogens the epithelial cells divide in a controlled manner when the level of this hormones abnormal epithelial cells divide in uncontrolled manner and further undergoes some additional changes which leads to development of breast cancer.
Breast cancer is the cancer of mammary gland due to uncontrolled cells division of mammary epithelial cells of the lobules or milk duct of the gland.
Uncontrolled cell division in the fibroblast of the breast stromal tissue is called sarcoma.
"Accumulation of genetic abnormalities, over time, leads to development of a colony of cells which acquired the proliferation potential and outpace the surrounding cells"
Origin Of Breast Cancer
Like most of the cancers breast cancer is also arises from the single abnormal cell which experience initial mutations and start proliferating abnormally and exponentially result in ductal hyper-proliferation which lead to in situ and invasive carcinoma and subsequently get metastases.
As a result of accumulation of large number of individual genetic mutations complex internal signalling system of a cell get altered.
When assembled in a single breast cell, disrupt the control system to the extent that the cell functions autonomously in an erratic and irregular manner.
Continual replication of a corrupted cell results in the formation of a colony of abnormal cells that may accumulate other additional aberrant mutations which gives an additive advantage for the proliferation of abnormal cells.
Both genetic and epigenetic changes are responsible for the cell to become cancerous.
Genetic changes are the resultant of sequence of random, accidental, spontaneous mutations during normal stem cell replication.
Genetic changes are get repaired by DNA damages repair system of the cells.
When the defence system is corrupted, cells carrying the abnormal genes are able to avoid elimination, eventually passing abnormal mutations from one cell generation to the next.
Accumulation of genetic abnormalities, over time, leads to development of a colony of cells which acquired the proliferation potential and outpace the surrounding cells.
Previous studies suggested role of steroid hormones in the induction of the genetic mutation in vitro cultured stem cells these steroid hormones also increases the rate occurrence of genetic mutation in vitro conditions.
"Cytokines secreted by resident or infiltrating cells of the microenvironment either support or inhibits the tumor growth"
Tumor micro-environment also play important role in the progression of the breast cancer.
Breast cancer tumor microenvironment consist of fibroblast, adipocytes epithelial cells, stromal cells and infiltrating cells.
Cytokines secreted by resident or infiltrating cells of the microenvironment either support or inhibits the tumor growth.
Cytokines are small molecular proteins which required in picomolar concentration for their biological activity.
Cytokines are important component of the host defence system mainly responsible for the intercellular communication.
Some cytokines have immune suppressive effect to suppress host immune response after clearance of foreign pathogen.
Cancer cells start secreting these tumor suppressive cytokines to suppress the host immune response against cancer cells and thus these cytokines support the tumor growth alternatively.
"Genetic changes are get repaired by DNA damages repair system of the cells"
Steroid receptor are important determinant for the deciding the treatment for the breast cancer.
Estrogen receptor(ER), progesterone receptor (PR), herceptin receptor (Her2/neu).
Estrogen receptor is most frequently expressed in 70-80% breast cancer while progesterone receptor expressed in 50-70% of the breast cancer.
Androgen receptor, a steroid receptor also play important role in progression of breast cancer.
Several studies reported androgen receptor expressed in 70-90% breast cancer cases however, in some sub types of breast cancer AR receptor positivity associated with poor prognosis while in other sub types it is associated with good prognosis and increased cell overall survival suggest that complex role of androgen in breast cancer.
However, there are debatable study out there about the role of different cytokines in breast cancer and also response of breast cancer cells with different cytokines and androgen receptor and their target genes. In addition, effect of androgen (DHT) and SARM on cytokines profile and on cytokine signalling in breast cancer cells in not well characterized.