Mufudza2012 - Estrogen effect on the dynamics of breast cancer
Breast cancer is the second most common cancer in women around the world1. The initiation of breast cancer is due to transforming (genetic and epigenetic) events at a cellular level. Tumor is progressed by the accumulation of additional genetic changes combined with clonal expansion and selection. However, Some of the studies have focused mainly on the tumor epithelial cells in other case the potential involvement of other epithelial and myoepithelial cells and the stroma in tumor progression have not been investigated in intensely. There are several factors that may increase the chance of developing breast cancer, some of which can be changed while for others there are no ways. Some of these factors include of alcohol, obesity, high dose radiation, hormonal aberration etc. Besides having first degree family history of breast cancer increases the risk of having a breast cancer by two-fold. Although, having a high-risk factor or several does not mean that one will automatically develop breast cancer 2.
The hormone estrogen is essential for normal development of reproductive system and functioning of human organs important for childbearing like ovaries, uterus and breasts as well as maintaining of menstrual cycles. But estrogen has also been implicated to be involved in causing cancer. It can cause cancer in two ways. Firstly, acting as a mitogen that induce breast tissue to increase mitosis and that leads to cancers due to error in cell division. Secondly, certain metabolites of estrogen can act as carcinogens by directly damaging DNA and thereby causing cancer3(Figure 1).
A deterministic mathematical model was developed that showed the general dynamics of breast cancer with immune response. The effect of estrogen is then incorporated in the model showing that the presence of extra estrogen increases the risk of developing breast cancer. The model consists of four population model that includes tumor cells, host cells, immune cells and estrogen. It is divided into two parts. First part is Estrogen free model and second is model with estrogen
Figure 1: Estrogen inducing breast cancer 4
Figure 2: Graphs showing propagation of normal cells (a), tumor cells (b) and immune cell (c) with estrogen variation.
Results and Conclusion
The results show that the model is stable when the immune resistance is greater than growth rate. They have shown that increasing the rate of production of estrogen (pi) from 0 to 0.3, 0.6, 0.9 makes the system unstable implying additional estrogen would increase the rate of tumor development. This is supported by Figure 2 (A) which show that normal cells grow normally without excess estrogen level (pi=0) and with increase rate of estrogen level (pi >0 ) the normal cell growth is negatively affected. Although with increasing estrogen level it is favorable for tumor cell population. With low rate of estrogen production (pi = 0) level the tumor cells can be checked by immune cell but rises to uncontrollable level as the system becomes unstable due to increase in estrogen level (pi= 0.3,0.6, 0.9) denoted by Figure 2(B).
Figure 2 (C) shows that immune levels are reduced with the increase in estrogen level making the immune system weak and instable to fight against developing cancer whereas the estrogen free model is stable.
The presence of excess estrogen will lead into situation where the disease become uncontrollable and no control measures can stabilize the system in presence of excess estrogen. The results clearly state a negative relationship between estrogen amounts and tumor cell development. Although it must be stated that this whole model might fall short in certain cases where sometimes the formation of cancer depends on the genetics on individual like the ability of DNA to resist change in structure and the natural estrogen present in that individual.
1. Cancer Fact and Statistics 2011. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2011.html. Accessed December 6, 2019.
2. Cancer Facts & Figures 2012 | American Cancer Society. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2012.html. Accessed December 6, 2019.
3. Yager JD, Davidson NE. Estrogen Carcinogenesis in Breast Cancer. N Engl J Med. 2006;354(3):270-282. doi:10.1056/NEJMra050776
4. ER-positive breast cancer: Risk factors, symptoms, and treatment. https://www.medicalnewstoday.com/articles/316779.php#hormones-and-breast-cancer.