One in every eight women will develop invasive breast cancer. Recently, breast cancer has been a hot topic in research. There have been studies reporting that estrogen and iron may play a role in the fight against the cancer.

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Albert (Dong Han) Kim

Red Class

December 20, 2011

Dupont Essay

Title: Estrogen and Iron: A Cure for Breast Cancer?

One in every eight women will develop invasive breast cancer. Recently, breast cancer has been a hot topic in research. There have been studies reporting that estrogen and iron may play a role in the fight against the cancer. Estrogen and iron are two important growth factors in a female’s body development. Estrogen influences the growth, differentiation, and function of tissues of the female reproductive system (Zhu et al, 1998). Iron is essential for oxygen transport, DNA synthesis, and energy metabolism (Ganz, 2008). Estrogen and family history are well-established risk factors for breast cancer (BC) (Clemons et al, 2001). However, estrogen cannot fully explain why young women diagnosed with BC are more likely to have a higher risk of recurrence and mortality than their older counterparts (Klauber-DeMore et al, 2005). Paradoxically, when overall systemic estrogen levels are decreased, BC incidence rate is higher in post-menopausal women than in premenopausal women (Benz, 2008).

It has been investigated whether an imbalance in iron levels could account for some important BC features, which are unexplained by estrogen. Young post-pubescent women in reproductive years are exposed to high systemic estrogen levels endocrinologically regulated by the hypothalamus-pituitary-ovary axis (Prior, 2005). Menstruation, resulting from the detachment of the endometrial matrix prepared for egg fertilization, marks this age group. In the absence of fertilization, the matrix, mixed with blood, is shed monthly. This monthly blood loss commonly results in iron deficiency among women of this age group (Zimmermann et al, 2007). Therefore, the natural biological system in young women is high estrogen and low iron.

 As women pass through the transitional phase, ovarian functioning diminishes and then ceases. Systemic levels of estrogen drop and become static from the previous pattern of cyclic, but high levels. Cessation of menstruation marks latter stage of this transition. Observations have been made with levels of ferritin, an iron storage protein with a capacity of binding up to 4,500 atoms of iron per molecule of ferritin (Torti et al, 2002), and transferrin, an iron transport protein with two binding sites for iron, are significantly higher in postmenopausal women than in premenopausal women (Ali et al, 2002). While estrogen levels decrease during the menopausal transition, a concomitant but inverse change occurs in iron levels. For example, levels of serum ferritin are increased by 2-3 fold. Therefore, the reverse is true in older women: low estrogen and high iron.

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Changes in estrogen levels during menopausal transition have been considered a unique feature in women and the effects of estrogen on BC are well documented (Clemons et al, 2001). Separate studies on estrogen and iron as a function of age and menopausal status have concluded to younger pre-menopausal women have high systemic estrogen but low iron levels (Huang, 2008). Older post-menopausal women have low systemic estrogen but high iron levels (Subramanian et al, 2008). 

This observation led the development of simple tissue culture models that simultaneously mimic levels of iron and estrogen in pre- and postmenopausal women and the detection of the inhibitory ...

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