Estrogen binding to the estrogen receptor (ER) promotes proliferation in mammary

Question

Estrogen binding to the estrogen receptor (ER) promotes proliferation in mammary cells. ER+ breast cancers are treated with anti-estrogen therapies that target estrogen or ER. This causes a loss of proliferation of the tumor cells. However, ER+ tumors that also overexpress HER2, a receptor tyrosine kinase, do not usually show reduced proliferation upon anti-estrogen therapies, and alternative therapies must be used. Propose why the ER+/HER2+ tumors do not show reduced proliferation when treated with anti-estrogen:s.

Explanation / Answer

One of the major reason's of breast cancer is excessive secretion of hormones estrogen and herceptin in the body. The breast tissues bear the receptors for these hormones and once these hormones bind to these receptors, they get internalized into the mammary cells and promote extensive cellular proliferation, thus cancer. Thus, anti-estrogen and anti-herceptin therapies are generally used to either cure or at least control extensive cellular proliferation/cancer in the breast tissues.

However, there are some ER+ mammary tissues present in some patients which do not respond to anti-estrogen or anti-herceptin therapies. These rare cases of breast cancer show tolerance against these hormones and discrete cellular mechanism. Studies have shown that presence of estrogen and herceptin receptors in these cells promotes cellular proilferation, and even in the absence of these hormones, the mammary tissues are able to modulate autocrine secretion of these hormones which in turn promotes cellular division. Thus, this suggests that whereas hormone negative tissues are susceptible to anti-hormone therapies as they do not mediate autocrine hormone secretin, hormone positive tissues are not susceptible to anti-hormone therapeis as they are able to maintain autocrine secretions. Hence, treating such cancerous tissues with anti-hormone therapies generally bears no clinical relevance.

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