Overexpression of Androgen Receptors and Tamoxifen Resistance

Breast tissue and breast cancer tumors can express a number of different hormone receptors.  While we generally hear about estrogen receptors, progesterone receptors and HER2 receptors most frequently, androgen receptors have also been shown to be present in breast cancer tissues.  While the role of androgen receptors in breast cancer is still uncertain, some early studies have shown that androgen receptor expression might be associated with better breast cancer outcomes , something I've blogged about before .  However, recent breast cancer research suggests that the level of androgen receptors might have an important impact on breast cancer.

A new breast cancer study has examined the impact of androgen receptor expression on breast cancer response to tamoxifen.  For their study, the breast cancer researchers first measured androgen receptor expression levels in breast cancer tumors and then tested the effect of these levels on tamoxifen resistance.  The study investigators reported that

• Tamoxifen-resistant breast tumors had elevated levels of androgen receptor expression and decreased levels of estrogen receptor-alpha expression.
• Breast cancer cells over-expressing the androgen receptors in culture or implanted into mice were shown to be resistant to tamoxifen treatment.
• Treatment with a compound to block androgen receptor activity reversed this tamoxifen resistance.
• In cells over-expressing the androgen receptor, tamoxifen activated estrogen receptors instead of blocking their activity.

These are potentially important results that could have a substantial impact on breast cancer therapy.  While previous studies have suggested that the presence of androgen receptors in breast cancer might support better outcomes, this new study suggests that when these receptors are present at too high of a level breast cancer tumors might become resistant to tamoxifen therapy.  In these cases, treatment with androgen receptor blockers might prevent tamoxifen resistance.  However, it is unclear if this will also negate the possible benefits of androgen receptors on breast cancer outcomes.  Additional pre-clinical and clinical studies will be needed to better understand this relationship between the level of androgen receptors and breast cancer.

While the medical community continues to find way to improve breast cancer treatments, we can proactively make changes in our lifestyle to help reduce our risk of breast cancer.  Read my book Fight Now: Eat & Live Proactively Against Breast Cancer to learn more.