Precision treatment options impacting breast cancer

Tamoxifen has been used to treat breast cancer for a number of years, reducing the recurrence rate to ~30%. The effectiveness of tamoxifen is not consistent, however, with resistance to treatment a common observation in therapy. A team from the University of Bergen in Norway, have identified a biomarker which they believe is the root of tamoxifen resistance.

In their recent paper published in the Journal of Personalized Medicine, the team focuses on how tamoxifen is broken down in the body.  Tamoxifen, when broken down in the body, leaves two metabolites – endoxifen and 4-hydroxy-tamoxifen – both of which are active in attacking breast cancer cells. The lack of clinical studies on these 2 metabolites has made it difficult for researchers to assess their specific impact on the disease.

A specific enzyme – CYP2D6 – is largely responsible for the levels of endoxifen that circulate in the body following treatment with tamoxifen. The research team examined previous research to clarify the impact of genetic subtypes of CYP2D6 to understand if there was an individual component to the problem of resistance.

The team looked at levels of endoxifen and used this to correlate against the effectiveness of tamoxifen treatment, using endoxifen levels as a measure of metabolic resistance to treatment. The team identified that variants of the CYP2D6 gene is impacted by race. For example, a reduced activity is implicated in around 40% of Asian patients, but only 6% of patients of African and European descent. Other subtypes of the gene also exist, with varying degrees of activity in metabolising tamoxifen.

The researchers believe that research in this area can lead to the development of a more precise algorithm for predicting endoxifen levels, based on the genetic makeup of patients around the CYP2D6 gene. This information can be used to help clinicians find the most appropriate dose of tamoxifen for breast cancer patients, even decide if CYP2D6 blockers might help identify therapeutic options.

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