UJI researchers develop a new method of analysis that allows advancing the individual response to treatment of breast cancer with tamoxifen



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## UJI researchers develop a new method of analysis that allows advancing the individual response to treatment of breast cancer with tamoxifen Individuals metabolize medicine differently according to their genetic variation

23/03/2015 |
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* [![ cancer-mama tamoxifen_web](/com/noticies/2015/03/2q/cancer-mama/tamoxifen_web.jpg)](#)

Tamoxifen is a prodrug widely used in the treatment of breast cancer, but the response of people to it depends on their ability to metabolize it into endoxifen. Researchers of the Department of Analytical Chemistry at the Universitat Jaume I; of the Department of Criminology and Forensic Sciences at Dr. H.S. Gour University in Sagar, India; and of the Provincial Hospital of Castellón have developed a new method that allows, through a simple blood test, knowing in a short time the way each patient metabolizes the drug, information that is useful to learn the possible response to treatment, and depending on it, allows adjusting the drug dose.

The success of the treatment based on tamoxifen depends fundamentally on the ability of one the enzymes of the cytochrome P450 family to metabolize the drug and transform it into its most active metabolite, endoxifen, which antitumor activity is far superior to tamoxifen. Researchers of the research group Bioanalytical Chemistry at the UJI and the Laboratory of Molecular Pathobiology of the Provincial Hospital of Castellón, Josep Esteve, Juan Vicente Peris and Enrique Ochoa, explain that "the family of cytochrome P450 consists of many genes, one of which contains many CYP2D6 genetic variations (polymorphisms), some more active than others for the metabolism of many drugs, among which tamoxifen stands out. Doctors do not normally have genetic information and, therefore, do not know the responsiveness of the patient. It is important to keep in mind that there are also other factors influencing responsiveness as diet or drug interactions."

A possible way to evaluate individual response to tamoxifen is to measure the levels of the prodrug and its derivatives in peripheral blood of the patient. The method developed applies the so-called micellar liquid chromatography with fluorescence detection for quantifying endoxifen and tamoxifen in plasma samples taken to breast cancer patients at least one month after them being given the treatment. “The analysis allowed seeing the metabolic capacity of tamoxifen in patients when testing the variations in the levels of tamoxifen and endoxifen, which in turn were correlated with the genetic analysis of polymorphisms of the CYP2D6 gene, which classified the patients in ultrafast, extended, intermediate and poor metabolizers. This analysis allowed founding such association, which allows, using a simple MLC analysis, a better adjustment of the drug, increasing the chances of successful treatment”, the researchers explain.

The researcher of the UJI, Josep Esteve, notes that "compared to other existing methods, the approach developed allows testing for assessing the ability of metabolization of tamoxifen in a clinical laboratory within a reasonable time and without the high costs that other tests involve".

**Bibliographic reference:**

‪Enrique Ochoa de Aranda, Josep Esteve-Romero, Maria Rambla-Alegre, Juan Peris-Vicente, Devasish Bose.  ‪["Development of a methodology to quantify tamoxifen and endoxifen in breast cancer patients by micellar liquid chromatography and validation according the ICH guidelines](http://‪http://www.sciencedirect.com/science/article/pii/S0039914011000543)."  ‪*Talanta*. 84, 314-318 (2011).

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