Patients with breast cancer who have a specific genetic defect in the liver enzyme do not respond well enough to tamoxifen therapy.

Disruption of the metabolism of this drug leads to an increased risk of fatalities and more frequent recurrences of cancer.

These results were published by researchers from the Mayo Clinic Cancer Center and their colleagues from the Austrian Breast Cancer and Colorectal Cancer Research Group. The article devoted to this research can be found in the publication "Clinical Cancer Research".

Scientists have found that women with impaired hepatic enzyme CYP2D6 are not able to metabolize tamoxifen, as occurs in patients with normal enzyme activity. This pathology leads to serious consequences due to insufficient effectiveness of cancer therapy.

Lead researcher Dr. Matthew Goetz says that their study has fully confirmed that early onset of breast cancer in the treatment of tamoxifen in patients with a defect of CYP2D6, there are more relapses of cancer and an increase in mortality.

The study included monitoring the incidence of cancer recurrence and mortality in two groups who received a different treatment for breast cancer. The first group included women with an ER-positive type of breast cancer who received tamoxifen for 5 years. The second group included women who received tamoxifen for the first 2 years, and then continued treatment with an aromatase inhibitor anastrozole (which does not require the participation of the CYP2D6 enzyme) for 3 years.

The researchers found that in the first group, women with significant genetic disorders of CYP2D6 had a 2.5-fold higher mortality and a risk of recurrence compared to other patients. The incidence of recurrence of cancer and death among patients with moderate CYP2D6 disorders was 1.7 times higher than in women with normal enzyme activity.

Surprisingly, with subsequent switching from tamoxifen to anastrozole (second group), women with a defect in the CYP2D6 enzyme did not show an increase in mortality and the frequency of recurrence of the disease.

"It is the translation from tamoxifen to aromatase inhibitors that can be the true cause of the contradictory results of previous studies on this issue. Previously, it was simply not taken into account which drugs the patients switched after tamoxifen, "said lead researcher Dr. James Ingle from the Mayo Clinic.

Approximately 6% of women in Europe and the US have genetic abnormalities of the hepatic enzyme, which can disrupt their ability to respond normally to the treatment of breast cancer with tamoxifen. Blood tests can identify genetic disorders of the CYP2D6 enzyme, which would help identify these patients, but they are still not routine practice.

Dr. Michael Gnant, Professor of Surgery at the Medical University of Vienna, says: "The results of this successful international study are a very important step forward in the individualization of the approach to the therapy of breast cancer".

Some medicines for breast cancer work only in certain patients, so a full study of each patient before starting therapy is vital. For example, a previous study demonstrated that women with a low level of pERK protein in tumor-associated fibroblasts also respond poorly to tamoxifen therapy.

The researchers believe that women with a reduced metabolism of tamoxifen should be examined and, if necessary, transferred to aromatase inhibitors (no later than 2 years of treatment).

This will help to achieve high effectiveness of therapy.

In order for tamoxifen to act, in the body it must be completely converted into an active metabolite of endoxifene. Dr. Goetz, who now works at the National Cancer Institute of the United States, is trying to develop a method of administering to patients with a deficiency of CYP2D6 the very endoxifene - a ready active metabolite. His work is capable in the near future to resolve the problem of such patients.

medbe. en.