Breast cancer and genetics in Hispanic women
Breast cancer has been shown to be one of the leading causes of death in Hispanic women, and various reports indicate that breast cancer is more aggressive in the Hispanic population. The study of the role of genes and their effect on drug activity began when two separate reactions were observed when a test preparation was administered to the Hispanic group. While some people have been able to metabolize the drug probe, some people have developed signs that they cannot metabolize the drug at all. This started the study of the important role genes play in drug metabolism.
CYP2D6 is a group of liver enzymes that metabolize or break down 25% of all clinically available drugs. The CYP2D6 gene on chromosome 22 is responsible for the production of this enzyme in our body. A variety of drugs used to treat cancer are metabolized by this enzyme. The most relevant drug for breast cancer is tamoxifen and has been used for many years as an endocrine treatment for hormone-positive breast cancer with indications in the metastatic, adjuvant and preventive context. The lower toxicity of tamoxifen treatments compared to chemotherapy helps patients maintain their quality of life and delay the use of cytotoxic treatments (which lead to cell destruction) as long as possible.
Tamoxifen is metabolized by the enzyme CYP2D6 and converted into its active form called endoxifene, which then acts on the body. However, the CYP2D6 gene shows variability between populations and between different ethnic groups. This leads to fluctuations in the level of the CYP2D6 enzyme in the body, which leads to a difference in a person's ability to respond to the drug tamoxifen. The variability ranges from poor metabolizers with zero enzyme levels to ultra-fast metabolizers with very high enzyme levels in the body.
Recent research shows that 5-10% of Hispanic women are poor metabolizers. They are characterized by a slower metabolism of the drug because there are not enough amounts of enzyme. This could lead to the formation of tamoxifen because the body does not have an effective mechanism to eliminate the drug. Overall, the slower metabolism of slow metabolisers can have a cascading effect if several concomitant drugs metabolized by the CYP2D6 enzyme are administered, which increases the potential for undesirable drug effects. Poor metabolizers can therefore be advised to switch to a different treatment because they are unable to convert tamoxifen to its active form, endoxifene. It has been shown that the likelihood of relapse is about three times higher than that of normal metabolisers.
Ultrafast metabolizers still make up 5% of the Hispanic population. They are characterized by an above-average conversion of tamoxifen into its active form endoxifene, which leads to a high therapeutic effect of the drug. Although this population can get the same benefit from a dose lower than the standard dose of the drug, there are potential for serious side effects.
Genetic testing has recently been recommended by the FDA, resulting in a change in tamoxifen labeling that plays an important role in preventing breast cancer recurrence. Accredited DNA testing labs like Genelex offer post-doctor testing and provide personalized and safe reports on the effects of your genes on medication.
Advanced breast cancer - tamoxifen
Tamoxifen has been used to treat advanced breast cancer for 30 years and has long been the first endocrine therapy of choice. It is well tolerated and inexpensive, and serious side effects are rare. The survival rates are the same as chemotherapy, and although the initial response rates are lower, it provides first-aiders with a higher quality of life. Tamoxifen should not be used as a key treatment for advanced breast cancer without meaningful and compelling data from large randomized trials. Response rates depend on patient selection and are higher in patients with estrogen sensitive tumors.
Tamoxifen alone is similar in efficacy to estrogen or progestogen when used alone or in combination, but is better tolerated than most alternative endocrine therapies. In premenopausal patients, there is good evidence that the combination of tamoxifen and a luteinizing hormone-releasing hormone analog (LHRH) is superior to the single agent. This advantage of endocrine therapy in combination with tamoxifen does not necessarily lead to postmenopausal patients. Recently, third generation aromatase inhibitors have been compared with tamoxifen in postmenopausal patients with advanced breast cancer and may have been more effective with reduced side effects.
This opens up potentially beneficial new strategies with combined endocrine therapies - simultaneously and sequentially in patients before and after menopause. Given the proven sequential benefits of tamoxifen in advanced in situ disease and prevention for more than 30 years, aromatase inhibitors are very likely to be effective in all types of breast cancer that are endocrine-prone to breast cancer. Future clinical trials testing endocrine therapies for advanced breast cancer are expected to be extensive, have defined populations and similar biological parameters, and include intergroup collaborations similar to those established for adjuvant studies. This is important to avoid another 30 years for evaluating new endocrine therapies.