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Отнася се за т.н. TRIPLE POSITIVE BREAST CANCER (ХЕР 2+, ер+, пр+)
При пациенти, при които е установено ер+ и пр+ се налага да се прави хормоноподтискаща терапия с Тамоксифен или AI's инхибитори ( Фемара и др.).
При около 10% от пациентите Тамоксифен не се усвоява добре от организма. Тамоксифен не е активната част на самото лекарство. Чернодробните ензими и най-вече ензима CYP2D6 преработват Тамоксифена до активната съставка endoxifen, която именно подтиска ЕР+ и ПР+ рецепторите. При около 10% процента от пациентите с рак на гърдата, се наблюдва неспособност точно на този ензим CYP2D6 да превърне Тамоксифен до активната съставка endoxifen. Това води до неефективно лечение. Лекарите предполагат, че при тези пациенти / които не метаболизират добре Т./, Тамоксифен не само не успява да подтисне ЕР рецепторите, но и стимулира Хер 2 рецепторите.
/знаем, че хер 2 гена определя агресивността на тумора и вероятността бързо да метастазира/. Това води до активно увеличаване на раковите клетки.
Поради тази причина някои лекари избягват да изписват Тамоксифен, без направен тест за метаболитност на CYP2D6, тъй като проучвания сочат, че Тамоксифен при някои пациенти има две лица: в основната си роля подтиска ЕР, ПР-рецепторите, но също така"стимулира, храни" точно ХЕР2рецепторите. Разбира се има ХЕР2+ пациенти, които се повлияват много добре от Тамоксифен.
Ще се радвам, ако някой сподели дали в Б-Я може да се изследва чрез кръвен тест метаболитният статус на CYP2D6 ензима и по-този начин евентуално да се съди за ефективността на провежданото лечение с Тамоксифен.
ето статията на англ.
"Many of you may have seen references indicating that women with Her2+ BC don't do as well on tamoxifen as women with Her2- BC. In fact, there have been studies that demonstrated that tamoxifen can actually fuel Her2+ cancer growth in cell cultures. I asked my Mayo onc, given this, why shouldn't I have ovarian suppression (Lupron or ooph) and take an AI instead of tamoxifen? He explained to me that tamoxifen is not the active form of the drug. Tamoxifen is what is known as a pro-drug, it must be metabolized by the body into its active form called endoxifen. Unmetabolized tamoxifen can indeed fuel breast cancer growth. However, the metabolized form of the drug (endoxifen) is an extremely potent blocker of the estrogen receptor (recent research from Mayo has shown that endoxifen actually degrades estrogen receptors in cancer cells, slowing their growth). My onc went on to say that endoxifen is so potent, it blocks any stimulating effect tamoxifen has on breast cancer.
The potential problem is when tamoxifen is not effectively metabolized to endoxifen. An enzyme in the liver called CYP2D6 is responsible for the metabolism of tamoxifen into endoxifen. About 7% of Caucasians and African Americans are "poor metabolizers". They inherited a genetic form of the CYP2D6 gene that does not allow tamoxifen to be converted into endoxifen. In hormone receptor positive BC (the population including both Her2- and Her2+) poor metabolizers have significantly higher rates of breast cancer recurrence than good or "extensive metabolizers". There have been a few studies published that demonstrated this effect.
He went on to tell me that Her2+ poor metabolizers do exceptionally poorly on tamoxifen, much worse than even Her2- poor metabolizers.
There is a simple blood test that will tell you your metabilizer status. It costs only a few hundred dollars and some insurance will pay for it. I think its a good idea for all patients that are considering taking tamoxifen to be tested. But in light of what my onc told me about Her2+ BC having a much poorer prognosis if you are a poor metabolizer on tamoxifen, I think it is critical for Her2+ women.
Why not just go on an AI? My onc was very much in favor of tamoxifen for EMs due to quality of life issues and he was confident that Her2+ EMs do very well on tamoxifen. With trepidation, I went along with it; I have been on tamoxifen for a little over a year. Later, I found evidence that Her2+ EMs do, in fact, do very well on tamoxifen. (I'll explain in a later post as this one is getting very long).
In addition to "extensive metabolizers" (EMs) and "poor metabolizers" (PMs), there is also a group of people that inherited one of each gene. These people are termed "intermediate metabolizers (IMs) and in the Mayo study including all hormone receptor positive BCs (Her2- and Her2+) IMs fared slightly less well than EMs, but significantly better than PMs. We did not discuss the impact of IM status on Her2+ women.
Bottom line: If taking tamoxifen, please consider getting tested for metabolizer status. Also, stay away from drugs that interfere with the metabolism of tamoxifen."
Редактирано от nelly_83 на 08.02.11 01:39.
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Re: Въпрос за HER-2 [re: harico]
