Does anyone know about CYP2D6 and Tamoxifen?

Redcanoe

Hello, I was diagnosed with triple positive IDC this past fall and just completed TCH chemo and I'm about to start radiation. My oncologist is planning on prescribing Tamoxifen after I'm done radiation.

Due to my younger age, I was advised to take the color.com hereditary cancer test to see if there was a generic component (there isn't). However, there was also an analysis of how I metabolize drugs and I am an "intermediate metabolizer" of CYP2D6, which is the one associated with Tamoxifen.

I'm going to ask my oncologist about it but I'm finding it hard to find much information. I want to make an informed decision when discussing this. The alternative is ovarian suppression and an AI or a higher dose of Tamoxifen. Or maybe go ahead as planned?

Salamandra

My understanding is that the concern is that tamoxifen won't be as effective for women with that genetic variation, however that is based on the scientific understanding of the mechanisms involved rather than clinical/experimental evidence.

However, that variation is much more common among Asian women, and therefore they also more commonly use an alternative SERM - toremifene. In the USA, that drug is FDA approved for advanced cancer rather than prevention of recurrence in premenopausal women.

But as far as I could tell and in the end my doctor conceded, the research evidence for toremifene is just as strong as the clinical evidence for OS+AI in premenopausal women.

I ended up on toremifene because I couldn't tolerate tamoxifen, but I had to advocate for it.

Consider asking your doctor to look into it for you. It is a good and underutilized alternative.

Rah2464

I am an intermediate metabolizer on Tamoxifen. Salamandra is correct, there is not any study out there that correlates intermediate metabolizer to poor outcomes on Tamoxifen. Since I was premenopausal, my MO and I discussed that 1) no reduction of dosage for me was appropriate and 2) I had to be very careful not to add in any supplements that interfered with what processing I could do. So if there is a supplement I want to try, we discuss first. We just recently spoke about Curcumin. That was a no, as it interferes with the CYP2D6 pathway.

If you are going to go the Tamoxifen route, just a word of caution. Please get a baseline DEXA scan, and push for a scan in one year. I went two years before a rescan, and lost way too much bone mass. Tamoxifen taken premenopausally can be hard on your bones, albeit not as hard as an AI.

gb2115

I plan to ask about this at my next visit. I'm in the middle of dealing with a hormone positive recurrence after being on (and suffering through) tamoxifen for 4 years, so I question if it was working for me.

I've been off of it for a week and a half in preparation for mastectomy, and I seriously feel better. My joint and muscle pain is much improved.