Coming up on 4 years since surgery: some notes on endocrine therapy and more.

Next week will mark 4 years since my bilateral mastectomy. 

At the time, my doctors put me on Tamoxifen for endocrine therapy. One of my tumors was hormone-receptor positive (HR+, or ER/PR+, the most common type) and endocrine therapy was indicated for my treatment. 

In a nutshell, HR+ tumors are fed by the hormones estrogen and progesterone (not sugar, not carbs, not whatever the wellness "expert" on IG says). Endocrine therapy in this case targets estrogen. Mechanisms vary (more on that in a minute.

I was started on Tamoxifen because I was not in menopause. Pre-menopause, we make estrogen in the ovaries. This is largely estradiol (sometimes written as E2). Tamoxifen is a selective estrogen receptor modulator (SERM) that targets the receptors, or the little things on the outside of cells that allows the estrogen to act on it. 

Tamoxifen is generally well tolerated. 

I am not general.

If you're taking tamoxifen, you're probably pre-menopausal. But not for long! The SERMs essentially fast track the feeling of menopause. I stopped having periods pretty fast...but then my doctor warned me they could come back so bonus! Pregnancy was still possible, and I had to have my hormone IUD removed because of the cancer. I've said many times, cancer is the gift that keeps on giving.

I didn't have many of the gross side effects, except one: joint pain. Everywhere. Constant. Nothing helped. I talked through the options with my oncologist, and she was clear: we have the most data on Tamoxifen for my specific case. There were other treatment options but she wasn't as confident in them. I told her that pain didn't scare me, cancer did (I'm an aerialist! I'm used to pain! Hell, we found my cancer because I went in after dealing with hip pain for like 6 months.). We stayed the course.

Each time I see her, though, we do labs. We test my E2 levels. Since my periods stopped, we wanted a physiological marker for whether we thought I was in menopause. There are a lot of questions around E2 testing for non-endocrine therapy patients (i.e., it's not well supported by data!) but in my case it made more sense.

When my E2 levels dropped below measurable, and stayed there for a year, my doctor moved me off a SERM to an aromatase inhibitor.  Post menopause, our ovaries decrease their production of estrogen, and we start making it elsewhere (mostly adrenal glands with some help from fat and skin). Even more interesting, we make estrogen (at all ages) via a pathway that starts with cholesterol. Enzymes turn it into testosterone. In menopause, we don't make as much E2, but do make more Estrone (E1).

The diagram from Wikipedia below is my favorite (everyone in my postdoc lab had it printed above their desk!).

You don't need to really understand the diagram, but the take away is that once we have testosterone (in its various forms), there's an enzyme (fancy word for something that changes one thing into another) that turns testosterone into the estrogens. It's called aromatase.

An aromatase inhibitor (AI) stops the body from turning testosterone into estrogens, which, again feed the cancer cells, so we don't want that. Weirdly, studies show AIs don't work well on E2, which is why it's generally not indicated for pre-menopausal people.

A few months ago, I finally got to move to an AI and like magic, the symptoms stop. At this point, I'd like to point out that bodies are weird, because people react differently to all these medications, even though the end result is the same (DOWN WITH THE ESTROGENS!). Interestingly they rarely test for Estrone at this point; if they know someone is post-menopausal, then the drug will be an AI, and there's not a ton of information that can be gotten here. There's no established "safe" estrone levels, and estrone levels fluctuate like mad. There's some possible data showing it may be important to monitor estrogens in obese people but that's not yet standard of care and the data don't really show it. Finally, AIs work. And they bring estrone down to very, very low levels in the blood. Very, very low levels are very, very hard to measure, and require expensive testing that doesn't really add to the clinical picture. Again, I am not an oncologist, and none of this is medical advice.

In my new-found feeling fine, I was able to discern, for the first time in four years, what was actual injury and what was tamoxifen fucking up my day. And I learned that I've had a herniated disc for a year, and that elbow pain that wouldn't quit was actually some pretty severe tendonitis! Hooray!

So now I'm doing the run of treatments for this, starting with PT (this is when my PT told me that living at a pain level of 5-6 on a good day wasn't normal). After no progress on the back, I moved to a steroid epidural for the inflammation of the nerve (that was yesterday). 

The procedure was so simple and not painful. All the doctors, techs, nurses, PAs...they were wonderful. It is supposed to take 3-4 days to reach maximal effectiveness, and yesterday after the local wore off was not ideal, but not terrible. I learned at 3 AM that the epidural can cause insomnia but even despite that, I'm feeling better today than I have in a while.

I can't complain about progress, but these past few months have been the most insane of my work life (self-employed) that we've ever had. And I've had six doctor's appointments. In June I'm looking at another six or seven. This is expensive and exhausting, but my god it would be good to have a single fucking pain-free day. Unless it's a new aerial bruise. That kind of pain, I'll take.