Endocrine therapy for breast cancer: what's next and why?

Weird shit that's been in my body

This week, we got a microscope. Ostensibly, it's for diagnosing hardware issues, solder bridges, bad solder points, etc. We immediately put some prototypes under it and had a good old time, but the first actual pictures I have taken with it are these: the titanium clips they put in the tumors when they biopsied them. 

Refresher: before we knew I had cancer, I had a biopsy of my left breast. Then they spotted a weird thing in the right one, so that got a biopsy too. When they biopsied each tumor, they put a tiny titanium clip there to mark where they had sampled. This was meant to 1. make the spot easier to find in surgery, if it came to that, and 2. if it wasn't cancer, to mark the spot as a known weird spot on future imaging. It's like a flag that says nothing to see here, move along.

Anyway, the clips are one of things I got back from my friend in pathology and they don't look like much in the oversized containers they are in, so under the scope they went. Sadly, I no longer have titanium in me, but they will get framed and hung on a wall because I am that kind of weird.

But this post is about what's next: endocrine therapy: what, why, how.

What is endocrine therapy and why do you need it?

Everything I'll be talking about is specific to hormone-receptor positive (HR+) cancer, which is what I had. Both of my tumors were ER+ and PR+. That means on the outside of the tumor cells, they had little receptors for estrogen and progesterone, two hormones made in various places in my body, but most notably, the ovaries for premenopausal women (who have ovaries). After menopause, the estrogen levels drop, and the main production shifts to other tissues, like fat (!).

When estrogens and progesterone attach to those cancer cells, it allows them to make more cancer cells. This is bad. We don't want more cancer cells. (This is also why this type of cancer is sometimes called estrogen-fed cancer.)

I thought you had surgery to remove said cancer?

I did. But cells are tiny and cancer is a sneaky bastard. And even with a mastectomy, some tissue remains. Is there a single cell of that little bastard lurking in that remaining tissue? It is impossible to know. 

That's why, while I have a low likelihood of recurrence, it's hard to know if I am totally cancer free. Here's a good quick explainer on terms like remission, cancer-free, etc.

How does endocrine therapy for breast cancer work?

This is pretty technical, and I'll gloss over a LOT here. And if any random folks happen to find this post, it's not medical advice. I am not a doctor, at least not a real doctor, as my real-doctor brother reminds me. I don't know cancer so well, but I do know endocrinology.

Estrogens (plural because they are a group of hormones), testosterone, and progesterone (among others) are sex hormones, and are in a category of hormones called steroid hormones. They are all synthesized in the body from a molecule you've heard of: cholesterol. When I was doing my postdoc in an endocrine lab, we all had this figure printed and posted at our desks:

https://en.wikipedia.org/wiki/Steroid#Steroidogenesis

I used to have most of this memorized but now I focus more on routing PCBs so I've forgotten a lot sadly. 

In any case, it's really complicated and shows the molecular structures of all the hormones and pathways and all sorts of things you don't need to worry about but let's focus on a few things:

- All things are made from cholesterol. 

- there are several roads to the androgens, which include testosterone (T).

- Estradiol (E2), which is the dominant estrogen in premenopausal women, is made from testosterone: in fact, the molecules are VERY similar.

- Going from T to E2 is simple and is done by something called an enzyme. 

Don't worry about what an enzyme is, just know its name is Aromatase.

The goal is to stop feeding any cancer cells that may have not been removed with the surgery, which means we want to make sure that the tumor cells stop getting estrogens. 

There are a variety of medications out there that approach endocrine therapy in different ways, and really are tailored to different populations. It blew me away how MANY interesting studies out there, with so much more research being done, but there are a couple of main categories:

Selective estrogen receptor modulator: notably the drug tamoxifen. These don't prevent the body from making estrogen, but instead target the cancer cells and act like estrogen. But they AREN'T estrogen so rather than being "food" for the cancer cell, when it binds, it poisons it and prevents it from making more cancer cells. What's bizarre here is the "selective" part of that title -- tamoxifen targets breast tissue very specifically and in other tissue with estrogen receptors may act differently. Selective.

Aromatase inhibitors: notably anastrozole and exemestane. Aromatase is that thing we just talked about that makes testosterone into estrogen. Aromatase inhibitors make aromatase not do that. Simple.

Before menopause, estrogen levels are pretty high because the ovaries crank it out. After menopause, the ovaries hang up their hats, so to speak, and levels drop. The different types of drugs work for different women: generally, aromatase inhibitors are only given to women who are postmenopausal, though there are some neat clinical trials out there using oosuppression (aka ovarian suppression or ovarian ablation, where they use one of a variety of methods to prematurely put the patient into menopause) and then use an aromatase inhibitor. 

This is extremely simplified. Questions? If you know me, ask me.

What's the plan?

I'm young and premenopausal, which puts me squarely in the tamoxifen camp. Tamoxifen has been around for a few decades and we know a fair bit about the expected side effects: generally, it's well tolerated, and the side effects tend to be pretty minimal. 

I discussed options with my oncologist just in case I don't do well on the tamoxifen (and because I just generally had questions after reading so many papers). For example, a really cool set of trials (TEXT and SOFT, a layperson's explanation) has looked at whether using oosuppression in combination with tamoxifen or one of the aromatase inhibitors is helpful.

Oosuppression is nasty: it's done with medication, surgery, or through irradiation. None of these sound nice. Also, it comes with side effects: it's premature menopause, so it would mean lots of checking of bone density (which is unpleasant), and other nastiness. The trials seem to indicate that this extra step gave the most benefit in people with the highest risk of recurrence, so given my reasonably low risk, she said it was probably not indicated. I'm all for that!

So tamoxifen. Standard course is five years, so I'll be seeing tamoxifen at least as long as I'm seeing my surgeon...but there is some indication that younger people benefit from being on it for ten years, so for now, we are just saying it's a 5-10 year course, with room to re-evaluate as research turns up more and more information. Maybe there will be evidence that leads her to suggest we change the medication. Maybe I'll be one of the unlucky ones with a recurrence. Since it's all unknown, I'm going with what the science (and my oncologist) says is the best course of action for now, based on all the information we have.

So you're otherwise "normal" now then?

LOL I started this post with a picture of something that was once inside my body so I'm not sure that world would ever be used to describe me...but no.

I am lucky to get a half day in of work. When I've tried to do more, I've suffered for it. Yesterday I went to the post office and atm and then faceplanted for hours (actually backplanted because being face down isn't really an option quite yet). I tire easily and still eat all the protein. I'm not really up to being particularly social yet because I am just constantly wanting to nap.

The pain is manageable though I have entered a phase of physical therapy where the therapist explicitly told me I need to stay ahead of it and she was not wrong. Still have to wear sleeves too because of the armpit discomfort, but that is getting better and the end seems like it may be in sight.

But also, for four weeks post-op, I'm way better than I expected and none of those are complaints at all.