Letrozole (brand name Femara)

PatsyKB

I don't know if I should be starting a new thread but the one on Femara has been going on forever. I'm newly diagnosed, through with surgery and radiation and my MO just prescribed Letrazole.

So...new thread for sharing experiences, opinions, side effects, coping mechanisms, etc. What helps, what doesn't?

Side note: my OncotypeDX number came back annoyingly intermediate - 24. So chemo could be an option or not. The gain would be a 3% smaller recurrence probability. Is that enough to warrant what I'd go through with chemo? Of course OncotypeDX assumes a large tumor plus 5 years of Tamoxifen (my tumor was tiny 5mm and no Tamoxifen, but letrozole instead so does this change or alter the accuracy of the OncotypeDX prediction?

Carol2018

I think the new study that came out this week does not recommend chemo for those in the intermediate Oncotype range. You will have to see what MO says. MyMO says the letrazole reduces the likelihood of recurrence further than tamoxifen.

I started letrazole last week. I am having more hot flashes not too bad, and at times I feel a little light headed. Hoping my body adjusts quickly.

I am starting radiation in 2 weeks. Similar do to you except larger tumor.

mustlovepoodles

I've been on letrozole since March 2016. I have had no side effects. My hair and skin look good. I already had arthritis aches and pains, and those have not worsened. I actually lost weight on letrozole, though I have gained some back due to poor choices. My tumor was larger than yours, 1.9cm (19mm) and was also ER+PR-, which is more aggressive. My oncotype was 24, I think, and at the time the tumor board recommended chemo. With the latest study just out, I'm not sure whether they would make that recommendation today.

Lula73

Yes, letrozole has shown better efficacy than tamoxifen in clinical trials.

SEs on letrozole for me have been mild especially compared to what I went through on tamoxifen. I really don't think I could have done 5 years on tamoxifen, but I am confident I can do the 5 and likely the 10 years on letrozole. SEs I'm having: hot flashes, pain/stiffness in pointer finger on left hand down and around to tip of thumb in the mornings (but it goes away after a few minutes of using my hand), some hair loss/thinning (but less than on tamox), some short term memory issues and I'm not as good at multitasking anymore.

I take Solgar brand Curcumin daily for the hand pain & hot flashes and I take Biotin 5000mg daily for the hair thinning.

Lula73

I posted this explanation awhile ago on the Femara board. It explains how these anti-hormonal drugs work and goes in to why it's a 'one size fits all' dose, side effects, blood tests to check various levels and why it's important to shut down that last 20%...

Here's a basic rundown of how all this works:

Before menopause, most of the estrogen in a woman's body is made by the ovaries (approx 80%).

Smaller amounts of estrogen are made elsewhere in the body - Androgens produced by the adrenal glands are made into estrogen in fat tissue through a process known as aromatization (the aromatase enzyme is the key to the androgens being converted to estrogen by our fat cells). This process accounts for about 20% of our estrogen. AIs inhibit the aromatase action.

After menopause, the ovaries stop producing estrogen. This reduces our estrogen levels by about 80%. This leaves only the estrogen made by the aromatization process as our sole source of estrogen.

I'm thin. Does this mean I don't have to worry about the aromatization process and shouldn't need to take an AI or shouldn't need to take the full dose?

Everyone of us, regardless of BMI, size, weight, etc. has subcutaneous fat (the layer of fat that lies between the skin and muscle)
and some level of visceral fat (the fat behind the abdominal muscles that surrounds our organs), so aromatization will happen regardless of how thin or heavy you are.

It has been hypothesized that heavier women may have a higher risk of breast cancer with all other factors being equal compared to thinner women because of this process and the possibility of greater amounts of estrogen production. (key words: hypothesized & possibility). One would think though that since it all starts with the adrenals releasing androgens, that it would go back to how much androgens are released. This hypothesis would only apply to ER+ breast cancers. Anyway that's a whole other topic with no definitive evidence either way. On a side note, being overweight or obese is a risk factor for developing any type of cancer and is true regardless of gender.

Why is the dose not customized for me based on my weight?

There is a lot of discussion on various boards in multiple disease states about why a thin person takes the same dosage as a heavier person. Dosing of medications depends on several different factors and weight isn't always one of them. (Weight is usually a factor for children's dosing as their bodies are not fully developed and so much smaller with far less blood volume than an adult.) Let's take ibuproen or tylenol as an example: dose is based on weight in children but not adults for this very reason. We also know from phase 2 trials that there is an overdose threshold for both. But you likely don't think twice about popping 2-4 ibuprofen/2-3 tylenol at a time for a headache even though the bottle says to take 1-2. Very similar to pain relievers, when it comes to AIs and tamoxifen, weight is not considered a factor based on results from clinical trials. The AIs (as well as practically every other med on the planet) have been tested to find the dose that delivers the greatest efficacy with manageable side effects. Dosing tests are done in phase 2 clinical trials. This is where they test different doses for efficacy and analyze differences in dose vs weight, vs severity/duration of disease, etc. Phase 2 trials can be harder to come across in the public domain and may have to be requested from the pharmaceutical manufacturer. Phase 3 trials are the ones where you really see just how effective a given dose is as that's when they test for efficacy, safety and longer term outcomes. If it makes it through Phase 3 trials then you know the med is as effective/as safe as or more effective/safer than the gold standard drug that was first developed to do what the particular drug does and/or compared to placebo. If there is no gold standard drug in existence then its studied vs placebo for the desired effect with manageable side effects.

Side Effects and Placebo Effect:

Another thing on the side effects listed in the prescribing information of a medication. All the side effects listed may not be caused by taking the drug. You always have to look at the difference compared to placebo. The reason is study participants can experience a placebo effect. (Have you ever noticed how headache, nausea, GI issues and fatigue are listed as a side effect for just about every medication on the planet?) Additionally, if you're in a clinical trial and lets say you get the flu (headache, body ache, nasal/chest congestion, fever, sore throat, body aches, nausea, etc), you have to report those symptoms as side effects to the research doctor even though you know they were caused by the flu and not the drug. The size of the trial hopefully evens out the numbers when the side effect incidences are averaged.

Why isn't my Dr requesting blood work measuring my hormone levels?

They don't test for hormones when you're on an AI because what will you do with the information? You're already doing all you can do by being on the AI. Additionally its a complex and very expensive set of labs that are done and unless you've got something like precocious puberty or growth hormone disorder going on insurance typically will not pay for it (even then they don't like to pay for it). When you have your "hormones" tested by the OB/GYN they are usually just testing for the FSH (follicular stimulating hormone) results. Its kind of a backwards way of testing - the FSH levels go up as the estrogen levels go down. If your FSH levels are elevated that is an indicator of menopause. No need then to order the much more expensive test for estrogen levels. On an AI, your FSH numbers would be high and if we pulled an estrogen level it would be low.

Also if we look at the women taking tamoxifen, their circulating blood estrogen levels often go up on the drug because the estrogen is still being made but cannot enter the cells as tamoxifen blocks it's path. The body may at that point increase estrogen production in response to the lack of feedback from the cells. All this estrogen is now trapped in the blood. The liver will eventually metabolize it but sometimes the liver can't keep up and if you were to pull an estrogen level it would be elevated. FSH would also likely be high as well.

Why do we take AIs if its only addressing 20% of the overall estrogen levels?

When we hit menopause (naturally, surgically or med induced), that 20% just became our new 100%. By stopping the aromatase conversion process, we effectively take that estrogen level down to 0 (or almost 0). Even though the amount of estrogen is lower than before, it does not change the fact that the ER+ cancer cells use it for "food". As long as they have food they will continue to thrive. Here's an analogy: lets say you had an ant infestation at your dog' or cat's feeding dish over the scattered kibble that your pet didn't eat/got pushed out of the bowl. Would it make sense to physically remove all the ants you can see right now knowing there is a possibility that there may be some more in the wall that you can't see (surgery), perhaps lay down some poison to hopefully take care of any strays/reduce the size of the population (chemo if warranted) and then just clean up 80% of the dog/cat's food which allows the remaining ants to survive & reproduce (menopause) if your intent is to eradicate them? That remaining 20% of food just became those ant's new 100% of food; keeping in mind that the demand for that food also went down with the reduction in the ant population from the removal and/or poisoning. Why do some women have recurrence/mets while on AIs? A lot of it goes back to the oncotype tests and recurrence rates. Some cancers are just more aggressive than others and they grow and replicate faster than the AI can starve them. Many women have ER+ & PR+ cancers. Although menopause significantly lowers the amount of progesterone being produced, and we've effectively taken the estrogen level to 0, nothing is stopping the ovaries from producing the little bit they are still making (unless you've had them removed). This can also lead to recurrence/mets. If the cancer is triple + then the HER2 component can come into play as well.