LETROZOLE AND THE HALF WHO STOP TOO SOON
In one large study of 8,769 women prescribed hormone tablets after breast cancer, only 49 percent took them for the full planned time at the right schedule.
Women who stopped early had a higher risk of death in that study.
This post explains one of those tablets, letrozole, so that the years of treatment make sense.
WHAT LETROZOLE IS
Letrozole is a small 2.5 mg tablet taken once a day. Doctors use it for hormone receptor positive breast cancer in women after menopause. It is used after surgery to lower the chance of the cancer coming back, after five years of tamoxifen for extra protection, and in advanced cancer to keep the disease under control.
WHERE ESTROGEN COMES FROM AFTER MENOPAUSE
After menopause the ovaries make very little estrogen. Yet estrogen does not disappear. An enzyme called aromatase keeps making it in tissues around the body, and even inside the breast tumour itself. It does this by converting hormones from the adrenal glands into estrone and estradiol.
Some breast cancers use that estrogen as fuel to grow.
HOW LETROZOLE CUTS THE FUEL
Letrozole binds tightly to the iron centre of the aromatase enzyme and jams it. Picture a factory with one central machine that turns raw material into estrogen. Letrozole jams that machine.
Within two to three days, estrogen levels in the blood fall by 75 to 95 percent. In one small study, letrozole blocked more than 99 percent of the body's estrogen production in every woman tested.
The tablet is also precise. It leaves the stress hormone cortisol, the salt balancing hormone aldosterone and thyroid function essentially untouched.
WHY IT IS FOR WOMEN AFTER MENOPAUSE
In women whose ovaries are still active, cutting estrogen would be expected to make the brain push the ovaries even harder. For that reason, guidelines only use drugs like letrozole before menopause together with treatment that switches off the ovaries.
WHAT THE BIG TRIALS FOUND
In the BIG 1-98 trial of over 8,000 women, letrozole lowered the risk of the cancer returning compared with tamoxifen, and lowered the risk of it spreading to distant organs by 27 percent.
When researchers pooled data from nearly 32,000 women, five years of an aromatase inhibitor cut the risk of dying from breast cancer over ten years by about 40 percent compared with no hormone tablet at all.
Letrozole lowers risk. It does not guarantee anything, and it is not described as a cure. For a woman at medium or high risk after menopause, it sits at the centre of the plan. Exercise, diet and supplements support that plan. They never replace the tablet.
HOW THE BODY HANDLES IT
Letrozole is fully absorbed whether taken with food or not. It lasts about two days in the blood and takes two to six weeks to reach steady levels. The liver clears it mainly through an enzyme called CYP2A6.
Genes matter at this step.
Letrozole levels can vary more than tenfold between women on the same dose, partly because of CYP2A6 gene differences.
Slow metabolisers in one study cleared the drug 46 percent more slowly. This does not change dosing today, and no guideline uses genetic testing for letrozole doses yet.
THE SIDE EFFECTS, NAMED PLAINLY
The same estrogen that feeds the cancer also protects bones, joints and cholesterol. Removing it brings predictable costs.
In BIG 1-98, raised cholesterol appeared in 52 percent of women on letrozole. Hot flushes affected about a third. Joint pain affected about a quarter, and nearly half in another trial. Fractures occurred in 14.7 percent over about eight years of follow up, compared with 11.4 percent on tamoxifen.
Fatigue, dizziness and sleepiness are also listed. Rare but serious reactions include severe allergy, severe skin reactions and liver inflammation.
Letrozole must not be taken in pregnancy. Women who could become pregnant need a pregnancy test first and contraception during treatment and for at least three weeks after.
WHAT HELPS WITH SIDE EFFECTS
@ Exercise has the best evidence. In a year long trial, women who did 150 minutes of aerobic exercise a week plus strength training twice a week cut their worst joint pain by about 29 percent.
@ Acupuncture gave a small extra improvement over sham acupuncture in another trial.
@ Bone protection works. In a trial of 3,420 women on these tablets, an injection called denosumab halved the rate of first fractures.
@ Some medicines used for joint pain or hot flushes are antidepressants. Those are decisions for the prescriber, who weighs their own risks.
WHAT TO BE CAREFUL WITH
UK guidelines advise against soy isoflavone, red clover, black cohosh and vitamin E supplements for hot flushes in women with breast cancer.
In mice, high dose genistein from soy reversed letrozole's effect on tumours. That is animal evidence only, but it supports caution with concentrated supplements.
Hormone replacement therapy is normally stopped at diagnosis. Tamoxifen taken at the same time lowers letrozole levels by about 38 percent. Always show your pharmacist every supplement and medicine you take.
THE QUIET RISK OF STOPPING
Letrozole does not need tapering. The risk is stopping too soon. In the study mentioned at the start, stopping early was linked to a 26 percent higher risk of death, and taking tablets irregularly was linked to a 49 percent higher risk.
Another study used blood levels and found that 28 percent of women were not taking letrozole regularly, while only 3 percent said so.
If side effects are hard, say so. Your team can treat the side effect or review the plan. Never stop or change the dose on your own.
FIVE QUESTIONS TO TAKE TO YOUR NEXT CLINIC VISIT
#1 - How long is letrozole planned for in my case, and will extending it be considered.
#2 - Have I had a baseline bone density scan, and do I need bone protection.
#3 - How and when will my cholesterol be checked.
#4 - What can we do if joint pain or hot flushes become hard to live with.
#5 - Which supplements and other medicines are safe alongside letrozole.
Share it with someone who takes letrozole, or tell us in the comments which question you most want answered.
WHEN TO GET HELP FAST
Get emergency help for swelling of the face, lips or throat, trouble breathing, or blistering or peeling skin.
Contact your care team quickly for yellow skin or eyes, dark urine, chest pain, sudden breathlessness, a swollen painful leg, a fracture after a small fall, a sudden tendon injury, persistent low mood, possible pregnancy, a new lump, or any warning sign in your care plan.
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Prepared by Edward Paul Mshani, BPharm
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Disclaimer
This content is for educational purposes only and does not constitute medical advice, diagnosis or treatment. Do not stop, start or modify any prescribed medication or supplement regimen without consulting a qualified healthcare professional. Individual clinical decisions require personalised medical assessment.
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