Can’t tolerate tamoxifen……can I stop it?Andrea Huston
Have you been prescribed tamoxifen but can’t tolerate the side effects of the drug?
For many, tamoxifen’s side effects are too much to stomach and the prospect of enduring them for 5 years is not appealing even at the risk of cancer recurrence.
Tamoxifen is an option for hormone replacement therapy used to prevent recurrence of breast cancer in women with ER-positive tumors. Tamoxifen is prescribed as adjuvant hormone treatment for premenopausal and postmenopausal women while the aromatase inhibitors, anastrozole and letrozole, are approved for use in postmenopausal women.
When is tamoxifen prescribed?
Women with early stage ER-positive cancers have similar survival rates with or without tamoxifen. Tamoxifen is usually recommended for women at higher risk of cancer recurrence based on a tumor risk score assessed by OncotypeDX or Mammaprint. Women, who receive at least 5 years of tamoxifen treatment after breast cancer surgery, reduce their risk of cancer recurrence, or the risk of developing cancer in the other breast.
How does it work?
ER-positive tumors require estrogen for growth. A liver enzyme, CYP2D6, processes tamoxifen into endoxifen (4-OH-N-desmethyl-tamoxifen), a molecule that blocks the Estrogen Receptor, reducing the risk of cancer. Endoxifen and another molecule, afimoxifene, derived from tamoxifen are 30–100 times more potent than tamoxifen itself.
Women with inherently reduced activity of the CYP2D6 liver enzyme process tamoxifen into the potent endoxifen very slowly. As their liver cannot process tamoxifen at the expected rate, there is a build-up of tamoxifen in their body and they suffer from tamoxifen side effects and may also be at higher risk of cancer recurrence. In Canada, 7-10% of women process tamoxifen at reduced rates as their CYP2D6 enzyme does not function ideally and require alternative treatment such as aromatase inhibitors.
Hot flashes, mood swings, depression, and loss of libido are common and largely unavoidable side effects of tamoxifen. Women taking tamoxifen can also be at an increased risk of blood clots and stroke that is significantly increased in carriers of mutations in the F2 or F5 genes, which increases blood clotting.
Should you continue enduring these side effects?
Consider a pharmacogenetic test to assess your CYP2D6 liver enzyme – does it function normally? Or, at a reduced rate?
If the test determines that your CYP2D6 enzyme functions at a reduced rate, then you do not process tamoxifen efficiently and your physician can consider alternative treatments.
Also, women with reduced function in their CYP2D6 enzyme should avoid CYP2D6-dependent antidepressants and other medications processed by the enzyme.