If you are diagnosed with hormone receptor positive breast cancer before menopause you will most likely be prescribed Tamoxifen, a selective oestrogen receptor modulator (SERM) that has been shown to reduce the risk of breast cancer recurrence. The key benefit of this drug is that it protects hormone sensitive breast tissue and tumour cells from the effects of growth-promoting oestrogen – without completely suppressing oestrogen in the rest of the body. It’s a win-win!
There’s no doubt that Tamoxifen saves lives, but leaving oestrogen in circulation has been shown to increase the risk of other hormone-mediated cancers, and a proportion of women find that Tamoxifen adversely impacts their quality of life with increased pain, depression, headaches and mood changes – which can be severe. In my experience most women show tremendous courage in dealing with the balance of risks and benefits of breast cancer treatment and accept the downs with the ups. But in this case you don’t need to settle for the downside: nutritional therapy can help you mitigate the extra risk that Tamoxifen poses and minimise the mood and menopause effect that some women experience, without diminishing the benefits of the drug: a win-win-win!
The introduction of adjuvant hormonal therapy has made a significant contribution to breast cancer survival which has essentially doubled over the last 40 years: 86% of women in the UK now survive more than 5 years after diagnosis. (MacMillan, 2017). On the surface of it, Tamoxifen seems to offer a better choice to pre-menopausal breast cancer patients, but in leaving oestrogen unchecked it fails to cover off important risk factors. Long term use of Tamoxifen raises oestrogen levels, increasing the risk of other hormone-mediated cancers. Many women struggle to live with the side-effects of Tamoxifen and feel ambivalent about taking it; a few women feel that it makes their life unbearable and would rather run the risk of breast cancer recurrence than continue.
Since Tamoxifen is the default option for younger women after breast cancer, and many take it for ten years, it means trying to deal with debilitating side effects during the most demanding years of our lives. The side effects can make sleeping, smiling and having sex more difficult, which makes recovery more of a challenge and tends to increase damaging stress levels. Tuning up your diet and exercise regime, ensuring adequate sleep and relaxation can make a difference, but the real leverage happens when you understand your personal hormone levels and detoxification profile, and investigate the genes involved in oestrogen and Tamoxifen metabolism. Armed with this knowledge we can create a highly personalised diet and lifestyle plan that helps you focus on the areas that matter.
A personalised Tamoxifen profile can:
- Support optimal Tamoxifen protection
- Enhance the effect of Tamoxifen
- Reduce the side effects of Tamoxifen
- Reduce the adverse impact of Tamoxifen on oestrogen levels
- Reduce the increased risk from toxic oestrogen metabolites
- Support mood and motivation impacted by Tamoxifen
To understand how you can benefit requires an in-depth understanding of the way oestrogen works in breast cancer. Tumours are classified as oestrogen receptor positive (ER+) when they ‘overexpress’ the oestrogen receptor on their cell surface. The presence of these receptors tell us that oestrogen acts as a growth promotor and that blocking these receptors may help to stop growth and spread. While active oestrogen may promote tumour cell proliferation it is not normally the cause of cancer – researchers believe it’s more likely that carcinogenic oestrogen metabolites, or by-products, created during hormone detoxification, are responsible for cancer initiation. Where Tamoxifen increases circulating oestrogen, it can also raise levels of these toxic metabolites, leaving women at higher risk of new cancers in other hormonally sensitive tissues.
If you are interested in nutrition and natural health you will be no stranger to the concept of detoxification in the human body. Basically, ‘external’ toxins (environmental chemicals, endocrine disruptors, pharmaceuticals etc) and ‘internal’ toxins (spent products of metabolism such as hormones, neurotransmitters etc) are deactivated in a three-stage process: Phase 1 detoxification produces a highly reactive and often dangerous metabolite that is designed to bind (quickly) to a Phase 2 molecule which neutralises and makes it easier to excrete via Phase 3 which transports waste from cells and into the bowel or bladder for elimination.
For oestrogen detoxification, problems arise when Phase 1 metabolism is too fast so that carcinogenic metabolites accumulate, when Phase 2 pathways are too slow to keep up, and when antioxidant levels can’t cope with the damage. This is a problem for all of us since modern diet, lifestyle and environmental exposure strongly influence the way detoxification pathways work, and many factors that we understand to be damaging – like sugar, alcohol, smoking, stress and being overweight – tend to increase Phase 1 pathways, overwhelming our detoxification capacity.
But some of us have an extra risk based on inherited genetic factors. Polymorphisms on these pathways can make us more vulnerable to detoxification damage and my clinical work suggests that these issues are often a factor for younger women with breast cancer. Understanding the way your body works (via functional and nutrigenetic testing) can help you find out if you need extra protection from Tamoxifen, and manage your personal cancer risk with simple and specific diet and lifestyle changes.
Blood levels of tamoxifen are also highly dependent on individual genetic differences as well as diet and lifestyle habits. As a pro-drug, Tamoxifen relies on liver pathways to be converted to endoxifen, the active form and, again, these pathways differ from one individual to another. Since Tamoxifen is processed down more than a dozen different genetic pathways it is highly susceptible to individual genetic polymorphisms and, while the consequences are still not fully understood, we do know that differences in these pathways can impact your level of protection, your hormonal environment and your neurotransmitter balance. The genes involved are further impacted by other drugs – especially anti-depressants. To maintain good Tamoxifen protection we want to avoid speeding up detoxification pathways as it can result in the drug being deactivated too quickly and reducing your protection.
According to the Breast Cancer Now charity more than a third of women struggle with depression after breast cancer treatment and, from clinical experience, I know that women on Tamoxifen seem to be more at risk. The general consensus on Tamoxifen and depression seems to be that it is caused by a lack of oestrogen – but in clinic I don’t see the same issues with women on aromatase inhibitors (which totally suppress oestrogen) so I suspect that there is a more direct interference with neurotransmitter activity that hasn’t been clearly identified. As a results, many women face the unhappy dilemma of living with depression or reducing their Tamoxifen protection. This is another area where nutritional therapy can make a big difference and a thorough understanding of the nutrigenomic aspects of neurotransmitters can help us to boost mood safely.
Given the potential for wide variation in Tamoxifen metabolism, it’s surprising that we don’t do more to monitor blood levels of endoxifen, the active drug; currently all women are given an identical dose which essentially means that every woman has a different level of protection.
There’s still a lot to learn – it took us a long time to recognise that women on anti-depressants at the same time as Tamoxifen were probably not adequately covered – but what we do know can make a significant difference to your ability to live with and live longer with Tamoxifen.
Digging deep into your Tamoxifen metabolism is only possible with the help of nutrigenomic and functional testing, and then it involves a change in diet and lifestyle habits. If you are open to exploring this please book a free chat using the link on the right.
I hope it goes without saying that this is all about optimising treatment and it’s not meant as an ‘alternative’. You should never make any changes to your treatment plan without discussing it with your GP or oncologist.
Binkhorst, L., Mathijssen, R. H. J., Jager, A., & van Gelder, T. (2015, March 1). Individualization of tamoxifen therapy: Much more than just CYP2D6 genotyping. Cancer Treatment Reviews. W.B. Saunders Ltd. https://doi.org/10.1016/j.ctrv.2015.01.002
Brauch, H., Mürdter, T. E., Eichelbaum, M., & Schwab, M. (2009, October 1). Pharmacogenomics of tamoxifen therapy. Clinical Chemistry. https://doi.org/10.1373/clinchem.2008.121756
Cheng, S., Castillo, V., Welty, M., Alvarado, M., Eliaz, I., Temm, C. J., … Sliva, D. (2017). BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. BMC Complementary and Alternative Medicine, 17(1). https://doi.org/10.1186/s12906-017-1621-7
Desmarais, J. E., & Looper, K. J. (2010, December). Managing menopausal symptoms and depression in tamoxifen users: Implications of drug and medicinal interactions. Maturitas. https://doi.org/10.1016/j.maturitas.2010.08.005
Desmarais, J. E., & Looper, K. J. (2009, December). Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. Journal of Clinical Psychiatry. https://doi.org/10.4088/JCP.08r04856blu
Eliaz, I., & Sliva, D. (2019). BreastDefend Enhances Effect of Tamoxifen in Estrogen Receptor-positive Human Breast Cancer in Vitro and in Vivo (pp. 38–38). Ital Publication. https://doi.org/10.28991/iccr-2019-008
Hansten, P. D. (2018). The Underrated Risks of Tamoxifen Drug Interactions. European Journal of Drug Metabolism and Pharmacokinetics, 43(5), 495–508. https://doi.org/10.1007/s13318-018-0475-9
Hervik, J. A., & Mjaland, O. (2015). Breast cancer! Then the side effects of tamoxifen, hot flashes day and night, i was exhausted, my quality of life was zero. A qualitative study. Supportive Care in Cancer, 23(1), S378. Retrieved from http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L72162339
Kornreich, C., Dan, B., & Vandriette, Y. (2010). Suicidal risk in a patient receiving tamoxifen treatment for breast cancer. Primary Care Companion to the Journal of Clinical Psychiatry. https://doi.org/10.4088/PCC.09l00828blu
Thomson, C. A., Chow, H. H. S., Wertheim, B. C., Roe, D. J., Stopeck, A., Maskarinec, G., … Thompson, P. A. (2017). A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Research and Treatment, 165(1), 97–107. https://doi.org/10.1007/s10549-017-4292-7
Yamazaki, R., Inokuchi, M., Ishikawa, S., Myojo, S., Iwadare, J., Bono, Y., … Fujiwara, H. (2015). Tamoxifen-induced ovarian hyperstimulation during premenopausal hormonal therapy for breast cancer in Japanese women. SpringerPlus, 4(1), 1–5. https://doi.org/10.1186/s40064-015-1223-0