Many patients with advanced breast cancer use herbs and supplements, as well as other treatments like relaxation and massage, to relieve symptoms. However, many patients are taking herbs or supplements that may be harmful or interact with their cancer medications. Most cancer drugs and most foods, herbs and supplements are broken down by the same liver enzyme pathways; a particular example is grapefruit, which therefore interacts with trastuzumab and paclitaxel (among many others). Two supplements that don’t appear to interact with any medications are melatonin and omega-3. Patients should always tell their doctors what supplements and herbs they are taking (and don’t forget to mention grapefruit!). However, it’s a ‘two-way street’, as doctors also need to remain open-minded or their patients will conduct their own research and may reach dangerous conclusions.
Here's BCAC’s report of a talk on this topic at the recent ABC7 conference:
What else besides the cancer medication – what is good and what is bad? The interactions.
Dr André Dourado, Mama Help – Breast Cancer Support Center, Portugal
The scale of use of complementary medicines
In a Canadian study[1], 50% of patients had used complementary medicine after diagnosis, most commonly herbal substances. A Swedish study[2] showed that one third of the population use complementary medicines with one quarter still using them after a cancer diagnosis. The most commonly used modalities in both studies were vitamins, minerals and herbal products, relaxation and massage. Over half of patients surveyed in the Swedish study[2] thought that their cancer care provider should be able to not only discuss complementary medicines but should consider these treatment modalities in their cancer care. However, most patients do not tell their providers what they are taking. This can be very dangerous because, critically, both studies also found that patients are taking substances that are inherently harmful or that are likely to interfere with the action of cancer treatments. Of particular concern is the use of amygdalin (also B17), a compound found in bitter almonds and which releases cyanide when in contact with saliva. Even Vitamin D, also commonly used, can interfere with cancer treatments depending on the dose.
Most drugs and many foods are metabolised by the same liver enzymes
Everything we ingest including food and supplements could interfere with cancer treatments. Most drugs are activated by the liver using phase I and II liver enzymes – phase I are mainly called cytochrome P450 enzymes, and phase II enzymes cause the conjugation pathways. Interactions can also occur on target cells, increasing or decreasing their sensitivity to the cancer treatment. Finally, some compounds can affect the behaviour of the drug once it’s activated. Most herbs and vegetables interact to some degree with phase I and phase II liver enzymes – in fact, it is almost impossible to eat a vegetable that doesn’t interact.
One of the most potent examples is grapefruit, which can inhibit cytochrome CYP3A4 for 3–7 days, and this is the enzyme that metabolises around 50% of drugs. This action can increase the half-life of paclitaxel and docetaxel and reduce the activation of the prodrug cyclophosphamide and of tamoxifen. Turmeric blocks CYP2D6 and 3A4 and also induces activation of one of the phase II liver enzymes. This will affect a lot of cancer drugs. Turmeric is believed to reduce cancer risk – it may also increase sensitivity of breast cancer cells to some drugs. However we must be very careful with turmeric and it is advisable not to use it during cancer treatment.
Some key drugs used in advanced breast cancer and their known interactions (click here to see a table showing the full list)
Known interactions
Trastuzumab is degraded by liver enzyme CYP3A4 – turmeric may increase the half-life of trastuzumab. High risk of interactions.
CDK4/6 inhibitors – Palbociclib is metabolized by the CYP3A forms of liver enzymes, so has the potential to interact with a lot of supplements. Ribociclib is also the same family, so it’s also very risky to use supplements or take herbal teas with this treatment. Abemaciclib the same. Avoid grapefruit, pomegranate, St John’s wort, any kind of liver detox herbs (silymarin, desmodium artichoke) and large quantities of garlic, oranges, and fennel/anise teas.
PARP inhibitors – Olaparib is metabolised by the same cytochrome family so is at risk of the same interactions – but not talazoparib.
More information needed
Antibody-drug conjugates generally appear to be metabolized less by cytochrome enzymes, but there is little information to guide this, so we must be careful.
Immunotherapies – Pembrolizumab is not metabolised by CYP450 but because it might increase cytokines it can indirectly interact with other substances that are metabolised by CYP450. Dostarlimab is not directly involved with cytochromes but there is insufficient information on any potential indirect effects.
Melatonin and omega-3 – two ‘safe’ supplements?
So what can patients do? Non-invasive therapy is always advised – yoga, mindfulness, massage, and acupuncture. Use supplements but with care and choose wisely. One example is melatonin. The most important antioxidant in the human body, melatonin is in all human cells but especially in neurons and immune cells. Melatonin works as an immune booster and is in fact a natural aromatase inhibitor. There are many studies on use of melatonin with chemotherapy, radiotherapy and targeted therapies, and melatonin reduces side effects and tends to improve results. Another compound that can be used is omega-3 – either docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA). Omega-3 is mainly used for cachexia (cancer-induced weight loss) or to increase cancer cell sensitivity to cancer drugs.
Doctors must remain open-minded
Dr Dourado concluded by saying that doctors should remain open-minded or their patients will conduct their own research and may reach dangerous conclusions. Oncology teams should explain that there is potential for interactions between supplements and cancer drugs, and that it is advisable to consult an integrative oncology expert.
References
- Buckner CA, et al. Complementary and alternative medicine use in patients before and after a cancer diagnosis. Curr Oncol. 2018 Aug;25(4):e275-e281. doi: 10.3747/co.25.3884.
- Wode K, et al. Cancer patients’ use of complementary and alternative medicine in Sweden: a cross-sectional study. BMC Complementary and Alternative Medicine volume 19, Article number: 62 (2019)
DISCLAIMER:
The table accompanying this article has been prepared by the presenter Dr André Dourado. Consult your oncologist before starting any supplements – even if they seem reticent to talk about it.
This ESMO booklet has a section on how to talk about this topic: European Society for Medical Oncology. Getting the Most out of your Oncologist. https://www.esmo.org/for-patients/getting-the-most-out-of-your-oncologist
It is unwise to implement any new diet or impose strict dietary restrictions during cancer treatments. Fruits and vegetables are recommended in all cancer guidelines and there is no clinical evidence that limiting plant foods has any measurable effect on the course of cancer.
Marion Barnett
19 November 2023
