Breast cancer is the most common cancer in women, it develops in breast tissue. The disease is most common in women, but men can get breast cancer as well. Breast cancer is a heterogeneous disease, which means that there are multiple types of breast cancer, each with its own characteristics, prognosis and treatment. Three subtypes of breast cancer that can be distinguished are: hormone sensitive (or hormone-insensitive), HER2-positive (or HER2 negative) and triple negative breast cancer. Research on cell lines and laboratory animals shows that cannabinoids may be effective in each of these subtypes of breast cancer. Clinical trials (human trials) are still lacking, so caution is advised when interpreting the results below.
Cannabinoids and Hormone-sensitive breast cancer
Hormone-sensitive tumors grow under the influence of certain hormones, namely estrogen and progesterone. The presence of estrogen receptors (ER) and progesterone receptors (PR) in breast cancer cells make this subtype of breast cancer susceptible to hormone therapy. These therapies focus on the blocking of estrogen signaling. Target strategies include the removal of the ovaries, which is the endogenous source of estrogen. Drug therapy is also possible, which include for example medication that blocks the activity of certain enzymes necessary for the production of estrogen.
Research on cell lines in laboratories have shown that cannabinoids can have an anti-proliferative effect on hormone-sensitive breast cancer cells. In these case, anti-proliferative means that the growth of these tumors is inhibited by cannabinoids. This effect is observed for the endogenous cannabinoid anandamide. The effect of anandamide can be explained by the fact that it has high affinity with one of the cannabinoid receptors, namely CB1. Also, the migration of hormone-sensitive breast cancer cells seems to be prevented by anandamide. Caffarel and colleagues conclude that the present scientific evidence for these ideas is still weak and that more research is needed .
Cannabinoids and HER2-positive breast cancer
We speak of a HER2-positive breast cancer when there is too much of the protein HER2 present on the tumor. HER2 stimulates tumor growth. There is a need for drugs which can inhibit the activity of HER2 for this form of breast cancer.
Some cannabinoids can have an effect on breast cancer cells in which HER2 is present. Cannabinoids do this through their activity on one of the cannabinoid receptors, in this case CB2. Among other things, the stimulation of this receptor ensures that more AKT is active. AKT is an enzyme activator which inhibits the multiplication of cells (and thus inhibits tumor growth). The cannabinoid THC has a high affinity with CB2 receptors, which means that THC highly “works” on CB2 receptors. CBD has a much lower affinity with CB2 receptors.
In studies with mice it has been observed that THC has both an inhibitory effect on the rate at which tumors grow, as well as on the number of tumors that come to development. It’s nice that this effect can be largely explained by the activation of the CB2 receptor, because the psychoactive effects of THC (a high or stoned feeling) are not caused by the activation of the CB2 receptor, but instead by activating CB1 receptors. In other words, if somehow only CB2 receptors can be activated, then no psychoactive effect occurs. That’s good news, because the psychoactive effect of THC is often not sought after when THC is used as medication .
Cannabinoids and triple negative breast cancer
In triple negative breast cancer the protein HER2 is lacking, and the receptors for ER and PR (estrogen and progesterone) are absent. Hormonal therapy therefore is unsuited for this subtype of breast cancer. Also, there is no standard treatment for this form of breast cancer and the prognosis for this group of patients as a whole is not good.
There is evidence that cannabinoids could be effective in the treatment of triple negative breast cancer. A whole range of synthetic cannabinoids have been tested in culture (in laboratories). In each of these studies it was found that these synthetic cannabinoids had an anti-proliferative effect (the multiplication of cells was inhibited, and therefore the growth of the tumor). This effect was caused by the activation of both CB1 and CB2 receptors.
Not only synthetic cannabinoids have been studied on their effect against breast cancer, also phytocannabinoids (cannabinoids derived from plants) have been studied. The most studied phytocannabinoid against triple negative breast cancer is CBD. CBD has a low affinity with the cannabinoid receptors CB1 and CB2, which means that it is hardly “working” on these receptors. Nevertheless, in different studies with cell lines it was found that CBD has an anti-proliferative effect. How exactly CBD causes this effect is not entirely clear, but there are some ideas. One of these ideas is that the effect is caused by the combination of the direct activation of TRPV1-receptors and the indirect activation of CB2 receptors (via anandamide). The possibility that TRPV1, CB2 (and also CB1) are involved in apoptosis (programmed cell death) was ruled out in another study. Instead, it seems that CBD has an effect on the endoplasmic reticulum and/or processes of autophagy. Through this route CBD seems to promote apoptosis. The same thing has been observed for CBD in other types of cancer.
The inhibitory effect of CBD on the proliferation of breast cancer cells has also been demonstrated in vivo (in organisms, in this case lab animals). It must be noted though, that in one study tumors became CBD resistant after three weeks and CBD administration no longer had an effect .
Tumor promoting effects of cannabinoids
In the vast majority of studies on the effects of cannabinoids in cancer an anti-tumor effect is found. This is true not only for breast cancer, but also for several other types of cancer. Nevertheless, it must be noted that in a minority of studies also a tumor-promoting effect of cannabinoids is observed. The reason is not clear, although there are several theories. For example, it’s possible that dosage plays a role here (in which low doses promote proliferation and high doses inhibit proliferation). Also, the absence of CB1 and CB2 receptors in certain tumor cells could make that these tumors are not receptive to the effects of cannabinoids. Further, it is thought that the effect of cannabinoids on the immune system may play a role. However, what we need to conclude for now is that we simply do not yet know how cannabinoids work exactly and that more research is needed. Until then it is important to be cautious when considering the use of cannabinoids against cancer .
Advice for the use of cannabinoids against breast cancer
There is evidence that cannabinoids may be helpful in fighting breast cancer. However, all these indications come from studies in cell lines and lab animals. If we want to know how effective cannabinoids are in the treatment of cancer in humans, we cannot simply find the answer in these studies. For really answering this question clinical trials are needed. However, not everyone has the time to wait for the results of clinical trials. For this group of patients, it may be worthwhile to consider the use of cannabinoids. For both THC and CBD there is evidence that they have an effect against breast cancer. CBD is a safe substance. THC is also generally considered to be safe, like CBD it has a very low toxicity, but must still be used with caution. THC can have some adverse effects, especially the psychoactive effect (getting high or stoned) is often experienced as unpleasant for medical use. In addition, the use of THC lowers blood pressure and heart rate goes up . Finally, there is a possibility that THC (or cannabis in general) has undesirable interactions with other medications. Please click here to find out more about safe use of cannabinoids.
When you are considering the use of cannabinoids for (breast) cancer, always consult your doctor or specialist first. Possibly cannabinoids can simply be used in addition to regular treatment.
- Caffarel, M.M., Andradas, C., Pérez-Gómez, E., Guzmán, M., Sánchez, C. (2012). Cannabinoids: a new hope for breast cancer therapy? Cancer Treatment Reviews, 38: 911-918.
- Pertwee, R.G. (2014). Handbook on cannabis. Oxford: Oxford University Press
- Not available online