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research focus 13 cannapatientcare.com october/november 2021 | cannabis patient care Surveys Surveys of patients with breast cancer indicate that a signifi- cant portion of patients (42% in one study) have used cannabis to treat their symptoms. These patients tend to find cannabis provides relief for most symptoms or side effects, including insomnia; joint and muscle aches, discomfort, stiffness, or pain; anxiety, stress; and nausea or vomiting (8,9). Clinical Trials No clinical trials have yet been performed to assess cannabis's efficacy for treating symptoms and side effects specifically of breast cancer. However, many clinical trials of generic "can- nabis," as well as of specific cannabinoids have been tested and shown to be efficacious for treating symptoms generally associated with cancer and cancer treatment, including nausea or vomiting, pain, appetite, fatigue, anxiety, and depression. Notably, three of the four cannabis pharmaceuticals that have been government-approved—Dronabinol (1986 in US), Nabilone (1981 in Canada, 1985 in US), and Sativex (2010 in UK)—were approved to treat cancer-related symptoms and side effects. [Note: The fourth cannabinoid pharmaceutical approved for medical use is Epidiolex, approved by the FDA in 2018 for the treatment of epilepsy.] Increases Effectiveness of Traditional Treatments In preclinical studies, researchers have shown that cannabi- noids enhance the anti-cancer effects of various other che- motherapy treatments in breast cancer cells (10), as well as in other cancer cell types (11). Treats Breast Cancer Scientists have discovered multiple pathways for preventing the growth and spread of breast cancer cells. Preclinical studies have well-established the potential for cannabis to address most of these pathways. Yet, while there are case reports, there have not yet been any clinical studies on cannabis for prevent- ing the growth or spread specifically of breast cancer. Preclinical studies on breast cancer cell lines have estab- lished the following findings. Induces Cell Cycle Arrest Caffarel and colleagues provide a succinct description of cell cycle arrest, together with cannabis's role in managing the process when it goes awry (12): "There are very few critical decisions that cells must take during their lifetime. Basically, these are whether to proliferate, differentiate, or die. A tight regulation of the cell cycle is crucial to control all these de- cisions, and its deregulation has devastating consequences, such as cancer. It has been proposed that cannabinoids, the active components of Cannabis sativa, play a role in the con- trol of the aforementioned decisions. For example, they can modulate survival, proliferation, and differentiation depend- ing on the cell type and its physiopathologic context." Inhibits Proliferation Cell proliferation is the speed at which cancer cells replicate themselves. "If the cancer cells are dividing more rapidly, it means the cancer is faster growing or more aggressive" (13). There is a substantial body of preclinical research establish- ing that endo-, phyto-, and synthetic cannabinoids inhibit the proliferation of breast cancer tumors with cell types ER+ (11,14), HER-2+ (15,16), and TNBC (15,17). Induces Apoptosis Apoptosis is a natural process used by the body to rid itself of unneeded or abnormal cells (19). As with cell proliferation, there is also a substantial body of preclinical research estab- lishing that endo-, phyto-, and synthetic cannabinoids promote apoptosis in breast cancer tumors with cell types ER+ (12,21), HER-2+ (12), and TNBC (21-22). Blocks Angiogenesis Tumors release chemicals that induce angiogenesis—the forma- tion of new blood vessels—through which tumors draw their resources (23). Several preclinical studies show that endo- and synthetic cannabinoids block angiogenesis in TNBC (24,25). Blocks Invasion, Metastasis, and Migration Cancer cells spread from one location in the body to another using a specific process, called metastasis (26): "The process of tumour-cell invasion and metastasis is conventionally under- stood as the migration of individual cells that detach from the primary tumour, enter lymphatic vessels or the bloodstream and seed in distant organs." There is a substantial body of pre- clinical research establishing that endo-, phyto-, and synthetic cannabinoids inhibit invasion, metastasis, and migration in breast cancer tumors with cell types ER+ (6,18), HER-2+ (3,6,14,16), and TNBC (3,6,14,16). Table I: Breast cancer stratification Receptor Status Type ER PR HER-2 Distribution of BC Cases Prognosis Luminal A + + - 50% Good Luminal B + + ± 20% Fair HER-2+ - - + 15% Poor Basal/TNBC - - - 15% Poor ER: Estrogen receptor, PR: progesterone receptor, HER: Human epidemal growth factor receptor, BC: breast cancer, TNBC: triple negative breast cancer Source: Biyskin, N et al (2015). Molecular Classification of Breast Carinoma from Traditional, Old-Fash- ioned Way to A New Age, and A New Way, J Breast Health