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research focus 12 cannabis patient care | vol. 2 no. 3 cannapatientcare.com Overview of Research on Cannabis for Breast Cancer B Y R U T H F I S H E R T HE EARLIEST SCIENTIFIC research on the effects of cannabinoids on cancer cells date back to the mid-1970s, with Louis Harris' investigations of tet- rahydrocannabinol's (THC) inhibition of cancer growth (1,2). Research on cannabis as a potential treatment specifi- cally for breast cancer didn't begin for another 20 years, un- til the 1990s. Since then, there have been several thousand preclinical studies, most of which have been conducted only within the last 10 years. Scientific research on breast cancer is thus still in its early stages. What have we learned about can- nabis to treat breast cancer? Let's take a look. Breast Cancer Is Diverse Breast cancer tumors are extremely heterogeneous in nature, as noted by Rahman and colleagues (3): "Breast cancer shows intra-tu- mor heterogeneity at molecular, genomic and phenotypic levels." One aspect of this diversity is tumor cells' different patterns of expression of both hormone receptors and cannabinoid receptors. Stratified Based on Receptor Status The most reliable way of stratifying different breast cancer types is that based on hormone receptor expression, that is, whether or not the tumors contain estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor 2 (HER-2). The presence of any of these hormone receptors provides a target or pathway by which to attack the cancer (see Table I) (3). Breast cancer tumors that express hormone receptors (Lu- minal A, Luminal B, or HER-2+) may be treated using hormone therapy, which interferes with the body's own production and effects of these hormones on promoting tumors. Howev- er, breast cancer tumors that do not express hormone recep- tors (triple negative breast cancer, or TNBC) do not respond to hormone therapy. Other treatment options for all breast can- cer types include chemotherapy (oral or IV administration of drugs to stop cancer cell growth) or radiation therapy (4). Cannabis Has Diverse Effects on Breast Cancer Cannabis has been found to "selectively and differentially affect" different types of breast cancer cells (5). This is due to a combination of factors. First, the patterns in which cannabinoid receptors (CB1 and CB2) are expressed on tumors differ across cancer cell types (3,5). Next, CB2 receptors are more prevalent than CB1 receptors: CB1 is detected in 28% of breast cancer carcinomas, while CB2 is detected in 72% of carcinomas, where both CB1 and CB2 are found more often in HER-2 positive tumors (3). Finally, different cannabinoids that bind to the same type of receptor can cause different downstream effects on cancer cells. This phenomenon is known as biased signaling (6). Research on Cannabis Use for Breast Cancer There is a large body of preclinical and clinical research that includes all three forms of cannabinoids: endocannabinoids (made by the body), phytocannabinoids (made by plants), and synthetic cannabinoids (man-made). The research examines how cannabinoids may be used to treat cancer in general, as well as to treat specific forms of cancer, such as astrocytoma, glioblastoma, head and neck, breast, Hodgkin lymphoma, leu- kemia, skin, and squamous cell cancer. The research reported herein is focused specifically on studies of cannabinoid treat- ments for breast cancer. Cannabis has been found to provide relief to breast can- cer patients in three different ways: (i) cannabis addresses the symptoms associated with either the cancer itself or the side effects from cancer medications; (ii) cannabis increases the ef- ficacy of complementary cancer treatments; and (iii) canna- bis attacks the cancer itself. At the same time, however, a few studies have, in fact, found that cancer may promote tumor growth in breast cancer cells. Let's take a closer look at what the studies have to say for each of these types of effects of cannabis on breast cancer. Addresses Symptoms and Side Effects of Treatment The list of side effects associated with cancer and can- cer treatments is lengthy. Commonly reported side effects include, among others, pain, anxiety, depression, fatigue, insomnia, nausea or vomiting, and weight problems (7). There is a large body of research supporting the efficacy of cannabis for use in treating most of these symptoms and side effects of breast cancer.