8.3 Breast Cancer


Breast cancers are classified in various ways. Ductal cancers start in the milk ducts. Lobular cancers begin in the milk glands. Invasive cancers have spread to other parts of the breast. 70-80% of breast cancers are invasive ductal cancers. One also sees the term adenocarcinoma, referring to cancers that start in the epithelial cells lining the ducts and lobules. Breast cancer is the second most common cause of cancer death among women.

Invasive ductal carcinoma begins in a milk duct and then invades surrounding tissue[breastcancer.org]. The cancer releases cancer cells into the blood stream where the most aggressive survive to establish new metastatic tumors. In addition, the original tumor attracts circulating cancer cells in a self-seeding process. The tumor's attractants are IL-6 and IL-8[Kim_2009].

Cancers that respond to estrogen are referred to as HR-positive. Cancers that respond to progesterone are PR-positive. And cancers that produce too much of the HER2 protein are HER2 positive. Cancers that meet none of these criteria are said to be triple-negative.

Virtually all of the research reported below consists of in vitro studies. It is suggestive of but not necessarily indicative of how cannabis compounds relate to human breast cancer.

Killing Cancer Cells

CBD induces programmed cell death in triple-negative breast cancer cells[cyt-cbd][cyt-cbd2]. THC induces apoptosis of HER2 positive breast cancer cells[cyt-thc].

α-Terpinolene is cytotoxic against adenocarcinoma cells[cyt-terp]. Linalool acts synergistically with the chemotherapy drug doxorubicin in fighting adenocarcinoma[cyt-lin].

The cannabis flavonoid apigenin is cytotoxic against HER2-positive breast cancers[cyt-api2][cyt-api3]. Apigenin is also effective against androgen-responsive human breast cancer cells[cyt-api4].

BCPO (β-caryophyllene oxide) induces apoptosis in several kinds of breast cancer cells[bcpo1][bcpo2].

α-humulene, together with the chemotherapy drug paclitaxel, has exhibited significant cytotoxic activities against invasive ductal breast cancer cells, especially when combined with β-caryophyllene[cyt-hum].

Stopping Cell Replication

THC inhibits cell cycle progression in cancerous breast epithelial cells[repl-thc]. THC was able to impair tumor angiogenesis in a mouse model of HER2-positive breast cancer[repl-thc3].

Inhibiting Invasion and Metastasis

CBD limits invasion and metastasis in adenocarcinoma cells[inv-cbd]. So does CBDA[inv-cbda][inv-cbda2]

Controlling Cytokines

Elevated IL-6 levels are generally associated with poor prognosis and low survival rates in patients with breast cancer. IL-6 is known to stimulate growth, invasion, and metastasis[Masjedi_2018]. IL-6 triggers signs of malignancy, both in human ductal breast cancer and in normal mammary glands[Sansone_2007]. High levels of IL-1α and IL-6 are significantly correlated with a poor prognosis[Zong_2016].

Elevated IL-1β directly promotes the invasiveness of triple-negative breast cancer cells[Jeon_2016]. IL-1β induces IL-6 production and increases invasiveness and estrogen-independent growth in human breast cancer cells[Oh_2016].

IL-22 promotes breast cancer, but the release of IL-22 is dependent on the release of IL-1β[Voigt_2017][Markota_2018]. IL-1β and IL-17 are implicated in breast cancer metastasis[Verstegen_2019].

For general ideas on controlling cytokines, see Taming Inflammatory Cytokines

Controlling Gene Expression

CBD turns off the ID1 oncogene in several types of breast cancer[inv-cbd][gene-cbd2]. CBDA lowers the COX2 gene as well as the ID1 gene. Both genes are overexpressed in invasive ductal carcinoma[gene-cbda]. THC limits progression by turning off the CDC2 gene[Caffarel_2006].


cyt-cbd. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Article. Ashutosh Shrivastava, Paula M Kuzontkoski, Jerome E Groopman, Anil Prasad et al. Molecular Cancer Therapeutics. Published 2011 July.

cyt-thc. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition [in vitro study]. Article. María M Caffarel, Clara Andradas, Emilia Mira, et al. Molecular cancer. Published 2010 Jul 22.

cyt-cbd2. Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma [xenograft study]. Article. Ligresti, Aniello Schiano Moriello, Katarzyna Starowicz. The journal of pharmacology and experimental therapeutics. Published 2006 September.

cyt-lin. Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells. Article. Raffaella Ravizza, Marzia B Gariboldi, Roberta Molteni, Elena Monti. Oncology Reports. Published 2008 September 1.

cyt-terp. Helichrysum gymnocephalum Essential Oil: Chemical Composition and Cytotoxic, Antimalarial and Antioxidant Activities, Attribution of the Activity Origin by Correlations [in vitro study]. Article. Samia Afoulous, Hicham Ferhout, Emmanuel Guy Raoelison, et al. Molecules. Published 2011 October.

cyt-api2. Degradation of HER2/neu by apigenin induces apoptosis through cytochrome c release and caspase-3 activation in HER2/neu-overexpressing breast cancer cells. Article. Tzong-Der Way, Ming-Ching Kao, Jen-Kun Lin. FEBS Letters. Published 2004 November 30.

cyt-api3. Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells. Abstract. Eun Jeong Choi, Gun-Hee Kim. The journal of nutritional biochemistry. Published 2009 April.

cyt-api4. Apigenin Induces Apoptosis through a Mitochondria/Caspase-Pathway in Human Breast Cancer MDA-MB-453 Cells. Article. Eun Jeong Choi, Gun-Hee Kim. Journal of clinical biochemistry and nutrition. Published 2009 April 25.

bcpo1. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation [in vitro study]. Abstract. Kyung-Ran Park, Dongwoo Nam, Hyung-Mun Yun, et al. Cancer Letters. Published 2011 Aug 26.

bcpo2. β-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase [in vitro study]. Abstract. Chulwon Kim, Somi K Cho, Shweta Kapoor, et al. Molecular carcinogenesis. Published 2013 June 13.

cyt-hum. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel [in vitro study]. Abstract. Jean Legault, André Pichette. Journal of pharmacy and pharmacology. Published 2007 December.

repl-thc. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Article. María M Caffarel, David Sarrió, José Palacios, et al. Cancer Research. Published 2006 July 1.

repl-thc3. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition [in vitro study]. Article. María M Caffarel, Clara Andradas, Emilia Mira, et al. Molecular cancer. Published 2019.

inv-cbd. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Article. Sean D McAllister, Ryuichi Murase, Rigel T Christian, et al. Breast cancer research and treatment. Published 2010 September 22.

inv-cbda. Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Article. Shuso Takeda, Shunsuke Okajima, Hiroko Miyoshi, et al. Toxicology letters. Published 2012 November 15.

inv-cbda2. Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. PDF article. Shuso Takeda, Hiroyuki Okazaki, Eriko Ikeda, et al. Toxicomics Report. Published 2014 June 30.

gene-cbd2. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Article. Sean D McAllister, Rigel T Christian, Maxx P Horowitz, et al. Molecular cancer therapeutics. Published 2007 November.

gene-cbda. Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. Article. Shuso Takeda, Hiroyuki Okazaki, Eriko Ikeda, et al. The Journal of toxicological sciences. Published 2014.

Verstegen_2019. IL17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Full text. Verstegen N J M, Ciampricotti M, Hawinkels L J A C. Nature. Online 2019 March 30.

Masjedi_2018. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Full text. Masjedi A, Hashemi V, Hojjat-Farsangi M, et al. Biomedicine & Pharmacotherapy. 2018 December.

Sansone_2007. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. Full text. Sansone P, Storci G, Tavolari S, et al. The Journal of clinical investigation. Online 2007 December 3.

Zong_2016. Expression of IL-1α and IL-6 is Associated with Progression and Prognosis of Human Cervical Cancer. Full text. Song Z, Lin Y, Ye X, et al. international medical journal of experimental and clinical research. 2016 November 20.

Jeon_2016. Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone. Abstract. Jeon M, Han J, Jin Nam S, et al. Chemico-biological interactions. 2016 August 25.

Oh_2016. IL-1β induces IL-6 production and increases invasiveness and estrogen-independent growth in a TG2-dependent manner in human breast cancer cells. Full text. Oh K, Lee O-Y, Park Y, et al. BMC Cancer. Online 2016 September 8.

breastcancer.org. Invasive Ductal Carcinoma (IDC). Exposition. Unattributed. breastcancer.org. Undated.

Kim_2009. Tumor self-seeding by circulating cancer cells. Full text. Kim M-Y, Oskarsson T, Acharyya S, et al. Cell. Online 2009 December 24.

Voigt_2017. Cancer cells induce interleukin-22 production from memory CD4 + T cells via interleukin-1 to promote tumor growth. Abstract. Voigt C, May P, Gottschlich A, et al. Proceedings of the National Academy of Sciences (US). Online 2017 November 17.

Markota_2018. Targeting interleukin-22 for cancer therapy. Full text. Markota M, Endres E, Kobolda S. Human vaccines & immunotherapeutics. Online 2018 May 17.

Caffarel_2006. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Abstract. Caffarel M M, Srrió D, Palacios J, et al. Cancer Research. 2006 July 1.