Medical Cannabis for Breast Cancer

Summary

There is plenty of promising evidence that cannabinoids from cannabis (phytocannabinoids), especially cannabidiol (CBD), may be helpful when treating various types of breast cancer when combined with chemotherapy or radiation therapy, particularly ER-positive breast cancer. However, there are few clinical trials, meaning that we need to explore further before making any definitive claims about cannabis’ efficacy for breast or any other type of cancer.

Introduction

Breast cancer is one of the most common types of cancer and affects women of many ages, with the incidence rate rising steadily from age 45 and more steeply from age 55. The median age of diagnosis is 62. About 1 in 8 U.S. women (about 13%) will develop invasive breast cancer over the course of their lifetime. It is the second most common type of cancer amongst women after skin cancer. Breast cancer is the second leading cause of cancer death in women in the U.S. after lung cancer.

About 287,850 new cases of invasive breast cancer will be diagnosed in women in the U.S. in 2022, of which an estimated 43,250 women may, unfortunately, pass away. Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases. About 1 out of every 100 breast cancers diagnosed in the United States is found in a man. In men, breast cancer is more likely to occur when they are 60+.

Risk factors for developing breast cancer are numerous. They include:

• Obesity
• Lack of physical exercise
• Alcoholism
• Tobacco use
• Hormone replacement therapy (HRT)
• Having children at a late age (or not at all)
• Ionizing radiation
• Early onset of menstruation
• Liver disease
• Having a prior history of breast cancer or another type of cancer
• Family history of breast cancer
• Old age.

In males, Klinefelter syndrome is also a risk factor. Klinefelter syndrome is a rare genetic condition in which a male has an extra X chromosome.

Approximately 5-10% of breast cancer cases result from genetic predisposition, where breast cancer type 1 susceptibility protein (BRCA1) and breast cancer type 2 susceptibility protein (BRCA2) is inherited from one’s parents. Most cases of breast cancer are found in women aged over 50.

What is Breast Cancer?

Breast cancers are often broken down into the type of receptor they affect. If breast cancer cells have estrogen receptors, the cancer is called “ER-positive (ER+) breast cancer.” If breast cancer cells have progesterone receptors, the cancer is called “PR-positive (PR+) breast cancer.” If breast cancer cells have HER2 receptors, the cancer is called HER2-positive. If the breast cancer is none of these three, it is called “triple negative breast cancer.”

The most common types of breast cancer are:

• Invasive ductal carcinoma (IDC): The most common type of breast cancer. Cancer cells begin in the ducts and then grow outside the ducts into other parts of the breast tissue. Around 70% of breast cancers are of this type.
• Invasive lobular carcinoma (ILC): With ILC, cancer cells begin in the lobules and then spread from the lobules to the breast tissues that are close by.
• Ductal carcinoma in situ (DCIS): A breast disease that may lead to invasive breast cancer. Unlike the two above, the cancer cells are only in the lining of the ducts and have not spread into other tissues in the breast. The two cancers above may also spread to other parts of the body.

Less common types of breast cancer include:

• Triple negative breast cancer: The cancer cells don’t have estrogen (ER) or progesterone receptors (PR) and make little to none of the protein HER2. Approximately 15% of all breast cancers are of this type. It is a particularly aggressive and deadly form of breast cancer. African-American women are most at risk of this type of cancer.
• Inflammatory breast cancer: Cancer cells block lymph vessels in the skin, causing the breast to look inflamed. Around 1% to 5% of all breast cancers are of this type.
• Paget disease of the breast: This starts in the breast ducts, spreads to the skin of the nipple, then to the areola (the dark circle around the nipple). 1-3% of breast cancer cases are of this type.
• Angiosarcoma: This breast cancer type starts in cells that line blood vessels or lymph vessels and can also involve the tissue or skin of the breast. Angiosarcomas make up less than 1% of all breast cancers.
• Phyllodes tumors: These develop in the breast’s connective tissue (stroma), in contrast to carcinomas, which develop in the ducts or lobules. Phyllodes tumors are usually benign, but some can become malignant.

Signs of breast cancer include:

• An unexpected lump or swelling in the breast
• A change in breast shape
• Dimpling of the skin
• Nipple discharge
• Pain in the nipple area
• An inverted nipple
• Red, flaky, or scaly patch of skin

Signs that the disease has spread include:

• Bone pain
• Swollen lymph nodes
• Shortness of breath
• Yellowing of the skin

How is Breast Cancer Treated?

Thanks to medical research and advancements, the five-year survival rates for breast cancer in countries like the U.S. and U.K. are between 80% and 90% (2012-2018). Depending on the type of cancer, the most common treatment methods include:

• Chemotherapy: This treatment uses compounds that can shrink or kill cancerous cells. These can be given in pill form or through your veins.
• Radiation therapy: Radiation is used in limited amounts to kill cancer cells. Care must be taken to ensure that other types of breast cancer do not form after radiation therapy.
• Biological therapy: This therapy works with your body’s immune system to help it fight cancer cells. Biological therapy may also be used to manage the side effects of other types of cancer treatment.
• Hormonal therapy: This blocks cancer cells from getting the hormones they need to grow.
• Targeted therapy: A type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread.
• Surgery: Doctors cut out the cancerous tissue.

Surgery to remove the cancerous tissue is the most common treatment, of which a mastectomy (partial or complete removal of the breast) is the most severe. Surgery is often combined with chemotherapy, radiation therapy, or hormone therapy to kill any leftover cancer cells after surgery. Selective estrogen receptor modulator (SERM) drugs like raloxifene (Evista) and tamoxifen (Nolvadex) may be prescribed to prevent and treat ER-positive breast cancer. You can find a complete list of medications approved to treat breast cancer in the U.S. here.

Regular checkups are carried out for five years after going into remission. Some may get treatment for swelling and a hardening or thickening of the lungs (fibrosis), which occurs after radiation therapy and causes breathlessness, a dry cough, or chest pain for approximately 2-3 months afterward. Psychotherapy may also be offered for any stress, anxiety, and depression that occurs before, during, and after cancer treatment.

How Might Medical Cannabis Help Manage Breast Cancer?

Conventional treatments work very well for many types of breast cancer. Still, some types (e.g., triple negative breast cancer) are very aggressive and do not respond as well to chemotherapy or radiation therapy.

Different forms of treatment are needed, and medical cannabis and cannabinoids could represent one of them, as cannabis contains a plethora of anti-inflammatory compounds like tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and beta-caryophyllene.

THC and CBD may also be helpful in treating the side effects of chemotherapy and cancer pain. These cannabinoids can help manage nausea, appetite loss, anxiety, and insomnia that can occur during chemotherapy and radiotherapy.

CBD may also enhance the efficacy of radiation therapy, which can help kill cancer cells more effectively and efficiently and reduce the chances of another cancer occuring due to long-term radiotherapy.

Many people may also have a hypersensitivity to many breast cancer drugs, as they are often powerful drugs that can cause several side effects. These include dizziness, tremors, liver toxicity, deep vein thrombosis, pulmonary embolism, and an increased chance of stroke. Some drugs, like tamoxifen, can increase the chances of endometrial cancer. As tamoxifen is a SERM, it acts as a partial agonist of estrogen receptors on the endometrium and has been linked to endometrial cancer in some women.

Patients with variant forms of the gene CYP2D6 (a liver enzyme) may not receive full benefit from tamoxifen or some other breast cancer drugs. This is because such variations in liver enzymes reduce the speed of metabolization of drugs like tamoxifen, thereby reducing efficacy.

Selective serotonin reuptake inhibitors (SSRIs) like paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) can decrease the effectiveness of tamoxifen, as these antidepressants compete for the CYP2D6 enzyme. So, those looking to manage depression or anxiety alongside their cancer may find some use in medical cannabis.

We must be careful, though, and ensure that the chemotype (i.e., its constituent cannabinoids, terpenes, and flavonoids) and dose of cannabis-based medications matches the type of cancer being treated.

For example, lower doses or ratios of THC may be needed for estrogen-positive breast cancer, as THC is an estrogenic compound that can increase estrogen levels in the body, helping cancer grow. Although there is no definitive evidence showing that THC-rich cannabis can stimulate the growth of ER-positive breast cancer cells, it is important to keep this in mind.

For those who are immunocompromised, it is also important to ensure that the cannabis they are using is free from mold, mildew, pesticides, and other contaminants to prevent infection. Avoiding the smoking of cannabis may also be ideal for those going through any type of cancer, as smoking any substance has carcinogenic properties (even if cannabis smoke is less carcinogenic than some other types of smoke, like tobacco smoke).

Key Information and Takeaways

Breast Cancer Studies

• Total studies = 49
• Animal studies = 11 (all positive)
• Human trial = 3 (2 positive, 1 inconclusive)
• Laboratory study = 24 (all positive)
• Meta-analyses = 11 (all positive)
• 98% studies positive (48 studies), 2% studies inconclusive (1 study)
• 12 studies included THC (all positive)
• 11 studies included CBD (all positive)
• 2 studies included CBG (both positive)
• 1 study includes THCV (positive)
• 1 study includes CBC (positive)
• 1 study includes THCA (positive)
• 3 studies include CBDA (all positive)
• 1 study included CBN (positive)
• 2 studies included a combination of THC and CBD (both positive)
• 6 studies include anandamide (all positive)
• 4 studies include 2-arachidonoylglycerol (2-AG) (all positive)
• Potential efficacy = Moderate to High. Most studies are positive, but one of the human trials was inconclusive.

Potentially Useful Cannabis Compounds

Cannabinoids

• Tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA/THCa)
• Cannabidiol (CBD) and cannabidiolic acid (CBDA/CBDa)
• Tetrahydrocannabivarin (THCV)
• Cannabichromene (CBC)
• Cannabinol (CBN)
• Cannabigerol (CBG)

Terpenes

• Beta-caryophyllene
• Myrcene
• Pinene
• Limonene
• Linalool
• Borneol
• Humulene

Flavonoids

• Cannflavins A, B and C
• Quercetin
• Rutin
• Luteolin
• Kaempferol

Potential Pros

• Medical cannabis can help reduce cancer pain and the side effects of chemotherapy and radiation therapy (e.g., nausea, cachexia).
• A broad mixture of cannabinoids may be ideal for managing breast cancer, and there are many positive studies showing that many cannabinoids can be helpful in breast cancer treatment. There are some suggestions that cannabinoids can slow down the growth of cancer cells or instruct them to self-destruct (apoptosis) by attaching to cannabinoid receptors on some types of cancerous cells.
• A combination of THC and CBD may increase sensitivity to radiation therapy, reducing the amount needed overall.
• Cannabis contains many antioxidative properties and stress- and inflammation-busting terpenes and flavonoids, many of which have anti-cancer potential that may increase the efficacy of chemotherapy.
• Medical cannabis may be useful for managing anxiety, insomnia, and depression that may occur alongside cancer and cancer treatment.
• Medical cannabis contains cannabinoids like THC and CBD, which can alleviate chronic pain associated with cancer and cancer treatment.
• Medical cannabis may be particularly helpful for difficult-to-treat cancers.

Potential Cons

• Some theorize that too high a dose of THC may increase the growth of ER+ cancer cells. However, some THC is useful, and CBD may be particularly useful for breast cancer: “AEA [anandamide] and THC induce apoptosis in ER+ breast cancer cells, while CBD trigger [sic] autophagy to promote apoptosis. AEA, THC, and CBD impair growth of ER+ breast cancer cells by disrupting cycle progression. AEA, THC, and CBD affect aromatase and ERα expression levels in ER+ breast cancer cells.”
• Those undergoing immunotherapy should avoid medical cannabis and cannabinoid treatment, as it may interfere with treatment and reduce survival rates.
• Not all cancers are cannabinoid-responsive, including some types of breast cancer. More studies are needed to see what types of cancer cannabis can help treat, what ratios are needed, and at what dose.
• It is of utmost importance that your medication is as pathogen-free as possible, as one of the side effects of chemotherapy is a suppressed immune system.

Conclusion

There is a reasonable amount of evidence to suggest that medical cannabis and phytocannabinoids (plant cannabinoids) may be useful for managing and potentially even treating breast cancer.

Human trials are few and far between, and without the clinical data, we cannot say for sure how effective cannabis might be. The general consensus is that there is not enough evidence to say for sure whether cannabis or any of its compounds or derivatives can reliably treat any form of cancer. There is a large enough body of evidence to merit further exploration, especially regarding the rarer and more treatment-resistant forms of breast cancer. CBD shows much promise, in particular, but a mixture of cannabinoids may be ideal for their therapeutic and anti-cancer properties (and to take advantage of the entourage effect).