Breast Cancer and Cannabis: Cautions and Considerations when Recommending Medicinal Cannabis for Patients with Breast Cancer

Breast Cancer and Cannabis: Cautions and Considerations when Recommending Medicinal Cannabis for Patients with Breast Cancer
Potential benefits and risks of managing Breast Cancer Symptoms and Treatment Side Effects with Medicinal Cannabis
Presented by: Kristin Wohlschlagel, RN and Elizabeth Sherwood, RN, ANP, MS ~~ Specializing in Oncology, Hospice and Palliative Care
September, 2019: Pasadena, California ~~ CannMed Conference

This information is based on:
● Observations and interviews with more than 1,200 patients with Breast Cancer who use(d) medicinal cannabis
● The majority of patients had breast cancer but we also interacted with hundreds of patients with other cancers as well.
● Pre-clinical and clinical research articles
● Personal communication with top Researchers and Practitioners from around the world and more than 2 years of intense focus
● Ongoing formal survey efforts to determine Patterns of Use & Results; Challenges/Benefits; Information Sources used, and more.

Clinical Observations:
● Tens of thousands of cancer patients are using medicinal cannabis, often without any guidance from healthcare practitioners
● Most clinicians, even those recommending cannabis, and patients reported believing there were no real risks of adverse drug interactions.
● With lower oral dosing of no more than 75 to 100 mg of CBD, and/or 25 mg of THC/THCa per day, or moderate inhaled doses, interactions appear minimal, if at all. Most appeared to have *no* adverse effects, only benefits.
● Medicinal Cannabis, used with some reasonable caution, provided profound benefits to most patients, including often extremely effective symptom control of:

1. Pain, (especially nerve and bone); Insomnia; Nausea; Anxiety; body aches and joint inflammation. It appears to also help patients to better tolerate their conventional side effects, thereby assisting completion of their conventional treatment protocol or
   treatment plan.

Patterns of clinical cancer regression or suppression responses are emerging among many cancer subtypes. Patterns appear to closely match what subtypes pre-clinical researchers indicated *may* be possible.
● Not all breast cancer subtypes appear equally vulnerable to anticancer mechanisms of cannabinoids, especially to THC and/or THCa.
● Most cancers are appearing somewhat vulnerable to significant dosing of at least CBD but the THC/THCa dosing needs careful consideration and monitoring.
● Approximately 30-50% of Patients dosing with large amounts of THC, above about 50-100 mg per day, reported faster tumor growth within 6 to 8 weeks, which slowed within 1 month of reducing THC and/or THCa dosing to 25 mg or less per day.

1. Perhaps they suppressed their Helper T-cell proliferation enough to allow for faster tumor growth *and* their particular cancer subtype was not vulnerable to THC and/or THCa1?

● Patterns of response provide clinical information and foundations for clinical research.

Breast Cancer and Cannabis: Drug interaction Potential:
● Cannabidiol (CBD & CBDa) may potentially act as a moderate inhibitor of at least: CYP2C19, CYP2D6 and CYP3A4 as well as p-Glycoprotein transport.

1. Most notably, interactions with CYP3A4 appear to begin happening at about 75 mg of oral CBD per day, with stronger effects seen at 100+ mg per day.

● THC & THCa may potentially act as a moderate inhibitor of at least CYP2C9, CYP2C19, CYP3A4 as well as p-Glycoprotein transport.

1. Interactions with CYP450 appear to begin happening at about 50 to 100 mg of oral THC per day, but seems much less certain.

Apparent drug interactions observed, using large oral doses with,

● Blood thinners such as Warfarin, Coumadin, Lovenox (increased bleeding times observed)
● Tamoxifen concern: This is a prodrug and requires CYP450 metabolism to its more effective metabolites. Therefore use with large, especially oral, doses of cannabis medicines could interfere with metabolism.
● Oral breast cancer treatments such as: palbociclib (Ibrance), ribociclib (Kisqali) as we repeatedly observed:

1. Decreased neutrophils; Increased fatigue and/or Elevated liver enzymes, likely due to CYP3A4 inhibition of clearance of these drugs, which are toxic to the liver; Patients were using over about 75 to 100 mg CBD orally per day, when this pattern appeared.

Considering the use of Cannabis with Immunotherapies:
Because most commonly used immunotherapies depend on robust Helper T-cell proliferation for anticancer effects, avoid or minimize concurrent use with immunotherapies, such as PDL1 inhibitors, due to potential suppression of Helper T-Cells with high doses of THC/THCa, especially if their pathology testing showed very high chance of immunotherapy potential benefit.

Common immunotherapy drug names are: Pembrolizumab (Keytruda); Nivolumab (Opdivo) and Atezolizumab (Tecentriq).

The immunosuppressive effects of high-doses of cannabis must be outpaced by the anticancer effects of cannabis dosing(1).
● This appears under-appreciated by most patients and even their recommending cannabis healthcare practitioners.
● Researchers studying anticancer effects of cannabinoids clearly explain this immunosuppression risk1
● Medicinal cannabis is often extremely effective in managing autoimmune diseases, which involve abnormal and harmful Helper T-cell proliferation. Some are getting profound benefits when higher doses of THC/THCa are used to suppress Helper T-cell proliferation.
● But for *some* cancer patients, this same effect appears to allow for faster tumor growth. Observed with THC & THCa.
● Reassessment of tumor regression or progression must be done within 6 to 8 weeks of starting any high dose cannabis protocol, as with *any* therapy. Continued monitoring is crucial, as adjustments may be needed.

Best results with Breast Cancer treatment appear most often when both optimized conventional and cannabis therapies are carefully used together, rather than exclusively as an “either/or” option. Unfortunately, many using medicinal cannabis in the hope of treating their cancer do not realize this.
● In some cases, patients reporting significant cancer/tumor regression after using large doses of cannabis appear to be only suppressing at least some remaining cancer cells and the cancer progresses again after cannabis dosing is stopped.
● If cannabis dosing is working and is well tolerated by the patient, it may need to be continued at some significant level to continue to suppress their cancer. There appear to be no valid “easy” ways to determine best “maintenance” dosing.
● We urgently need to begin considering “what’s next” for these patients, as there appears to be very strong potential benefit in combination therapies.

Breast Cancer Subtypes and patterns of Cannabinoid Therapy Response (CTR):
HER2-Positive Ductal Breast Cancer (regardless of Hormonal status):
● Appears most likely to benefit from doses of THC above 25 to 50 mg per day. Observed likelihood of benefit: 80%
● Appears compatible and to enhance effectiveness of Trastuzumab (Herceptin); Trastuzumab plus DM1 (Kadcyla);
● Because most anti-HER2 drugs do not cross the Blood Brain Barrier (BBB) yet HER2+ Breast Cancer often does, the potential benefits of cannabinoids for these patients seems most urgently deserving of Clinical Trials(2).

Triple Negative Ductal Breast Cancer (TNBC):
● Appears somewhat likely to benefit from doses of THC above 25 to 50 mg per day. Observed likelihood of benefit: 40-50%
● This very aggressive subtype of Breast Cancer has fewer good treatment options.
● Many patients with TNBC are using Cannabis in the hope for benefit and to allow them to reduce their need for repeated chemotherapy protocols, as TNBC recurs often. Preclinical researchers confirm there may be CB2 overexpression in some(3).

Estrogen Receptor (ER)-Positive but Progesterone Receptor (PR)-negative (or low percentage) that is also HER2-Negative Ductal Breast Cancer:
● Appears somewhat likely to benefit from doses of THC above 25 to 50 mg per day. Observed likelihood of benefit: 40-50%

ER-Positive and PR-Positive (high percentages for both) that is also HER2-Negative, Ductal Breast Cancer:
● Appears LEAST likely to benefit from doses of THC above 25 to 50 mg per day. Observed likelihood of benefit: 10%
● At least 30 women, observed over a span of 3 years, reported clearly that their tumor activity INCREASED dramatically after about 6 weeks of THC doses above 50-100+ total mg. per day, regardless of CBD dosing or any “ratio” of THC and CBD.
● Pre-clinical researchers published some limited data showing this subtype of breast cancer may overexpress Cannabinoid Receptor 2 (CB2) much less often than other subtypes(3).
● Most common subtype of Breast Cancer therefore this information is important to consider.

Inflammatory Breast Cancer and Lobular Breast Cancer:
● Rare subtypes without enough observations to provide any patterns of response to cannabis yet.

Conclusion and Steps Forward:
● Cannabis appears to have a very promising role in Breast Cancer care but there is primarily pre-clinical research at this time.
● Pathology report details that seem associated with more THC vulnerability are Grade 3 as well as HER2-Positive status.
● As we strive to serve our patients, collaboration among researchers and clinicians will ideally lead to better outcomes as guidelines for care become more established.
● Acknowledging that all medicines, including plant-based medicines, may interact is a foundation of good medicine.
● Collaboration, Education and Advocacy are required to move the benefits of cannabis into conventional oncology treatment.
● Combination therapies may provide the best outcomes.

We are exploring various assessment methods, for:
● HER2 Activity -- with serum HER2 Elisa or other testing in addition to common cancer antigens, to assess initial and ongoing therapeutic responses to any therapy used, cannabis or conventional. This is in addition to standard imaging techniques, such as CT-PET scans. Valid assessment methods assist with monitoring cancer’s response to cannabis, just like any other therapy.
● Pathology report details from biopsies and Genomic tumor analysis for eventual better understanding of which may indicate potential cannabinoid efficacy.

Disclaimer: Please do not consider any information presented herein to be medical advice or to encourage reckless self-treatment with large doses of medicinal cannabis preparations. The goal of this presentation is educational and is intended for Healthcare Practitioners and Researchers. Any reference to THC, THCa or CBD actually means THC-rich or CBD-rich cannabis medicines as I did not observe anyone knowingly using only isolated cannabinoids.

I am deeply grateful for the brave:
● Patients and Support Groups, Researchers, Physicians and Nurses
● Dedicated Medicinal Cannabis Advocates & Medicine Makers around the world who have generously shared their knowledge & experiences with me.

Without their determined efforts, often at great personhttps://www.pnas.org/content/116/9/3863/tab-article-infoal risk, none of this would be possible.

References:
1. Anticancer mechanisms of Cannabinoids. Velasco G, Sánchez C, Guzmán M. Current Oncology. 2016;23(Suppl 2):S23-S32. doi:10.3747/co.23.3080. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
2. Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer. Sandra Blasco-Benito, Estefanía Moreno, Marta Seijo-Vila, Isabel Tundidor, Clara Andradas, María M. Caffarel, Miriam Caro-Villalobos, Leyre Urigüen, Rebeca Diez-Alarcia, Gema Moreno-Bueno, Lucía Hernández, Luis Manso, Patricia Homar-Ruano, Peter J. McCormick, Lucka Bibic, Cristina Bernadó-Morales, Joaquín Arribas, Meritxell Canals, Vicent Casadó, Enric I. Canela, Manuel Guzmán, Eduardo Pérez-Gómez, Cristina Sánchez. Proceedings of the National Academy of Sciences Feb 2019, 116 (9) 3863-3872; DOI: 10.1073/pnas.1815034116 https://www.pnas.org/content/116/9/3863/tab-article-info
3. Δ9-Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation. María M. Caffarel, David Sarrió, José Palacios, Manuel Guzmán and
Cristina Sánchez. DOI: 10.1158/0008-5472.CAN-05-4566 Published July 2006. https://cancerres.aacrjournals.org/content/66/13/6615

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Kristin Wohlschlagel, RN and Elizabeth Sherwood, RN, ANP, MS, are members of the Oncology Nurses Society and the American Cannabis Nurses Association.

They are Oncology & Hospice Nurse Navigators, supporting many with metastatic and treatment-resistant disease, especially those with rare subtypes of cancer with no effective conventional therapies
available to them. We work with patients, families and their Oncology and other Healthcare Teams.
Contact information: Email: kristin@nursekristin.com or Phone: 808-747-3507 and liz@nursekristin.com or Phone: 919-260-6058