It’s been a while since I discussed medical marijuana, even though it’s a topic I’ve been meaning to come back to since I first dubbed medical marijuana to be the equivalent of herbalism and discussed how the potential of cannabinoids to treat cancer has been, thus far, unimpressive, with relatively modest antitumor effects. The reason I refer to medical marijuana as the “new herbalism” is because the arguments made in favor of medical marijuana are very much like arguments for herbalism, including arguments that using the natural plant is superior to using specific purified cannabinoids, appeals to how “natural” marijuana is, and claims of incredible effectiveness against all manner of diseases, including deadly diseases like cancer, based on anecdotes and testimonials. Now, as I pointed out before, not only am I not opposed to the legalization and regulation of marijuana for recreational use, even though I’ve never tried it myself, but I support it. What I do not support are claims for medical effects that are not backed up with good scientific evidence, and for medical marijuana most claims fall into that category. That’s why I tend to view medical marijuana as a backdoor way to get marijuana legalized. Personally I’d rather advocates of marijuana legalization drop the charade, argue for legalization, and stop with the medical nonsense.

The last time around, I discussed the evidence supporting claims that “cannabis cures cancer” and found them to be wanting based on science. I didn’t however, discuss the “cannabis cures cancer” testimonial machine that drives the claim that marijuana is useful for treating cancer; at least, I only touched on it by discussing briefly Rick Simpson, who claims that his hash oil cures approximately 70% of patients with terminal cancer and a published anecdote in which it was claimed that hemp oil was effective in treating acute lymphoblastic leukemia. (It wasn’t. At least, the evidence presented was not convincing.) Since then, I’ve wanted to revisit the topic of “cannabis cures cancer” testimonials, and, for whatever reason, now seems like a good time to do it.

Stephanie LaRue

Last week, I discovered the “cannabis cures cancer” testimonial of a young woman named Stephanie LaRue. Hers is a sad story in that she was diagnosed at a young age (30 years old) after her boyfriend found a lump in her breast and misdiagnoses by three different doctors. In many ways, her story is an inspiring one based on her will to fight and her activism, which have led her to have served on the Board of Directors for the Los Angeles Susan G. Komen for the Cure, Southern California’s Breast Cancer Network of Strength, and the USC Norris Cancer Center’s Cancer Survivorship Advisory Council. Near and dear to my heart, she also is very much into rescuing and fostering many wounded, mistreated and special needs dogs. Indeed, I approach this particular testimonial with more than a little trepidation because there’s an incredible amount to admire about LaRue and, more importantly, her involvement with Komen and other breast cancer charities means that people I respect and admire (who might read this) very well might know her—or even be friends with her. Still, given the direction her story has taken, I feel obligated to discuss it.

Here’s a video of her from 2007 when she was still undergoing chemotherapy:

Notice the themes we see so often in cancer patients, particularly young cancer patients: Why me? There must be a reason. It can’t have “just happened”. Breast cancer is a disease of older women. (Indeed, the mean age at diagnosis is around 61.) There must have been something in the environment. Possibly. As I’ve pointed out before, for breast cancer, environment- and lifestyle-attributable causes account for a much smaller fraction of cancer diagnoses than most people believe, and 1.8% of cases of breast cancer occur in women 34 and under. Given that there are approximately 233,000 new cases of breast cancer diagnosed every year in the U.S., that means that close to 4,200 women under 34 are diagnosed each year with breast cancer. Still, being diagnosed with breast cancer at age 30 is unusual; so it’s understandable that LaRue would wonder why it happened to her.

Worse, LaRue was diagnosed with Stage IV disease, as described in an article by Sonja Renea published on the Medical Jane website entitled “Meet Stefanie LaRue: Cancer Survivor and Medical Marijuana Advocate“:

Stefanie was sent home several times with several rounds of antibiotics, which is quite telling of younger folks being misdiagnosed. By the time she could be tested thoroughly, the cancer had spread to her bones. Doctors diagnosed her with Stage 4 Metastatic Breast Cancer, which is cancer that has spread beyond the breast to other organs in the body. The prognosis was grim: she was given a year to live, at most.

Three weeks later, Stefanie began her first round of chemotherapy. To make matters worse, she had to to [sic] cope with her employer, who showed little sympathy for her situation. Despite her job in commercial real estate being very stressful, she was expected to work through her cancer treatment.

This is a big problem with health care in the U.S. besides the difficulty many people have affording health insurance, a problem only partially alleviated by the Affordable Care Act (a.k.a. Obamacare), which didn’t exist in 2005. You can be diagnosed with metastatic breast cancer and still be screwed as far as work goes. It happens far too often in this country.

So LaRue ended up quitting her job and filing for disability. She underwent six rounds of chemotherapy and then a mastectomy. At this point reading her story I had a question. If LaRue had bone metastases, it’s not clear to me why her surgeon and oncologist would recommend that she undergo a mastectomy. Three possible reasons suggest themselves to me as a breast surgeon. One is that it was done to prevent the primary tumor from growing through the skin and turning into en cuirasse disease, although usually such surgery is not done right after chemotherapy but when the tumor has started to grow again. Another is that she had a complete radiologic response to the chemotherapy, meaning that all her breast and bone disease disappeared. When that happens and the patient has been rendered “no evaluable disease” (NED), we will often treat her as though she were not stage IV and undertake surgery with curative intent. The final possibility is that surgery was done with the intent of prolonging survival even though metastases were still present. It’s been an ongoing controversy in breast cancer over whether removing the primary tumor prolongs survival in stage IV disease or whether the apparent improvement in survival due to surgery is due to selection bias; that is, bias towards healthier patients with less aggressive disease who are chosen to undergo surgery preferentially. More recent evidence suggests that removing the primary probably doesn’t improve survival, but that was not at all clear back in 2005. (To be honest, it still isn’t quite clear.)

On her website, LaRue reports that her tumor was 8 cm in diameter (which is big). Apparently her tumor didn’t shrink enough to be removed in a lumpectomy; so she needed a mastectomy:

After chemo she had surgery to remove the cancer. But her margins were not clear, so another surgery followed. She was left with only skin and a nipple on the right side of her chest. Her breast surgeon had scraped all the way down to the chest wall removing all the breast tissue possible but sparing the skin. Despite the advanced stage of her cancer, she got to keep the outside of her breast because she had a skin-sparing mastectomy. A plastic surgeon was later able to reconstruct her breast, restoring her shape, her femininity and her sexuality.

At this point in my reading, I was unclear as to why a surgeon would do a skin-sparing mastectomy in a patient with stage IV disease. Most plastic surgeons are reluctant to do reconstruction in such a patient because reconstruction can be a big operation, and if the patient isn’t expected to live more than a year it just doesn’t make a lot of sense to have the patient spend a significant chunk of her remaining time recovering from surgery, having additional surgeries to “touch up” the reconstruction. The willingness of her surgeon and plastic surgeon to undertake a skin sparing mastectomy and reconstruction suggests to me that she had a very good response to the chemotherapy and/or that her prognosis as a stage IV patient was viewed as being considerably more favorable than usual.

Whatever the case, during the chemotherapy that she underwent before her surgery, LaRue looked to alternative medicine to ease her symptoms:

She found help with an integrative oncologist at UCLA, where she learned how to make changes to her diet, use natural supplements, get acupuncture, and work on personal fitness; all of which are integrative, complementary, and alternative treatments to go along with chemotherapy.

Now here’s the thing. As a patient with stage IV disease, LaRue did really well for eight years. It’s hard to find a good detailed description of what happened between November 2005 (when she was diagnosed with breast cancer) and 2013, but she didn’t start using cannabis oil until 2013, which means that conventional oncology is what got her through nearly eight out of the nine and a half years she’s survived with her stage IV cancer. It’s important to remember that when looking at a lot of the articles about LaRue, because before 2013, although she had gone all in for “integrative oncology,” she hadn’t yet discovered cannabis and was still being treated with mostly conventional medicine. So, between 2006, when she finished her initial treatment, and at least September 2013, when she posted a series of images to Instagram of her hospitalization for thoracoscopic surgery, conventional medicine is what kept LaRue alive. So when Sonja Renea of the Medical Jane website writes that “Stefanie LaRue was 30 years old when she was diagnosed with Stage 4 Metastatic Breast Cancer and given the dismal prognosis of less than a year to live” and follows it up with, “That was nine years ago,” she is being deceptive.

This is how it’s described in the Medical Jane:

In 2013 Stefanie had a Video-Assisted Thoracoscopic Surgery (VATS) and the results were not good. This was now her third reoccurrence of cancer. The chemo sensitivity testing concluded there were five lines of chemo treatments that would work on the tumors.

Stefanie declined the treatment. “I did my homework. I researched as much as I could. I watched. I listened. I read. I contacted. I prayed. Most of all, I believed. I weighed my options, which were essentially chemotherapy or cannabis oil, and I decided to take the natural route this time…” she says.

Stefanie followed the Rick Simpson Oil (RSO) protocol until she was cancer-free. “Cannabis oil killed all of the tumors in my body. My monthly lab and quarterly scan results are proof that the cannabis oil treatment worked,” she says. Her doctor, who had previously been skeptical, now credits these “alternative” treatments as the reason for her speedy recovery.

On Instagram, LaRue described it thusly in a posting dated October 2, 2013:

Dear cancer, as we both know, yesterday was a big day of news. And sadly for you, you lost. You lost your “upper hand” you tried to claim in that you were potentially showing up again (unwelcomed in my body) not as a metastatic reoccurrence, but as a possible new primary cancer. Which would have been a much more challenging ass kickin match between you and I. None the less, I would have enjoyed. But since you are now known as the same initial metastatic breast cancer reoccurring, I hope you are preparing for what is coming to you. Because now I have the upper hand. When the chemo sensitivity tests are complete on my biopsy tissue at Caris Labs we will know exactly what to come after you and all your little friends with! Poor you. I know your still cowardly hiding in my body but you have pissed off some pretty important people that care a lot about me and guess what… Now they too are coming in to whip your ass!!!

We’ve encountered Caris Labs before in the context of discussing Stanislaw Burzynski’s incompetent “personalized gene-targeted cancer therapy.” Basically, Caris is a company that will do various genomic tests and immunohistochemistry on a tumor sample to try to identify which targeted agents it might be sensitive to. I’ve basically discussed how the routine use of such a test is premature, given that there isn’t any good evidence that using a test like the one from Caris or other competing tests results in better response rates or prolonged survival, but such tests have still proliferated and their use is not uncommon, even in academic medical centers.

In any case, at this point in the fall of 2013, LaRue was facing her third recurrence of cancer. Unfortunately, this is a story very much like the many alternative cancer cure testimonials I’ve deconstructed over the years in that we lack a lot of key information, which means that I can only speculate. First, we don’t know how extensive a cancer recurrence LaRue had. Given that she underwent thoracoscopic lung surgery (a thoracoscope is like a laparoscope, except that instead of letting a surgeon operate in the abdomen it allows the thoracic surgeon to operate in the chest with minimal incisions), presumably she had a lung nodule. In a patient with stage IV disease, most such lesions would be biopsied using a core needle under CT scan guidance, rather than excised surgically through a laparoscope. Why did the surgeon choose this course?

A couple of possible reasons suggest themselves from the story. First, perhaps she did undergo a CT-guided core needle biopsy and the diagnosis was uncertain. Certainly LaRue’s Instagram posting, in which she gloats over her tumor for not being a new primary tumor but just the same as the other recurrences of her original tumor, suggests that this could be the case. After all, a new suspicious lung nodule in a breast cancer patient is usually considered a new metastasis until proven otherwise. In any case, in patients with metastatic disease, a tissue diagnosis is always imperative before beginning treatment if at all feasible. Another possibility is that this tumor, whatever doctors thought it was before surgery, was the only site of disease detectable. In such a case, particularly in a young patient who had been doing well for nearly eight years even if she did have stage IV disease, strong consideration would be given for excising the cancer and eliminating the only known site of disease even though the evidence that metastasectomy (removing the metastasis) will prolong survival in breast cancer is mostly without controls and thus prone to selection bias. (Metastasectomy of liver and lung metastases can definitely prolong survival in colorectal cancer.) Still, there is evidence that in select patients removing pulmonary metastases can result in significant survival benefit. Whether LaRue is one of those select patients is unclear.

So here’s what I think probably happened. After surgery LaRue (understandably) did not want to undergo further chemotherapy. For whatever reason, she latched on to Rick Simpson’s hemp oil as the treatment that would control her cancer. How she found out about it and why she became convinced it would cure her, it’s hard to say from publicly available information. In the Medical Jane story, LaRue proclaims that “cannabis oil killed all the tumors in my body” and that her “monthly lab and quarterly scan results are proof that the cannabis oil treatment worked.” It is, of course, impossible to confirm or dispute this assessment without knowing what all her scans showed.

There is, however, a photo on Instagram of LaRue receiving a shot, which she identifies as Xgeva, which LaRue described as “bone mets maintenance.” And so it is. It’s a monoclonal antibody against the RANK ligand, a protein that acts as the primary signal for bone removal, and it prevents fractures in patients with bone metastases. So this implies that LaRue still has bone metastases. It also makes one wonder what other non-chemotherapy conventional therapy she might be taking. There’s also a post by her on Twitter asking about Afinitor (everolimus):

Afinitor is a drug that inhibits an enzyme called mTOR and is used in cancer that is positive for the estrogen receptor after it develops resistance to anti-estrogen therapy. Apparently she did not take Afinitor, because on March 14, 2014 LaRue posted a photo on Twitter:

In the photo, LaRue is receiving an injection of Zoladex (goserelin), a drug used to suppress production of sex hormones. In other words, six months after her thoracoscopy, LaRue was receiving conventional medical therapy, specifically a treatment to shut down her ovaries’ production of estrogen. Thus, LaRue appears to be the case of a cancer patient who chose unproven alternative medicine but at the same time continued to receive conventional medical therapy for her cancer and did very well. As is the case with most such patients, she attributes her excellent outcome, at least after her most recent relapse, far more to the alternative treatments (in this case, Rick Simpson’s hemp oil) than she does to the conventional therapy she is also taking, even after her discovery of hemp oil. I also can’t help but point out that the very fact that LaRue survived nearly eight years with stage IV cancer before discovering hemp oil is a pretty strong argument that from a biological standpoint her tumor is pretty indolent, as some tumors positive for the estrogen receptor are; so it’s not surprising that she would still be alive a year and a half after her thoracoscopy on Zoladex and Xgeva alone (plus whatever other conventional medical therapy she is receiving). Only LaRue and her oncologist know for sure, though, and her oncologist can’t tell anyone without her permission.

Cannabis versus breast cancer

As much as I admire the grace and determination with which Stefanie LaRue has endured over 9 years after her cancer diagnosis, as a cancer doctor it bothers me profoundly that she has allowed herself to fall under the spell of the “cannabis cures cancer” alternative medicine crowd, in particular Rick Simpson. I discussed Simpson the last time I wrote about cannabis and cancer. As I said at the time, Rick Simpson is just like cancer quacks the world over, who have no firm evidence to back up their miraculous-sounding cure rates and excuse their failures by blaming the treatment patients had before they started the quackery. Quacks like Rick Simpson do those who think that cannabinoids have promise in treating cancer no favors.

I also discussed how the vast majority of studies touted by the “cannabis cures cancer” advocates tend to be preclinical studies in cell culture or animal models that show relatively modest antitumor effects due to various cannabinoids. Indeed, this article on Medical Jane, “Studies Show Cannabinoids May Help Fight Triple-Negative Breast Cancer“, fails to provide particularly convincing evidence that they do. Before I look at the studies, I can’t help but note that triple negative breast cancer is breast cancer that makes neither the estrogen receptor (ER), the progesterone receptor (PR), nor overexpressed HER2. Yet the article invokes Stefanie LaRue, who clearly has ER(+) breast cancer.

Another thing that needs to be pointed out. Every single one of the studies invoked by Medical Jane has nothing to do with hemp oil, be it Rick Simpson’s hemp oil or some other type. Each of the studies examines either purified cannabinoids or, in the case of this study, a chemically modified cannabinoid. This study cited in Molecular Cancer, for instance, looks Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist. Both inhibit the growth of HER2(+) breast cancer cells in cell culture and in mice, but the concentrations needed are pretty high, with an IC50 (concentration that is 50% of maximum inhibition) in the range of 5 to 10 μM, concentrations achievable with injection of purified compound but certainly not by smoking pot

You are also unlikely to achieve these levels by drinking hemp oil, which, by the way, usually contains so little THC that it is below the limit of detection for common assays and manufacturers brag that it’s impossible to fail a drug test if you’re consuming hemp seed oil because “THC levels in our products are barely measurable.” Of course, I do realize that Rick Simpson calls his oil hemp oil even though it’s really cannabis oil derived from the buds rather than the seeds, but even he brags that “following the dosage previously described, many people can take the full treatment and never get high,” which implies that his oil achieves nowhere near the concentration of THC in the blood necessary to be active against cancer. Moreover, oral bioavailability of THC from such oils is notoriously low, between 4-20%, making it unlikely that concentrations well above the 10 μM necessary to inhibit or kill more than 50% of the cancer cells are achievable with oral dosing.

Thus, the various studies cited, such as this one, which shows inhibition of the epidermal growth factor pathway by purified cannabidiol (CBD), a non-psychotropic cannabinoid; this one, the aforementioned study that examines purified Δ9-THC and JWH-133 against HER2(+) breast cancer; and this one, which also examines CBD in breast cancer, are interesting and very preliminary. Moreover, they all examine cannabinoids purified from cannabis, and one even examines a chemically modified cannabinoid. In other words, even if cannabinoids make the jump from preclinical models to humans, these studies do not support the use of medical marijuana, either smoked as the plant or ingested as an oil, to treat breast cancer. They also do not suggest sufficient activity to produce miracle cures of stage IV cancer as described by Rick Simpson. Indeed, a recent review concludes that “current preclinical data does not yet provide robust evidence that systemically administered Δ9-THC will be useful for the curative treatment of cancer,” although CBD might have a role based on preclinical data.

Neither cannabinoid, however, is likely to be curative for advanced cancer. It’s possible that specific cannabinoids might have a role to play in the multimodality treatment of cancer, but, given what we know about them from preclinical studies, it’s highly unlikely that cannabinoids, medical marijuana, or Rick Simpson’s hemp oil can cure stage IV cancer of any kind.

Hope versus hype

I have no doubt that Stefanie LaRue honestly believes that Rick Simpson’s hemp oil is the reason why she’s still alive today and doing so well. I can’t help but point out that Stanislaw Burzynski’s patients, for example, also honestly believe that his antineoplastons are what saved their lives, even though even Burzynski can’t produce good evidence that they have antitumor activity. Depressingly, it just goes to show how even such an accomplished woman can fall prey to the same human cognitive shortcomings that we all share and confuse correlation with causation. If it were just her, I wouldn’t have felt obligated to write this post, but LaRue makes it very clear that not only does she believe that Rick Simpson’s hemp oil allowed her to heal herself of her longstanding metastatic cancer:

But she plans on becoming an evangelist for Rick Simpson’s hemp oil and medical marijuana:

In this video she notes that she’s had multiple recurrences and they’re all gone, after which she challenges the viewer to “explain that.” Believe it or not, personally, I’d be overjoyed if something as simple as hemp oil could treat stage IV cancer so effectively. I really would, as it would mean that I’d rarely have to see a breast cancer patient die. However, although I can’t be sure without a lot more information (which is highly unlikely to be forthcoming) and I do have to concede the possibility, albeit remote, that Rick Simpson’s hemp oil is the reason why LaRue has survived a year and a half since her last new metastasis, I nonetheless suspect that it is far more likely than not that it is the Zoladex and the Xgeva (not to mention whatever other conventional treatments that LaRue may be taking that she hasn’t mentioned on social media) that are keeping her going now, combined with her disease’s already-demonstrated indolent biology.

And long may they continue to do so!

For nearly eight years, Stefanie LaRue fought a battle with courage, inspiring intelligence, and grace. Her story was (and still is) a story of hope for women with stage IV cancer that they can live a long time with the disease with good quality of life. Unfortunately, a year and a half ago her story took a turn into pseudoscience, becoming a cautionary tale of how even the most intelligent, ambitious, and determined person can be subject to magical thinking. This would not be an issue with me were it not that, inadvertently, and with the best of intentions, LaRue has declared her determination to promote Rick Simpson’s hemp oil as a cancer cure, using her own story as an example of what it can do. Given her proven history of advocacy and her numerous accomplishments with organizations like the Komen Los Angeles County Affiliate from 2008 to 2010 (before she discovered hemp oil), I can’t help but be worried that she will in her quest to save women from stage IV breast cancer end up doing exactly the opposite for some women.

I still hold out hope that, given her history, LaRue will eventually realize that her true story is a cause for hope for women with stage IV disease. Thanks to advances in breast cancer care, more and more women with stage IV disease are living a lot longer than expected, even ten years, all with no need to resort to unproven treatments promoted with testimonials, like Rick Simpson’s hemp oil.

That’s the real reason for hope.

 

 

Posted by David Gorski

Dr. Gorski's full information can be found here, along with information for patients. David H. Gorski, MD, PhD, FACS is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute specializing in breast cancer surgery, where he also serves as the American College of Surgeons Committee on Cancer Liaison Physician as well as an Associate Professor of Surgery and member of the faculty of the Graduate Program in Cancer Biology at Wayne State University. If you are a potential patient and found this page through a Google search, please check out Dr. Gorski's biographical information, disclaimers regarding his writings, and notice to patients here.