So-called “alternative” medicine is made up of a hodge-podge of health care practices and treatments based on beliefs that are unscientific, pre-scientific, and pseudoscientific. These modalities include practices as diverse as homeopathy, traditional Chinese medicine, reflexology, reiki and other forms of “energy medicine” based on vitalism, chiropractic, and naturopathy, and that’s a short list of the quackery that falls under the rubric of the term “alternative medicine.” Unfortunately, this unscientific, pre-scientific, and pseudoscientific hodge-podge of treatments rooted in nonsense are rapidly being “integrated” into real medicine, thanks to an unfortunately influential movement in medicine whose members have been seduced into thinking that there might be something to them and view “integrating” them into medicine as means of practicing more “holistic” and “humanistic” medicine. This “integration” started out by being called “complementary and alternative medicine” (CAM) but now among believers the preferred term is usually “integrative medicine,” largely because it eliminates the word “alternative,” which implies (correctly) that the modality is not real medicine, and “complementary,” which implies a subsidiary status, a status of being nice to have but not essential.

Particularly harmful is the hostility towards conventional medicine that often strongly correlates with use of alternative medicine. Indeed, some people even choose to rely on alternative medicine instead of real medicine to treat cancer. Unsurprisingly, the results of such a decision are generally not very good. Actually, they are almost always terrible. Very, very terrible indeed. Not surprisingly, the use of alternative medicine is associated with bad outcomes. Cancer patients who might have survived die because of it. It’s not as though it hasn’t been studied either, although the main studies I’m aware of tend to look at the bad outcomes in patients who choose alternative medicine. There is another question, and it’s one that a new study published in JAMA Oncology last week seeks to answer. It’s a study that briefly made the news, producing headlines like:

The study itself is entitled CAM Use and Chemotherapy Initiation Among Women With Invasive Non-Metastatic Breast Cancer. Interestingly enough, the first author is someone we’ve met before, Heather Greenlee, a naturopath at Columbia University. She’s the one who wrote “evidence-based” guidelines for the Society for Integrative Oncology (SIO) regarding CAM use in breast cancer patients. This time around, she’s actually doing something useful: Looking at the correlation between CAM use and chemotherapy refusal with an oncologist named Dawn L. Hershman, MD.

Basically, this study examined a cohort of 685 women with nonmetastatic breast cancer recruited from multiple sites, including Columbia University Medical Center, Kaiser Permanente Northern California, and the Henry Ford Health System. The women were all under 70 years old and part of the Breast Cancer Quality of Care (BQUAL) study, a prospective cohort study Of these women, 306 (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network Guidelines. The investigators looked at factors that correlated with use or nonuse of chemotherapy in women for whom chemotherapy was indicated. Specifically, in baseline interviews they looked at the use of five different CAM types: vitamins and/or minerals; herbs and/or botanicals; other natural products; mind-body self practice; mind-body practitioner-based practice. From these interviews, each patient was defined as falling into one of three categories: any use, dietary supplement use, and mind-body use. Also, a CAM index score was developed to sum all five modalities.

When I first read the abstract, my first thought was: WTF? There’s a lot more to CAM than just vitamins, herbs, botanicals, and “mind-body” practices. It turns out, however, that the definitions were quite broad and in line with the National Center for Complementary and Integrative Health (NCCIH) definitions. For example, mind-body self practices included yoga and meditation, while practitioner-based mind-body practices included modalities as varied as acupuncture, reiki, and meditation. Special diets and multivitamins were excluded from the definition of CAM, because, according to the authors, these are commonly used and often not categorized as CAM. They justified the definition thusly in the introduction:

Studies often define CAM using a broad, nonspecific definition that includes any therapies or approaches that are a complement or alternative to conventional medical therapies. However, when defining clinical populations using CAM, it may be more useful to consider CAM using specific subcategories, such as dietary supplements and mind-body practices. Dietary supplements include vitamins, minerals, botanicals, and other natural products. Mind-body practices include practices such as yoga, meditation, qi gong, acupuncture, and massage. In the oncology setting, patients may use both dietary supplements and mind-body practices to relieve symptoms, for general health and wellness promotion and to increase their sense of hope and control, though the evidence base for mind-body practices is stronger than for dietary supplement use. Patient motivations and the benefits they hope to obtain may also differ between these 2 categories of CAM. It has been hypothesized that CAM use may be a risk factor for not initiating standard oncology treatments because patients may be exploring other alternative treatment approaches or because conventional oncology treatments are not congruent with patient belief systems. However, prior studies on CAM use among patients with breast cancer have not differentiated whether standard oncology treatments were indicated based on clinical characteristics of patients.

Fair enough, such as this definition is. CAM is basically vaguely defined anyway, and the number of subdivisions seems to be decreasing, so that pretty much everything that’s not dietary supplements, botanicals, or natural products falls into “mind and body” practices. If you’re going to study CAM, you have to choose a definition, and that’s not a straightforward task. Besides, when recognizing CAM, I sometimes have a hard time not invoking the old trope about pornography: I know it when I see it. In any case the authors did univariate and multivariate analyses looking for associations between current use of any CAM (yes/no), current dietary supplement use (yes/no), current mind-body use (yes/no), and number of CAM modalities currently used (range 0-5) and subsequent chemotherapy initiation. Demographic and clinical factors were tested as potential confounders. Here’s what they found:

Baseline CAM use was common and reported by 598 women (87%).

Chemotherapy was initiated by 272 women for whom chemotherapy was indicated (89%).

Among women for whom chemotherapy was indicated, dietary supplement use was associated with markedly less chemotherapy initiation (odds ratio: 0.16, meaning they were 84% less likely to accept chemotherapy).

For every one unit increase in the CAM score, the odds ratio for chemotherapy use was 0.64.

There was no association between mind-body practices and chemotherapy initiation.

There was no association between CAM use and chemotherapy use in women for whom the need for chemotherapy was judged to be discretionary.

The results are summarized below in this table:

TABLE

The authors note one surprising part of this result:

Women for whom chemotherapy is discretionary will likely have different reasons for chemotherapy initiation compared with women for whom chemotherapy is indicated. Here, we found that CAM use in the discretionary group was not associated with chemotherapy initiation. We hypothesized that CAM use would be associated with chemotherapy initiation among the discretionary group because there is more leeway in the decision making process, but we did not find that this was true. Instead, in the group with a clear clinical indication for chemotherapy, users of CAM were significantly overrepresented among the relatively small group that did not receive this indicated treatment.

That last sentence makes an important point. One of the weaknesses of this study is that the number of patients for whom chemotherapy was definitely indicated but who declined it was small, only 34 patients. It’s not clear how generalizable its results are. I, too, also found it odd that use of dietary supplement use negatively correlated with chemotherapy initiation while use of the more “woo-ey” therapies that fall under the category of mind-body treatments did not. Remember again: “Mind-body” doesn’t just encompass yoga, but also the purest quackery, such as reiki, acupuncture, other energy medicine, and the like. Unfortunately, the data aren’t granular enough to look at the use of specific “mind-body” modalities and their association with chemotherapy initiation. The same problem applies to the dietary supplement categories, because homeopathic remedies could easily be lumped under that category. With such small numbers, though, combining modalities into categories is unavoidable.

The authors do, however speculate:

By nature, dietary supplement use differs from mind-body practices. Dietary supplements are ingested substances, whereas mind-body practices include behaviors and body-work. Presumably, patients with cancer who use either type of CAM hope to achieve a health-related benefit. In the general population, users of dietary supplements often use these products to improve or maintain overall health or for organ-specific health reasons (eg, heart, joint, skin). A population-based study of patients with cancer reported that patients with cancer took dietary supplements because “it was something they could do to help themselves” to boost immune function and to improve energy. In contrast, users of mind-body practices often do so for psychological benefits (eg, stress, anxiety, depression) and pain management. Distinguishing these motivations for use may explain our findings.

Perhaps. There might be something to this. It could also be that patients taking herbal remedies or dietary supplements are taking them instead of chemotherapy rather than in addition to chemotherapy. After all, herbal remedies, if they actually work to do anything, do so because they contain substances that act as drugs. Of course, there is also no good scientific evidence that any dietary supplement has an antitumor effect that decreases the risk of recurrence.

One area where this study is seriously lacking is hinted at. The authors mention that they didn’t look at genomic profiling tests that predict risk of recurrence, such as the OncoType, because such tests were not widely in use at the time subjects were being recruited for BQUAL. They wondered if perception of risk of recurrence affected the willingness of subjects to accept chemotherapy, which is not an unreasonable question. I note that the investigators had information on the single biggest determinant of risk of recurrence, stage at diagnosis, as well as other predictors, such as tumor markers. They could easily have estimated a ten year risk of recurrence based on those factors (or a range of recurrence risks, such as low, medium, or high) and then looked for a correlation, although I doubt they would have found one in this dataset because it’s too small.

I refer to this because risks versus benefits are a key consideration for any treatment. Chemotherapy is unpleasant and can result in serious side effects. If the benefit isn’t perceived as worth it, then a patient is much less likely to agree to use it. I’ve discussed adjuvant chemotherapy many times, often in the context of patients turning it down. In brief, adjuvant chemotherapy is administered after surgery in order to decrease the risk of recurrence. As is pointed out in the accompanying editorial by Robert Zachariae, adjuvant chemotherapy does decrease overall mortality and delays in chemotherapy decrease its effectiveness.

Of course, chemotherapy has different levels of benefit depending upon how high the risk of cancer recurrence is. That’s the reason why there are so many testimonials of patients who refused chemotherapy. They did, however, have primary surgery, which can be enough, particularly in earlier stage breast cancer. The motivation to undergo chemotherapy could be much less in a patient with stage I cancer, for whom the risk of recurrence might be less than 10% and the absolute benefit of chemotherapy on overall survival might only be 2-3% than it would be in a patient with stage III cancer for whom the risk of recurrence might be 50-60% or more, depending on the aggressiveness of the tumor, and the absolute survival benefit of 20% or even more, a much more convincing benefit.

Regardless if you buy the results of this study or not (and I’m not sure that I entirely do), Zachariae does use it to make an excellent point:

To provide the best evidence-based decision support regarding CAM use—including whether to use CAM as a complementary or alternative treatment to AC—oncologists need to be actively involved in discussing CAM use with their patients. Only by acknowledging that communication about CAM use is an important part of cancer care will oncologists be able to help patients to make sufficiently informed choices about CAM use. However, as shown in a systematic review of the available literature, a considerable proportion (20%-77%) of patients with cancer who use CAM do not disclose their CAM use, the main reasons for nondisclosure being the physician’s lack of inquiry; the patient’s anticipation of the physician’s disapproval, disinterest, or inability to help; and the patient’s perception that disclosure of CAM use is irrelevant to his or her conventional care.

Despite my strong opposition to CAM in general as unscientific, pre-scientific, and pseudoscientific, when it comes to CAM use in my own patients, I take a very pragmatic approach. (Believe it or not.) I will not recommend, prescribe, or encourage CAM use, and, if asked, I am honest in my assessment of any given CAM modality, but I will not tell them not to use it either, unless I have a good reason to suspect that whatever it is they are doing could interfere with science-based treatment. Of course, for me to accomplish that, I need to know a lot about CAM, and I do. Unfortunately, the vast majority of oncologists do not. This study reiterates the need for oncologists to know enough to be able to address CAM use with their patients.

Their patients’ lives could depend on it.