Combatting the alt-med stereotype of oncologists anxious to administer toxic chemotherapy

It is an article of faith among believers in alternative cancer cures that conventional oncology consists mainly of a bunch of money-hungry surgeons and oncologists who want nothing more than to cut, poison, and burn patients with cancer and charge them enormous sums of money to do so for as long as they can until the poisonous chemotherapy finally kills them. It is an evil and malicious caricature, of course. People don’t endure four years of medical school, three to five years of residency, and three years of fellowship in order to be able to cut, poison, and burn without regard for whether it’s actually helping patients. If making money is what you want to do, there are strategies far less long and brutal to accomplish that end. Moreover, even physicians who are into the money perhaps more than they should be generally still went into medicine to help people and still do want to help people. One really has to wonder what sort of sick, twisted mind can imagine that so many other human beings would be so willing to intentionally harm people. Yes, there does exist the occasional evil doctor. (Dr. Farid Fata, who administered chemotherapy far longer than patients needed in order to defraud Medicare, comes to mind.)

It is also an article of faith among these people who believe in alternative cancer cures that chemotherapy does not work. Well, they might concede that it saves 2% of patients with cancer based on an old, poorly analyzed study from Australia, in a gambit I like to refer to as the “2% gambit.” It’s BS, of course. Chemotherapy does work, and can in some cases works really well. They also routinely confuse adjuvant chemotherapy, which is chemotherapy administered after curative surgery for cancer to decrease the risk of cancer recurrence, with primary chemotherapy, which is when chemotherapy is used as a primary treatment for cancer. This leads to a great many alternative cancer cure testimonials in which the patient underwent surgery but refused adjuvant chemotherapy and now attributes his or her survival to “natural” or “alternative” cancer treatments. In fact it was the surgery that cured the cancer, and these patients were just lucky not to have had a recurrence. The testimonials of Suzanne Somers and Hollie Quinn are examples of this form of testimonial. So is the cancer cure testimonial of Chris Wark, of Chris Beat Cancer.

Wark was unfortunate enough to develop colon cancer as a young man and underwent surgery for it. Because his tumor had spread to his lymph nodes, he was at a high risk of recurrence, and chemotherapy was recommended. Wark refused in favor of naturopathic quackery. Fortunately, he lucked out and survived. Unfortunately, he’s now so convinced of the efficacy of alternative medical therapies that he’s now promoting them and the myths I mention above. It’s belief in those myths that allow him cite something like Groundbreaking study finds half of breast cancer patients don’t need chemo with a snarky “Sorry, big pharma”):

The shocking results of the long awaited MINDACT clinical trial are in. Many breast cancer patients have been receiving chemotherapy treatments they didn’t need, and that made no difference in their survival.

This is thanks to a genetic test called MammaPrint, which determined that nearly half the women slated for chemotherapy based on standard clinical recommendations didn’t need it.

After surgery to remove their tumors, early-stage breast cancer patients (0-3 positive nodes) with a MammaPrint score recommending against chemotherapy had a 95% survival rate, said co-researcher Laura van ‘t Veer, the test’s inventor.
“That’s very high, and we showed that it doesn’t differ between those who are treated and those who are not treated by chemotherapy,” said van ‘t Veer, leader of the breast oncology program at the University of California, San Francisco Diller Family Cancer Center.

Mr. Wark is rather behind the times. The development of genetic tests that predict benefit from chemotherapy is very much a hot area of research right now. Indeed, in breast cancer, we’ve been using just such a test for several years now: The OncoType DX test, which was intended for patients with cancers that have not spread to the axillary lymph nodes yet, have the estrogen and/or progesterone receptor (i.e., are hormone receptor-positive), and are negative for the HER2 protein. While this might sound like a small subset of cancers, it’s actually the most common variety of breast cancer. The Oncotype is a 21-gene test in which—yes—21 genes are measured by PCR and a recurrence score calculated. High recurrence scores definitely benefit from chemotherapy, and low recurrence scores definitely do not. Unfortunately, there is an intermediate range of scores for which the benefit (or lack thereof) from chemotherapy benefit is uncertain, and we expect the results of a clinical trial testing whether there is benefit in chemotherapy for intermediate scores to be reported soon. We also soon expect to know whether the OncoType recurrence score is useful in patients with cancer and 1-3 positive lymph nodes, patients who now routinely receive chemotherapy. The point is, this test is already in use in routine clinical practice; indeed its use is recommended in national guidelines. Until recently, it was by far the most favored test in the US because it could be performed on paraffin-embedded tissue.

The MammaPrint test is similar to the OncoType, except that it uses 70 genes to generate a recurrence score. Now, 70 genes are not necessarily better than 21. Be that as it may, though, the main reason MammaPrint was not favored in the US was because it required fresh tissue, which made it a lot less convenient. Since the test was updated to be used with paraffin-embedded tissue it appears to be gaining popularity. MammaPrint has an advantage over OncoType in that it can be used in cancers that are hormone receptor-positive or -negative.

Now, the MINDACT (Microarray In Node negative and 1-3 positive lymph node Disease may Avoid ChemoTherapy) clinical trial is a multi-center, prospective, phase III randomized study comparing the MammaPrint gene expression signature with a common clinical-pathological prognostic tool that I’ve discussed many time before while discussing alternative cancer cure testimonials (Adjuvant! Online) in selecting patients with negative or 1-3 positive nodes for adjuvant chemotherapy in breast cancer. The trial was set up this way (note that “C” = clinicopathological criteria and “G” = MammaPrint gene test):

The participants were then divided into four groups: 2,745 were categorized as having low risk of recurrence by both risk-assessment methods (G-low/C-low), 1,806 were categorized as having high risk of recurrence by both risk-assessment methods (G-high/C-high), 592 were categorized as having high risk of recurrence by MammaPrint and low risk of recurrence by Adjuvant! Online (G-high/C-low), and 1,550 were categorized as having low risk of recurrence by MammaPrint and high risk of recurrence by Adjuvant! Online (G-low/C-high).

Patients categorized as G-low/C-low were assigned to no adjuvant chemotherapy while those categorized as G-high/C-high were assigned to adjuvant chemotherapy. Patients categorized as G-high/C-low or G-low/C-high were randomly assigned adjuvant chemotherapy or no adjuvant chemotherapy.

If you look at the abstract, you’ll see that use of the of the MammaPrint led to a 14% absolute reduction in chemotherapy use and patients with unfavorable looking tumors but low G-scores treated without chemotherapy exhibited a 94.7% survival. In other words, this is high level evidence that this predictive gene test recurrence score works and treatment can be guided based on its use.

So, yes, a significant percentage of women who are normally be recommended to undergo adjuvant chemotherapy based solely on clinicopathologic criteria could do just as well without it. This is indeed a great result, and I look forward to the publication of the full paper given that, since I didn’t attend the American Association for Cancer Research (AACR) meeting this year I didn’t see the original presentation of the MINDACT results and only read about them later.

So what is the point? To Chris Wark, this is:

However, even if this test says you will benefit from chemotherapy, you should know that the word “benefit” rarely means cure. It typically just means temporary tumor shrinkage. After which, the cancer often grows and spreads much more aggressively. To further educate yourself in order to make an informed decision, I suggest you read these posts about chemo, and download my free guide 20 Questions For Your Oncologist.

Come to think of it, one of these days I’m going to have to examine Wark’s “20 questions.” In the meantime, however, I can say that Mr. Wark is truly clueless here. His gloating reveals a profound misunderstanding of the MINDACT trial and its very intent. For early stage breast cancer, the primary treatment is surgery. There is no tumor left to shrink with chemotherapy. The chemotherapy is administered to “mop up” microscopic tumor deposits that might remain, and it is very good at that, which is why the multimodality chemotherapy regimens have contributed to a decrease in mortality from breast cancer of close to 25% over the last 25 years.

But here’s the real reason why I mentioned Wark’s reporting of the MINDACT trial. What this trial shows is exactly the opposite of the alt-med “alternative cancer cure” view that oncologists exist only to administer chemotherapy. While it is true that there are a lot of women who receive chemotherapy who probably didn’t need it, it’s not because oncologists want to give lots of chemotherapy. It’s because we couldn’t predict which of these women will benefit from chemotherapy. We just knew what percentage of a group of women treated with chemotherapy would survive who would otherwise have died. We couldn’t predict which individuals would benefit or not. Gene tests like the OncoType and MammaPrint are now changing that. We now can predict, albeit not 100% by any means, which individual women are likely to benefit from chemotherapy and which are not. And guess what? Oncologists love it! Fewer women with cancer receive chemotherapy, and chemotherapy use declines. And guess what else? I myself have worked with investigators right here in Michigan to document that the OncoType DX test has led to a decrease in chemotherapy use. We’re working on the manuscript now and hope to publish it by the end of the year.

It turns out that we cancer doctors don’t like the status quo, in which chemotherapy is administered to many more women than benefit from it and are working to figure out ways to reduce that number and make sure only the women who are likely to benefit from chemotherapy receive it. Breast cancer isn’t the only cancer for which we are seeking ways to do this, either.

Imagine that. Certainly, people like Chris Wark can’t.