Angelina Jolie, radical strategies for cancer prevention, and genetics denialism

I had been debating whether to blog about Angelina Jolie’s announcement last week in a New York Times editorial entitled My Medical Choice that she had undergone bilateral prophylactic mastectomy because she had been discovered to have a mutation in the BRCA1 gene that is associated with a very high risk of breast cancer. On the one hand, it is my area of expertise and was a big news story. On the other hand, it’s been nearly a week since she announced her decision, and the news story is no longer as topical as it was. Also, I’ve already written about it a couple of times on my not-so-super-secret other blog, making the division of blogging…problematic. So, if some of this is a bit repetitive to those who are also fans of my more—shall we say?—insolent persona, I apologize, but try to be patient. I will be doing more than just rehashing a couple of posts from last week (although there will unavoidably be at least a little of that), because there have been even more examples of reactions to Jolie’s announcement that provide what I like to consider “teachable moments.” I will start by asserting quite bluntly that in my medical opinion, from the information I have available, Angelina Jolie made a rational, science-based decision. How she went about the actual mechanics might have had some less than scientific glitches along the way (more about that later), but the basic decision to remove both of her breasts to prevent breast cancer associated with a BRCA1 mutation that she carried was quite reasonable and very defensible from a scientific standpoint.

One advantage of waiting nearly a week to write about this story is that it provided me with the opportunity to sit back and observe the reactions that Jolie’s decision provoked. One thing that I really didn’t expect (although in retrospect maybe I should have) is the pure denialism on display that genes have any effect whatsoever on cancer. I say “in retrospect I should have” because I’ve written at least a couple of times before about how quacks use and abuse the term “epigenetics” in the same way that they abuse the word “quantum” and how they seem to believe that wishing makes it so (through epigenetics, of course!) to the point where they believe that genetics is irrelevant to cancer. Indeed, they go far beyond that, asserting that, in essence, environment is all. From what I’ve been reading thus far, the second strongest strain of reaction to Jolie’s announcement (after revulsion at the “mutilation” of women that it represented to certain quacks) is pure denial that mutations in BRCA1 and BRCA2 genes portend such a high risk of ultimately developing breast cancer. This denial is often accompanied by conspiracy mongering about BRCA1 and BRCA2 mutations being a “conspiracy” on the part of the “cancer industry” and Myriad Genetics & Laboratories, the company that holds the patents on BRCA1 and BRCA2, to increase genetic testing and preventative mastectomies. Myriad happens to have a complete monopoly on BRCA1 and BRCA2 testing because of this patent and has been criticized for its high prices and stifling of competition. There is currently a case before the U.S. Supreme Court regarding whether human genes are patentable under the law. I’m not a big fan of Myriad, and I’ll tell you why later. (Not that it matters; I’m stuck with them for now.) My personal distaste for Myriad Genetics aside, this sort of conspiracy mongering is part and parcel of the quack approach to denying the significance of BRCA1 mutations.

This denial is usually coupled with confident blather that Angelina Jolie didn’t need to undergo “disfiguring” surgery to prevent BRCA1-associated breast cancer but instead could have achieved the same—or even better!—risk reduction if only she had used this magic herb or that miracle supplement and making certain “lifestyle” changes. It’s utter nonsense, of course, but it’s everywhere.

Before I get to the reactions to Jolie’s announcement, let’s first take a look at what she did, why, and the science behind it.

BRCA mutations, Angelina Jolie’s cancer risk, and preventative surgery

On May 14, in the NYT editorial page, after recounting how her mother had battled breast cancer for nearly a decade only to succumb to it at age 56, Angelina Jolie described trying to reassure her children that she wouldn’t die the same way, announcing:

We often speak of “Mommy’s mommy,” and I find myself trying to explain the illness that took her away from us. They have asked if the same could happen to me. I have always told them not to worry, but the truth is I carry a “faulty” gene, BRCA1, which sharply increases my risk of developing breast cancer and ovarian cancer.

My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer, although the risk is different in the case of each woman.

Only a fraction of breast cancers result from an inherited gene mutation. Those with a defect in BRCA1 have a 65 percent risk of getting it, on average.

Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could. I made a decision to have a preventive double mastectomy. I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer, and the surgery is more complex.

BRCA1 and BRCA2 are genes in which certain mutations are most commonly associated with either breast or ovarian cancer, although they are also associated less strongly with several other cancers as well, such as cervical cancer, uterine cancer, pancreatic cancer, early onset prostate cancer (men) and colon cancer (BRCA1) or pancreatic cancer, stomach cancer, gallbladder and bile duct cancer, and melanoma (BRCA2). BRCA1 codes for a protein known as breast cancer type 1 susceptibility protein, a protein belonging to the RING-type zinc finger (RNF) family whose function involves repairing damaged DNA. Specifically, it repairs double-stranded breaks. In the nucleus of a variety of normal cells, the BRCA1 protein interacts with other proteins, such as RAD51 and BARD1, to repair double stranded breaks resulting from radiation and other environmental exposures, as well as breaks that occur during natural processes, such as homologous recombination. The BRCA1 protein is important in multiple functions, including transcription (conversion of the DNA sequence to RNA message), repair of double-stranded DNA breaks, ubiquitination, and other functions. If BRCA1 can’t repair the break, it then promotes cell cycle arrest and apoptosis (programmed cell death). The result of defects in BRCA1 function is increased sensitivity to anything that causes DNA damage and an increased risk of the development of cancer. BRCA2 encodes a protein that, while very different in structure from BRCA1, serves a similar function, namely the repair of double-stranded DNA breaks.

Mutations in BRCA1 and BRCA2 are associated with familial cancer syndromes, most commonly involving breast and ovarian cancer, but not limited to these cancers. Moreover, it needs to be understood that BRCA mutations are not binary. You do not either “have the mutation” or not. There are many mutations, some of which confer high risk of cancer, others of which confer increased risk but not nearly as high, and some of which whose significance is unknown. In other words, BRCA mutations produce a spectrum of increased risk, ranging from the 87% lifetime risk of breast cancer cited by Angelina Jolie based on the mutation she has to unknown significance (and possibly not even any increased risk of breast cancer). The same is true of BRCA2 mutations, although the maximal risk for breast cancer even the worst mutations in BRCA2 produce are not as high as the maximal risk from BRCA1 mutations. In any case, a good genetic counselor will go through these risks and explain the significance of the dozens of mutations that are known. Either that, or quacks will seize upon various BRCA mutations of either unknown significance or that produce only mildly elevated risk, as though these were the mutations for which doctors recommend preventative surgery. This complexity is why I’m a firm believer that genetic testing for BRCA mutations should usually not be done outside of a center with either skilled genetic counselors or a physician trained in genetic counseling who can explain the risk and help the patient weigh the pros and cons of genetic testing and, if that testing is positive, the various surveillance and preventative strategies available for women carrying BRCA mutations. Also very important is to weigh the ethical and practical issues of genetic testing, such as whether a mutation carrier should inform her family, what effects that it might have on her ability to obtain health insurance, and the many other issues that are inextricably bound with genetic testing, not the least of which is affordability.

In other words, recommendations should be personalized by practitioners using science-based practice. (I know. I couldn’t resist.) It should also be remembered that in the US, BRCA mutations account for only a small minority of cases of early onset breast cancer (2-3%) and ovarian cancer (8%), a proportion that can vary widely based on geography and ethnicity. To put it another way, approximately 25% of women with a breast cancer diagnosis are younger than 50 years, and almost 10% of these women will have a BRCA mutation So, while there is a point to be made that most breast cancers are not associated with BRCA mutations, for carriers of mutations with a high risk of breast or ovarian cancer the mutation is already there, and the risk is already there. The point no longer applies.

All of this leads to recommendations regarding who should be screened. At my cancer center and many others, we use the recommendations of the National Comprehensive Cancer Network (NCCN) guidelines (summarized here). These include:

  • A personal history of breast cancer at age 50 or younger
  • A personal history of triple negative breast cancer (breast cancer that is estrogen receptor-negative, progesterone receptor-negative and HER2/neu receptor-negative)
  • A personal or family history of male breast cancer
  • A personal or family history of bilateral breast cancer (cancer in both breasts)
  • A personal history of ovarian cancer
  • A parent, sibling, child, grandparent, grandchild, uncle, aunt, nephew, niece or first cousin diagnosed with breast cancer at age 45 or younger
  • A mother, sister, daughter, grandmother, granddaughter, aunt, niece or first cousin diagnosed with ovarian cancer
  • A family history of both breast and ovarian cancers on the same side of the family (either mother’s or father’s side of the family)
  • Ashkenazi Jewish heritage and a family history of breast or ovarian cancer

Indeed, there is even a little BRCA mutation carrier risk calculator that can be used to estimate a patient’s risk of being a mutation carrier based on family and personal history.

In the end, although Angelina Jolie tells us that she is a BRCA1 mutation carrier, she does not tell us which specific mutation she carriers. She does tell us that her doctors told her that the specific mutation conferred upon her an 87% lifetime risk of developing breast cancer and a 50% lifetime risk of ovarian cancer. As a result, she decided to undergo a prophylactic bilateral mastectomy with immediate reconstruction and apparently will undergo bilateral oophorectomy (removal of her ovaries) later, her rationale being that her risk of breast cancer is higher and her breast surgery was “more complex.” It’s not an unreasonable rationale for prioritizing preventative surgery that way.

What Angelina Jolie did

Conceptually, what Angelina Jolie decided to do was simple, but the actual mechanics of carrying it out was complex. Basically, to put it bluntly, she decided to have both of her breasts removed. That’s the big picture, the basic decision. However, there is often a lot more to bilateral mastectomy than just removing the breasts, particularly when one factors in the options for reconstruction. A woman like Angelina Jolie is exceedingly unlikely to have a bilateral mastectomy without some form of immediate reconstruction, given her career. Some women choose the option of no reconstruction, however, and their choice must be respected.

Jolie decided to have her breast surgery done through a clinic that I’ve heard of before, the Pink Lotus Breast Center, which advertises itself thusly:

The Pink Lotus Breast Center is a comprehensive and integrative breast center exclusively dedicated to the prevention, screening, diagnosis and treatment of breast cancer.

Expedited scheduling; quick answers; less stress; top doctors; female-run; not hospital-owned; no facility fees; and a single location for all of your needs. Just a few of the many reasons why PLBC’s integrative approach to breast care is unsurpassed and puts each patient first, every single time!

If you think this doesn’t sound promising, you’re correct to a point. Pink Lotus first came to my knowledge when Sheryl Crow had her breast cancer treated there by partial mastectomy (colloquially called “lumpectomy”). She now has an imaging center at Pink Lotus named after her, and Pink Lotus advertises “screening ultrasound” for women with dense breasts, even though there is no good evidence to support such a practice. Apparently, Shannon Tweed was also treated there. Unfortunately, Pink Lotus is not above using these celebrities rather shamelessly to promote itself, as a quick perusal of its website will show, including Sheryl Crow’s Ultimate Breast Cancer Prevention Guide, which is chock full of questionable recommendations and overblown assertions, including recommendations to drink lots of green tea for breast cancer prevention.

The Pink Lotus Breast Center also features a detailed description of the treatment Angelina Jolie underwent written by her surgeon Dr. Kristi Funk, whose credentials appear quite impressive (although I must admit that I couldn’t find any publications on breast cancer by her on PubMed, although it is certainly possible that they were published under her maiden name, which I do not know). Unfortunately, she is also enamored of “integrative medicine.” Angelina Jolie appears to have undergone a mixture of the science-based (bilateral prophylactic mastectomy for risk reduction due to BRCA1 mutations) tinged with pure pseudoscience, like recommending homeopathic remedies such as Arnica Forte (which consists of Arnica Montana 30x, Bromelain, Antioxidants, Bioflavonoids) as a means of decreasing bruising during surgery, plus Exchem and Lymphomyosot (“to help eliminate anesthesia from the system”). Yes, I’m referring to “detox,” which is the purpose for which Lymphomysot is advertised.

From a strictly surgical point of view, three aspects of Jolie’s care caught my eye. First, she chose implants for reconstruction rather than tissue flaps. Next, of course, was the “nipple delay,” in which the tissue underlying the nipple is cut in order to “improve the blood flow.” At the time this tissue is cut, a biopsy is taken of the ductal tissue underlying the nipple in order to rule out cancer. The idea is that the nipple delay procedure cuts the normal blood supply to the nipple three weeks ahead of time and thus “forces” the nipple to rely on the surrounding skin for its blood supply, thus making the chance of nipple necrosis (in which the nipple turns black and falls off due to low blood flow) much less likely. It’s a procedure usually reserved only for patients who have had previous breast surgery around the nipple. Not having looked into the scientific literature on the procedure for a long time, I decided to do a bit of searching in PubMed to see if I could find more science-based information about it. In reality, there is little or no evidence that nipple delay is useful as a routine procedure in women of average risk of nipple loss after nipple-sparing mastectomy; its use is generally indicated only in women thought to be at a high risk for nipple loss due to previous surgery in the area, as summarized in this study by noted breast surgeon Armando Giuliano, which concluded that “surgical delay of the nipple areolar complex 7–21 days before nipple-sparing mastectomy allows safe preservation of the nipple–areolar complex in patients who generally would not be considered candidates for nipple-sparing mastectomy.” Now maybe Angelina Jolie had previous surgery in the area of the nipple-areolar complex. We know she didn’t have ptotic breasts. On the other hand, Angelina Jolie was a smoker, and there are lots of reports that she still is a smoker. That is definitely a risk factor for wound complications after breast surgery, thanks to decreased blood flow. So maybe that’s the reason why she was offered a nipple delay, although that alone doesn’t seem like enough.

Finally, more questionable is the use of a procedure known as prophylactic dye injection. During breast cancer surgery, we do a procedure known as sentinel lymph node (SLN) biopsy, which involves injecting (usually) two kinds of dye before surgery: A short-lived radiotracer and a blue dye, both of which are taken up by the lymphatics and head to the first draining lymph node (or lymph nodes) under the arm, known as the axillary lymph nodes. These nodes are removed and checked for cancer. In the old days (about 12 to 15 years ago), we used to remove all the lymph nodes under the arm in a procedure known as axillary dissection. These days, we get the same information (whether the axillary lymph nodes are involved or not) with much less morbidity using the sentinel lymph node procedure. When we do prophylactic mastectomies, however, we don’t know if there’s cancer there. There probably isn’t, although there might be. Consequently, we usually do sentinel lymph node biopsies, in case there is cancer in one of the breasts, because once the breast is gone we can no longer do that procedure, and SLN biopsy is pretty low risk. However, that is not acceptable at Pink Lotus, or so it would appear:

Whenever a breast contains cancer and the armpit lymph nodes cannot be felt on exam, we routinely perform a sentinel node biopsy, which is the removal of the first nodes that receive breast lymphatic drainage. By injecting blue dye into the breast, which then travels to the lymph node(s), we find out if cancer spread beyond the breast. Until now, the trend has been not to perform sentinel node biopsies in conjunction with prophylactic (preventive) mastectomies since the discovery of cancer in breasts removed prophylactically only ranges from 2-8%. Therefore, most women do not want to take the additional risks associated with a sentinel node biopsy, especially since they can have complications, such as pain, numbness, arm swelling (lymphedema), fluid buildup (seroma), limited arm movement, and infection. This dilemma has been resolved with a new technique that was pioneered at the Pink Lotus Breast Center, called Prophylactic Breast Dye Injection, or PBDI. PBDI allows the sentinel node to be identified, but not surgically removed, giving more control and peace of mind to women. I developed this technique while treating Angelina, and I hope other women will now benefit from it. It was at her friendly insistence that I wrote the rationale for it in our blog post, Prophylactic Breast Dye Injection.

If you peruse the rationale published by Dr. Funk, you’ll find that she invented this procedure in February 2013. I’ll actually give Dr. Funk credit. PBDI is actually not a bad idea. In fact, in concept, it’s a pretty good idea. However, by Dr. Funk’s own admission, it’s also a new idea thought up by her while treating Jolie that is completely unproven. (One wonders whether Jolie balked at bilateral SLN biopsy.) Hence, from my perspective it is irresponsible to promote PBDI in the context of Angelina Jolie’s surgery given that, also by Dr. Funk’s own admission, there is no evidence for the superiority (or even non-inferiority) of the procedure compared to standard sentinel lymph node biopsy. She even includes a disclaimer:

Disclaimer: We at the Pink Lotus Breast Center have started using the PBDI technique very recently. It is currently unknown which factors influence the precise length of time that the dye remains in the sentinel nodes. Further studies in that regard are needed.

In that case, Dr. Funk and colleagues should be doing preclinical trials in animals and clinical trials in humans to answer the question of what factors determine how long the dye persists in the sentinel nodes and why, not offering this procedure to, in essence, any woman undergoing prophylactic mastectomy.

Still, Angelina Jolie did undergo an appropriate procedure (overall) after finding out that she carried a dangerous BRCA1 mutation, and I can’t criticize her for that. Having done so, according to a recently published model, she has significantly decreased her risk of dying before age 70. For example, a typical 25 year old woman has an 84% chance of living to be 70. Of those not surviving, 11% die of breast or ovarian cancer, the rest of other causes. However, a 25 year old woman with a BRCA1 mutation who undergoes no screening or preventative treatment has only a 53% chance of living to be 70. 77% of the women with BRCA1 mutations who die before 70 die from breast or ovarian cancer. The effectiveness of interventions to reduce risk are summarized below (PO = prophylactic oophorectomy; PM = prophylactic mastectomy):

With no intervention, survival probability by age 70 years is 53% for BRCA1 mutation carriers versus 84% for the general US population (Table 2). The most effective single intervention is PO at age 40, yielding a survival probability of 68% by age 70, which represents a 15% absolute gain compared with no intervention (68% v 53%). Delaying PO to age 50 yields half the survival gain provided by PO at age 40 (8%: 61% v 53% with no intervention). In comparison, PM at age 25 yields a 13% gain relative to no intervention, whereas delaying PM to age 40 yields a small (2%) decrement in gain compared with PM at age 25. Breast screening alone from ages 25 to 69 yields the lowest gain (6%).

The most effective combination strategy is PM at age 25 plus PO at age 40, providing a 26% survival gain by age 70 compared with no intervention (79% v 53%). Postponing PM until age 40, in the presence of screening from ages 25 to 39 and PO at age 40, reduces survival gain by 2%. Eliminating PM and substituting breast screening from ages 25 to 69 while performing PO at age 40 reduces survival gain by an incremental 3%. When added to PO at age 40, breast screening offers 5% lower survival probability than does PM at age 25 (74% v 79%) and 3% lower survival probability than does PM at age 40 (74% v 77%). If PO is delayed until age 50, breast screening offers 5% lower survival probability than PM at age 40 (69% v 74%). Results by age 80 are similar (Table 2). Figure 1A presents survival probability, and Figure 2A presents distribution of health status by age 70 years in BRCA1 mutation carriers under various intervention scenarios.

There is copious other literature that prophylactic surgery can greatly decrease the risk of death due to breast or ovarian cancer in BRCA1 and BRCA2 mutation carriers. Indeed, prophylactic surgery tends to be the single most efficacious intervention for this purpose, although intensive screening with MRI and mammography can also be effective for breast cancer mortality reduction. (Unfortunately, there is no good screening test for ovarian cancer, which tends to be deadlier, making this option much less attractive.) It should be noted, however, that surgery is not foolproof and does not reduce the risk of cancer to zero. Mastectomies do not remove every last cell of breast epithelial tissue at risk for cancer, for instance. We as practitioners of science-based medicine must be careful not to oversell the benefits of preventative surgery for cancer.

Unfortunately, cranks have no such qualms about exaggerating the harms and minimizing the benefits of such surgery.

Angelina Jolie and science-based medicine versus genetics denialism

It took less than a day for various quacks to attack Angelina Jolie’s decision, as reasonable and science-based as it was, to undergo prophylactic bilateral mastectomies to prevent breast cancer. First out of the box, as is all too frequently the case when it comes to despicably using and abusing celebrity health stories, was the “Health Ranger” Mike Adams, founder of the website. He’s done it before many times, for example about Patrick Swayze’s pancreatic cancer. Then, of course, he worked himself into a fine lather of righteous indignation over Christina Applegate’s “maiming” when she announced that she had undergone bilateral mastectomies for her breast cancer and a BRCA1 mutation. You can tell a lot by Adam’s chosen title, Angelina Jolie inspires women to maim themselves by celebrating medically perverted double mastectomies.

First, you need to take note. The purpose of this article is blatant, and it’s to sell stuff. After Adams has seemingly gotten his readers all fired up over the horror of Jolie’s decision to “maim” herself, the very last section of the article advertises this:

Inform yourself and you can protect your body from the insane, knife-wielding cancer surgeons. Get the New Cancer Solutions CD set and empower yourself with real answers rather than cancer industry disinformation and deadly propaganda.

It comes complete with a video (included in Adams’ despicable article) that has to be seen to be believed, entitled The female anatomy of Modern Medicine. In any case, the CD includes a talk by Adams himself entitled The Consciousness of Cancer, which is billed as a “new way” of looking at cancer. No doubt it is, but also no doubt it is a way that has nothing to do with science. From the title, my guess is that Adams subscribes to something similar to the German New Medicine or Andreas Moritz‘s “wisdom of cancer cells” quackery, in which cancer is represented as a survival mechanism.

Now that that point is out of the way (and it’s arguably the most important point, which is why I skipped to the end of Adams’ screed first), Let’s get a real taste of what Adams thinks, if you can stand it and if you can call it “thinking”:

Angelina Jolie announced yesterday that she had both of her breasts surgically removed even though she had no breast cancer. She carries the BRCA1 gene, and she has been tricked into believing that genetic code is some sort of absolute blueprint to disease expression — which it most certainly is not. Countless millions of women carry the BRCA1 gene and never express breast cancer because they lead healthy, anti-cancer lifestyles based on smart nutrition, exercise, sensible sunlight exposure and avoidance of cancer-causing chemicals.

Jolie, like many other women who have been deluded by cancer quackery, decided the best way to prevent the risk of breast cancer was not to lead a healthy, anti-cancer lifestyle, but rather to surgically remove her breasts in what she describes as “three months of medical procedures.”

…just in case, you know. Because you can never be too careful these days, with the cancer industry scaring women half to death at every opportunity. “My breasts might murder me!” seems to be the slogan of many women these days, all of whom are victims of outrageous cancer industry propaganda and fear mongering.

And later Adams adds:

Oh, what a mess Jolie has made of herself. She has maimed her own body with no medical justification whatsoever, then celebrated this horrible disfiguration through some sort of twisted perception of what womanhood really is. Being an empowered woman doesn’t mean cutting off your breasts and aborting live babies — even though both of these things are often celebrated by delusional women’s groups. Being an empowered woman means protecting your health, your body and your womanhood by honoring and respecting your body, not maiming it.

And, Adams “coup de grace”:

Wonderful? To cut off parts of your body that have NO disease? With this logic, abortions are cancer prevention, too, because those babies might one day grow up and develop tumors. Better to kill them early and “prevent cancer,” right?

One can’t help but note that Adams is indulging in a favorite pastime of quacks every where: Denialism of genetics and wishful thinking that genetics doesn’t rule. Yes, it’s true that in some cases genetics doesn’t rule. If a gene doesn’t have a high penetrance, interacts with other genes, or has an activity that is highly influenced by environment, genetics isn’t always destiny, but in the case of the particular BRCA1 mutation that Jolie reports having, there is an 87% lifetime risk of developing breast cancer. Given that breast cancer is a type of cancer that is not highly lifestyle- and diet-dependent (note, that is not to say that lifestyle and diet have no effect, just that the effect tends to be relatively small), no amount of “anticancer lifestyle, “smart nutrition,” and “avoidance of cancer-causing chemicals” is going to lower that 85% chance of breast cancer by very much, no matter how much Adams’ wishful thinking might try to mislead other women that such interventions can.

Adams then followed up with a post entitled
How Angelina Jolie was duped by cancer doctors into self mutilation for breast cancer she never had:

With her breasts removed, she says her risk of breast cancer is now reduced to a mere 5 percent. The same bizarre logic can also be applied to men who cut off their testicles to “prevent testicular cancer” or people who cut out their colons to “prevent colorectal cancer.” But that would be insane, so nobody does that, because one of the most basic principles of medicine is that you don’t subject patients to the considerable risks and costs of surgery and anesthesia to remove organs that have no disease!

If there existed a gene mutation that conferred a similar risk of testicular cancer as Angelina Jolie’s BRCA1 mutation does for breast cancer, you can be assured that there would be consideration of prophylactic surgery or medication. Also, people do remove their colons to prevent colorectal cancer. Adams is even more ignorant than I thought, apparently never having heard of, for example, familial adenomatous polyposis (FAP). It’s a condition in the colon in which there are numerous polyps that predispose patients with condition to colon cancer such that by age 40 or 50 the risk approaches 100%. The treatment? Prophylactic colectomy. Yes, that’s right, removal of the colon to prevent colorectal cancer. There’s also hereditary non polyposis colorectal cancer (HNPCC), which involves a mutation in a gene with a similar function to that of BRCA1, the gene in which Angelina Jolie had a mutation that predisposed to breast cancer, specifically a gene involved in the repair of DNA damage. The risk from HNPCC isn’t as high as it is for FAP, but it’s plenty high, more than high enough to justify prophylactic surgery to avoid colon cancer.

Sadly, Adams is not alone in his ignorance of oncology. There’s also Sayer Ji, who claimed that vaccines are “transhumanism” that subverts evolution and made one of the most spectacularly clueless arguments against evidence-based medicine I’ve ever seen, dismissing it as a “coin flip.” This time around, Ji’s denying that genes cause cancer, the same way that Adams did, but he tries to put a “science-y” sounding gloss on the statement:

Despite the commonplace refusal of so-called ‘evidence-based medicine’ to acknowledge the actual evidence of genetics, we moved into a Post-Genomic era over a decade ago following the completion of first draft of the entire human genome in 2000. At that moment, the central dogma of molecular biology – that our DNA controls protein expression, and therefore disease risk – was disproved. Our genome was found to contain roughly 20,000 genetic instructions – not even enough to account for the 100,000 proteins in the human body!

As a result, we must now accept that factors beyond the control of the gene, known as epigenetic factors, and largely determined by a combination of nutrition, psychospiritual states that feed back into our physiology, lifestyle factors, and environmental exposures, constitute as high as 95% of what determines any disease risk. In fact, even the psychological trauma associated with being diagnosed with cancer can drive malignancy via adrenaline-mediated multi-drug resistance,[i] and according to a recent NEJM study, lead up to a 26-fold increased risk of heart-related deaths in the seven days following diagnosis.[ii]

Epigenetics. You keep using that word. I do not think that it means what you think it means. Ji also doesn’t seem to understand that through alternative splicing and various other mechanisms, one gene can easily produce multiple different proteins. Not only is Ji ignorant of oncology, but he’s ignorant of biology.

Ji also beats on the straw man that I mentioned at the very beginning of this post, namely the belief that you either “have the gene” or don’t when it comes to BRCA1 and BRCA2. Indeed, he even goes so far as to twist himself in knots when he perseverates over an observation that there is actually a known BRCA2 mutation that has been associated with a lower risk of cancer. So what? The existence of such a mutation is irrelevant to the question of whether Angelina Jolie made the right choice in undergoing bilateral mastectomy.

If you don’t believe me when I say that cranks and quacks completely deny the reality that certain gene mutations are so highly associated with cancer, I can’t resist finishing with some truly ignorant commentary by a man named Richard Schulze, a.k.a., the Herb Doc. First, Schulze denies that BRCA1 is even a problem:

But specifically, with breast cancer, scientists think that they have discovered a gene, they refer to as BRCA1, that is a genetic marker for the potential development of breast cancer. The reason I say “think” is simply because almost all this testing science is proven false or at least faulty a decade or so later, like the AIDS test, or the PSA test for prostate cancer (that has now been proven defective), or giving millions of mammograms to young women whose breast tissue was too dense to see anything, which caused breast cancer and so this practice is now condemned. Regardless of the history of medical testing blunders, many women who test positive for this particular BRCA1 gene are now opting to have their healthy breasts removed, as did Angelina Jolie in February.

And I am telling you right now, that in a decade or two, surgically cutting off healthy breasts because someone tests positive for the BRCA1 gene will be seen as a huge horrific medical mistake.

Maybe so, but only if sometime between now and two decades from now we discover a drug that reduces the risk of breast cancer in BRCA mutation carriers as much as prophylactic surgery does. Even in that case, depending on the safety and efficacy of the drug, it wouldn’t be an unreasonable decision to opt for a one-time surgery over potentially decades of taking a pill every day. Besides, we have to work within the context of the science that we have now. For example, the Halsted radical mastectomy, as “barbaric” as it is perceived now, was not an unscientific or inappropriate treatment 100 years ago. Given that adjuvant chemotherapy and radiation therapy did not exist back then, if a cancer was going to be cured, surgery was the only modality that could cure it. Given that there was no mammographic screening back then, most breast cancers were pretty large by the time they were noticed; so if surgery was the only way to cure breast cancer, then it had to be radical surgery to get all of it. And the radical mastectomy was more efficacious than any other procedure at the time. Surgery’s mistake was to continue to do more radical surgery once evidence beginning in the middle part of the last century started to make it clear that such radical surgery was not necessary. But that’s a minor issue compared to Schulze’s mix of misinformation (HIV denialism, misunderstanding of mammography, and the like) with issues that medical science, not quacks, is already working on correcting. None of this stops Schulze from opining:

All that genetic markers say is that you have the potential to develop a disease, like breast cancer. It simply means that you have genes in your body, that when stimulated, irritated or woken up, can mutate and develop into cancer. Well, what wakes these genes up is no mystery, and ALL medical and cancer researchers know exactly what turns these genes on, but they don’t want to touch this subject, simply because it’s unpopular. What turns these genes on and makes them mutate, is junk food, toxic chemicals, French fries, pharmaceutical drugs… the list is long; it’s the aftermath of the American Dream.

Except that, in the presence of genetic markers as strongly associated with cancer as BRCA1 and BRCA2, there is very little that diet, lifestyle, and the like can do to lower the risk significantly. There is one thing, though, at least in the case of BRCA2-related breast cancers, that is quite effective in lowering risk, but Schulze won’t like it. I’m talking about Tamoxifen, which significantly reduces the risk by as much as 62%. Unfortunately, it’s not as clear whether Tamoxifen is as effective in preventing BRCA1-associated tumors because they tend to be estrogen receptor-negative. Either way, contrary to what Schulze is saying, it’s not diet and lifestyle that can reduce risk in the case of BRCA mutations. It’s either surgery or—gasp!—pharmaceutical drugs.

The bottom line

Celebrity health stories like that of Angelina Jolie are a two-edged sword. On the one hand, Jolie made a perfectly rational, evidence-based choice to undergo prophylactic bilateral mastectomy. I don’t like the center she chose or how that center uses “integrative medicine” and seems a bit too eager to jump the gun on using surgical procedures that haven’t yet been validated in clinical trials, but her overall decision, if you can ignore the mechanics of how she carried out that decision, was sound. As such, her story can raise awareness and potentially help increase the rate of genetic testing in women who are candidates for it, as genetic counseling and testing are woefully underutilized.

Her case also publicizes various socioeconomic and political issues. There’s no doubt about it, Jolie is filthy rich, thanks to the success of her and her fiance Brad Pitt in Hollywood. She has access to the best of everything, and she doesn’t have to worry about paying for BRCA testing, prophylactic mastectomy, or the very finest breast reconstructive surgery available. Most women can’t say that, and, unfortunately, as has been pointed out, the issue of genetic testing can result in dilemmas for some women. Although the Patient Protection and Affordable Care Act will, when fully implemented, require that appropriate, evidence-based genetic testing and preventative surgery be covered, until now many women could not afford genetic testing and did not have insurance companies that covered preventative surgery, much less breast reconstruction. Moreover, there is the potential problem that publicity will result in a push for more screening in women for whom there is not an indication, with the potential to cause harm.

Finally, there is the issue of the gene test itself, on which Myriad Genetics has a monopoly. If there’s one thing the quacks have written that has a bit of traction, it’s the criticism of Myriad, whose patent has crushed any competing BRCA mutation tests. I said before I’m not a fan of Myriad. I view its stranglehold on BRCA testing as stifling innovation, which is why I’m glad that the U.S. Supreme Court is hearing a case against Myriad about the legal validity of its patents. Even though Myriad’s patents are only good for two more years, one can only hope that a precedent is established. I also can’t help but wonder whether all these newer next generation sequencing tests coming out will mean the end of Myriad’s monopoly anyway, given that they will give information on all potential cancer-associated gene mutations, including BRCA mutations. To the extent that the Angelina Jolie case sheds light on this issue, it’s all to the good.

In the end, leaving aside all these political and class issues, however, the decision regarding preventative surgery is an intensely personal one. Angelina Jolie made her decision based on evidence, and I can’t argue with her decision. Were she my patient, I would have counseled her to do what she did, minus the homeopathic remedies “integrated” into her care. What I find particularly ironic is how a common theme running through so much of the criticism quacks are sending Jolie’s way is that she made the wrong decision, that she was “duped” by the “cancer industry.” The contempt, although denied with a disclaimer of how they “understand” how difficult the decision was, is palpable. I thought “alternative” health was all about empowering the patient to make her own decisions. Apparently such “empowerment” is only admirable to people like Mike Adams, Sayer Ji, and Robert Schulze, if the empowered patient makes a decision they agree with.

Posted in: Basic Science, Cancer, Medical Ethics, Science and the Media

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