On refusing adjuvant therapy for cancer…this time without alternative medicine

As I mentioned yesterday, one of the things I do on this blog that I consider to be a public service is to analyze cancer cure testimonials that are used to sell alternative medicine. Indeed, I did just that yesterday for a testimonial by someone Chris Wark, who will probably feature again one more time this week; that is, unless I have another Dug the Dog moment. In the meantime, this being Breast Cancer Awareness Month and all, a related article came to my attention. Although it doesn’t have anything to do with alternative medicine, it does, like the story of Chris Wark, have everything to do with refusing chemotherapy. I knew the article was going to annoy me as soon as I saw the title, I’ve refused chemo for breast cancer because the gain isn’t worth all the pain: After a double mastectomy, one woman defends a hugely controversial choice. Although it lacks the purely magical thinking that Wark’s testimonial exhibited, it’s disturbing in another way.

The woman who refused chemotherapy is named Sally Becker, and she is known, apparently, as the “Angel of Mostar” for her work as a charity volunteer saving hundreds of lives in war-torn Bosnia. I’ll be honest; I had never heard of her before. For purposes of this discussion, though, it doesn’t matter. What does matter is that four months ago she was diagnosed with breast cancer. Eighteen months before, she had felt a pea-sized lump in her breast, saw a doctor, and got a workup. The workup was apparently negative, but that workup didn’t include a biopsy. Not knowing more, I don’t know if this was appropriate management or not, but earlier this year she noticed changes in her breast:

When I noticed further changes in the same breast earlier this year, I went back to the clinic.

The area around the nipple was puckered and I knew this was a bad sign. I underwent two mammograms, an ultrasound and five biopsies and, two hours later, it was confirmed (by the same radiologist) that it was likely I had Invasive Lobular Cancer (ILC), a condition that starts in the milk-producing glands and makes up around 15 per cent of all breast cancer cases.

However, it is one of the most difficult cancers to detect, especially if the tissue is dense, as on routine mammograms it is often ‘invisible’, presenting more like a spider’s web than a single lump.

Two months later I had a 6cm tumour removed. I chose to opt for a double mastectomy because, with this type of cancer, there’s a higher risk of the disease appearing in the other breast. I was also concerned that a mammogram might not pick it up.

The treatment chosen was not unreasonable, although I tend not to be a fan of double mastectomies in the absence of a gene mutation that predisposes for breast cancer at a high probability, such as a BRCA1 gene mutation. However, in a case like this an argument can be made for bilateral mastectomy. Be that as it may, the specific type of surgery Becker had doesn’t matter when it comes to deciding whether or not adjuvant chemotherapy is needed to decrease the rate of recurrence. The specific indications for adjuvant chemotherapy have evolved over the years, but basically the equation boils down to considering the risk of recurrence, whether or not the tumor makes proteins for which targeted agents exist (such as the estrogen receptor, which is targeted by Tamoxifen, or HER2, which is the target for Herceptin), and the potential side effects of the chemotherapy. We know from the rest of the story that Becker’s tumor was estrogen receptor-positive, because if it weren’t she wouldn’t have been offered Tamoxifen. I don’t know for sure what stage cancer she had

We also know that her oncologist has said that she has a 20-30% of her cancer recurring. Going back to Adjuvant! Online, the oncology decision tool that I used yesterday, it takes some educated guesses about her tumor to come up with the risk of recurrence that she quotes. We also have to consider that the risks in Adjuvant! Online are all calculated assuming that standard of care is followed, and standard of care for a tumor greater than 5 cm in diameter does include radiation after mastectomy. I also assumed that Becker’s tumor was lymph node negative, because otherwise the recurrence risks rapidly skyrocket. So I used a tumor that was greater than 5 cm in diameter, estrogen receptor-positive, grade 2, and in a woman who is in perfect health. This produces an estimated 10 year risk of dying of around 30%. In this case, adding hormonal therapy (i.e., Tamoxifen), improves the odds by 7.8%, while adding chemotherapy improves the odds by 3.7%. The combination results in a 10.6% absolute increase in ten year survival. You can also look at it as a 43% relative decrease in the risk of dying.

Given these figures, one can make an argument that maybe chemotherapy might not be worth it, although, I must point out, many women would disagree and do disagree. They disagree so much that they actually do undergo chemotherapy for a smaller absolute benefit than that. Also, these days there are at least two gene tests that can guide decisions regarding chemotherapy. In the US, we tend to use the OncoType test, a test that is currently only approved for node-negative, estrogen receptor-positive tumors. OncoType produces a recurrence score based on the levels of 21 different genes. A high recurrence score, as you might guess, means a high risk of recurrence. These tumors are treated with chemotherapy. A low recurrence score indicates a much lower risk of recurrence, but also is associated with relative resistance to chemotherapy. These tumors generally do not get chemotherapy. Then there are intermediate scores, for which it is not clear whether the risk-benefit profile of chemotherapy justifies its use; clinical studies are ongoing for these tumors.

Naturally, Becker justifies her decision with all sorts of rationalizations. They’re not entirely unreasonable, but I have to wonder if she really understands them:

The oncologist advised having radiotherapy to my chest wall to kill any active cancer as well as chemotherapy to mop up any stray cancer cells elsewhere in my body – and then five to ten years of hormone therapy to prevent the cancer coming back.

At first, I assumed I had no choice but to climb on the conveyor belt to cancer hell. But, after some research and realising that in my case the treatments on offer could do more harm than good, I jumped off.

There are some breakthrough treatments out there, such as Tamoxifen, which have proven to help prevent cancer recurring. But they can have side-effects such as womb cancer, blood clots and bone disease – and I’m not brave enough to go there.

When I told my oncologist about my decision, he just looked at me in despair. He’s not the only one – to some family and friends my decision is both unfathomable and controversial, especially as I have a 14-year-old daughter Billie.

Shouldn’t I do everything I can to make sure I am around as long as possible to be with my daughter, I hear them ask?

My answer to them is simple: I want to be there for her, but I can’t do that while coping with the brutal and even dangerous side-effects of the treatments on offer.

Ms. Becker has a serious case of not being able to weigh risks versus benefits. You get the idea of where she is coming from from her reference to the “conveyor belt to cancer hell.” It’s true that chemotherapy can be rough, but she makes it sound as though it will make her unable to be their for her daughter. True, she might be feeling quite under the weather for the five months or so that it takes to do the full chemotherapy regimen, but then that’s it. Her hair will grow back and she will get back to normal. As for the risks from Tamoxifen, there’s an even bigger disconnect. The risk of clots, for instance, is less than 1% and only a small fraction of these are life-threatening. The risk of endometrial cancer is elevated by Tamoxifen from around 5 cases in 1,000 to 16, cases in 1,000. that’s a three-fold increased risk, but still only around 1%, and nearly all of these cancers are detected at an early stage that can be easily treated. Indeed, in women over 50, the risk of deep venous thrombosis was increased by Tamoxifen from 0.89 per 1,000 to 1.33 per 1,000, an increase of 0.44 per 1,000. Pulmonary embolism (blood clots from the deep venous thrombosis in the leg traveling to the lung) was increased from 0.44 to 0.96 per 1,000, or by 0.52 per 1,000. Are these risks that need to be understood? Certainly. Are they risks that outweigh the potential benefits of Tamoxifen? Certainly not, but Becker makes it sound as though by taking Tamoxifen she’d be taking an enormous risk of these complications that far outweighs the benefit.

The chance of dying in the next ten years is not the only thing to worry about. For instance, combined chemotherapy and Tamoxifen decrease the risk of recurrence from 52% to around 30%. The reason these numbers are higher is because many recurrences can be “salvaged” with additional treatment and not all recurrences kill within ten years. Worse, she is promoting misinformation by saying that “chemotherapy makes a difference of only 1 or 2 per cent to the chances of being disease-free after five years – so, in my case at least, there would be little benefit.” That might have been true if Ms. Beck’s cancer were only a stage I cancer; indeed in that case, barring a high OncoType score most oncologists would have recommended only Tamoxifen, not chemotherapy. However, Ms. Beck’s tumor is far more advanced than that. Again, unless she had a low Oncotype score, the potential benefit of chemotherapy is not that small, and the potential benefit of Tamoxifen is considerably greater, at less toxicity.

In some ways, though, Ms. Beck’s refusal to undergo radiation therapy is as big a problem. A 6 cm tumor is considered a locally advanced cancer, and in node-negative locally advanced cancers, the risk of recurrence in the chest wall is around 15-20%. For a woman with disease like Becker’s post-mastectomy radiation can significantly decrease that. As you might recall from the case of Michaela Jakubczyk-Eckert, chest wall recurrences are a horrible, horrible thing. It’s called en cuirasse carcinoma, a horrible, painful, and nasty manifestation of breast cancer in which the breast cancer recurrence grows on the chest wall in nodules that eventually coalesce into large contiguous tumor masses. When breast cancer progresses to this point, the en cuirasse tumor often bleeds and becomes necrotic, leaving the unfortunate woman with a chest wall covered with bloody, partially dying tumor that smells like rotting meat–mainly because it is in essence rotting meat, with living tumor in and around it. By not accepting radiation therapy at least, Becker is taking a much higher risk of this happening to her. Sure, the odds are in her favor; it’s probably only a 15-20% risk that she’s taking, and if recurrences are caught early enough they can be excised and radiated with a decent chance of control; so the odds of her developing en cuirasse disease are lower than that.

So why is Becker so afraid of adjuvant therapy? Well, she does make a not unreasonable argument that, if her chances of recurring are 20-30% her chances of not recurring are 70-80%, which is not bad. Perhaps. It is also her right to make that choice for herself, even if I think it’s not a good choice and is based on a view that makes it sound as though chemotherapy will destroy her life forever and Tamoxifen will damn her to blood clots, pulmonary emboli, and uterine cancer. It is rather amazing how a woman like her can understand her odds without further treatment reasonably well but exaggerate the risks and downplay the benefits of adjuvant therapy. Given how aware she is of the odds, surely she knows the real risks of Tamoxifen and chemotherapy by the numbers. So, no, it doesn’t bother me overmuch that Ms. Becker decided that she didn’t want radiation, chemotherapy, or Tamoxifen for herself. It does, however, bother me to see the bad arguments she is spouting that seem custom-designed to dissuade other women from choosing those adjuvant therapies and thus lead some of them to suffer fates as horrible as en cuirasse disease, distant metastasis, and death.

For example:

For example, standard surgery for breast cancer used to involve removing tissue from the shoulder, the chest wall, ribs – anything and everything that could be removed without killing the woman.

In the Twenties, Geoffrey Keynes, a doctor at Bart’s Hospital in London, refused to follow this standard practice – instead he removed only the tumour and then gave radiotherapy.
He was universally ridiculed, with ‘lumpectomy’ coined as a term of derision by his colleagues.

Today, the lumpectomy is standard procedure. Yet if Keynes did that today, and a patient died down the line, he would probably be sued for medical negligence.

No doubt Ms. Becker got this story from Siddhartha Mukherjee’s The Emperor of All Maladies.

Yes, in retrospect, it’s always obvious that new ways of treating disease that turn out to be better than the old way were better. It’s never so obvious at the time. One also has to remember that radiation was not widely available. The reason why the Halsted radical mastectomy took hold is because back when Halsted developed it surgery was the only modality that could cure breast cancer, and the breast cancers he treated tended to be large and locally advanced. In the absence of effective adjuvant therapy, radical surgery was it as far as potential cure goes. No one argues these days that the Halsted radical mastectomy outlived its usefulness by at least two or three decades, but comparing this issue to her refusal of standard-of-care adjuvant therapies is deceptive. After all, one notes that without radiation, breast conserving surgery is not safe; the risk of local recurrence can be 25% to 50%, depending on the characteristics of the tumor. In the 1920s, radiation therapy was incredibly primitive.

I also have a problem with Ms. Becker using her battle with cancer to promote this:

Following the death of his wife, the novelist Josephine Hart, two years ago from ovarian cancer, Lord (Maurice) Saatchi put forward a Medical Innovation Bill that would allow just this to happen.

This would mean that as long as they have approval from the patient and other doctors – and follow guidelines – doctors could try alternatives, such as drugs still undergoing trials, or a new surgical technique. I will be giving it my full support when the Bill is presented to the House of Commons on Friday, because it could benefit millions.

First off, what Ms. Becker did was not in any way radical, novel, or experimental. It is basically a variant on the old standard of care before adjuvant radiation therapy and adjuvant chemotherapy were developed, minus the removal of all the axillary lymph nodes. We know the risks of what she did, the potential price she might pay, and what the increase in the risk of her paying that price is because she eschewed effective adjuvant therapy. What this bill sounds as though it would do is to give free rein to “medical mavericks,” from the creative to pure quacks, to do whatever they want to do without all those pesky ethics boards and without actually protecting human subjects taking part in what will be in essence research using N of 1 trials without rigor. The very reason for clinical trials and the extensive infrastructure to oversee their conduct and ethics is because just letting doctors do what they want to do results in abuses of human subjects. The way Keynes just experimented based on an idea with little or no preliminary data in the 1920s might have been acceptable 90 years ago because we didn’t know any better; it’s not now.

She also confidently proclaims that this law could benefit millions. More likely it could put millions at risk of being harmed. After all, most experimental medical treatments fail. Only a small fraction of them make it through all the clinical trials. Some turn out to be more harmful than beneficial. Some, like surgical techniques, ultimately turn out to be beneficial, but during the “learning phase” could cause significant injury. (The example of laparoscopic cholecystectomy comes to mind; in the 1990s when it was replacing open gallbladder surgery it carried a much higher risk of injury to the common bile duct.)

Although Ms. Becker has every right to decide what is best for her for whatever reason she wishes, when she uses her experience as a breast cancer survivor who refused adjuvant therapy to promote ideas like this, she needs to be called out, breast cancer survivor or not.