1. Sledge, George W. JR. MD

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I've had this conversation a hundred times. My patient, still stunned by her recent breast cancer diagnosis, asks the "why me?" question. She doesn't smoke, or drink to excess, and has lived a pretty unexceptionable life. Her family history is devoid of breast or ovarian cancer. And yet here she sits, her life forever altered by the Latinate-sounding words of a pathology report, and she has no idea why she is here.

GEORGE W. SLEDGE JR.... - Click to enlarge in new windowGEORGE W. SLEDGE JR., MD. GEORGE W. SLEDGE JR., MD, is Professor of Medicine and Chief of the Division of Oncology at Stanford University.His

I can't help her, not in any meaningful sense. I explain that most women do not have a family history or an inherited predisposition. I explain that we have a number of risk factors related to the internal hormonal milieu, things like early menarche and late menopause and breast feeding and the number of childbirths, but I cannot mount any enthusiasm for these as personal risk factors for her. There are hundreds of women walking by my clinic every day with the same risk factors, and most will never get breast cancer.


When you get right down to it, I usually end up saying, it's just bad luck.


I thought about these doctor-patient interactions while reading the recent paper in Science (2015;347:78-81) by Cristian Tomasetti and Bert Vogelstein of Johns Hopkins. The authors performed a fairly simple analysis, matching up the number of stem cell divisions in a given organ with the reported incidence of that organ's cancer. They concluded that there was a clear and fairly strong relationship between the two: the more stem cell divisions, the greater the likelihood of cancer.


They concluded that only a third of the variation in cancer risk between different tissues was attributable to either the environment or an inherited predisposition. The majority is due to "bad luck." "Bad luck" now enters the scientific literature as the cause of most human cancer.


The paper has already, in the few weeks since its publication, elicited a striking range of responses-one would almost say, of emotions-in both lay and scientific circles. Google "bad luck and cancer" and you will see a mountain of references. The article induced an almost visceral response in readers, or at least in newspaper editors.


And among scientists, who have been quick to respond to the paper (for an elegant analysis read the recent Cancer Letter interview with Barnett Kramer). One unhappy cancer biologist told me "this just proves that they'll publish anything in Science."


Part of the reaction is based on the paper's technical elements. Because of a paucity of data on stem cell divisions in breast and prostate cancer-two rather common human cancers-these were left out of the analysis. Also, the take-home message that two-thirds of variation in cancer risk is due to random mutations in normal stem cells has attracted attention. Two-thirds of variation in risk is not the same thing as saying two-thirds of human cancer is due to "bad luck." Not all tissues are created equal in terms of their cancer incidence, so a correlation coefficient between "all cancer types" is not the same as "all cancers." The Science press release, interestingly, made this mistake.


Unfortunate Message

But what rendered many apoplectic was the "lessons learned" aspect of the correlation. If most cancer is "bad luck," then cancer primary prevention efforts will inevitably prove futile. And indeed, many news outlets drew exactly this message from the paper, and from interviews with the authors. The paper itself is much more nuanced, but nuance makes for bad headlines.


It is an unfortunate message. Lung cancer, the leading cause of cancer death in the United States, is largely preventable. Cervical cancer, a viral disease, is largely preventable, as is hepatocellular carcinoma. Large percentages of head and neck cancer, esophageal cancer, bladder cancer, and skin cancer (among others) are largely preventable. If the public views lung cancer as "bad luck," why quit smoking? If cervical cancer is "bad luck," why bother to vaccinate your 12-year-old daughter? Why put on sunscreen if skin cancer is "bad luck"?


"Bad luck" absolves one of responsibility, and therefore of any need to live one's life in a healthy way. If a man with a gambling addiction goes broke at the racetrack, "bad luck" is a useful excuse. If a two-pack-a-day smoking habit, another addictive behavior, leads to small cell lung cancer, "bad luck" implies the smoker is not responsible.

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The other problem with the paper is the very concept of "bad luck." A public that believes in ghosts to a greater degree than evolution may take an essentially supernatural view of "bad luck." "Bad luck" may not, in the universal hierarchy, be at quite the same as divine will or destiny or fate. But some of my patients believe that there is a degree of supernatural intent at work there, cancer as cosmic payback for a youthful indiscretion, or a family curse at work.


The world is full of superstitions, and many of these are medical: the belief, enshrined by generations of ER doctors, that the full moon floods the emergency room with crazies, or that Friday the 13th increases the trauma load. Statistically not the case, a PubMed search assures me, but I've heard it affirmed dozens of times. For what it's worth, the only strong correlation I ever saw in the ER was with the Super Bowl or the World Series: heart attacks could wait until the end of the game.


In Ireland there is a common belief that a Saturday hospital discharge is bad luck, and associated with rapid readmission: "Saturday flit, short sit." Some 13.7 percent of patients interviewed for a study published in the Irish Medical Journal would refuse a Saturday discharge, and 40 percent of doctors would humor them.


One thinks of Shakespeare's lovely line in Hamlet: "There's a special providence in the fall of a sparrow." At some level we want our lives to have a special providence, even our personal catastrophes: "I got cancer because I was doomed to get cancer" may be more satisfying than what the authors of the Science paper actually meant: a stochastic process, a probabilistic event without any deeper meaning.


Pascal, Bohr, & Einstein

In short, we mean "bad luck" in the sense first described by Pascal in the 17th century. Pascal, attempting to understand games of chance, rendered the supernatural natural: you lost that card game because the odds were against you, not the gods. Kiss the dice for good luck all you want, but when they roll on the table randomness prevails.


Pascal was an essentially gloomy philosopher/mathematician: though religiously devout, his blinding mathematical brilliance had the effect of stripping the universe of mystery. He was also terrified by what he saw through the telescope: "Le silence eternel de ces espaces infinis m'effraie." The eternal silence of these infinite spaces frightens me: he believed the universe to be essentially random, but did not like what it implied.


Nor was he the only great scientist who detested randomness, The great 20th century debate between Bohr and Einstein over quantum theory largely boiled down to the issue of randomness. "God does not play at dice," Einstein famously said. Bohr supposedly responded "Albert, stop telling God what to do with his dice."


But even Bohr allowed for the possibility of good luck, keeping a horseshoe above his door, as was then a common superstition in Denmark. Asked whether he really believed that it brought him good luck, he replied "Of course not... but I am told it works even if you don't believe in it."


It's a principle that I can endorse. So, after a second opinion, as we shake hands and prepare to leave the room, my last words to the patient are always "best of luck to you."