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Faulty BRCA1, BRCA2 genes: how poor is the prognosis?

We take a critical look at the meaning behind the number 87% given to 25-year-old Sophie, a BRCA1 and BRCA2 carrier. Sophie has been told she has an 87% chance of getting breast cancer. She is contemplating a preventive double mastectomy after genetic counseling and her physician's advice. Some 92% of British general practitioners are in favor of prophylactic mastectomy as a treatment option for women similar to Sophie. The treatment decision results, to a very large extent, from the size of the number (87%) alone. The central argument of this study is that physicians, their patients, and the public need a much better understanding on what is meant by probability estimates of 0.87. The figure on its own does not tell us much, and we need to be very cautious in its interpretation. It is important to know that the very same genetic and statistical models, and observed data, resulting in a verdict of an 87% lifetime chance of getting breast cancer, based on BRCA1, BRCA2, and familial information, simultaneously show Sophie to have a greater than 99% chance of surviving beyond the next 5 years cancer free. If she succeeds-the chances are overwhelmingly in her favor-then, given that fact, her chances of surviving a further 5 years are once again greater than 98%. Her chances of not dying due to breast cancer over the next 20 years are greater than 97%, a percentage that changes little if instead of 20 we write the number 30. In a word, although the diagnosis of a faulty BRAC gene may be a disappointment, there is no immediate peril and no need for undue alarm. Sophie, and her primary care providers, can carefully consider her options without feeling that they are under any kind of acute pressure. Whatever the threat, it is not an imminent one.

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