Genetic aspects of breast cancer.

Of all the factors contributing to breast cancer risk, a strong family history of the disease is the most powerful. Familial clustering is said to have been noted by the Ancient Romans but formal documentation began in the mid-nineteenth century (reviewed in Ref. 1). The French physician Paul Broca noted that in one family (probably his wife's) over four generations 10 out of 24 women had died from breast cancer while several more individuals, of both sexes, had suffered other malignancies. He concluded that this very large excess of cancers could not reasonably be attributed to chance. At the same time he recognized that occasional familial clusters of relatively common conditions would be expected even in the absence of any genetic predisposition and discounted several published reports of 'hereditary cancers', including some of the families collected by his English contemporary Sir James Paget.