A hypothesis-generating search for new genetic breast cancer syndromes - a national study in 803 Swedish families

Four thousand families from counselling clinics in Sweden were eligible for study. Families with breast cancer only were excluded, as were families with mutations in genes already known to be associated with malignant diseases. We identified 803 families with two or more cases of breast cancer and at least one other type of cancer. The observed proportion of different types of non-breast cancer was compared with the percentage distribution of non-breast cancer tumours in Sweden in 1958 and 1999.We found tumours in the colon, ovary, endometrium, pancreas and liver, as well as leukaemia in a significantly larger proportion of the study population than in the general population in both years. These tumours were also seen among families where several members had one additional tumour, suggesting that malignancies at these sites, in combination with breast tumours, could constitute genetic syndromes. Endometrial carcinoma has not previously been described in the context of breast cancer syndromes and the excess of malignancies at this site could not be explained by secondary tumours. Thus, we suggest that endometrial carcinoma and breast cancer constitute a new breast cancer syndrome. Further investigation is warranted to categorize phenotypes of both breast and endometrial tumours in this subgroup.Breast cancer is by far the most frequently diagnosed malignant tumour in females: one Swedish woman in ten will be affected during her lifetime [1]. Most cases occur late in life and are sporadic. A Scandinavian twin study has revealed that hereditary factors are important in 27% of all breast cancers [2], and 5-10% of the cases appear to be the result of autosomal dominant genes [3]. Familial aggregations of breast cancer have been observed all over the world; in general, early onset and bilateral disease are two important features in these families [4].Studies have revealed that autosomal dominant inherited mutations in certain genes are associated with an increased risk of