Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101986 women without the disease

Background Women with a family history of breast cancer are at increased ri sk of the disease, but no study has been large enough to characterise relia bly how, over women's lives, this risk is influenced by particular familial patterns of breast cancer. This report, on the relevance of breast cancer in first-degree relatives, is based on combined data from 52 epidemiologica l studies. Methods Individual data on breast cancer in first-degree relatives (mothers , sisters, and daughters) of 58 209 women with breast cancer and of 101986 controls were collected, checked, and analysed centrally. Risk ratios for b reast cancer were calculated by conditional logistic regression, stratified by study, age, menopausal status, number of sisters, parity, and age when the first child was born. Breast-cancer incidence and mortality rates for p articular family histories were calculated by applying age-specific risk ra tios to breast-cancer rates typical for more-developed countries. Findings Altogether 7496 (12.9%) women with breast cancer and 7438 (7.3%) c ontrols reported that one or more first-degree relatives had a history of b reast cancer: 12% of women with breast cancer had one affected relative and 1% had two or more. Risk ratios for breast cancer increased with increasin g numbers of affected first-degree relatives: compared with women who had n o affected relative, the ratios were 1.80 (99% CI 1.69-1.91), 2.93 (2.36-3. 64), and 3.90 (2.03-7.49), respectively, for one, two, and three or more af fected first-degree relatives (p<0.0001 each). The risk ratios were greates t at young ages, and for women of a given age, were greater the younger the relative was when diagnosed. The results did not differ substantially betw een women reporting an affected mother (9104) or sister (6386). Other facto rs, such as childbearing history, did not significantly alter the risk rati os associated with a family history of breast cancer. For women in more-dev eloped countries with zero, one, or two affected first-degree relatives, th e estimated cumulative incidence of breast cancer up to age 50 was 1.7%, 3. 7%, and 8.0%, respectively; corresponding estimates for incidence up to age 80 were 7.8%, 13.3%, and 21.1%. Corresponding estimates for death from bre ast cancer up to age 80 were 2.3%, 4.2%, and 7.6%. The age when the relativ e was diagnosed had only a moderate effect on these estimates. Interpretation Eight out of nine women who develop breast cancer do not hav e an affected mother, sister, or daughter. Although women who have first-de gree relatives with a history of breast cancer are at increased risk of the disease, most will never develop breast cancer, and most who do will be ag ed over 50 when their cancer is diagnosed. In countries where breast cancer is common, the lifetime excess incidence of breast cancer is 5.5% for wome n with one affected first-degree relative and 13.3% for women with two.