Cancer risk in close relatives of women with early-onset breast cancer - apopulation-based incidence study

Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the s tudy was to quantify the risks for cancers of the breast, ovary and other s ites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Reg istry were searched, and 2860 women were found in whom breast cancer was di agnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occ urrence through to 31 December 1993 was determined within the Cancer Regist ry's files and compared with national incidence rates. Women with early-ons et breast cancer were at a nearly fourfold increased risk of developing a n ew cancer later in life (268 observed vs 68.9 expected). The excess risk wa s most evident for second cancer of the breast (181 vs 24.5) and for ovaria n cancer (20 vs 3.3). For mothers and sisters, risks for cancers of the bre ast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast-ovarian cancer were very strong predictors of fami lial risks, with one in four female relatives predicted to develop breast a nd/or ovarian cancer by age 75. Mothers had a slightly increased risk of co lon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5-7.4) and especially brothers (29; 7.7-74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer be fore age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with brea st cancer.