Modification of risk for subsequent cancer after female breast cancer by a family history of breast cancer.

An increased risk of second primary cancers may depend on many reasons, including therapy for the first cancer and heritable causation. Population level data are not available exploring the risks of subsequent cancers after breast cancer considering a familial history of breast cancers. We used the nation-wide Swedish Family-Cancer Database to investigate such risks, based on 43,398 first invasive female breast cancers. Standardized incidence ratios (SIRs) were calculated for the second cancer after breast cancer using rates for first cancer as a reference. Many cancers at discordant sites were increased after breast cancer. SIRs for subsequent neoplasms in women who had a family history of breast cancer were increased for ovarian (2.0) and endometrial (1.8) cancers and for acute lymphoid leukemia (12.7) and myelofibrosis (9.4). The data suggest that the familial aggregation of breast and endometrial cancers may be explained by yet unidentified heritable causes. The remarkably high risks for second acute lymphoid leukemia and myelofibrosis, both characterized by chromosomal aberrations, in women with a family history of breast cancer may signal heritable defects in the ability to process DNA damage caused by ionizing radiation and chemotherapy.