Effect of multiplicity, laterality, and age at onset of breast cancer on familial risk of breast cancer: a nationwide prospective cohort study

The objective of this nationwide prospective cohort study is to find out the risk of breast cancer (BC) in relatives of patients with multiple BCs by laterality and age at diagnosis of first BC. Having family history of single (HR 1.8; 95 % CI 1.8–1.9) or multiple (HR 2.7; 95 % CI 2.6–2.9) BC was associated with higher risk of BC. Those with an FDR with contralateral BC at any age had the highest risk of familial cancer except at age <40 in which those whose young FDR was affected by multiple ipsilateral BC had the highest risk (HR 9.7; 95 % CI 6.0–15.6). The familial risk of BC in these families decreased as the subject’s and FDRs’ age at diagnosis of first BC increased. The HR was still significantly increased (2.2) for old individuals (>60) having a FDR with contralateral BC at an advanced age (≥80). Despite the common belief that later onset breast cancer is more associated with sporadic breast cancer, our data suggest that breast cancer at any age in the family is associated with some increase in the familial risk, though that risk decreases as the age of onset increases. Contralateral and multiple ipsilateral breast cancers might be associated with distinct shared familial risk factors. Our results have implication for genetic counseling and urge gene identification studies.