Genetic Implications of Bilateral Breast Cancer: a Population Based Cohort Study

Background: Women with breast cancer are at high risk of bilateral breast cancer. We aimed to assess the incidence of bilateral breast cancer in relation to age and time since diagnosis of first cancer.

Methods: We analysed a population-based cohort of 123757 women with a first primary breast cancer diagnosed in Sweden from 1970 to 2000 for frequency of bilateral breast cancers and deaths by means of record linkage. Second primary breast cancers were categorised as synchronous bilateral breast cancers if diagnosed within 3 months of the first primary cancer or as metachronous if diagnosed more than 3 months after diagnosis of first primary cancer.

Findings: We identified 6550 women who had developed bilateral breast cancer. Age-incidence patterns of synchronous and unilateral breast cancer were similar, although the absolute rates of synchronous bilateral cancer were 50-100 times lower than those of unilateral cancer. A woman aged 80 years or older is at least twice as likely to be diagnosed with synchronous bilateral breast cancer than is a woman younger than 40 years. In the first 20 years after diagnosis of primary breast cancer, incidence of metachronous bilateral cancer decreased from about 800 per 10(5) person-years to 400 per 10(5) person-years in patients diagnosed with primary breast cancer before the age of 45 years, whereas incidence remained at 500-600 per 10(5) person-years in those age 45 years or older at diagnosis. After 30 years' follow-up, cumulative risk of metachronous bilateral breast cancer was about 15% irrespective of age at first primary breast cancer.

Interpretation: The higher than expected risk of synchronous bilateral breast cancer could be explained by non-genetic factors. By contrast, incidence of metachronous bilateral cancer fits neither a model of highly penetrant genes nor aggregation of environmental risk factors.