Family history of breast cancer as a second primary malignancy in relatives: a nationwide cohort study

BACKGROUND: With the increasing number of breast cancer (BC) diagnosed as a second primary malignancy after a first primary non-breast cancer (BCa-2), it is unclear about the familial risk of BC among women with a first-degree relative (FDR, parents or siblings) affected by a BCa-2. METHODS: In this Swedish nationwide cohort study, 5315 women with a FDR affected by BCa-2 and 115,048 women with a FDR affected by BC as the first primary cancer (BCa-1) were followed for the first primary invasive BC diagnosis. Relative risk (RR) of BC was estimated through Poisson regression by using 2,743,777 women without a family history of cancer as reference. The risk was stratified by the diagnostic age of BC in FDR, proband type, the time interval between the first primary cancer and BCa-2 in FDR as well as the site of first primary cancer diagnosed in FDR before BCa-2. We also calculated the cumulative incidence of BC from birth to a specific age for the three groups. RESULTS: The cumulative incidence from birth to age 70 was 10% among women with a family history of BCa-2. The RR of BC with a family history of BCa-2 (RR, 1.68, 95%CI, 1.49 to 1.88) was comparable to that with BCa-1 (1.68, 1.63 to 1.73). The risk was largely consistent irrespective of proband type. The age of onset of BCa-2 in FDR (RR (early-onset), 1.72 vs. RR (late-onset) 1.67) had less influence on the risk compared to BCa-1 in FDR (1.89 vs. 1.63). In the analysis stratified by the time between the first primary cancer and BCa-2 in relatives, the risks were largely similar. For the site of first primary cancer diagnosed in FDR before BCa-2, the increased BC risk was found in women whose FDRs were diagnosed with first primary gastric, colorectal, endometrial, ovarian, nervous system and endocrine gland cancers, and non-Hodgkin lymphoma. CONCLUSIONS: Women with a family history of BCa-2 have a similar overall BC risk as those with a family history of BCa-1. The risk varied according to the site of first primary cancer diagnosed in FDR before BCa-2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08925-y.