Abstract
BackgroundWith 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.MethodsIn 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.ResultsThe 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.ConclusionsWomen 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.
Highlights
Breast cancer (BC) is the leading cause of cancer death among women worldwide [1]
When BCa-2 was diagnosed in mother or sister, the risk was still equivalent to that with family history of BCa-1, but it was high for women with male first-degree relative (FDR) affected by BCa-2 (2.19, 0.98 to 4.87)
The principal finding of this nationwide population-based cohort study was that a diagnosis of either BCa-1 or BCa-2 is associated with a similar breast cancer (BC) risk for their family members, We excluded women who had multiple FDRs affected by BCa-2 and women who had FDRs affected by BCa-2 later developed with third, fourth or even fifth primary cancers, which could be the reason that we observed slightly lower familial risk (1.68)
Summary
Breast cancer (BC) is the leading cause of cancer death among women worldwide [1]. Family history of BC in first-degree relative (FDR) is one of the important risk factors. While there is limited evidence on the familial risk associated with the diagnosis of BC as a second primary malignancy after a cancer other than BC (BCa-2). Some of the risk factors that lead to a diagnosis of BCa-2, such as treatment from the first primary cancer, are absent for BCa-1 and are not shared among family members. Despite that BC is the most common second primary cancer among women [7], it is unknown whether the familial risk remains unchanged when the FDRs are diagnosed with a BCa-2. 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
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