Analysis of Breast Cancer Family History, Estrogen Receptor Status, and Breast Cancer Outcomes in Sweden

IMPORTANCE: Breast cancer (BC), the most prevalent cancer among women globally, is a heterogeneous disease, with prognosis differing by estrogen receptor (ER) status. Having a family history of BC increases the risk of BC; however, it is unclear whether family history is associated with the prognosis of overall and ER-specific BC. OBJECTIVE: To assess whether a family history of BC is associated with the prognosis of overall and ER-specific BC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was based on data from several national registers in Sweden. All female residents of Stockholm who were born after 1932; had their first BC diagnosis between January 1, 1991, and December 31, 2019; and had at least 1 identified female first-degree relative (FDR) were included. Women who were diagnosed with other types of cancer before their BC diagnosis, were older than 75 years at diagnosis, or had distant metastasis at diagnosis were excluded. A total of 28 649 women were included. Data were analyzed from January 10, 2022, to December 20, 2022. EXPOSURES: Family history of BC, defined as 1 or more female FDRs diagnosed with BC. MAIN OUTCOMES AND MEASURES: Patients were followed up until BC-specific death, censoring, or end of follow-up on December 31, 2019. The role of family history in BC-specific mortality was investigated using flexible parametric survival models among the full cohort, ER-positive subgroup, and ER-negative subgroup, adjusting for demographic characteristics, tumor characteristics, and treatments received. RESULTS: Among 28 649 patients, the mean (SD) age at BC diagnosis was 55.7 (10.4) years; 19 545 (68.2%) had ER-positive BC, and 4078 (14.2%) had ER-negative BC. Overall, 5081 patients (17.7%) had at least 1 female FDR diagnosed with BC, while 384 (1.3%) had a family history of early-onset BC (FDR diagnosed before age 40 years). During the follow-up period (median [IQR], 8.7 [4.1-15.1] years), 2748 patients (9.6%) died of BC. Multivariable analyses revealed that having a family history of BC was associated with a lower risk of BC-specific death among the full cohort (hazard ratio [HR], 0.78; 95% CI, 0.65-0.95) and the ER-negative subgroup (HR, 0.57; 95% CI, 0.40-0.82) in the first 5 years, after which no association was observed. However, having an early-onset family history was associated with a higher risk of BC-specific death (HR, 1.41; 95% CI, 1.03-2.34). CONCLUSIONS AND RELEVANCE: In this study, patients with a family history of BC did not necessarily have a worse prognosis. Those with ER-negative status and a family history of BC had more favorable outcomes in the first 5 years after diagnosis, possibly due to enhanced motivation to receive and adhere to treatment. However, patients with a family history of early-onset BC had worse survival, suggesting that genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research.