Family history of breast cancer, mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

Abstract

Background: This study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.

Methods: Women aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.

Results: Of the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40-49 years: aHR 1.96, 95% confidence interval [CI] 1.85-2.08; age 50-64 years: aHR 1.70, 95% CI 1.58-1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78-2.14).

Conclusion: Family history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.

Keywords: Breast cancer risk; Breast density; Family history of breast cancer.

Fig. 1

Flow diagram of the selection of eligible population.

Fig. 2

Cumulative Incidence of Subsequent Breast Cancer, by First-Degree Family History, Mammographic Breast Density, and Age Group. The red lines represent women with a family history of breast cancer, and the blue lines represent women without a family history of breast cancer. The vertical solid lines represent the age group of 40-49 years, the dotted lines represent the age group of 50-64, and the dashed lines represent the age group of ≥65 years. Gray's tests were used to assess statistical differences between curves with and without family history in each subgroup.