Abstract
We evaluated the heterogeneity of the effect of known risk factors on breast cancer development based on breast density by using the Breast Imaging-Reporting and Data System (BI-RADS). In total, 4,898,880 women, aged 40–74 years, who participated in the national breast cancer screening program in 2009–2010 were followed up to December 2018. Increased age showed a heterogeneous association with breast cancer (1-year hazard ratio (HR) = 0.92, 1.00 (reference), 1.03, and 1.03 in women with BI-RADS density category 1, 2, 3, and 4, respectively; P-heterogeneity < 0.001). More advanced age at menopause increased breast cancer risk in all BI-RADS categories. This was more prominent in women with BI-RADS density category 1 but less prominent in women in other BI-RADS categories (P-heterogeneity = 0.009). In postmenopausal women, a family history of breast cancer, body mass index ≥ 25 kg/m2, and smoking showed a heterogeneous association with breast cancer across all BI-RADS categories. Other risk factors including age at menarche, menopause, hormone replacement therapy after menopause, oral contraceptive use, and alcohol consumption did not show a heterogeneous association with breast cancer across the BI-RADS categories. Several known risk factors of breast cancer had a heterogeneous effect on breast cancer development across breast density categories, especially in postmenopausal women.
Highlights
Breast cancer is the most common cancer in women worldwide, accounting for 24.4% of all types of cancer; breast cancer is the leading cause of cancer death in women [1]
For participants with Breast Imaging-Reporting and Data System (BI-RADS) density category 1, increased age was associated with a decreased risk of breast cancer (HR = 0.92; 95% confidence intervals (CIs) = 0.90–0.93); no association was observed in participants with
Other risk factors did not show a heterogeneous association with breast cancer across BI-RADS categories
Summary
Breast cancer is the most common cancer in women worldwide, accounting for 24.4% of all types of cancer; breast cancer is the leading cause of cancer death in women [1]. In Asian countries, breast cancer incidence is lower; it has rapidly increased over the past decades. Changes in demographic factors associated with social and economic development, including lifestyle and reproductive risk factors, increase in breast cancer screening, and awareness in the region, have been attributed to this trend [1,2]. High mammographic density increases the risk of breast cancer; women with a breast tissue density ≥ 75% have a 4–5 times higher risk compared with those with a density < 5% [3,4]. The effect of mammographic density on breast cancer risk has been investigated previously. Studies have suggested that breast density is associated with risk factors of breast cancer such as age, reproductive factors, and body mass index (BMI) [5,6,7].
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