Determinants of Mammographic Density Change

Abstract

Background: Mammographic density (MD) is a strong risk factor for breast cancer. We examined how breast cancer risk factors are associated with MD area (cm²) change across age.

Methods: We conducted a cohort study of 31 782 Swedish women ages 40-70 years at time of baseline mammogram. Lifestyle and reproductive risk factors were assessed by a web-based questionnaire. MD was measured as dense area using the STRATUS method (mean over the left and right breast). Linear regression analyses with adjustments for age, body mass index (BMI), and menopausal status at baseline were performed to assess the association between breast cancer risk factors and mean baseline MD. To investigate mean MD change across age, linear regression analyses with adjustments for age, BMI, menopausal status, and age at last mammogram were performed. All tests of statistical significance were two-sided.

Results: Except for oral contraceptive use, established lifestyle and reproductive risk factors for breast cancer were associated with baseline mean MD. The overall average annual MD change was -1.0 cm². BMI and physical activity were statistically significantly associated with MD change. Lean women (BMI <20 kg/m²) had a mean MD change of -1.13 cm² per year (95% confidence interval = -1.25 to -1.02) compared with -0.46 cm² per year (95% confidence interval = -0.57 to -0.35) for women with BMI 30 or higher. The annual MD change was -0.4 cm² larger in women who were very physically active compared with less physically active women.

Conclusions: Our results indicate that all risk factors for breast cancer, except oral contraceptive use, are associated with baseline MD but that only age, BMI, and physical activity are determinants of MD change.

Figure 1.

Flow chart describing the exclusion criteria for 70 874 women in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort.

Figure 2.

Mean baseline mammographic dense area (cm²) as a function of age at mammography screening and established lifestyle factors including: A) body mass index ( <20, 20–24.9, 25–29.9, ≥30 kg/m²), B) smoking status (never, former, current), C) alcohol consumption (0, 0.1–10.0, >10 g/d), and D) physical activity (<40, 40–44, 45–49.9, ≥50 metabolic equivalent of task-h/d) at study entry.

Figure 3.

Mean baseline mammographic dense area (cm²) as a function of age at mammography screening and reproductive risk factors including: A) age at first birth (<20, 20–25, >25 years), B) number of children (0, 1–2, ≥3), C) breast-feeding duration among parous women (0, 1–5, 6–12, >12 months), D) time since last birth (<10, ≥10 years) at study entry, and E) age at menarche (<13, ≥13 years).

Figure 4.

Mean baseline mammographic dense area (cm²) as a function of age at mammography screening and A) oral contraceptive use (never, ever), B) menopausal hormone therapy (MHT) use in postmenopausal women (never, former, current) (because only a few postmenopausal women currently used MHT and were <50 years old [n = 42], we included only postmenopausal women ≥50 years old in this graph), and C) family history of breast cancer (yes, no) at study entry.