Abstract
Background Some studies have already proposed an inverse association between vitamin D levels
and breast density. As breast density is already considered an established risk factor
for breast cancer, such a connection could offer a new starting point for the prevention
of breast cancer.
Material and Methods To investigate this suggested connection, a total of 412 pre- and 572 post-menopausal
women for whom mammography was indicated were recruited into this cross-sectional
study. In addition to a questionnaire-based interview on the patientʼs general and
gynecological medical history, her eating habits and lifestyle, serum levels of 25-hydroxyvitamin
D [25(OH)D], calcium, phosphate and creatinine were determined. Breast density was
determined by mammography and categorized as 1 to 4 according to the ACR classification.
In addition to performing descriptive analysis to get a better overview of the data,
a number of multivariate regression models were developed to determine the impact
of confounders and the connection between vitamin D and mammographic density.
Results More than half of all participants had low levels of 25(OH)D (< 20 ng/ml) and only
a small minority of women (5.7 %) had what are currently considered to be optimal
serum levels of 25(OH)D of at least 30 ng/ml. The significant majority of the cohort
had a medium mammographic density (n = 463 had ACR 2; n = 343 had ACR 3). Logistic
regression analysis showed that lower 25(OH)D serum levels were associated significantly
more often with high rather than medium breast density. This association remained,
even after adjusting for other factors which influence breast density such as age,
BMI and menopausal status (p = 0.032 for ACR 4 vs. ACR 2; p = 0.028 for ACR 4 vs.
ACR 3). When the same analysis was done separately for pre-menopausal and post-menopausal
women, BMI in both groups was found to be inversely correlated with breast density
and this inverse correlation was highly significant. In post-menopausal women, age
was found to be similarly correlated while 25(OH)D did not appear to be associated
with ACR. In pre-menopausal women the opposite was the case: although there was no
correlation between age and breast density, higher vitamin D levels tended to be associated
with lower breast density (p = 0.06 for ACR 2 vs. ACR 4) in this smaller sample (n = 412).
When vitamin D-rich food and food supplements were also taken into account, regular
intake of vitamin D preparations was associated with lower breast density; this association
achieved borderline statistical significance (p = 0.05 for ACR 3 vs. ACR 4). When
the analysis also took menopausal status into account, the breast density of pre-menopausal
women was lower following regular vitamin D intake and this lower breast density of
pre-menopausal women was statistically highly significant (p < 0.001 for ACR 1 and
ACR 2 vs. ACR 4, respectively). This effect was not found in post-menopausal women.
Frequent intake of vitamin D-containing nutrition had no significant impact on ACR
in either of the groups.
Conclusion These results reinforce the assumption previously proposed by several authors that
higher levels of 25(OH)D pre-menopause and vitamin D substitution are associated with
lower breast density and could reduce the risk of breast cancer. The findings did
not confirm any post-menopausal association between vitamin D and mammographic breast
density.
Key words
Vitamin D - breast density - BMI - age - menopausal status
