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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Eur J Clin Nutr. Author manuscript; available in PMC Jun 1, 2011.
Published in final edited form as:
PMCID: PMC2900248

Serum 25-hydroxyvitamin D levels and mammographic density among premenopausal women in a multiethnic population


While some evidence suggests a protective role of vitamin D against breast cancer, epidemiologic findings are inconsistent. The current study investigated the relation of serum 25-hydroxyvitamin D (25(OH)D) levels with mammographic density. Baseline serum samples from 182 premenopausal women including 67 Caucasians and 74 Asians from a nutritional trial were analyzed for 25(OH)D. Mammographic density was assessed using a computer assisted method. Serum 25(OH)D was not associated with mammographic density after adjustment for confounders (body mass index (BMI), age at mammogram, Asian ethnicity, age at first birth, parity and age at menarche). 25(OH)D levels were significantly lower in Asians than in Caucasians, but no significant ethnic differences in mammographic density were observed after adjusting for BMI. Although the current results indicate serum 25(OH)D levels were not associated with mammographic density among premenopausal women, a possible protective effect of vitamin D against breast cancer may be mediated through other pathways.

Keywords: Vitamin D, 25-Hydroxyvitamin D, mammographic density, breast cancer


While some evidence suggests a protective role of vitamin D against breast cancer (Lowe et al., 2003), epidemiologic findings are equivocal. Some found that high intake of vitamin D or higher levels of circulating 25-hydroxyviatmin D ((25(OH)D), a biomarker for vitamin D status, is associated with a decreased risk of breast cancer (Bérubé et al., 2004; Bérubé et al., 2005; Brisson et al., 2007) whereas others reported no associations (Knight et al., 2006; Mishra et al., 2008).

Mammographic density is considered a strong predictor of breast cancer risk and women with high density are 4 to 6 times more likely to develop the disease (Boyd et al., 1998). In addition to anthropometric, reproductive, genetic, and hormonal factors, dietary or circulating micronutrients such as vitamin D may also influence mammographic density. The objective of the current study was to examine the association between serum 25(OH)D and mammographic density using baseline serum samples from a nutritional trial (Maskarinec et al., 2004) involving premenopausal women of different ethnic backgrounds

Materials and Methods

Subjects and study design

The study protocol was approved by the Institutional Review Board of the University of Hawaii. As described previously (Maskarinec et al., 2004), 220 women aged 35 to 46 years were randomly assigned to either the soy intervention or the control group. Only the baseline samples and data were used in our study as the effect of soy intervention was not of interest; 25(OH)D levels were available for 182 participants.

The ethnic distribution was: 67 Caucasians; 74 Asians (49 Japanese, 14 Chinese and11 Filipinos); 22 Hawaiians; and 19 of mixed/other ethnicities. Due to the relatively small sample size for Hawaiian and mixed /other ethnicities, ethnic differences were only examined between Asians and Caucasians.

Serum analysis

Serum 25(OH)D was measured using a double-antibody enzyme-linked immunosorbent essay kit (Immunodiagnostic Systems, Ltd., Fountain Hills, AZ). For quality control, a pooled serum sample donated by 10 premenopausal center employees was analyzed with each individual batch.

Mammographic data collection

Computer assisted mammographic density assessment was conducted using a method described by Byng et al. (Byng et al., 1994). The mammographic measures included the total breast area, the dense area of the breast, and percent breast density (mammographic density) calculated as the ratio of the dense area to the total area. The intraclass correlation coefficients (ICC), an indicator of reproducibility, were 0.93 for the dense area and 0.998 for the total breast area, resulting in an ICC of 0.95 for percent breast density (Maskarinec et al., 2004).

Statistical analysis

Analysis of variance was used to examine the relation between serum 25(OH)D and mammographic density and to compare mammographic density levels across quartiles of 25(OH)D. SAS software (SAS Institute, Cary, NC) was used for all statistical analyses and values of P < 0.05 were considered statistically significant. Analyses were also adjusted for body mass index (BMI), Asian ethnicity, age at mammogram, parity, age at first birth and age at menarche.


Mean BMI and 25(OH)D levels were significantly lower and percent breast density was relatively higher in Asians than in Caucasians (Table 1). After adjusting for BMI, ethnic differences remained for 25(OH)D (P = 0.006), but not for breast density (P = 0.58).

Table 1
Characteristics of study participants by ethnicity

Although serum 25(OH)D levels were significantly correlated with breast density, this association disappeared after adjusting for confounders (p = 0.71).

Mean values of mammographic densities were compared across quartiles of 25(OH)D (Q1, < 54.2 nM; Q2, 54.2 – 69.0 nM; Q3, 69.0 – 85.7 nM; Q4, > 85.7 nM) (Table 2). Although unadjusted breast density was lower for the lowest quartile, the difference did not reach statistical significance. After adjusting for confounders, the mean values were similar across quartiles (47.5%, 49.4%, 48.4% and 43.3%).

Table 2
Mammographic density values across quartiles of serum 25(OH)D levels in 182 premenopausal women


Our results indicate that serum 25(OH)D levels were not associated with mammographic densities among premenopausal women. This is in agreement with Knight et al. (Knight et al., 2006) who also reported no association among both pre- and post-menopausal women. However, a significant correlation between dietary or blood vitamin D and breast density has been suggested by others. Bérubé et al. (Berube et al., 2004) found that increasing vitamin D intake was associated with lower breast density among women aged 40 to 60 years. This finding was later repeated in a separate study for premenopausal but not for postmenopausal women (Berube et al., 2005). The same research group also reported synchronized seasonal variations of plasma 25(OH)D and breast density, suggesting that changes in blood vitamin D seem to be inversely related to changes in breast density (Brisson et al., 2007).

There are possible explanations for the lack of association observed in our study. First, there might truly be no association between serum 25(OH)D levels and breast cancer risk as predicted by mammographic density, or the association was too weak to be detected without a considerably greater number of subjects. Second, vitamin D exposure earlier in life may be more important to mammographic density and breast cancer risk (Knight et al., 2006). However, two published studies (Cui and Rohan, 2006) failed to establish an association between adolescent vitamin D intake and breast cancer risk in adulthood. In addition, Mishra et al. (Mishra et al., 2008) assessed dietary vitamin D intakes at different ages through adulthood in relation to breast density in a British birth cohort and found no association at any age. Third, it is possible that the potential protective effects of vitamin D against breast cancer may be mediated through other pathways than those associated with mammographic density.

Serum 25(OH)D levels were significantly lower in Asians than in Caucasians. However, the relatively higher mean value of breast density observed in Asians compared to Caucasians was mainly confounded by the ethnic differences in BMI as the importance of ethnicity in our statistical model was considerably reduced after adjusting for this variable.

In conclusion, serum 25(OH)D levels were not associated with mammographic densities in this sample of premenopausal women, suggesting path ways other than breast density may be involved with any potential protective role of vitamin D against breast cancer.


Financial Support The research was supported by the National Institutes of Health grants R03CA130061 and S10RR020890. The original study was supported by NCI grant R01CA80843.


Conflict of interest Authors declare no conflict of interest.


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