To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer.

This was a clinic-based case–control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing.

University-based breast referral clinics.

One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls.

There were significant mean differences in 1,25-D levels (pmol ml−1) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference ± SE: −11.08 ± 0.76), and black cases had higher 1,25-D levels than black controls (mean difference ± SE: 4.54 ± 2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case–control differences in 25-D levels in either group.

These data are consistent with a protective effect of 1,25-D for breast cancer in white women.