Low bone density in premenopausal women at high risk for breast cancer

1532 Background: Tamoxifen when used in the high estrogen milieu of premenopausal women may reduce bone density. However, the proportion of premenopausal women at increased risk for breast cancer who have low bone density and are likely to take tamoxifen is unknown. Methods: Premenopausal women attending a high-risk clinic were invited to take part in an ongoing prospective study assessing bone mineral density (BMD) loss. Women on bisphosphonates or those previously treated with selective estrogen receptor modulators were excluded. BMD was measured by DEXA, serum 25-hydroxyvitamin D (25OHD) by chemiluminescence, and information on risk factors for osteoporosis and breast cancer was obtained by questionnaire. Results: 106 premenopausal women were entered between April and October 2008. Median age was 42 (range 23–57), median body mass index (BMI) was 25 kg/m2 (range 15–44). All but two were Caucasian. 13% had a prior biopsy with atypical hyperplasia (AH) or in situ carcinoma, 36% had a family history of osteoporosis, 56% took calcium supplements, and 47% took vitamin D supplements. Median sun exposure was 480 minutes per month, the majority with sunscreen. Median serum 25OHD was 34 ng/ml. Five had deficiency (< 20 ng/mL), and 45 women deficiency or insufficiency (< 32 ng/mL). Seven subjects ages 31 to 48 had evidence of low BMD (T-score of less than -1.0 in the spine or hip.) One woman with low BMD by DEXA had a 25OHD level < 32 ng/ml. Women with low BMD had lower BMIs (median of 22 vs. 25 kg/m2, p = 0.020) than women with normal bone density. There was no difference in history of vitamin D and calcium supplement use, and low 25OHD levels did not explain the low T-scores. Information on vitamin D receptor polymorphisms associated with BMD loss is pending. Importantly, 21% of women with a prior biopsy demonstrating AH or in situ carcinoma had evidence of bone density loss compared to 4% of women without such a biopsy (p = 0.048). Conclusions: Premenopausal women with a history of AH or in situ carcinoma are most likely to take tamoxifen for primary prevention and in our ongoing study have a high enough incidence of low bone density to make baseline assessment by DEXA a consideration, particularly for those with predisposing factors such as low BMI and lack of sun exposure. No significant financial relationships to disclose.