Bone Mineral Density and Breast Cancer Incidence and Mortality in Postmenopausal Women: A Long-Term Follow-Up Study

Brozek, Wolfgang; Nagel, Gabriële; Ulmer, Hanno; Concin, Hans

doi:10.1089/jwh.2018.7310

Cited by 6 publications

(8 citation statements)

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“…4 Nevertheless, epidemiological studies of BMD and the risk of breast cancer have produced inconsistent results. [5][6][7][8][9][10] The disparity of findings may be explained by differences in study design, small sample sizes, residual confounding, or selection bias. Most studies were conducted in postmenopausal women, and it is still not clear whether BMD is associated with breast cancer risk in premenopausal women.…”

Section: Introductionmentioning

confidence: 99%

“…With the decrease of circulating estrogen in postmenopausal women, the incidence of osteoporosis increases significantly with age, whereas the increment in breast cancer incidence markedly slows down 4 . Nevertheless, epidemiological studies of BMD and the risk of breast cancer have produced inconsistent results 5‐10 . The disparity of findings may be explained by differences in study design, small sample sizes, residual confounding, or selection bias.…”

Section: Introductionmentioning

confidence: 99%

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Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis

Zhang

Mao

et al. 2022

Cancer

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BACKGROUND Estrogen is involved in both bone metabolism and breast cancer proliferation. However, evidence about the risk of breast cancer according to women's bone mineral density (BMD) is scarce, and little is known about their causal associations. METHODS Women participating in the UK Biobank cohort were used to investigate the association between BMD and the risk of breast cancer using Cox regression models. Instrumental variants associated with estimated BMD (eBMD) were extracted from genome‐wide association studies with European ancestry. Logistic regression was used to calculate the genetic association with breast cancer in the UK Biobank and 2‐sample Mendelian randomization (MR) analyses to assess their causal associations with breast cancer. Finally, the pleiotropic conditional false discovery rate (cFDR) method was conducted to further detect common genetic variants between BMD and breast cancer. RESULTS Compared with the general population, postmenopausal women with BMD T scores <−2.5 had a lower risk of breast cancer (hazard ratio [HR], 0.77; 95% CI, 0.59‐1.00), and this effect was stronger in women with fracture (HR, 0.31; 95% CI, 0.12‐0.82). In MR analysis, no causal associations between eBMD and breast cancer were observed. The cFDR method identified 63 pleiotropic loci associated with both BMD and breast cancer, of which CCDC170, ESR1, and FTO might play crucial roles in their pleiotropy. CONCLUSIONS An association between BMD and the risk of postmenopausal breast cancer in the UK Biobank was observed, whereas no evidence supported their causal association. Instead, their association could be explained by pleiotropic genetic variants leading to the pathology of osteoporosis and breast cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis

Zhang

Mao

et al. 2022

Cancer

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“…Brozek et al reported that BMD was not found to be a predictor for BC in their study population of younger postmenopausal women [26]. In another large sample of 13.698 patients, BMD in general was identified as a weak predictor of breast cancer.…”

Section: Discussionmentioning

confidence: 84%

Evaluation of baseline fracture risk in younger postmenopausal women with breast cancer using different risk assessment methods

et al. 2020

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Objective Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. Methods Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. Results Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10-year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. Conclusion Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

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confidence: 96%

“…Or does higher bone density increase the risk of breast cancer? Other relevant research results are different; they show that higher or lower bone density is not associated with breast cancer and that BMD cannot predict the risk of breast cancer [7][8][9] .There are many risk factors associated with breast cancer and BMD. Hormone levels may play an important role in breast cancer and osteoporosis 10,11 .…”

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confidence: 98%

Mendelian randomization analyses of associations between breast cancer and bone mineral density

Wang

Liu

et al. 2023

Sci Rep

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The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10−4) as might its ER+ subtype (FDR = 1.51 × 10−4). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10−6). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10−3) as could total testosterone (TT) (FDR = 5.81 × 10−3). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10−6) as could TT (FDR = 5.55 × 10−4). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.

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Bone Mineral Density and Breast Cancer Incidence and Mortality in Postmenopausal Women: A Long-Term Follow-Up Study

Cited by 6 publications

References 44 publications

Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis

Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis

Evaluation of baseline fracture risk in younger postmenopausal women with breast cancer using different risk assessment methods

Mendelian randomization analyses of associations between breast cancer and bone mineral density

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