Association between Bone Mineral Density and Incidence of Breast Cancer

Fraenkel, Merav; Novack, Victor; Liel, Yair; Koretz, Michael; Siris, Ethel S.; Norton, Larry; Shafat, Tali; Shany, Shraga; Geffen, David

doi:10.1371/journal.pone.0070980

Cited by 21 publications

(21 citation statements)

References 19 publications

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“…The clinical relevance of our finding that osteoblast-lineage cells instigate systemic changes promoting tumor growth and dissemination is supported by several clinical studies, which have linked alterations in bone homeostasis with the risk of breast cancer (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). High bone mineral density (BMD) has long been associated with increased risk of breast carcinogenesis and increased risk of metastasis in breast cancer patients (42,(44)(45)(46)(47)(48)52).…”

Section: Discussionmentioning

confidence: 67%

HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice

Devignes

Aslan

Brenot

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally. Remarkably, HIF signaling in osteoblast-lineage cells also promotes breast cancer growth and dissemination remotely, in the lungs and in other tissues distant from bones. Mechanistically, we found that activation of HIF signaling in OPCs increases blood levels of the chemokine C-X-C motif ligand 12 (CXCL12), which leads to a systemic increase of breast cancer cell proliferation and dissemination through direct activation of the CXCR4 receptor. Hence, our data reveal a previously unrecognized role of the hypoxic osteogenic niche in promoting tumorigenesis beyond the local bone microenvironment. They also support the concept that the skeleton is an important regulator of the systemic tumor environment.

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Section: Discussionmentioning

confidence: 67%

HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice

Devignes

Aslan

Brenot

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…However, regarding fracture risk of women with BC, study results are conflicting. A number of authors indicated that women with a higher BMD are at higher risk for developing breast cancer suggesting that there is a difference in baseline BMD of women with BC and healthy women [2,3,[20][21][22][23]. Zambetti et al revealed BMD as a significant prognostic factor for local or distant breast cancer recurrence.…”

Section: Discussionmentioning

confidence: 99%

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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“…1,2 However, data on the risk of osteoporotic fractures in women with BC are conflicting. Early studies did not find a lower risk for osteoporotic fracture among patients who developed BC.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer survivors are at an increased risk for osteoporotic fractures not explained by lower BMD: a retrospective analysis

et al. 2015

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Background:An association between higher bone mineral density (BMD) and the diagnosis of breast cancer (BC) has been reported. Data on the risk of osteoporotic fractures in women with BC are conflicting.Aims:The objective of this study was to assess fracture risk adjusted for BMD in women with and without BC, and to assess whether fracture risk in BC patients is attributed to BMD or BC characteristics.Methods:Using electronic medical records of patients who underwent dual energy X-ray absorptiometry BMD studies at Soroka University Medical Center between February 2003 and March 2011, we identified women with subsequent diagnosis of osteoporotic fractures. BC status, demographic, health characteristics, BMD, and other laboratory findings were assessed. In BC patients data on grade, stage, and treatment were collected. Primary outcome was osteoporotic fracture, analyzed by Cox proportional hazards regression models.Results:During a median follow-up of 4.9 years in 17,110 women with BMD testing (658 BC patients), 1,193 women experienced an osteoporotic fracture (62 in BC and 1,131 in no-BC groups). In multivariate analysis adjusted for age, body mass index (BMI) and BMD, hazard ratio (HR) for any osteoporotic fracture in women with BC was 1.34 (P=0.026). BMD was similar among women with and without BC who fractured. BC patients who experienced an osteoporotic fracture had a trend for less-advanced BC, lower rates of chemotherapy treatment, and higher rates of tamoxifen treatment.Conclusions:BC survivors are at increased risk of an osteoporotic fracture, which is not explained by worse BMD. Chemotherapy or aromatase inhibitors did not contribute substantially to fracture risk among our BC survivors.

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Association between Bone Mineral Density and Incidence of Breast Cancer

Cited by 21 publications

References 19 publications

HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice

HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice

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

Breast cancer survivors are at an increased risk for osteoporotic fractures not explained by lower BMD: a retrospective analysis

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