Brown Ronald B, Bigelow Philip, Dubin Joel A
School of Public Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Cancers (Basel). 2023 Oct 21;15(20):5093. doi: 10.3390/cancers15205093.
Breast cancer is associated with phosphate toxicity, the toxic effect from dysregulated phosphate metabolism that can stimulate tumorigenesis. Phosphate toxicity and dysregulated phosphate metabolism are also associated with bone mineral abnormalities, including excessive bone mineral loss and deposition. Based on shared associations with dysregulated phosphate metabolism and phosphate toxicity, a hypothesis proposed in the present mixed methods-grounded theory study posits that middle-aged women with incidence of breast cancer had a greater magnitude of changes in bone mineral density over time compared with women who remained cancer-free. To test this hypothesis, a mixed-effects model was used to analyze the associations of breast cancer incidence with spinal bone mineral density changes in the U.S. Study of Women's Health Across the Nation. Compared with women in the cohort who remained cancer-free, women who self-reported breast cancer had higher bone mineral density at baseline, but had more rapid losses in bone mineral density during follow-up visits. These findings agree with the hypothesis that a greater magnitude of changes in bone mineral density over time is associated with breast cancer in a cohort of middle-aged women. The findings also have implications for studies investigating dysregulated phosphate metabolism and phosphate toxicity as causative factors of bone metastasis in metastatic breast cancer. Additionally, the authors previously found increased breast cancer risk associated with high dietary phosphate intake in the same cohort of middle-aged women, and more studies should investigate a low-phosphorus diet to reduce bone mineral abnormalities and tumorigenesis in breast cancer patients.
乳腺癌与磷酸盐毒性有关，磷酸盐代谢失调产生的毒性作用会刺激肿瘤发生。磷酸盐毒性和磷酸盐代谢失调还与骨矿物质异常有关，包括骨矿物质过度流失和沉积。基于与磷酸盐代谢失调和磷酸盐毒性的共同关联，在本项基于混合方法的扎根理论研究中提出的一个假设认为，与未患癌症的女性相比，患乳腺癌的中年女性随时间推移骨矿物质密度的变化幅度更大。为了验证这一假设，在美国全国女性健康研究中，使用混合效应模型分析乳腺癌发病率与脊柱骨矿物质密度变化之间的关联。与队列中未患癌症的女性相比，自我报告患有乳腺癌的女性在基线时骨矿物质密度较高，但在随访期间骨矿物质密度下降更快。这些发现与以下假设一致：在中年女性队列中，随时间推移骨矿物质密度变化幅度更大与乳腺癌有关。这些发现对于研究磷酸盐代谢失调和磷酸盐毒性作为转移性乳腺癌骨转移的致病因素也具有启示意义。此外，作者此前在同一中年女性队列中发现，高膳食磷酸盐摄入量与乳腺癌风险增加有关，更多研究应探讨低磷饮食以减少乳腺癌患者的骨矿物质异常和肿瘤发生。
