Construction and validation of risk prediction model for breast cancer bone metastasis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Shiyuan , MIN Dan , LIU Pei ,  WU Bin

1. Department of Breast Surgery, Sichuan Provincial Center for Gynaecology and Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;

Corresponding author：

WU Bin, Email: wwbb129@sina.com

Keywords：

breast cancer; bone metastasis; risk factor; predictive model

DOI：

10.7507/1007-9424.202309009

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To identify the risk factors of bone metastasis in breast cancer and construct a predictive model. Methods The data of breast cancer patients met inclusion and exclusion criteria from 2010 to 2015 were obtained from the SEER*Stat database. Additionally, the data of breast cancer patients diagnosed with distant metastasis in the Affiliated Hospital of Southwest Medical University from 2021 to 2023 were collected. The patients from the SEER database were randomly divided into training (70%) and validation (30%) sets using R software, and the breast cancer patients from the Affiliated Hospital of Southwest Medical University were included in the validation set. The univariate and multivariate logistic regressions were used to identify risk factors of breast cancer bone metastasis. A nomogram predictive model was then constructed based on these factors. The predictive effect of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis. Results The study included 8 637 breast cancer patients, with 5 998 in the training set and 2 639 (including 68 patients in the Affiliated Hospital of Southwest Medical University) in the validation set. The statistical differences in the race and N stage were observed between the training and validation sets (P<0.05). The multivariate logistic regression analysis revealed that being of white race, having a low histological grade (Ⅰ–Ⅱ), positive estrogen and progesterone receptors status, negative human epidermal growth factor receptor 2 status, and non-undergoing surgery for the primary breast cancer site increased the risk of breast cancer bone metastasis (P<0.05). The nomogram based on these risk factors showed that the AUC (95% CI) of the training and validation sets was 0.676 (0.533, 0.744) and 0.690 (0.549, 0.739), respectively. The internal calibration using 1 000 Bootstrap samples demonstrated that the calibration curves for both sets closely approximated the ideal 45-degree reference line. The decision curve analysis indicated a stronger clinical utility within a certain probability threshold range. Conclusions This study constructs a nomogram predictive model based on factors related to the risk of breast cancer bone metastasis, which demonstrates a good consistency between actual and predicted outcomes in both training and validation sets. The nomogram shows a stronger clinical utility, but further analysis is needed to understand the reasons of the lower differentiation of nomogram in both sets.

Citation： XU Shiyuan, MIN Dan, LIU Pei, WU Bin. Construction and validation of risk prediction model for breast cancer bone metastasis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(1): 56-61. doi: 10.7507/1007-9424.202309009 Copy

1.	Anwar SL, Avanti WS, Dwianingsih EK, et al. Risk factors, patterns, and distribution of bone metastases and skeletal-related events in high-risk breast cancer patients. Asian Pac J Cancer Prev, 2022, 23(12): 4109-4117.
2.	Pantel K, Hayes DF. Disseminated breast tumour cells: biological and clinical meaning. Nat Rev Clin Oncol, 2018, 15(3): 129-131.
3.	Coleman RE, Smith P, Rubens RD. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer, 1998, 77(2): 336-340.
4.	李奕颖, 苏静, 李孟圈. 乳腺癌骨转移的影响因素分析及预测模型构建. 河南医学研究, 2021, 30(2): 211-215.
5.	章锐, 阮剑, 赵建国. 基于SEER数据库构建的远处转移性乳腺癌的预后列线图. 安徽医药, 2022, 26(9): 1781-1785.
6.	Ye LJ, Suo HD, Liang CY, et al. Nomogram for predicting the risk of bone metastasis in breast cancer: a SEER population-based study. Transl Cancer Res, 2020, 9(11): 6710-6719.
7.	Makhoul I, Montgomery CO, Gaddy D, et al. The best of both worlds—managing the cancer, saving the bone. Nat Rev Endocrinol, 2016, 12(1): 29-42.
8.	Wang R, Zhu Y, Liu X, et al. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage Ⅳ breast cancer. BMC, Cancer, 2019, 19(1): 1091.
9.	Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer, 2009, 9(4): 302-312.
10.	孟红霞, 张浩强, 乔永杰, 等. 唑来膦酸联合放射治疗对乳腺癌骨转移的疗效. 临床与病理杂志, 2018, 38(7): 1463-1468.
11.	中国抗癌协会骨肿瘤和骨转移瘤专业委员会. 乳腺癌骨转移临床诊疗专家共识. 中国肿瘤临床, 2022, 49(13): 660-669.
12.	DeSantis CE, Fedewa SA, Goding Sauer A, et al. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin, 2016, 66(1): 31-42.
13.	Diessner J, Wischnewsky M, Stüber T, et al. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer. BMC Cancer, 2016, 16: 307. doi: 10.1186/s12885-016-2345-7.
14.	Koizumi M, Yoshimoto M, Kasumi F, et al. An open cohort study of bone metastasis incidence following surgery in breast cancer patients. BMC Cancer, 2010, 10: 381.
15.	Pulido C, Vendrell I, Ferreira AR, et al. Bone metastasis risk factors in breast cancer. Ecancermedicalscience, 2017, 11: 715. doi: 10.3332/ecancer.2017.715.
16.	Ma W, Wang X, Xu G, et al. Distant metastasis prediction via a multi-feature fusion model in breast cancer. Aging (Albany NY), 2020, 12(18): 18151-18162.
17.	Chen J, Zhu S, Xie XZ, et al. Analysis of clinicopathological factors associated with bone metastasis in breast cancer. J Huazhong Univ Sci Technolog Med Sci, 2013, 33(1): 122-125.
18.	Hofbauer LC, Rachner TD, Coleman RE, et al. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol, 2014, 2(6): 500-512.
19.	Hinz N, Baranowsky A, Horn M, et al. Knockdown of AKT3 activates HER2 and DDR kinases in bone-seeking breast cancer cells, promotes metastasis in vivo and attenuates the TGFβ/CTGF axis. Cells, 2021, 10(2): 430.
20.	Korde LA, Gralow JR. Can we predict who’s at risk for developing bone metastases in breast cancer?. J Clin Oncol, 2011, 29(27): 3600-3604.
21.	Xiong Z, Deng G, Huang X, et al. Bone metastasis pattern in initial metastatic breast cancer: a population-based study. Cancer Manag Res, 2018, 10: 287-295.
22.	Yang L, Du W, Hu T, et al. Survival in breast cancer patients with bone metastasis: a multicenter real-world study on the prognostic impact of intensive postoperative bone scan after initial diagnosis of breast cancer (CSBrS-023). Cancers (Basel), 2022, 14(23): 5835.
23.	James JJ, Evans AJ, Pinder SE, et al. Bone metastases from breast carcinoma: histopathological-radiological correlations and prognostic features. Br J Cancer, 2003, 89(4): 660-665.
24.	Smid M, Wang Y, Klijn JG, et al. Genes associated with breast cancer metastatic to bone. J Clin Oncol, 2006, 24(15): 2261-2267.

1. Anwar SL, Avanti WS, Dwianingsih EK, et al. Risk factors, patterns, and distribution of bone metastases and skeletal-related events in high-risk breast cancer patients. Asian Pac J Cancer Prev, 2022, 23(12): 4109-4117.
2. Pantel K, Hayes DF. Disseminated breast tumour cells: biological and clinical meaning. Nat Rev Clin Oncol, 2018, 15(3): 129-131.
3. Coleman RE, Smith P, Rubens RD. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer, 1998, 77(2): 336-340.
4. 李奕颖, 苏静, 李孟圈. 乳腺癌骨转移的影响因素分析及预测模型构建. 河南医学研究, 2021, 30(2): 211-215.
5. 章锐, 阮剑, 赵建国. 基于SEER数据库构建的远处转移性乳腺癌的预后列线图. 安徽医药, 2022, 26(9): 1781-1785.
6. Ye LJ, Suo HD, Liang CY, et al. Nomogram for predicting the risk of bone metastasis in breast cancer: a SEER population-based study. Transl Cancer Res, 2020, 9(11): 6710-6719.
7. Makhoul I, Montgomery CO, Gaddy D, et al. The best of both worlds—managing the cancer, saving the bone. Nat Rev Endocrinol, 2016, 12(1): 29-42.
8. Wang R, Zhu Y, Liu X, et al. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage Ⅳ breast cancer. BMC, Cancer, 2019, 19(1): 1091.
9. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer, 2009, 9(4): 302-312.
10. 孟红霞, 张浩强, 乔永杰, 等. 唑来膦酸联合放射治疗对乳腺癌骨转移的疗效. 临床与病理杂志, 2018, 38(7): 1463-1468.
11. 中国抗癌协会骨肿瘤和骨转移瘤专业委员会. 乳腺癌骨转移临床诊疗专家共识. 中国肿瘤临床, 2022, 49(13): 660-669.
12. DeSantis CE, Fedewa SA, Goding Sauer A, et al. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin, 2016, 66(1): 31-42.
13. Diessner J, Wischnewsky M, Stüber T, et al. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer. BMC Cancer, 2016, 16: 307. doi: 10.1186/s12885-016-2345-7.
14. Koizumi M, Yoshimoto M, Kasumi F, et al. An open cohort study of bone metastasis incidence following surgery in breast cancer patients. BMC Cancer, 2010, 10: 381.
15. Pulido C, Vendrell I, Ferreira AR, et al. Bone metastasis risk factors in breast cancer. Ecancermedicalscience, 2017, 11: 715. doi: 10.3332/ecancer.2017.715.
16. Ma W, Wang X, Xu G, et al. Distant metastasis prediction via a multi-feature fusion model in breast cancer. Aging (Albany NY), 2020, 12(18): 18151-18162.
17. Chen J, Zhu S, Xie XZ, et al. Analysis of clinicopathological factors associated with bone metastasis in breast cancer. J Huazhong Univ Sci Technolog Med Sci, 2013, 33(1): 122-125.
18. Hofbauer LC, Rachner TD, Coleman RE, et al. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol, 2014, 2(6): 500-512.
19. Hinz N, Baranowsky A, Horn M, et al. Knockdown of AKT3 activates HER2 and DDR kinases in bone-seeking breast cancer cells, promotes metastasis in vivo and attenuates the TGFβ/CTGF axis. Cells, 2021, 10(2): 430.
20. Korde LA, Gralow JR. Can we predict who’s at risk for developing bone metastases in breast cancer?. J Clin Oncol, 2011, 29(27): 3600-3604.
21. Xiong Z, Deng G, Huang X, et al. Bone metastasis pattern in initial metastatic breast cancer: a population-based study. Cancer Manag Res, 2018, 10: 287-295.
22. Yang L, Du W, Hu T, et al. Survival in breast cancer patients with bone metastasis: a multicenter real-world study on the prognostic impact of intensive postoperative bone scan after initial diagnosis of breast cancer (CSBrS-023). Cancers (Basel), 2022, 14(23): 5835.
23. James JJ, Evans AJ, Pinder SE, et al. Bone metastases from breast carcinoma: histopathological-radiological correlations and prognostic features. Br J Cancer, 2003, 89(4): 660-665.
24. Smid M, Wang Y, Klijn JG, et al. Genes associated with breast cancer metastatic to bone. J Clin Oncol, 2006, 24(15): 2261-2267.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Construction and validation of risk prediction model for breast cancer bone metastasis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content