Prognostic nomogram for patients with metastatic breast cancer: a study based-SEER database_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TANG Lingfeng , YAN Ping , SHU Xiujie ,  TU Gang

Department of Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China;

Corresponding author：

TU Gang, Email: tugang68@126.com

Keywords：

breast cancer; metastasis; nomogram prediction model; survival analysis; SEER database

DOI：

10.7507/1007-9424.202006027

Video：

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Objective To explore the risk factors affecting the prognosis of patients with metastatic breast cancer (MBC) and construct a nomogram survival prediction model.Methods The patients with MBC from 2010 to 2013 were collected from surveillance, epidemiology, and end results (SEER) database, then were randomly divided into training group and validation group by R software. SPSS software was used to compare the survival and prognosis of MBC patients with different metastatic sites in the training group by log-rank method and construct the Kaplan-Meier survival curve. The Cox proportional hazards model was used to analyze the factors of 3-year overall survival, then construct a nomogram survival prediction model by the independent prognostic factors. The C-index was used to evaluate its predictive value and the calibration curve was used to verify the nomogram survival prediction model by internal and external calibration graph.Results A total of 3 288 patients with MBC were collected, including 2 304 cases in the training group and 984 cases in the validation group. The data of the two groups were comparable. The median follow-up time of training group and validation group was 34 months and 34 months, respectively. In the training group, the results of Cox proportional hazards model showed that the older, black race, higher histological grading, without operation, ER (–), PR (–), HER-2 (–), and metastases of bone, brain, liver and lung were the risk factors of survival prognosis (P<0.05) and constructed the nomogram survival prediction model with these independent prognostic factors. The nomogram survival prediction showed a good accuracy with C-index of 0.704 [95%CI (0.691, 0.717)] in internal validation (training group) and C-index of 0.691 [95%CI (0.671, 0.711)] in external validation (validation group) in predicting 3-year overall survival. All calibration curves showed excellent consistency.Conclusion Nomogram for predicting 3-year overall survival of patients with MBC in this study has a good predictive capability, and it is conducive to development of individualized clinical treatment.

Citation： TANG Lingfeng, YAN Ping, SHU Xiujie, TU Gang. Prognostic nomogram for patients with metastatic breast cancer: a study based-SEER database. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(3): 309-315. doi: 10.7507/1007-9424.202006027 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Geiger S, Cnossen JA, Horster S, et al. Long-term follow-up of patients with metastatic breast cancer: results of a retrospective, single-center analysis from 2000 to 2005. Anticancer Drugs, 2011, 22(9): 933-939.
3.	于倩, 佟仲生, 汪旭, 等. 转移性乳腺癌临床病理特征及预后分析. 肿瘤, 2012, 32(8): 609-614.
4.	Mariotto AB, Etzioni R, Hurlbert M, et al. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev, 2017, 26(6): 809-815.
5.	Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
6.	Wang ZX, Qiu MZ, Jiang YM, et al. Comparison of prognostic nomograms based on different nodal staging systems in patients with resected gastric cancer. J Cancer, 2017, 8(6): 950-958.
7.	Balachandran VP, Gonen M, Smith JJ, et al. Nomograms in oncology: more than meets the eye. Lancet Oncol, 2015, 16(4): e173-e180.
8.	Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6): 1471-1474.
9.	Harrell FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med, 1996, 15(4): 361-387.
10.	陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况. 中国肿瘤临床, 2015, 42(13): 668-674.
11.	Beadle BM, Woodward WA, Buchholz TA. The impact of age on outcome in early-stage breast cancer. Semin Radiat Oncol, 2011, 21(1): 26-34.
12.	Youlden DR, Cramb SM, Yip CH, et al. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med, 2014, 11(2): 101-115.
13.	马焱, 何红, 王赛男. 多西他赛解救治疗不同年龄组转移性乳腺癌的临床研究. 实用肿瘤学杂志, 2019, 33(4): 352-356.
14.	Rapiti E, Verkooijen HM, Vlastos G, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol, 2006, 24(18): 2743-2749.
15.	Lobbezoo DJ, van Kampen RJ, Voogd AC, et al. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res Treat, 2013, 141(3): 507-514.
16.	National Cancer Institute. Breast Cancer (PDQ): Treatment. Stage ⅢB, inoperable ⅢC, Ⅳ, recurrent, and metastatic breast cancer. www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page8.
17.	National Health and Medical Research Council. Clinical practice guidelines for the management of advanced breast cancer. Prepared by the iSource National Breast Cancer Centre Advanced Breast Cancer Working Group. Endorsed January 2001. www.nhmrc.gov.au/publications/synopses/cp76syn.htm.
18.	Rogoz B, Houzé de l’Aulnoit A, Duhamel A, et al. Thirty-year trends of survival and time-varying effects of prognostic factors in patients with metastatic breast cancer—a single institution experience. Clin Breast Cancer, 2018, 18(3): 246-253.
19.	Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol, 2015, 16(13): 1380-1388.
20.	Fitzal F, Bjelic-Radisic V, Knauer M, et al. Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase Ⅲ ABCSG-28 POSYTIVE trial. Ann Surg, 2019, 269(6): 1163-1169.
21.	Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery, 2002, 132(4): 620-627.
22.	Warschkow R, Güller U, Tarantino I, et al. Improved survival after primary tumor surgery in metastatic breast cancer: a propensity-adjusted, population-based SEER trend analysis. Ann Surg, 2016, 263(6): 1188-1198.
23.	Thomas A, Khan SA, Chrischilles EA, et al. Initial surgery and survival in stage Ⅳ breast cancer in the United States, 1988–2011. JAMA Surg, 2016, 151(5): 424-431.
24.	Fields RC, Jeffe DB, Trinkaus K, et al. Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage Ⅳ breast cancer after controlling for site of metastasis. Ann Surg Oncol, 2007, 14(12): 3345-3351.
25.	King TA, Lyman JP, Gonen M, et al. Abstract P2-18-09: TBCRC 013: A prospective analysis of the role of surgery in stage Ⅳ breast cancer. Cancer Res, 2014, 73(24 Supplement): P2-18-09.
26.	Wang K, Shi Y, Li ZY, et al. Metastatic pattern discriminates survival benefit of primary surgery for de novo stage Ⅳ breast cancer: A real-world observational study. Eur J Surg Oncol, 2019, 45(8): 1364-1372.
27.	曲明阳, 李森, 赵胜男, 等. 乳腺癌脑转移患者危险因素分析. 中国普通外科杂志, 2011, 20(11): 1184-1187.
28.	Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature, 2000, 406(6797): 747-752.
29.	董国雷, 赵伟鹏, 佟仲生. 三阴性乳腺癌靶向治疗进展. 中国肿瘤临床, 2019, 46(12): 649-652.
30.	Ali SM, Leitzel K, Chinchilli VM, et al. Relationship of serum HER-2/neu and serum CA15-3 in patients with metastatic breast cancer. Clin Chem, 2002, 48(8): 1314-1320.
31.	Swain SM, Kim SB, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol, 2013, 14(6): 461-471.
32.	Chen F, Fujinaga T, Sato K, et al. Clinical features of surgical resection for pulmonary metastasis from breast cancer. Eur J Surg Oncol, 2009, 35(4): 393-397.
33.	Yoshimoto M, Tada K, Nishimura S, et al. Favourable long-term results after surgical removal of lung metastases of breast cancer. Breast Cancer Res Treat, 2008, 110(3): 485-491.
34.	袁芃, 徐兵河, 张频, 等. 21 例乳腺癌术后孤立性肺转移的临床分析及预后. 中国肿瘤临床, 2010, 37(12): 698-700, 709.
35.	Bacalbasa N, Dima SO, Purtan-Purnichescu R, et al. Role of surgical treatment in breast cancer liver metastases: a single center experience. Anticancer Res, 2014, 34(10): 5563-5568.
36.	Margonis GA, Buettner S, Sasaki K, et al. The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. HPB (Oxford), 2016, 18(8): 700-705.
37.	Tait CR, Waterworth A, Loncaster J, et al. The oligometastatic state in breast cancer: hypothesis or reality. Breast, 2005, 14(2): 87-93.
38.	Niwińska A, Pogoda K, Murawska M, et al. Factors influencing survival in patients with breast cancer and single or solitary brain metastasis. Eur J Surg Oncol, 2011, 37(7): 635-642.
39.	Chidel MA, Suh JH, Reddy CA, et al. Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys, 2000, 47(4): 993-999.
40.	Sperduto PW, Wang M, Robins HI, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys, 2013, 85(5): 1312-1318.
41.	Le Scodan R, Stevens D, Brain E, et al. Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol, 2009, 27(9): 1375-1381.
42.	陈菲. 乳腺癌骨转移患者预后相关因素. 中国肿瘤生物治疗杂志, 2020, 27(2): 191-198.
43.	周婕, 何伟星, 敖翔, 等. 乳腺癌骨转移放疗后的生存预测因素分析. 广东医学, 2016, 37(15): 2287-2290.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Geiger S, Cnossen JA, Horster S, et al. Long-term follow-up of patients with metastatic breast cancer: results of a retrospective, single-center analysis from 2000 to 2005. Anticancer Drugs, 2011, 22(9): 933-939.
3. 于倩, 佟仲生, 汪旭, 等. 转移性乳腺癌临床病理特征及预后分析. 肿瘤, 2012, 32(8): 609-614.
4. Mariotto AB, Etzioni R, Hurlbert M, et al. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomarkers Prev, 2017, 26(6): 809-815.
5. Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
6. Wang ZX, Qiu MZ, Jiang YM, et al. Comparison of prognostic nomograms based on different nodal staging systems in patients with resected gastric cancer. J Cancer, 2017, 8(6): 950-958.
7. Balachandran VP, Gonen M, Smith JJ, et al. Nomograms in oncology: more than meets the eye. Lancet Oncol, 2015, 16(4): e173-e180.
8. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6): 1471-1474.
9. Harrell FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med, 1996, 15(4): 361-387.
10. 陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况. 中国肿瘤临床, 2015, 42(13): 668-674.
11. Beadle BM, Woodward WA, Buchholz TA. The impact of age on outcome in early-stage breast cancer. Semin Radiat Oncol, 2011, 21(1): 26-34.
12. Youlden DR, Cramb SM, Yip CH, et al. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med, 2014, 11(2): 101-115.
13. 马焱, 何红, 王赛男. 多西他赛解救治疗不同年龄组转移性乳腺癌的临床研究. 实用肿瘤学杂志, 2019, 33(4): 352-356.
14. Rapiti E, Verkooijen HM, Vlastos G, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol, 2006, 24(18): 2743-2749.
15. Lobbezoo DJ, van Kampen RJ, Voogd AC, et al. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res Treat, 2013, 141(3): 507-514.
16. National Cancer Institute. Breast Cancer (PDQ): Treatment. Stage ⅢB, inoperable ⅢC, Ⅳ, recurrent, and metastatic breast cancer. www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page8.
17. National Health and Medical Research Council. Clinical practice guidelines for the management of advanced breast cancer. Prepared by the iSource National Breast Cancer Centre Advanced Breast Cancer Working Group. Endorsed January 2001. www.nhmrc.gov.au/publications/synopses/cp76syn.htm.
18. Rogoz B, Houzé de l’Aulnoit A, Duhamel A, et al. Thirty-year trends of survival and time-varying effects of prognostic factors in patients with metastatic breast cancer—a single institution experience. Clin Breast Cancer, 2018, 18(3): 246-253.
19. Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol, 2015, 16(13): 1380-1388.
20. Fitzal F, Bjelic-Radisic V, Knauer M, et al. Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase Ⅲ ABCSG-28 POSYTIVE trial. Ann Surg, 2019, 269(6): 1163-1169.
21. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery, 2002, 132(4): 620-627.
22. Warschkow R, Güller U, Tarantino I, et al. Improved survival after primary tumor surgery in metastatic breast cancer: a propensity-adjusted, population-based SEER trend analysis. Ann Surg, 2016, 263(6): 1188-1198.
23. Thomas A, Khan SA, Chrischilles EA, et al. Initial surgery and survival in stage Ⅳ breast cancer in the United States, 1988–2011. JAMA Surg, 2016, 151(5): 424-431.
24. Fields RC, Jeffe DB, Trinkaus K, et al. Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage Ⅳ breast cancer after controlling for site of metastasis. Ann Surg Oncol, 2007, 14(12): 3345-3351.
25. King TA, Lyman JP, Gonen M, et al. Abstract P2-18-09: TBCRC 013: A prospective analysis of the role of surgery in stage Ⅳ breast cancer. Cancer Res, 2014, 73(24 Supplement): P2-18-09.
26. Wang K, Shi Y, Li ZY, et al. Metastatic pattern discriminates survival benefit of primary surgery for de novo stage Ⅳ breast cancer: A real-world observational study. Eur J Surg Oncol, 2019, 45(8): 1364-1372.
27. 曲明阳, 李森, 赵胜男, 等. 乳腺癌脑转移患者危险因素分析. 中国普通外科杂志, 2011, 20(11): 1184-1187.
28. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature, 2000, 406(6797): 747-752.
29. 董国雷, 赵伟鹏, 佟仲生. 三阴性乳腺癌靶向治疗进展. 中国肿瘤临床, 2019, 46(12): 649-652.
30. Ali SM, Leitzel K, Chinchilli VM, et al. Relationship of serum HER-2/neu and serum CA15-3 in patients with metastatic breast cancer. Clin Chem, 2002, 48(8): 1314-1320.
31. Swain SM, Kim SB, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol, 2013, 14(6): 461-471.
32. Chen F, Fujinaga T, Sato K, et al. Clinical features of surgical resection for pulmonary metastasis from breast cancer. Eur J Surg Oncol, 2009, 35(4): 393-397.
33. Yoshimoto M, Tada K, Nishimura S, et al. Favourable long-term results after surgical removal of lung metastases of breast cancer. Breast Cancer Res Treat, 2008, 110(3): 485-491.
34. 袁芃, 徐兵河, 张频, 等. 21 例乳腺癌术后孤立性肺转移的临床分析及预后. 中国肿瘤临床, 2010, 37(12): 698-700, 709.
35. Bacalbasa N, Dima SO, Purtan-Purnichescu R, et al. Role of surgical treatment in breast cancer liver metastases: a single center experience. Anticancer Res, 2014, 34(10): 5563-5568.
36. Margonis GA, Buettner S, Sasaki K, et al. The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. HPB (Oxford), 2016, 18(8): 700-705.
37. Tait CR, Waterworth A, Loncaster J, et al. The oligometastatic state in breast cancer: hypothesis or reality. Breast, 2005, 14(2): 87-93.
38. Niwińska A, Pogoda K, Murawska M, et al. Factors influencing survival in patients with breast cancer and single or solitary brain metastasis. Eur J Surg Oncol, 2011, 37(7): 635-642.
39. Chidel MA, Suh JH, Reddy CA, et al. Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases. Int J Radiat Oncol Biol Phys, 2000, 47(4): 993-999.
40. Sperduto PW, Wang M, Robins HI, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys, 2013, 85(5): 1312-1318.
41. Le Scodan R, Stevens D, Brain E, et al. Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol, 2009, 27(9): 1375-1381.
42. 陈菲. 乳腺癌骨转移患者预后相关因素. 中国肿瘤生物治疗杂志, 2020, 27(2): 191-198.
43. 周婕, 何伟星, 敖翔, 等. 乳腺癌骨转移放疗后的生存预测因素分析. 广东医学, 2016, 37(15): 2287-2290.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Prognostic nomogram for patients with metastatic breast cancer: a study based-SEER database

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