Analysis of metastatic sites and prognosis of newly diagnosed stage <b>Ⅳ</b> breast cancer patients based on SEER database_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Hongying ¹ , ZHANG Chao ² , CHEN Maoshan ³ , SU Xiaohan ⁴ , TAN Qiao ⁴ , QIAN Shuangqiang ⁴ , HOU Lingmi ^1,2,4 ,  XIE Shaoli ⁴

1. Department of Thyroid and Breast Surgery, Nanchong Fifth People’s Hospital (Affiliated Hospital of China West Normal University), Nanchong, Sichuan 637000, P. R. China;
2. Department of Thyroid and Breast Surgery, Yingshan Hospital of West China Hospital, Sichuan University, Nanchong, Sichuan 637000, P. R. China;
3. Department of Thyroid and Breast Surgery, Affiliated Suining Central Hospital of Chongqing Medical University, Suining, Sichuan 629000, P. R. China;
4. Department of Thyroid and Breast Surgery, Breast Cancer Biotargeting Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;

Corresponding author：

XIE Shaoli, Email: xsl675086087@yeah.net

Keywords：

breast cancer; metastatic site; prognosis; molecular subtype; SEER database

DOI：

10.7507/1007-9424.202306009

Video：

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Objective To explore the relationship between the metastatic sites and prognosis in newly diagnosed stage Ⅳ breast cancer. Methods The data of newly diagnosed female patients with stage Ⅳ invasive breast cancer with complete follow-up data from SEER database from 2010 to 2015 were grouped according to different metastatic sites, and the differences of breast cancer-specific survival (BCSS) in different metastatic sites were analyzed by univariate and multivariate Cox. Kaplan-Meier method was used to draw the survival curve, and log-rank test was used to analyze the prognostic factors of BCSS in newly diagnosed stage ⅳ breast cancer. Results A total of 8 407 patients were included in the final analysis. Among them, 5 619 (66.84%) patients were confirmed with bone metastasis only, 1 483 (17.64%) patients with lung metastasis only, 1 096 (13.04%) patients with liver metastasis only, and 209 (2.49%) patients with brain metastasis only. The median follow-up time was 22 months, with 4 180 (49.72%) breast cancer-related deaths and a median BCSS of 39 months in those patients. The location of metastasis in newly diagnosed stage Ⅳ invasive breast cancer was significantly correlated with BCSS (χ²=151.07, P<0.001). Multivariate Cox model analysis showed that the BCSS was worse in patients with liver metastasis [HR=1.34, 95%CI (1.21, 1.49), P<0.001], lung metastasis [HR=1.09, 95%CI (1.04, 1.14), P<0.001] and brain metastases [HR=1.28, 95%CI (1.20, 1.36), P<0.001] than in patients with bone metastases. Further subgroup analysis showed that the BCSS of breast cancer patients with different molecular subtypes and different metastatic sites were also significantly different (P<0.05). Patients with brain and liver metastases in the HR⁺/HER2^– subtype had worse BCSS than those with bone metastases (P<0.001). Patients with brain metastases in the HR⁺/HER2⁺ subtype had worse BCSS than those with bone metastases (P=0.001). In HR^–/HER2⁺ subtype, the BCSS of patients with liver metastasis, lung metastasis and brain metastasis were worse than that of patients with bone metastasis (P<0.05). In HR^–/HER2^– subtype, the BCSS of patients with brain metastasis and liver metastasis were worse than that of patients with bone metastasis (P<0.05) . Conclusion The prognosis of newly diagnosed stage ⅳ breast cancer patients with different metastatic sites is different, and the prognosis of different molecular subtypes and different metastatic sites is also different.

Citation： ZHANG Hongying, ZHANG Chao, CHEN Maoshan, SU Xiaohan, TAN Qiao, QIAN Shuangqiang, HOU Lingmi, XIE Shaoli. Analysis of metastatic sites and prognosis of newly diagnosed stage Ⅳ breast cancer patients based on SEER database. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(9): 1079-1086. doi: 10.7507/1007-9424.202306009 Copy

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2.	Trapani D, Ginsburg O, Fadelu T, et al. Global challenges and policy solutions in breast cancer control. Cancer Treat Rev, 2022, 104: 102339.
3.	Kuerer HM, Smith BD, Krishnamurthy S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol, 2022, 23(12): 1517-1524.
4.	Ueno T. Surgical management of metastatic breast cancer: a mini review. Front Oncol, 2022, 12: 910544.
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8.	Castelo M, Lu J, Paszat L, et al. Long-term survival in elderly women receiving chemotherapy for non-metastatic breast cancer: a population-based analysis. Breast Cancer Res Treat, 2022, 194(3): 629-641.
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14.	Yuan Y, Lee JS, Yost SE, et al. PhaseⅠ/Ⅱ trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur J Cancer, 2021, 154: 11-20.
15.	Harbeck N. Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer. Breast, 2022, 62 Suppl 1(Suppl 1): S12-S16.
16.	Gianni L, Huang CS, Egle D, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol, 2022, 33(5): 534-543.
17.	Huang M, Haiderali A, Fox GE, et al. Economic and humanistic burden of triple-negative breast cancer: A systematic literature review. Pharmacoeconomics, 2022, 40(5): 519-558.
18.	Nakhjavani M, Samarasinghe RM, Shigdar S. Triple-negative breast cancer brain metastasis: An update on druggable targets, current clinical trials, and future treatment options. Drug Discov Today, 2022, 27(5): 1298-1314.
19.	Gao JJ, Cheng J, Bloomquist E, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol, 2020, 21(2): 250-260.
20.	Prat A, Chaudhury A, Solovieff N, et al. Correlative Biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA phase Ⅲ studies. J Clin Oncol, 2021, 39(13): 1458-1467.
21.	Fan Y, Wang Y, He L, et al. Clinical features of patients with HER2-positive breast cancer and development of a nomogram for predicting survival. ESMO Open, 2021, 6(4): 100232.
22.	Lopez-Tarruella S, Echavarria I, Jerez Y, et al. How we treat HR-positive, HER2-negative early breast cancer. Future Oncol, 2022, 18(8): 1003-1022.
23.	Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast, 2021, 57: 5-17.
24.	Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell, 2020, 37(4): 496-513.
25.	Barzaman K, Karami J, Zarei Z, et al. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol, 2020, 84: 106535.

1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin, 2023, 73(1): 17-48.
2. Trapani D, Ginsburg O, Fadelu T, et al. Global challenges and policy solutions in breast cancer control. Cancer Treat Rev, 2022, 104: 102339.
3. Kuerer HM, Smith BD, Krishnamurthy S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol, 2022, 23(12): 1517-1524.
4. Ueno T. Surgical management of metastatic breast cancer: a mini review. Front Oncol, 2022, 12: 910544.
5. Schlam I, Tolaney SM, Tarantino P. The efficacy of trastuzumab-deruxtecan for the treatment of patients with advanced pretreated HER2-low breast cancer. Expert Rev Anticancer Ther, 2023 Jan 24. doi: 10.1080/14737140.2023.2171993. Online ahead of print.
6. Lin C, Wu J, Ding S, et al. Subdivision of M1 stage for de novo metastatic breast cancer to better predict prognosis and response to primary tumor surgery. J Natl Compr Canc Netw, 2019, 17(12): 1521-1528.
7. Chen MT, Sun HF, Zhao Y, et al. Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: A SEER population-based analysis. Sci Rep, 2017, 7(1): 9254.
8. Castelo M, Lu J, Paszat L, et al. Long-term survival in elderly women receiving chemotherapy for non-metastatic breast cancer: a population-based analysis. Breast Cancer Res Treat, 2022, 194(3): 629-641.
9. Zou S, Tong Q, Liu B, et al. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer, 2020, 19(1): 145.
10. Khan SA, Zhao F, Goldstein LJ, et al. Early local therapy for the primary site in de novo stage Ⅳ breast cancer: results of a randomized clinical trial (EA2108). J Clin Oncol, 2022, 40(9): 978-987.
11. Bilani N, Yaghi M, Main O, et al. Metastasectomy versus radiation of secondary sites in stage Ⅳ breast cancer: Analysis from a national cancer registry. Breast, 2021, 60: 185-191.
12. Anderson DN, Port ER. Surgery No More ? Managing the primary tumor in stage Ⅳ breast cancer. J Clin Oncol, 2022, 40(9): 927-931.
13. Soran A, Dogan L, Isik A, et al. The effect of primary surgery in patients with de novo stage Ⅳ breast cancer with bone metastasis only (protocol BOMET MF 14-01): A multi-center, prospective registry study. Ann Surg Oncol, 2021, 28(9): 5048-5057.
14. Yuan Y, Lee JS, Yost SE, et al. PhaseⅠ/Ⅱ trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer. Eur J Cancer, 2021, 154: 11-20.
15. Harbeck N. Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer. Breast, 2022, 62 Suppl 1(Suppl 1): S12-S16.
16. Gianni L, Huang CS, Egle D, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol, 2022, 33(5): 534-543.
17. Huang M, Haiderali A, Fox GE, et al. Economic and humanistic burden of triple-negative breast cancer: A systematic literature review. Pharmacoeconomics, 2022, 40(5): 519-558.
18. Nakhjavani M, Samarasinghe RM, Shigdar S. Triple-negative breast cancer brain metastasis: An update on druggable targets, current clinical trials, and future treatment options. Drug Discov Today, 2022, 27(5): 1298-1314.
19. Gao JJ, Cheng J, Bloomquist E, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol, 2020, 21(2): 250-260.
20. Prat A, Chaudhury A, Solovieff N, et al. Correlative Biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA phase Ⅲ studies. J Clin Oncol, 2021, 39(13): 1458-1467.
21. Fan Y, Wang Y, He L, et al. Clinical features of patients with HER2-positive breast cancer and development of a nomogram for predicting survival. ESMO Open, 2021, 6(4): 100232.
22. Lopez-Tarruella S, Echavarria I, Jerez Y, et al. How we treat HR-positive, HER2-negative early breast cancer. Future Oncol, 2022, 18(8): 1003-1022.
23. Salvo EM, Ramirez AO, Cueto J, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast, 2021, 57: 5-17.
24. Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell, 2020, 37(4): 496-513.
25. Barzaman K, Karami J, Zarei Z, et al. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol, 2020, 84: 106535.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of metastatic sites and prognosis of newly diagnosed stage Ⅳ breast cancer patients based on SEER database

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