Effect of extranodal extension of axillary lymph node on prognosis of triple-negative breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Yan ¹ , WANG Zheng ² ,  ZHANG Hao ²

1. Graduate School of Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China;
2. Department of Breast Surgery, Nanyang Central Hospital, Henan 473000, P. R. China;

Corresponding author：

ZHANG Hao, Email: rxwk0377@126.com

Keywords：

triple-negative breast cancer; extranodal extension of axillary lymph nodes; clinicopathologic feature; disease free survival; overall survival

DOI：

10.7507/1007-9424.202404010

Video：

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Objective To investigate the effect of extranodal extension of axillary lymph nodes on the prognosis of triple-negative breast cancer (TNBC). Methods The TNBC patients with axillary lymph node metastasis admitted to the Nanyang Central Hospital from January 2017 to January 2019 were collected, and the patients were assigned into a negative soft tissue group and positive soft tissue group according to the status of soft tissue of external lymph node. The clinicopathologic characteristics and prognosis of the two groups were compared, and the factors affecting the prognosis were analyzed. Results A total of 216 patients were included, 123 and 93 of whom were in the negative soft tissue group and positive soft tissue group, respectively. Compared with the patients in the negative soft tissue group, the patients in the positive soft tissue group had a higher proportion of higher histological grade (grade Ⅲ), more number of metastatic lymph node (10 or more), and greater tumor diameter (5 cm or more), P<0.05. The 5-year cumulative disease-free survival (DFS) rate of the negative soft tissue group was higher than that of the positive soft tissue group (83.3% vs. 70.2%, χ²=? , P=0.008). The 5-year cumulative overall survival (OS) rate had no statistically significant difference between the the negative soft tissue group and positive soft tissue group (82.1% vs. 75.3%, χ²=? , P=0.161). The results of multivariate analysis showed that the higher histological grade (grade Ⅲ) and extranodal extension of axillary lymph nodes were the risk factors affecting the OS and DFS of the TNBC patients (P<0.05). It was also found that the number of metastatic lymph nodes (10 or more) and higher HER-2 expression were the risk factors affecting the OS of the TNBC patients (P<0.05), but which were not related to the DFS of the TNBC patients (P>0.05). Conclusion The prognosis of TNBA patients with extranodal extension of axillary lymph nodes is worse, especially those with histological grade Ⅲ, lymph node metastasis number >10, and higher HER-2 expression.

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Shao Y, Luo Z, Yu Y, et al. HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study. Front Endocrinol (Lausanne), 2022, 13: 1000704. doi: 10.3389/fendo.2022.1000704.
3.	Sporikova Z, Koudelakova V, Trojanec R, et al. Genetic markers in triple-negative breast cancer. Clin Breast Cancer, 2018, 18(5): e841-e850. doi: 10.1016/j.clbc.2018.07.023.
4.	López C, Gibert-Ramos A, Bosch R, et al. Differences in the immune response of the nonmetastatic axillary lymph nodes between triple-negative and luminal a breast cancer surrogate subtypes. Am J Pathol, 2021, 191(3): 545-554.
5.	Naxerova K. Defining the role of lymph node metastasis in systemic breast cancer evolution. EBioMedicine, 2020, 57: 102852. doi: 10.1016/j.ebiom.2020.102852.
6.	Gradishar WJ, Moran MS, Abraham J, et al. Breast cancer, version 3. 2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2022, 20(6): 691-722.
7.	Hultborn KA, Tornberg B. Mammary carcionma. The biologic character of mammary carcionma studied in 517 cases by a new form of malignancy grading. Acta Radiol Suppl, 1960, 196: 1-143.
8.	Naoum GE, Oladeru O, Ababneh H, et al. Pathologic exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol, 2024, 42(2): 157-169.
9.	Fujii T, Yajima R, Yamaguchi S, et al. Extracapsular invasion of sentinel lymph nodes is not associated with disease recurrence in breast cancer. Int Surg, 2014, 99(4): 305-308.
10.	Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol, 2020, 38(12): 1346-1366.
11.	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2019年版). 中国癌症杂志, 2019, 29(8): 609-679.
12.	Elwan A, Abdelrahman AE, Alnagar AA, et al. Clinicopathological features and treatment challenges in triple negative breast cancer patients: a retrospective cohort study. Turk Patoloji Derg, 2021, 37(2): 121-129.
13.	Al-Mahmood S, Sapiezynski J, Garbuzenko OB, et al. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res, 2018, 8(5): 1483-1507.
14.	Fisher ER, Gregorio RM, Redmond C, et al. Pathologic findings from the national surgical adjuvant breast project. (Protocol no. 4). Ⅲ. The significance of extranodal extension of axillary metastases. Am J Clin Pathol, 1976, 65(4): 439-444.
15.	Choi AH, Blount S, Perez MN, et al. Size of Extranodal extension on sentinel lymph node dissection in the American College of Surgeons Oncology Group Z0011 Trial Era. JAMA Surg, 2015, 150(12): 1141-1148.
16.	Eryilmaz MA, Muslumanoglu M, Ozmen V, et al. Breast conserving surgery in patients with multifocal/multicentric breast cancer. J BUON, 2011, 16(3): 450-453.
17.	Verheuvel NC, van den Hoven I, Ooms HW, et al. The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era. Ann Surg Oncol, 2015, 22(2): 409-415.
18.	Stitzenberg KB, Meyer AA, Stern SL, et al. Extracapsular extension of the sentinel lymph node metastasis: a predictor of nonsentinel node tumor burden. Ann Surg, 2003, 237(5): 607-612.
19.	Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med, 2002, 347(8): 567-575.
20.	Shigematsu H, Taguchi K, Koui H, et al. Clinical significance of extracapsular invasion at sentinel lymph nodes in breast cancer patients with sentinel lymph node involvement. Ann Surg Oncol, 2015, 22(7): 2365-2371.
21.	Ilknur GB, Hilmi A, Tülay C, et al. The importance of extracapsular extension of axillary lymph node metastases in breast cancer. Tumori, 2004, 90(1): 107-111.
22.	Mambo NC, Gallager HS. Carcinoma of the breast: the prognostic significance of extranodal extension of axillary disease. Cancer, 1977, 39(5): 2280-2285.
23.	Nottegar A, Veronese N, Senthil M, et al. Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis. Eur J Surg Oncol, 2016, 42(7): 919-925.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Shao Y, Luo Z, Yu Y, et al. HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study. Front Endocrinol (Lausanne), 2022, 13: 1000704. doi: 10.3389/fendo.2022.1000704.
3. Sporikova Z, Koudelakova V, Trojanec R, et al. Genetic markers in triple-negative breast cancer. Clin Breast Cancer, 2018, 18(5): e841-e850. doi: 10.1016/j.clbc.2018.07.023.
4. López C, Gibert-Ramos A, Bosch R, et al. Differences in the immune response of the nonmetastatic axillary lymph nodes between triple-negative and luminal a breast cancer surrogate subtypes. Am J Pathol, 2021, 191(3): 545-554.
5. Naxerova K. Defining the role of lymph node metastasis in systemic breast cancer evolution. EBioMedicine, 2020, 57: 102852. doi: 10.1016/j.ebiom.2020.102852.
6. Gradishar WJ, Moran MS, Abraham J, et al. Breast cancer, version 3. 2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2022, 20(6): 691-722.
7. Hultborn KA, Tornberg B. Mammary carcionma. The biologic character of mammary carcionma studied in 517 cases by a new form of malignancy grading. Acta Radiol Suppl, 1960, 196: 1-143.
8. Naoum GE, Oladeru O, Ababneh H, et al. Pathologic exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol, 2024, 42(2): 157-169.
9. Fujii T, Yajima R, Yamaguchi S, et al. Extracapsular invasion of sentinel lymph nodes is not associated with disease recurrence in breast cancer. Int Surg, 2014, 99(4): 305-308.
10. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol, 2020, 38(12): 1346-1366.
11. 中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2019年版). 中国癌症杂志, 2019, 29(8): 609-679.
12. Elwan A, Abdelrahman AE, Alnagar AA, et al. Clinicopathological features and treatment challenges in triple negative breast cancer patients: a retrospective cohort study. Turk Patoloji Derg, 2021, 37(2): 121-129.
13. Al-Mahmood S, Sapiezynski J, Garbuzenko OB, et al. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res, 2018, 8(5): 1483-1507.
14. Fisher ER, Gregorio RM, Redmond C, et al. Pathologic findings from the national surgical adjuvant breast project. (Protocol no. 4). Ⅲ. The significance of extranodal extension of axillary metastases. Am J Clin Pathol, 1976, 65(4): 439-444.
15. Choi AH, Blount S, Perez MN, et al. Size of Extranodal extension on sentinel lymph node dissection in the American College of Surgeons Oncology Group Z0011 Trial Era. JAMA Surg, 2015, 150(12): 1141-1148.
16. Eryilmaz MA, Muslumanoglu M, Ozmen V, et al. Breast conserving surgery in patients with multifocal/multicentric breast cancer. J BUON, 2011, 16(3): 450-453.
17. Verheuvel NC, van den Hoven I, Ooms HW, et al. The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era. Ann Surg Oncol, 2015, 22(2): 409-415.
18. Stitzenberg KB, Meyer AA, Stern SL, et al. Extracapsular extension of the sentinel lymph node metastasis: a predictor of nonsentinel node tumor burden. Ann Surg, 2003, 237(5): 607-612.
19. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med, 2002, 347(8): 567-575.
20. Shigematsu H, Taguchi K, Koui H, et al. Clinical significance of extracapsular invasion at sentinel lymph nodes in breast cancer patients with sentinel lymph node involvement. Ann Surg Oncol, 2015, 22(7): 2365-2371.
21. Ilknur GB, Hilmi A, Tülay C, et al. The importance of extracapsular extension of axillary lymph node metastases in breast cancer. Tumori, 2004, 90(1): 107-111.
22. Mambo NC, Gallager HS. Carcinoma of the breast: the prognostic significance of extranodal extension of axillary disease. Cancer, 1977, 39(5): 2280-2285.
23. Nottegar A, Veronese N, Senthil M, et al. Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis. Eur J Surg Oncol, 2016, 42(7): 919-925.

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