Risk factors of sentinel lymph node metastasis in early-stage breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DUAN Zhicai , CHEN Jianzhe , XIONG Jie , LÜ Xing ,  ZUO Huaiquan

Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province 646000, P. R. China;

Corresponding author：

ZUO Huaiquan, Email: 13982772996@163.com

Keywords：

early-stage breast cancer; sentinel lymph node biopsy; risk factors

DOI：

10.7507/1007-9424.202409035

Video：

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Objective To explore the risk factors affecting sentinel lymph node (SLN) metastasis in patients with early-stage (N0) breast cancer and establish a predictive model for SLN metastasis, so as to assist in decision-making of axillary surgery in clinical practice. Methods The unilateral early-stage breast cancer patients who underwent surgical treatment and SLN biopsy at the Affiliated Hospital of Southwest Medical University from September 2020 to December 2023 were selected as the study subjects. The univariate and multivariable logistic regression analyses were adopted to analyze the relevant risk factors of SLN metastasis, then a predictive model evaluating the risk of SLN metastasis was constructed. The area under receiver operating characteristic curve (AUC) was used to assess the distinguishing ability of risk factors for SLN metastasis. Results A total of 351 patients with early-stage breast cancer patients who met the inclusion criteria were enrolled, 136 of whom with SLN metastasis, the SLN metastasis rate was 38.7%. The results of the multivariate logistic regression analysis showed that the maximum tumor diameter >2.5 cm, estrogen receptor (ER) positive, Ki-67 >20%, and vascular invasion were the risk factors affecting SLN metastasis [maximum tumor diameter: OR(95%CI)=1.897(1.186, 3.034), P=0.008; ER positive: OR(95%CI)=2.721(1.491, 4.967), P=0.001; Ki-67 >20%: OR(95%CI)=1.825(1.125, 2.960), P=0.015; vascular invasion: OR(95%CI)=2.858(1.641, 4.976), P<0.001]. The AUC for the SLN metastasis by these four factors was 0.693(0.637, 0.749), with a sensitivity and specificity of 70.59% and 57.21%, respectively. Conclusions The results from this study suggest that SLN biopsy is recommended to guide postoperative adjuvant treatment strategies for cN0 early-stage breast cancer patients with a maximum tumor diameter >2.5 cm, ER positivity, Ki-67>20%, and vascular invasion. However, the predictive model constructed based on these four factors in this study has a general ability to distinguish the occurrence of SLN metastasis, then the reasons can be further analyzed in the future.

Citation： DUAN Zhicai, CHEN Jianzhe, XIONG Jie, LÜ Xing, ZUO Huaiquan. Risk factors of sentinel lymph node metastasis in early-stage breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(3): 354-358. doi: 10.7507/1007-9424.202409035 Copy

1.	邬昊, 吕青. 全球及中国乳腺癌的流行病学趋势及防控启示: 2018–2022年《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 796-802.
2.	Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA, 2017, 318(10): 918-926.
3.	Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol, 2010, 11(10): 927-933.
4.	Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011, 305(6): 569-575.
5.	Beltran-Bless AA, Kacerovsky-Strobl S, Gnant M. Explaining risks and benefits of loco-regional treatments to patients. Breast, 2023, 71: 132-137.
6.	Tan P H, Ellis I, Allison K, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology, 2020, 77(2): 181-185.
7.	梅放, 柳剑英, 薛卫成. 浸润性乳腺癌的组织学分级: Nottingham组织学分级系统. 中华病理学杂志, 2019, 48(8): 659-664.
8.	Allison K H, Hammond M E H, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol, 2020, 38(12): 1346-1366.
9.	中国临床肿瘤学会乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会. 人表皮生长因子受体2阳性乳腺癌临床诊疗专家共识(2021版). 中华医学杂志, 2021, 101(17): 1226-1231.
10.	Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: Updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst, 2021, 113(7): 808-819.
11.	中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组. 中国抗癌协会乳腺癌诊治指南与规范(2024年版). 中国癌症杂志, 2023, 33(12): 1092-1187.
12.	Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol, 2018, 19(10): 1385-1393.
13.	Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol, 2023, 41(12): 2159-2165.
14.	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.
15.	Martelli G, Boracchi P, Orenti A, et al. Axillary dissection versus no axillary dissection in older T1N0 breast cancer patients: 15-year results of trial and out-trial patients. Eur J Surg Oncol, 2014, 40(7): 805-812.
16.	Agresti R, Martelli G, Sandri M, et al. Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: A randomized clinical trial (INT09/98). Cancer, 2014, 120(6): 885-893.
17.	Reimer T, Stachs A, Veselinovic K, et al. Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer. EClinicalMedicine, 2022, 55: 101756. doi: 10.1016/j.eclinm.2022.101756.
18.	Gentilini O, Botteri E, Dadda P, et al. Physical function of the upper limb after breast cancer surgery. Results from the SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial. Eur J Surg Oncol, 2016, 42(5): 685-689.
19.	Gentilini O, Veronesi U. Staging the axilla in early breast cancer: Will imaging replace surgery?. JAMA Oncol, 2015, 1(8): 1031-1032.
20.	Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND Randomized clinical trial. JAMA Oncol, 2023, 9(11): 1557-1564.
21.	Choosing Wisely Society of Surgical Oncology. http://www.choosingwisely.org/ clinician-lists/sso-sentinel-node-biopsy-in-node-negative-women-70-and-over/.
22.	Diab SG, Elledge RM, Clark GM. Tumor characteristics and clinical outcome of elderly women with breast cancer. J Natl Cancer Inst, 2000, 92(7): 550-556.
23.	Wyld L, Reed MW. The need for targeted research into breast cancer in the elderly. Br J Surg, 2003, 90(4): 388-399.
24.	Achen MG, Jeltsch M, Kukk E, et al. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA, 1998, 95(2): 548-553.
25.	Marconcini L, Marchio S, Morbidelli L, et al. c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro. Proc Natl Acad Sci U S A, 1999, 96(17): 9671-9676.
26.	Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med, 2001, 7(2): 186-191.
27.	Liang Y, Zhang H, Song X, et al. Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol, 2020, 60: 14-27.
28.	Clusan L, Ferrière F, Flouriot G, et al. A basic review on estrogen receptor signaling pathways in breast cancer. Int J Mol Sci, 2023, 24(7): 6834. doi: 10.3390/ijms24076834.
29.	Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol, 2019, 116: 135-170.
30.	Hermansyah D, Indra W, Paramita DA, et al. Role of hormonal receptor in predicting sentinel lymph node metastasis in early breast cancer. Med Arch, 2022, 76(1): 34-38.
31.	Beresford MJ, Wilson GD, Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res, 2006, 8(6): 216. doi: 10.1186/bcr1618.
32.	Lashen AG, Toss MS, Katayama A, et al. Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study. Histopathology, 2021, 79(6): 1087-1098.
33.	Thangarajah F, Malter W, Hamacher S, et al. Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67. Breast, 2016, 30: 87-91.
34.	Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell, 2017, 168(4): 670-691.
35.	Gujam FJ, Going JJ, Edwards J, et al. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Crit Rev Oncol Hematol, 2014, 89(2): 231-241.
36.	Houvenaeghel G, Cohen M, Classe JM, et al. Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study. ESMO Open, 2021, 6(6): 100316. doi: 10.1016/j.esmoop.2021.100316.

1. 邬昊, 吕青. 全球及中国乳腺癌的流行病学趋势及防控启示: 2018–2022年《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 796-802.
2. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA, 2017, 318(10): 918-926.
3. Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol, 2010, 11(10): 927-933.
4. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011, 305(6): 569-575.
5. Beltran-Bless AA, Kacerovsky-Strobl S, Gnant M. Explaining risks and benefits of loco-regional treatments to patients. Breast, 2023, 71: 132-137.
6. Tan P H, Ellis I, Allison K, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology, 2020, 77(2): 181-185.
7. 梅放, 柳剑英, 薛卫成. 浸润性乳腺癌的组织学分级: Nottingham组织学分级系统. 中华病理学杂志, 2019, 48(8): 659-664.
8. Allison K H, Hammond M E H, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol, 2020, 38(12): 1346-1366.
9. 中国临床肿瘤学会乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会. 人表皮生长因子受体2阳性乳腺癌临床诊疗专家共识(2021版). 中华医学杂志, 2021, 101(17): 1226-1231.
10. Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: Updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst, 2021, 113(7): 808-819.
11. 中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组. 中国抗癌协会乳腺癌诊治指南与规范(2024年版). 中国癌症杂志, 2023, 33(12): 1092-1187.
12. Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol, 2018, 19(10): 1385-1393.
13. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol, 2023, 41(12): 2159-2165.
14. 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.
15. Martelli G, Boracchi P, Orenti A, et al. Axillary dissection versus no axillary dissection in older T1N0 breast cancer patients: 15-year results of trial and out-trial patients. Eur J Surg Oncol, 2014, 40(7): 805-812.
16. Agresti R, Martelli G, Sandri M, et al. Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: A randomized clinical trial (INT09/98). Cancer, 2014, 120(6): 885-893.
17. Reimer T, Stachs A, Veselinovic K, et al. Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer. EClinicalMedicine, 2022, 55: 101756. doi: 10.1016/j.eclinm.2022.101756.
18. Gentilini O, Botteri E, Dadda P, et al. Physical function of the upper limb after breast cancer surgery. Results from the SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial. Eur J Surg Oncol, 2016, 42(5): 685-689.
19. Gentilini O, Veronesi U. Staging the axilla in early breast cancer: Will imaging replace surgery?. JAMA Oncol, 2015, 1(8): 1031-1032.
20. Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND Randomized clinical trial. JAMA Oncol, 2023, 9(11): 1557-1564.
21. Choosing Wisely Society of Surgical Oncology. http://www.choosingwisely.org/ clinician-lists/sso-sentinel-node-biopsy-in-node-negative-women-70-and-over/.
22. Diab SG, Elledge RM, Clark GM. Tumor characteristics and clinical outcome of elderly women with breast cancer. J Natl Cancer Inst, 2000, 92(7): 550-556.
23. Wyld L, Reed MW. The need for targeted research into breast cancer in the elderly. Br J Surg, 2003, 90(4): 388-399.
24. Achen MG, Jeltsch M, Kukk E, et al. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA, 1998, 95(2): 548-553.
25. Marconcini L, Marchio S, Morbidelli L, et al. c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro. Proc Natl Acad Sci U S A, 1999, 96(17): 9671-9676.
26. Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med, 2001, 7(2): 186-191.
27. Liang Y, Zhang H, Song X, et al. Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol, 2020, 60: 14-27.
28. Clusan L, Ferrière F, Flouriot G, et al. A basic review on estrogen receptor signaling pathways in breast cancer. Int J Mol Sci, 2023, 24(7): 6834. doi: 10.3390/ijms24076834.
29. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol, 2019, 116: 135-170.
30. Hermansyah D, Indra W, Paramita DA, et al. Role of hormonal receptor in predicting sentinel lymph node metastasis in early breast cancer. Med Arch, 2022, 76(1): 34-38.
31. Beresford MJ, Wilson GD, Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res, 2006, 8(6): 216. doi: 10.1186/bcr1618.
32. Lashen AG, Toss MS, Katayama A, et al. Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study. Histopathology, 2021, 79(6): 1087-1098.
33. Thangarajah F, Malter W, Hamacher S, et al. Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67. Breast, 2016, 30: 87-91.
34. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell, 2017, 168(4): 670-691.
35. Gujam FJ, Going JJ, Edwards J, et al. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Crit Rev Oncol Hematol, 2014, 89(2): 231-241.
36. Houvenaeghel G, Cohen M, Classe JM, et al. Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study. ESMO Open, 2021, 6(6): 100316. doi: 10.1016/j.esmoop.2021.100316.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Risk factors of sentinel lymph node metastasis in early-stage breast cancer

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