Association between tumor location, tumor-to-skin distance, and axillary lymph node metastasis in breast cancer
Keywords:
breast cancer, axillary lymph node metastasis, tumor-to-skin distance, tumor locationAbstract
Breast cancer is the most commonly diagnosed cancer in women. Axillary lymph node metastasis (ALNM) is an essential prognostic factor, as a higher number of metastatic lymph nodes is associated with increased mortality and recurrence rates. The majority of lymphatic drainage from the breast occurs via dermal and subareolar plexuses. This study hypothesized that tumors located closer to the skin or within the subareolar region may have a higher propensity for ALNM via lymphatic pathways. These findings could guide future treatment strategies for breast cancer. However, only a limited number of studies have explored this hypothesis. This study was conducted a retrospective review of invasive breast cancer patients diagnosed and treated at Phrachomklao Hospital, Phetchaburi Province, from June 1, 2020, to June 30, 2024. Bivariate and multivariate logistic regression analyses were performed to evaluate the relationship between tumor location and tumor-to-skin distance with ALNM. Of the 200 eligible patients, 102 patients (51%) had positive axillary lymph node status. The analysis revealed tumors located in the subareolar region were significantly associated with an increased likelihood of ALNM (adjusted odds ratio=13.82, 95% confidence interval=1.59-119.51, p=0.017). However, the tumor-to-skin distance did not show a statistically significant relationship with ALNM. In summary, sonographic tumor location can serve as a prognostic factor for ALNM. Specifically, tumors located in the subareolar region are significantly associated with an increased likelihood of ALNM.
References
World Health Organization. 2024. Global cancer burden growing, amidst mounting need for services. [Internet] 2024 [cited 2024 April 28]. Available from: https://www.who.int/news/ item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services.
Beenken SW, Urist MM, Zhang Y, et al. Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg 2003;237(5):732-8;discussion 738-9. doi:10.1097/01.SLA.0000065289.06765.71.
Titipungul T, Intarawichian P, Waraasawapati S, et al. Axillary lymph node ratio is an independent prognostic factor in Thai breast cancer patients. Asian Arch Pathol 2015;11(1):26-35. (in Thai)
Burstein HJ, Curigliano G, Thürlimann B, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol 2021;32(10):1216-35. doi:10.1016/j.annonc.2021.06.023.
Giuliano AE, McCall LM, Beitsch PD, et al. ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node. J Clin Oncol 2010;28(18_suppl):CRA506-CRA. doi:10.1200/ jco.2010.28.18_suppl.cra506.
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):569-75. doi:10.1001/jama.2011.90.
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):918-26. doi:10.1001/jama.2017.11470.
Sávolt Á, Péley G, Polgár C, et al. Eight-year follow up result of the OTOASOR trial: The Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: A randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol 2017;43(4):672-9. doi:10.1016/j.ejso.2016.12.011.
Sávolt A, Polgár C, Musonda P, et al. Does the result of completion axillary lymph node dissection influence the recommendation for adjuvant treatment in sentinel lymph node-positive patients?. Clin Breast Cancer 2013;13(5):364-70. doi:10.1016/j.clbc.2013.04.004.
Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 2014;15(12):1303-10. doi:10.1016/S1470-2045(14)70460-7.
Bevilacqua JL, Kattan MW, Fey JV, et al. Doctor, what are my chances of having a positive sentinel node? A validated nomogram for risk estimation. J Clin Oncol 2007;25(24):3670-9. doi:10.1200/JCO.2006.08.8013.
Memorial Sloan Kettering Cancer Center. Breast cancer nomogram. 2024. [Internet] 2014 [cited 2024 May 9]. Available from: https://nomograms.mskcc.org/breast.
The University of Texas MD Anderson cancer center. Breast cancer nomogram to predict positive sentinel lymph nodes, without neoadjuvant chemotherapy. 2024. [Internet] 2011 [cited 2024 May 9]. Available from: https://www3.mdanderson.org/app/medcalc/bc_nomogram3/index.cfm?pagename=sln.
Nathanson SD, Wachna DL, Gilman D, et al. Pathways of lymphatic drainage from the breast. Ann Surg Oncol 2001;8(10):837-43. doi:10.1007/s10434-001-0837-3.
Suami H, Pan W-R, Taylor GI. Historical review of breast lymphatic studies. Clin Anat 2009;22(5):531-6. doi:10.1002/ca.20812.
Pavlista D, Eliska O. Cutaneous and subcutaneous lymphatic drainage of the breast. Lymphology 2005;38(2):92-102.
Chao C, Edwards MJ, Abell T, et al. Palpable breast carcinomas: a hypothesis for clinically relevant lymphatic drainage in sentinel lymph node biopsy. Breast J 2003;9(1):26-32. doi:10.1046/j.1524-4741.2003.09107.x.
Kern KA, Rosenberg RJ. Preoperative lymphoscintigraphy during lymphatic mapping for breast cancer: improved sentinel node imaging using subareolar injection of technetium 99m sulfur colloid. J Am Coll Surg 2000;191(5):479-89. doi:10.1016/s1072-7515(00)00720-1.
McMasters KM, Wong SL, Martin RC, et al. Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study. Ann Surg 2001;233(5):676-87. doi:10.1097/00000658-200105000-00012.
Essa MS, Faheem MH, Abdalla R, et al. The relationship between distance of breast cancer from the skin and incidence of axillary nodal metastasis in female patients with early cancer breast: correlation between radiological and pathological distance. EJS 2021;40(1):99-108. doi:10.4103/ejs.ejs_261_20.
Manjer J, Balldin G, Garne JP. Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden. Eur J Surg Oncol 2004;30(6):610-7. doi:10.1016/j.ejso.2004.04.008.
Yoshihara E, Smeets A, Laenen A, et al. Predictors of axillary lymph node metastases in early breast cancer and their applicability in clinical practice. Breast 2013;22(3):357-61. doi:10.1016/j.breast.2012.09.003.
Zhang Y, Li J, Fan Y, et al. Risk factors for axillary lymph node metastases in clinical stage T1-2N0M0 breast cancer patients. Medicine (Baltimore) 2019;98(40):e17481. doi:10.1097/md.0000000000017481.
Lohrisch C, Jackson J, Jones A, Mates D, Olivotto IA. Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer. J Clin Oncol 2000;18(15):2828-35. doi:10.1200/JCO.2000.18.15.2828
Cunningham JE, Jurj AL, Oman L, et al. Is risk of axillary lymph node metastasis associated with proximity of breast cancer to the skin?. Breast Cancer Res Treat 2006;100(3):319-28. doi:10.1007/s10549-006-9256-2.
Ansari B, Morton MJ, Adamczyk DL, et al. Distance of breast cancer from the skin and nipple impacts axillary nodal metastases. Ann Surg Oncol 2011;18(11):3174-80. doi:10.1245/s10434-011-1957-z.
Sivakanthan T, Tanner J, Mahata B, et al. Investigating the role of tumour-to-skin proximity in predicting nodal metastasis in breast cancer. Breast Cancer Res Treat 2024;205(1):109-16. doi:10.1007/s10549-023-07230-5.
Eom YH, Kim EJ, Chae BJ, et al. The distance between breast cancer and the skin is associated with axillary nodal metastasis. J Surg Oncol 2015;111(7):824-8. doi:10.1002/jso.23898.
Brenin DR, Manasseh DM, El-Tamer M, et al. Factors correlating with lymph node metastases in patients with T1 breast cancer. Ann Surg Oncol 2001;8(5):432-7. doi:10.1007/s10434-001-0432-7.
Sek P, Piekarski JH, Kubiak R, et al. Tumor Size and Pathologic Characteristics of Breast Cancer Analysis of 639 Early Breast Cancers. IJAIMS 2007;79(2):78-84; doi:10.2478/v10035-007-0013-y.
Wu JL, Tseng HS, Yang LH, et al. Prediction of axillary lymph node metastases in breast cancer patients based on pathologic information of the primary tumor. Med Sci Monit 2014;20:577-81. doi:10.12659/MSM.890345.
Garg M, Nagpal N, Sidhu DS, et al. Effect of lump size and nodal status on prognosis in invasive breast cancer: experience from rural India. J Clin Diagn Res 2016;10(6):Pc08-11. doi:10.7860/JCDR/2016/20470.8039.
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