Impact of Molecular Subtypes of Breast Cancer on Axillary Lymph Node Metastasis: A Tertiary Center Experience

Main Article Content

Dharmendra Singh
Soumen Mukherjee

Keywords

molecular subtypes, Breast cancer, Axillary lymph node, Metastasis

Abstract

Background: Axillary lymph node metastasis (ALNM) is one of the important prognostic factors of breast cancer. The objective of this study was to assess the risk of ALNM in different molecular subtypes determined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (her2neu) of breast cancer.


Methods: This retrospective study was conducted on patients who had undergone upfront breast conserving surgery (BCS) or modified radical mastectomy (MRM). Patients were classified as HR (hormone receptor) +/ her2neu- (ER or PR positive and her2neu negative), HR+/her2neu+ (ER or PR positive and her2neu positive), HR-/her2neu- (ER, PR and her2neu negative or triple negative or basal type), and HR-/her2neu+ (ER or PR negative and her2neu positive). The association between clinicopathological variables and ALNM was evaluated in logistic regression analyses.


Results: In this study, 476 patients met the inclusion criteria, and had 67.2% ALNM at diagnosis. ALNM was statistically significantly correlated with age ≤ 40 years (p=0.026), tumor grade (p=0.007), pathological tumor size (P<0.001), estrogen receptor (P=0.045), molecular subtypes (P=0.021), LVI (P<0.001), and PNI (P<0.001). Post Hoc test revealed that HR-/her2neu+ subtypes of breast cancer had the highest and HR+/her2neu- had the lowest risk of ALNM.  


Conclusion: ALNM may be predicted by molecular subtypes of breast cancer. The risk of ALNM is less in TNBC although it is clinically more aggressive. These findings may play an important role in gauging the individualized axillary management in breast cancer.

References

1. Global Cancer Observatory. Available from: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
2. India - Global Cancer Observatory. Available from: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf.
3. Cetin I, Topcul M. Triple negative breast cancer. Asian Pac J Cancer Prev. 2014;15(6):2427-31.
4. Layeequr Rahman R, Crawford SL, Siwawa P. Management of axilla in breast cancer - The saga continues. Breast. 2015;24(4):343-53.
5. Bevilacqua JL, Kattan MW, Fey JV, Cody HS, 3rd, Borgen PI, 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.
6. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869-74.
7. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492-502.
8. Lee JH, Kim SH, Suh YJ, Shim BY, Kim HK. Predictors of axillary lymph node metastases (ALNM) in a Korean population with T1-2 breast carcinoma: triple negative breast cancer has a high incidence of ALNM irrespective of the tumor size. Cancer Res Treat. 2010;42(1):30-6.
9. Ugras S, Stempel M, Patil S, Morrow M. Estrogen receptor, progesterone receptor, and HER2 status predict lymphovascular invasion and lymph node involvement. Ann Surg Oncol. 2014;21(12):3780-6.
10. Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, et al. Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009;208(3):341-7.
11. Manoharan N, Nair O, Shukla NK, Rath GK. Descriptive Epidemiology of Female Breast Cancer in Delhi, India. Asian Pac J Cancer Prev. 2017;18(4):1015-8.
12. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24(9):2206-23.
13. Meyer JS, Alvarez C, Milikowski C, Olson N, Russo I, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol. 2005;18(8):1067-78.
14. Edge S, Byrd D, Compton C, Fritz A, Greene F, et al. AJCC cancer staging manual. Springer. New York. 2010:648.
15. Kindts I, Laenen A, Depuydt T, Weltens C. Tumour bed boost radiotherapy for women after breast-conserving surgery. Cochrane Database Syst Rev. 2017;11:CD011987.
16. Harish S, Anand S, Prashar M, Lohia N, Singh S, et al. Intrinsic subtyping of breast cancer and its relevance with clinico-pathological features and outcomes in patients from North India: a single center experience. J NTR Univ Health Sci. 2020;9(3):164.
17. Lakshmaiah KC, Das U, Suresh TM, Lokanatha D, Babu GK, et al. A study of triple negative breast cancer at a tertiary cancer care center in southern India. Ann Med Health Sci Res. 2014;4(6):933-7.
18. Suresh P, Batra U, Doval DC. Epidemiological and clinical profile of triple negative breast cancer at a cancer hospital in North India. Indian J Med Paediatr Oncol. 2013;34(2):89-95.
19. Ambroise M, Ghosh M, Mallikarjuna VS, Kurian A. Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev. 2011;12(3):625-9.
20. Green M, Raina V. Epidemiology, screening and diagnosis of breast cancer in the Asia–Pacific region: current perspectives and important considerations. Asia Pac J Clin Oncol. 2008;4:S5-S13.
21. Raina V, Bhutani M, Bedi R, Sharma A, Deo SV, et al. Clinical features and prognostic factors of early breast cancer at a major cancer center in North India. Indian J Cancer. 2005;42(1):40-5.
22. Kumar N, Patni P, Agarwal A, Khan MA, Parashar N. Prevalence of molecular subtypes of invasive breast cancer: A retrospective study. Med J Armed Forces India. 2015;71(3):254-8.
23. Nene BM, Selmouni F, Lokhande M, Hingmire SJ, Muwonge R, et al. Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western India. Indian J Surg Oncol. 2018;9(3):374-80.
24. Doval DC, Radhakrishna S, Tripathi R, Kashinath RI, Talwar V, et al. A multi-institutional real world data study from India of 3453 non-metastatic breast cancer patients undergoing upfront surgery. Sci Rep. 2020;10(1):5886.
25. Gogoi G, Borgohain M, Saikia P, Fazal SA. Profile of molecular subtypes of breast cancer with special reference to triple negative: A study from Northeast India. Clin Cancer Investig J. 2016;5(5):374.
26. Ellis IO, Elston CW. Histologic grade. In: O'Malley FP, Pinder SE, editors. Breast Pathology. Philadelphia, PA: Elsevier; 2006: 225.
27. Chowdappa RG, Kajamohideen S, Venkitaraman B. Tumour Characteristics Predicting Axillary Nodal Metastasis in Early Breast Cancers-A Study from Southern India. J Clin Diagnostic Res. 2020;14(4).
28. Kunheri B, Raj RV, Vijaykumar DK, Pavithran K. Impact of St. Gallen surrogate classification for intrinsic breast cancer sub-types on disease features, recurrence, and survival in South Indian patients. Indian J Cancer. 2020;57(1):49-54.
29. Verma S, Bal A, Joshi K, Arora S, Singh G. Immunohistochemical characterization of molecular subtypes of invasive breast cancer: a study from North India. APMIS. 2012;120(12):1008-19.
30. Dawood S, Hu R, Homes MD, Collins LC, Schnitt SJ, et al. Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat. 2011;126(1):185-92.
31. Abubakar M, Sung H, Bcr D, Guida J, Tang TS, et al. Breast cancer risk factors, survival and recurrence, and tumor molecular subtype: analysis of 3012 women from an indigenous Asian population. Breast Cancer Res. 2018;20(1):114.
32. Liu G, Ren S, Yan Y, Zhang J, Luo Y, et al. Comparisons of the clinicopathological characteristics and the expression of tumor biomarkers among luminal, HER2-Enriched and triple negative breast cancer. Gen Med (Los Angel). 2015;3(184):2.
33. Park S, Koo JS, Kim MS, Park HS, Lee JS, et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry. The Breast. 2012;21(1):50-7.
34. Vaidyanathan K, Kumar P, Reddy C, Deshmane V, Somasundaram K, et al. ErbB-2 expression and its association with other biological parameters of breast cancer among Indian women. Indian J Cancer. 2010;47(1):8.
35. Si C, Jin Y, Wang H, Zou Q. Association between molecular subtypes and lymph node status in invasive breast cancer. Int J Clin Exp Pathol. 2014;7(10):6800.
36. He ZY, Wu SG, Yang Q, Sun JY, Li FY, et al. Breast Cancer Subtype is Associated With Axillary Lymph Node Metastasis: A Retrospective Cohort Study. Medicine (Baltimore). 2015;94(48):e2213.
37. Rossing M, Pedersen CB, Tvedskov T, Vejborg I, Talman ML, et al. Clinical implications of intrinsic molecular subtypes of breast cancer for sentinel node status. Sci Rep. 2021;11(1):2259.
38. Crabb SJ, Cheang MC, Leung S, Immonen T, Nielsen TO, et al. Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. Clin Breast Cancer. 2008;8(3):249-56.
39. Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, et al. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol. 2006;37(9):1217-26.
40. Lee JH, Suh YJ, Shim BY, Kim SH. The incidence and predictor of lymph node metastasis for patients with T1mi breast cancer who underwent axillary dissection and breast irradiation: an institutional analysis. Jpn J Clin Oncol. 2011;41(10):1162-7.
41. Reyal F, Rouzier R, Depont-Hazelzet B, Bollet MA, Pierga JY, et al. The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma. PLoS One. 2011;6(5):e20297.
42. Van Calster B, Vanden Bempt I, Drijkoningen M, Pochet N, Cheng J, et al. Axillary lymph node status of operable breast cancers by combined steroid receptor and HER-2 status: triple positive tumours are more likely lymph node positive. Breast Cancer Res Treat. 2009;113(1):181-7.
43. Gangi A, Mirocha J, Leong T, Giuliano AE. Triple-negative breast cancer is not associated with increased likelihood of nodal metastases. Ann Surg Oncol. 2014;21(13):4098-103.
44. Jones T, Neboori H, Wu H, Yang Q, Haffty BG, et al. Are breast cancer subtypes prognostic for nodal involvement and associated with clinicopathologic features at presentation in early-stage breast cancer? Ann Surg Oncol. 2013;20(9):2866-72.
45. Wiechmann L, Sampson M, Stempel M, Jacks LM, Patil SM, et al. Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol. 2009;16(10):2705-10.
46. Zhu X, Ying J, Wang F, Wang J, Yang H. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status in invasive breast cancer: a 3,198 cases study at National Cancer Center, China. Breast Cancer Res Treat. 2014;147(3):551-5.

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