Skip to main content Skip to main navigation menu Skip to site footer

Stromal Tumor Infiltrating Lymphocytes (TIL) as a potential prognostic biomarker for recurrence in Locally Advanced Breast Cancer (LABC) patients

  • Dannu Novriandhika ,
  • Dwi Hari Susilo ,
  • Dyah Fauziah ,
  • Priangga Adi Wiratama ,
  • Desak Gede Agung Suprabawati ,


Background: Tumor-infiltrating lymphocytes (TIL) serves as the host adaptive immune response in breast cancer. TIL has the potential to be an independent prognostic factor in breast cancer patients. In this study, we aimed to examine the association between stromal TIL and recurrence in locally advanced breast cancer patients.

Methods: A cohort retrospective study was conducted using medical records of female breast cancer patients with locally advanced breast cancer. We collected patients' data, including demographic data from the medical record. Stromal TIL was examined following the recommendations of the International TIL Working Group 2014.

Results: 75 samples were included with an average age of 49.5±8.4. Ductal carcinoma was the most common type histologically (88.0%). Luminal B Her2-negative was the predominant breast cancer subtype (32.0%). There was a significant association between the breast cancer subtype and disease-free survival (P – 0.014). The optimal cut-off to determine the recurrence of breast cancer was 15%. The sensitivity, specificity, PPV, NPV, and accuracy of TIL to predict the 24-month disease-free survival (DFS) were 80.5%, 82.4%, 84.6%, 77.8%, and 81.3%, respectively. Every 10% increase in TIL percentage could raise the DFS by 5.45 months (p=0.001). Patients with high TIL values had higher survival than those with low TIL values.

Conclusion: There was a significant correlation between the stromal TIL and the recurrence rate. The pre-therapy stromal TIL percentage can be employed as a potential biomarker to predict breast cancer recurrence, particularly in the first two years.


  1. World Health Organization (WHO). Breast cancer. WHO. 2018.
  2. Balogun OD, Formenti SC. Locally advanced breast cancer - strategies for developing nations. Front Oncol. 2015;5(4):89.
  3. Pusdatin Kementerian Kesehatan Republik Indonesia. Kanker Payudara. 2016.
  4. Vidiyanti C, Fauziah D, Suprabawati DGA. ER, PR, and HER-2/NEU Profile on Young Breast Cancer Carcinoma Patients. Folia Medica Indones. 2014;50(1).
  5. Hidayat YH, Ishardyanto H, Anniwati L. High Sensitive Troponin I and Extended Range C-Reactive Protein as Markers to Predict Cardiotoxicity in Locally Advanced Breast Cancer with Neoadjuvant CAF (Cyclophoshpamide, Adriamycin/Doxorubicin, 5Fluorouracil) Therapy. Folia Medica Indones. 2020;56(2):91–8.
  6. Winantyo VI, Tanggo VVCM, Ali I. Association of neutrophil-lymphocyte ratio (NLR) with the anthracycline-based neoadjuvant chemotherapy (NAC) clinical response in locally advanced breast cancer (LABC) in young women. Bali Med J. 2022;11(2):602–8.
  7. Devi DGAP, Purwanto H, Sandhika W. Changes in Ki67 expression and clinical response to neoadjuvant chemotherapy in locally advanced breast cancer (LABC). Bali Med J. 2021;10(3):925–31.
  8. Sasanpour P, Sandoughdaran S, Mosavi-Jarrahi A, Malekzadeh M. Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients. Asian Pac J Cancer Prev. 2018;19(9):2423–7.
  9. Li JJ, Chen S, Chen CM, Di GH, Liu GY, Wu J, et al. Pathological complete response as a surrogate for relapse-free survival in patients with triple-negative breast cancer after neoadjuvant chemotherapy. Oncotarget. 2017;8(11):18399–408.
  10. Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. Journal for ImmunoTherapy of Cancer. 2016;4:1-6
  11. Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.
  12. Yin W, Di G, Zhou L, Lu J, Liu G, Wu J, et al. Time-varying pattern of recurrence risk for Chinese breast cancer patients. Breast Cancer Res Treat. 2009;114(3):527–35.
  13. Kashiwagi S, Asano Y, Goto W, Takada K, Takahashi K, Noda S, et al. Use of Tumor-infiltrating lymphocytes (TILs) to predict the treatment response to eribulin chemotherapy in breast cancer. PLoS One. 2017;12(2):e0170634.
  14. Nasrudin AH, Ali I, Rahniayu A. Pengaruh Tumor Infiltrating Lymphocytes (TIL) Terhadap Respon Klinis Kemoterapi Neoajuvan Berbasis Antrasiklin Pada Kanker Payudara Lanjut Lokal Triple Negative. Universitas Airlangga; 2018.
  15. Wein L, Savas P, Luen SJ, Virassamy B, Salgado R, Loi S. Clinical Validity and Utility of Tumor-Infiltrating Lymphocytes in Routine Clinical Practice for Breast Cancer Patients: Current and Future Directions. Front Oncol. 2017;7:156.
  16. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILS) in breast cancer: Recommendations by an International TILS Working Group 2014. Annals of Oncology. 2015;6:259–71.
  17. Liedtke C, Hess KR, Karn T, Rody A, Kiesel L, Hortobagyi GN, et al. The prognostic impact of age in patients with triple-negative breast cancer. Breast Cancer Res Treat. 2013;138(2):591–9.
  18. Kasangian AA, Gherardi G, Biagioli E, Torri V, Moretti A, Bernardin E, et al. The prognostic role of tumor size in early breast cancer in the era of molecular biology. PLoS One. 2017;12(12):e0189127.
  19. Qiu J, Xue X, Hu C, Xu H, Kou D, Li R, et al. Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. J Cancer. 2016;7(2):167–73.
  20. Biglia N, Maggiorotto F, Liberale V, Bounous VE, Sgro LG, Pecchio S, et al. Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2013;39(5):455–60.
  21. Aziz S, Wik E, Knutsvik G, Klingen TA, Chen Y, Davidsen B, et al. Extra-nodal extension is a significant prognostic factor in lymph node-positive breast cancer. PLoS One. 2017;12(2):e0171853.
  22. Yang Z-J, Liu Y-X, Huang Y, Chen Z-J, Zhang H-Z, Yu Y, et al. The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score. Cancer Med. 2022:1-8
  23. Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, et al. Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(7):559–69.
  24. Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015;36(4):265–76.
  25. Dieci M V, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol Off J Eur Soc Med Oncol. 2015;26(8):1698–704.
  26. Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front Oncol. 2018;8:86.
  27. Wiranata S, Anjani IA, Saputra IP, Sadvika IG, Prabawa IPY, Supadmanaba IG, et al. Pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as a stage determination in breast cancer. Open Access Maced J Med Sci. 2020;8:1058-63.
  28. Dieci MV, Radosevic-Robin N, Fineberg S, van den Eynden G, Ternes N, Penault-Llorca F, et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Br. Semin Cancer Biol. 2018;52(2):16–25.

How to Cite

Novriandhika, D., Susilo, D. H., Fauziah, D., Wiratama, P. A., & Suprabawati, D. G. A. (2022). Stromal Tumor Infiltrating Lymphocytes (TIL) as a potential prognostic biomarker for recurrence in Locally Advanced Breast Cancer (LABC) patients. Bali Medical Journal, 11(3), 1691–1698.




Search Panel

Dannu Novriandhika
Google Scholar
BMJ Journal

Dwi Hari Susilo
Google Scholar
BMJ Journal

Dyah Fauziah
Google Scholar
BMJ Journal

Priangga Adi Wiratama
Google Scholar
BMJ Journal

Desak Gede Agung Suprabawati
Google Scholar
BMJ Journal