Review of tumor infiltrating lymphocytes assessment in breast cancer in routine diagnostic practice

Česká verzia

Authors: Pavel Dundr ^*1; Mária Gregová ¹; Michaela Bártů ¹; Martina Zimovjanová ²; Luboš Petruželka ²; Zuzana Bielčiková ²; Pavel Fabian ³; Radoslav Matěj ^4,5; Aleš Ryška ⁶ ; Kristýna Němejcová ¹
Authors place of work: Ústav patologie 1. LF UK a VFN v Praze ¹; Onkologická klinika 1. LF UK a VFN v Praze ²; Oddělení onkologické patologie, Masarykův onkologický ústav, Brno ³; Ústav patologie, 3. LF UK a FN Královské Vinohrady ⁴; Ústav patologie a molekulární medicíny, 3. LF UK a Fakultní Thomayerova nemocnice ⁵; Fingerlandův ústav patologie, LF UK a FN Hradec Králové ⁶
Published in the journal: Čes.-slov. Patol., 57, 2021, No. 3, p. 161-166
Category: Reviews Article

Summary

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.

Keywords:

breast cancer – tumor infiltrating lymphocytes – Prognosis – prediction

Zdroje

1. Hendry S, Salgado R, Gevaert T, et al. Assessing tumor-infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized method from the international immuno-oncology biomarkers working group: Part 2: Tils in melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and mesothelioma, endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumors. Adv Anat Pathol 2017; 24(6): 311-335.

2. Hendry S, Salgado R, Gevaert T, et al. Assessing tumor-infiltrating lymphocytes in solid tumors: A practical review for pathologists and proposal for a standardized method from the international immunooncology biomarkers working group: Part 1: Assessing the host immune response, tils in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research. Adv Anat Pathol 2017; 24(5): 235-251.

3. Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus immunoscore for the classification of colon cancer: A prognostic and accuracy study. Lancet 2018; 391(10135): 2128-2139.

4. Mlecnik B, Bifulco C, Bindea G, et al. Multicenter international society for immunotherapy of cancer study of the consensus immunoscore for the prediction of survival and response to chemotherapy in stage iii colon cancer. J Clin Oncol 2020; 38(31): 3638-3651.

5. Nemejcova K, Ticha I, Bartu M, et al. Comparison of five different scoring methods in the evaluation of inflammatory infiltration (tumor-infiltrating lymphocytes) in superficial spreading and nodular melanoma. Pigment Cell Melanoma Res 2019; 32(3): 412-423.

6. Dundr P, Nemejcova K, Bartu M, Ticha I, Jaksa R. Evaluation of inflammatory cells (tumor infiltrating lymphocytes - TIL) in malignant melanoma. Cesk Patol 2018; 54(1): 27-31.

7. Dundr P, Nemejcova K, Bartu M, et al. Evaluation of inflammatory cells (tumor infiltrating lymphocytes) in solid tumors. Klin Onkol 2017; 30(Suppl 3): 10-21.

8. Zavadova E, Spacek J, Vocka M, et al. Immunoscore and its predictive value for colorectal cancer. Klin Onkol 2015; 28 Suppl 4: S82-85.

9. Salgado R, Denkert C, Campbell C, et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in her2-positive early- stage breast cancer treated with lapatinib and trastuzumab: A secondary analysis of the neoaltto trial. JAMA Oncol 2015; 1(4): 448-454.

10. Denkert C, Wienert S, Poterie A, et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: Results of the ring studies of the international immuno-oncology biomarker working group. Mod Pathol 2016; 29(10): 1155-1164.

11. Loi S, Michiels S, Salgado R, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: Results from the finher trial. Ann Oncol 2014; 25(8): 1544-1550.

12. Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase iii randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin- -based chemotherapy: Big 02-98. J Clin Oncol 2013; 31(7): 860-867.

13. Xu T, He BS, Liu XX, et al. The predictive and prognostic role of stromal tumor-infiltrating lymphocytes in her2-positive breast cancer with trastuzumab-based treatment: A meta- analysis and systematic review. J Cancer 2017; 8(18): 3838-3848.

14. Burstein HJ, Curigliano G, Loibl S, et al. Estimating the benefits of therapy for early-stage breast cancer: The st. Gallen international consensus guidelines for the primary therapy of early breast cancer 2019. Ann Oncol 2019; 30(10): 1541-1557.

15. Denkert C, Loibl S, Noske A, et al. Tumor- -associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2010; 28(1): 105-113.

16. Carbognin L, Pilotto S, Nortilli R, et al. Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes: Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting. Oncologist 2016; 21(3): 283-291.

17. Melichar B, Študentova H, Kalábová H, et al. Predictive and prognostic significance of tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant systemic therapy. Anticancer Res 2014; 34(3): 1115-1125.

18. Hornychova H, Melichar B, Tomsova M, et al. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma. Cancer Invest 2008; 26(10): 1024-1031.

19. Loi S, Drubay D, Adams S, et al. Tumor-infiltrating lymphocytes and prognosis: A pooled individual patient analysis of early-stage triple- negative breast cancers. J Clin Oncol 2019; 37(7): 559-569.

20. Park JH, Jonas SF, Bataillon G, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple- -negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol 2019; 30(12): 1941-1949.

21. Yoon GY, Chae EY, Cha JH, et al. Imaging and clinicopathologic features associated with pathologic complete response in her2-positive breast cancer receiving neoadjuvant chemotherapy with dual her2 blockade. Clin Breast Cancer 2020; 20(1): 25-32.

22. Yang X, Rao J, Yang W, Shui R. Evaluation of the predictive and prognostic values of stromal tumor-infiltrating lymphocytes in her2-positive breast cancers treated with neoadjuvant chemotherapy. Target Oncol 2018; 13(6): 757-767.

23. Savas P, Salgado R, Denkert C, et al. Clinical relevance of host immunity in breast cancer: From tils to the clinic. Nat Rev Clin Oncol 2016; 13(4): 228-241.

24. Bertucci F, Goncalves A. Immunotherapy in breast cancer: The emerging role of PD-1 and PD-L1. Curr Oncol Rep 2017; 19(10): 64.

25. Schmid P, Salgado R, Park YH, et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: Results from the phase 1b open-label, multicohort keynote- 173 study. Ann Oncol 2020; 31(5): 569-581.

26. Stanton SE, Adams S, Disis ML. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: A systematic review. JAMA Oncol 2016; 2(10): 1354-1360.

27. Lundgren C, Bendahl PO, Ekholm M, et al. Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: Data from a randomised trial with long-term follow-up. Breast Cancer Res 2020; 22(1): 140.

28. Mao Y, Qu Q, Chen X, et al. The prognostic value of tumor-infiltrating lymphocytes in breast cancer: A systematic review and meta- -analysis. PLoS One 2016; 11(4): e0152500.

29. Wang K, Xu J, Zhang T, Xue D. Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis. Oncotarget 2016; 7(28): 44288-44298.

30. West NR, Milne K, Truong PT, et al. Tumor- -infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res 2011; 13(6): R126.

31. Ali HR, Provenzano E, Dawson SJ, et al. Association between cd8+ t-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol 2014; 25(8): 1536-1543.

32. Loi S. Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy. Oncoimmunology 2013; 2(7): e24720.

33. Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, Kazkaz GA. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: A meta-analysis. Breast Cancer Res Treat 2014; 148(3): 467-476.

34. Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (tils) in breast cancer: Recommendations by an international tils working group 2014. Ann Oncol 2015; 26(2): 259-271.

35. Board WCOTE. Breast tumours (5th ed.). Lyon, France: IARC Press; 2019:

36. Wein L, Savas P, Luen SJ, et al. 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.

37. Lehmann BD, Jovanović B, Chen X, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLOS ONE 2016; 11(6): e0157368.

38. Zou Y, Hu X, Zheng S, et al. Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis. EBioMedicine 2021; 63: 103137.

39. Dieci MV, Radosevic-Robin N, Fineberg S, 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 breast cancer. Semin Cancer Biol 2018; 52(Pt 2): 16-25.

40. Pruneri G, Lazzeroni M, Bagnardi V, et al. The prevalence and clinical relevance of tumor- infiltrating lymphocytes (tils) in ductal carcinoma in situ of the breast. Ann Oncol 2017; 28(2): 321-328.

41. Darvishian F, Ozerdem U, Adams S, et al. Tumor-infiltrating lymphocytes in a contemporary cohort of women with ductal carcinoma in situ (dcis). Ann Surg Oncol 2019; 26(10): 3337-3343.

42. Komforti M, Badve SS, Harmon B, Lo Y, Fineberg S. Tumor-infiltrating lymphocytes in ductal carcinoma in situ- assessment using three different methodologies and correlation with oncotype dx dcis score. Histopathology 2020; 77(5):749-759.

43. Knopfelmacher A, Fox J, Lo Y, Shapiro N, Fineberg S. Correlation of histopathologic features of ductal carcinoma in situ of the breast with the oncotype dx dcis score. Mod Pathol 2015; 28(9): 1167-1173.

44. Cha YJ, Ahn SG, Bae SJ, et al. Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: A retrospective analysis. Breast Cancer Res Treat 2018; 171(2): 295-302.

45. Huang J, Chen X, Fei X, et al. Changes of tumor infiltrating lymphocytes after core needle biopsy and the prognostic implications in early stage breast cancer: A retrospective study. Cancer Res Treat 2019; 51(4): 1336-1346.

46. Kim RS, Song N, Gavin PG, et al. Stromal tumor-infiltrating lymphocytes in nrg oncology/ nsabp b-31 adjuvant trial for early-stage her2-positive breast cancer. J Natl Cancer Inst 2019; 111(8): 867-871.

47. Kos Z, Roblin E, Kim RS, et al. Pitfalls in assessing stromal tumor infiltrating lymphocytes (stils) in breast cancer. NPJ Breast Cancer 2020; 6: 17.

48. O’loughlin M, Andreu X, Bianchi S, et al. Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: A multi-institutional study. Breast Cancer Res Treat 2018; 171(1): 1-9.