TUMOR-INFILTRATING LYMPHOCYTES IN TRIPLE NEGATIVE BREAST CANCER: CORRELATIVE ANALYSES OF OWN DATA AND LITERATURE REVIEW

  • Liubov Zakhartseva PhD, Head of Pathology Anatomy №1 Department, Bogomolets National Medical University, Kyiv, Ukraine
  • Mariia Yanovytska Assistant of Pathology Anatomy №1 Department, Bogomolets National Medical University, Kyiv, Ukraine
Keywords: Іntratumoral lymphocytes, breast cancer prognostic factors, tumor-infiltrating lymphocytes, breast cancer, triple negative breast cancer, tumor micro-environment.

Abstract

The article summarizes data and presents own study about the value of tumor-infiltrating lymphocytes as a prognostic factor for breast cancer including triple negative breast cancer lacking estrogen and progesterone receptors and HER2\new amplification. This tumor group is heterogeneous and has lower overall and disease-free survival rates; therapeutic options for this tumor group are limited compared to luminal and HER2-positive tumors. Triple negative breast tumors attract the attention of scientists as they require more individualized approach and additional prognostic factors in the treatment. The aim of this study is to conduct correlation analysis of tumor-infiltrating lymphocytes with survival rates, stage of disease and degree of differentiation of triple negative breast tumors. Also determination of the most "immunogenic" histological subgroups of triple negative breast cancer is done, as well as comparing of tumor-infiltrating lymphocytes measurement as a continuous number and divided into groups. Samples (n = 143) from patients with triple negative breast cancer undergoing treatment at the Kyiv City Clinical Oncology Center during 2010-2015 were used. The assessment of the number of tumor-infiltrating lymphocytes was performed on histological glasses retrospectively, following the recommendations of an international group for the determination of immune-oncological biomarkers. The number of tumor-infiltrating lymphocytes was evaluated as a continuous number and also divided into groups A (0-10%), B (10-40%) and C (40-90%). According to the results of the study, there was a high direct correlation between the continuous number of tumor-infiltrating lymphocytes and divided into groups (A, B, C). A weak direct correlation was found between tumor-infiltrating lymphocytes and tumor differentiation rates, a weak inverse correlation between tumor-infiltrating lymphocytes count and overall survival and stage of disease, in particular tumor size. The rate of tumor-infiltrating lymphocytes for all carcinomas with medullary characteristics was 100%, indicating a high "immunogenicity" of this histological subtype of tumors. The study confirms that tumor-infiltrating lymphocytes act as an additional prognostic marker for malignant breast tumors, in particular, triple negative breast cancer. Determination of tumor-infiltrating lymphocytes is advisable in the routine practice of the pathologist who investigates malignant breast tumors since it requires no additional reactions and is economically viable. It is advisable to use the recommendations of an international group of the determination of immuno-cancer biomarkers for the distribution of this indicator by groups A, B, C for convenience of description.

References

Бюлетень національного канцер-реєстру України №20. Київ-2019.

Alfonso, J. C. L., Schaadt, N. S., Schönmeyer, R., Brieu, N., Forestier, G., Wemmert, C., ... & Hatzikirou, H. (2016). In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium. Scientific reports, 6, 33322.

Chapman, J. R., Webster, A. C., & Wong, G. (2013). Cancer in the transplant recipient. Cold Spring Harbor perspectives in medicine, 3(7), a015677.

https://clinicaltrials.gov/ct2/results?cond=triple+negative+breast+cancer+immunotherapy&term=&cntry=&state=&city=&dist=

Degnim, A. C., Brahmbhatt, R. D., Radisky, D. C., Hoskin, T. L., Stallings-Mann, M., Laudenschlager, M., ... & Visscher, D. W. (2014). Immune cell quantitation in normal breast tissue lobules with and without lobulitis. Breast cancer research and treatment, 144(3), 539-549.

Denkert, C., von Minckwitz, G., Darb-Esfahani, S., Lederer, B., Heppner, B. I., Weber, K. E., ... & Schmitt, W. D. (2018). Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. The lancet oncology, 19(1), 40-50

Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The three Es of cancer immunoediting. Annu. Rev. Immunol., 22, 329-360.

Farkona, S., Diamandis, E. P., & Blasutig, I. M. (2016). Cancer immunotherapy: the beginning of the end of cancer? BMC medicine, 14(1), 73.

García-Martínez, E., Gil, G. L., Benito, A. C., González-Billalabeitia, E., Conesa, M. A. V., García, T. G., ... & de la Peña, F. A. (2014). Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast cancer research, 16(6), 488.

García-Teijido, P., Cabal, M. L., Fernández, I. P., & Pérez, Y. F. (2016). Tumor-infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clinical Medicine Insights: Oncology, 10, CMO-S34540.

Ghoncheh, M., Pournamdar, Z., & Salehiniya, H. (2016). Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev, 17(S3), 43-46.

Hammerl, D., Smid, M., Timmermans, A. M., Sleijfer, S., Martens, J. W. M., & Debets, R. (2018, October). Breast cancer genomics and immuno-oncological markers to guide immune therapies. In Seminars in cancer biology (Vol. 52, pp. 178-188). Academic Press.

Hendry, S., Salgado, R., Gevaert, T., Russell, P. A., John, T., Thapa, B., ... & Sanders, M. (2017). 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. Advances in anatomic pathology, 24(6), 311.

Huang, Y., Ma, C., Zhang, Q., Ye, J., Wang, F., Zhang, Y., ... & Peng, G. (2015). CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome. Oncotarget, 6(19), 17462.

Hussein, M. R., & Hassan, H. I. (2006). Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations. Journal of clinical pathology, 59(9), 972-977.

Lakhani, S. R. (Ed.). (2012). WHO Classification of Tumours of the Breast. International Agency for Research on Cancer.

Li, F., Zhao, Y., Wei, L., Li, S., & Liu, J. (2018). Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer. Cancer biology & therapy, 19(8), 695-705.

Mao, Y., Qu, Q., Chen, X., Huang, O., Wu, J., & Shen, K. (2016). The prognostic value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis. PloS one, 11(4), e0152500.

Mohammed, Z. M. A., Going, J. J., Edwards, J., Elsberger, B., & McMillan, D. C. (2013). The relationship between lymphocyte subsets and clinico-pathological determinants of survival in patients with primary operable invasive ductal breast cancer. British journal of cancer, 109(6), 1676.

Ohtani, H., Mori‐Shiraishi, K., Nakajima, M., & Ueki, H. (2015). Defining lymphocyte‐predominant breast cancer by the proportion of lymphocyte‐rich stroma and its significance in routine histopathological diagnosis. Pathology international, 65(12), 644-651.

Pistelli, M., Caramanti, M., Biscotti, T., Santinelli, A., Pagliacci, A., De Lisa, M., ... & Berardi, R. (2014). Androgen receptor expression in early triple-negative breast cancer: clinical significance and prognostic associations. Cancers, 6(3), 1351-1362.

Ravelli, A., Roviello, G., Cretella, D., Cavazzoni, A., Biondi, A., Cappelletti, M. R., ... & Bottini, A. (2017). Tumor-infiltrating lymphocytes and breast cancer: beyond the prognostic and predictive utility. Tumor Biology, 39(4), 1010428317695023.

Stanton, S. E., Adams, S., & Disis, M. L. (2016). Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA oncology, 2(10), 1354-1360.

Wei, B., Yao, M., Xing, C., Wang, W., Yao, J., Hong, Y., ... & Fu, P. (2016). The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis. OncoTargets and therapy, 9, 5567.

Published
2019-06-01
How to Cite
1.
Zakhartseva L, Yanovytska M. TUMOR-INFILTRATING LYMPHOCYTES IN TRIPLE NEGATIVE BREAST CANCER: CORRELATIVE ANALYSES OF OWN DATA AND LITERATURE REVIEW. USMYJ [Internet]. 2019Jun.1 [cited 2026Mar.21];110(2):31-2. Available from: https://mmj.nmuofficial.com/index.php/journal/article/view/68