Yanovytska M. Triple negative breast cancer: application of histological and immunohistochemical characteristics for prognostication of the clinical course of the disease

Breast cancer takes the leading place both in morbidity and mortality in the world among all malignant tumors in women. The subdivision of breast cancer into molecular subtypes significantly improved the prognosis of patients, because hormone therapy became avalaible for luminal types that have estrogen and progesterone receptors, as well as targeted therapy appeared for HER2/neu-positive cancer. However, triple negative breast cancer which was named so because it lacks estrogen and progesterone receptors as well as HER2/neu amplification, have limited treatment options and the worst morbidity rates. Uncertainty about treatment, questions about the aggressive and sometimes favorable course of these tumors and high levels of mutational load in most cases leave group of triple negative cancer aside from luminal and HER2-positive tumors and cause questions to scientists and oncologists. This study aims to solve these issues by improving the diagnostics of triple negative carcinomas and identifying current prognostic and predictive factors. The solution of this problem and obtaining of the study results was achieved through the use of a set of modern research methods for triple negative breast cancer: histological, immunohistochemical and statistical data processing. Histological analysis of 455 breast tumors and evaluation of immunohistochemical markers expression was performed to provide the necessary research. The first part of the study is a retrospective-prospective analysis of histological biopsy and operation material specimens and case histories of patients (n = 343) diagnosed with "triple negative breast cancer" without estrogen receptors (ER), progesterone (PR) and amplification of HER2/neu treated at the Kyiv City Clinical Oncology Center during 2009-2017 (retrospective archival material and prospective material from patients treated in 2017). Frequency of disease, structure, age distribution, assessment of overall and recurrence-free survival, and morphological features of tumors were established and analyzed. Also the number of tumor-infiltrating lymphocytes (surgical and biopsy material) and tumor stroma ratio (surgical material) were determined to evaluate their prognostic and predictive value for triple negative breast cancer in histological specimens stained with hematoxylin-eosin. Also 313 immunohistochemical reactions with androgen, TOP2A, PD-L1 were performed. In 44 cases, the study of PD-L1 expression was performed both on the material of preoperative biopsy and on the material of surgery after neoadjuvant chemotherapy with subsequent comparison of its expression. In the second part of the prospective study, 112 patients diagnosed with breast cancer (27 in luminal A group, 26 in luminal B group, 29 in HER2-positive group and 30 in triple negative group) were separately analyzed to assess PD-L1 expression. The comparison of the results for different breast cancer molecular subgroups was also established. According to the results of archival material and statistical data investigation, the specific share of triple negative carcinomas among all breast cancer is 11% ± 0.88%.