The density of tumor-infiltrating lymphocytes (TIL) is a predictive factor for response to neoadjuvant systemic therapy (NAST) in breast cancer. High TIL density correlates with higher complete pathologic remission (pCR) in triple negative and HER2 positive breast cancer. Additionally, not only TIL density but also subsets of immune cells in tumor stroma seem to play an important role in cancer and immune cell interaction and response to chemotherapy. Our aim is to determine TIL density and expression of CD 20, CD3, CD8, PD-L1, FOXP3 and PGM1 on core biopsy specimen and find a correlation with pCR.
We will conduct a prospective study on early breast cancer patients (n = 180) treated with NAST. Patients with breast tumor >2 cm will be suitable. All patients will underwent mammography, MR of breast, core biopsy of breast tumor, implantation of radiopaque marker into tumor, axillary ultrasound and fine needle biopsy of suspect nodes, CT scan of thorax and abdomen and bone scintigraphy. On core biopsy specimen histologic type, grade, estrogen and progesterone receptors, HER 2 status and MIB-1 will be determined. Additionally, TIL density will be determined on stromal part of tumor on H&E slides in accordance with International TIL Working Group. TIL density will be defined as the percentage of lymphocytes in tumor stroma: as a continuous variable and as two categories: low (0-59%) or high (60-100%). Immunohistochemical detection of CD 20, CD3, CD8, PD-L1, FOXP3 and PGM1 will be performed and each subpopulation of immune cells defined as percentage of all immune cells in tumor stroma. Patients with metastatic tumours and luminal A-like characteristics will be excluded. All other patients will undergo NAST with anthracyclines and taxanes and anti-HER2 therapy if indicated, followed by surgical treatment. The breast and axilla specimen will undergo pathologic examination. pCR will be defined as absence of invasive and carcinoma in situ in breast and axillary nodes. The primary objective will be correlation of CD20, CD3, CD8, PD-L1, FOXP3 and PGM1 with TIL density. The secondary objective will be correlation of subsets of immune cells in tumor stroma with pCR.
Clinical trial identification
EudraCT: 2018-000 547-11.
Legal entity responsible for the study
Institute of Oncology Ljubljana.
Slovenian Research Agency P3-0321.
All authors have declared no conflicts of interest.