Early Breast Cancer
Conditions
Keywords
TILs, CD8+ T-cells, breast cancer, adjuvant, dose-dense chemotherapy
Brief summary
T cells are a broad class of adaptive immune cells, while CD8⁺ T cells are a specific, specialized subset of T cells, defined by the presence of the CD8 surface receptor. T cells, matured in the thymus, consist of helper, cytotoxic and regulatory functions. This study aimed to evaluate the clinical importance of Tumor Infiltrating Lymphocytes (TILs) as well as CD8⁺ T cells in patients with early-stage breast cancer (eBC) treated with dose-dense sequential chemotherapy. The researchers aim to assess tumor samples for TILs and CD8⁺ T cells from eBC patients using immunohistochemistry (IHC). In particular, we will measure the following parameters: CD8+ T cells found in the tissue around the tumor \[stromal\], CD8+ cells found inside the tumor \[intratumoral\], the total number of CD8⁺ cells as well as stromal TILs \[cells in the surrounding tissue\]. The main point of this study was to better understand the way these immune cells are associated with patients' outcome in a large group of patients with eBC who were treated initially with surgery and then received a dose-intense adjuvant chemotherapy.
Detailed description
This study examines the prognostic significance of TILs and CD8+ in patients with eBC treated with dds-CT. From a total of 5,320 patients enrolled in seven prospective clinical studies conducted by the HECOG between 1996 and 2022, 3,646 patients were deemed eligible having donated tissue for central assessment and translational analysis. All patients had received adjuvant dds-CT, including taxanes and anthracyclines, as part of relevant protocols. Adjuvant endocrine therapy and radiotherapy were administered as clinically indicated. Tumor samples were assessed for stromal TILs, stromal CD8+ (sCD8+), intratumoral CD8+ (iCD8+), and total CD8+ density using immunohistochemistry on tissue microarray cores. Intrinsic breast cancer subtypes defined by immunohistochemistry (IHC4), a cost-saving surrogate of gene expression analysis, is frequently used to guiding treatment decisions based on the expression of ER (estrogen receptor), PgR (progesterone receptors, HER2, and Ki67. The analysis explores the prognostic value of these immune markers in the overall cohort and across different molecular subtypes.
Interventions
None listed
Sponsors
Hellenic Cooperative Oncology Group
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women older than 18 years with high-risk, operable eBC. * Histologically confirmed BC * All treated with adjuvant dose-dense sequential chemotherapy (dds-CT). * Tumor tissue specimen (FFPE) availability.
Exclusion criteria
* Lack of FFPE samples. * Bilateral disease. * Distal metastases. * Administration of different chemotherapeutic regimens. * Previous primary cancers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the long-term prognostic significance of TILs & CD8+ in term of OS | Time from study entry to death from any cause, assessed up to 120 months | Overall Survival (OS) |
| To investigate the long-term prognostic significance of TILs & CD8+ in term of DFS | Time from study entry to first recurrence (local, regional, distant) or death from any cause, whichever comes first, assessed up to 120 months | Disease-Free Survival (DFS) |
| To investigate the long-term prognostic significance of TILs & CD8+ in term of iBCFS | Time from study entry to invasive breast cancer recurrence or death, whichever comes first, assessed up to 120 months | Invasive Breast Cancer-Free Survival (iBCFS) |
Countries
Greece
Contacts
PRINCIPAL_INVESTIGATORFoteinos-Ioannis Dimitrakopoulos
Hellenic Cooperative Oncology Group
Outcome results
None listed