Modifications of Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative BC

Study of the Modifications of the Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative Breast Cancers

The prescription of neoadjuvant chemotherapy becomes a standard in women with HER2-positive or triple-negative breast cancer and allows a complete histological response (pCR) which represents a prognostic factor for survival. . The problem for patients who are not pCR is that they are currently receiving non-personalized adjuvant systemic treatment.

The identification of biomarkers present in the residual disease would be a criterion to guide the choice of post-neoadjuvant adjuvant systemic treatment, in order to personalize it.

At the present time, there is no published study describing extensively the immune micro-environment (ME) in breast cancer, whether before or after chemotherapy, nor its modification induced by chemotherapy.

The team therefore propose to study in a retrospective and monocentric series, the modifications of the immune ME induced by a "standard" neo-adjuvant chemotherapy in patients with triple-negative CS, whether they are in complete histological response or not (n = twice 50).

The main objective of this project is to describe the changes in the immune ME of triple-negative breast cancers induced by neoadjuvant chemotherapy for all patients (in pCR or not):

• Quantification of TILs and subtypes of TILs (CD4 and CD8)
• Expression of the three immune checkpoints that are PDL1, TIM3 and LAG3
• Describe the organization of the immune system (immunostaining on the same slide of the PDL1, TIM3 and LAG3 immune checkpoints)

Retrospective and monocentric translational study carried out on patients treated at the IUCT-Oncopole by neoadjuvant chemotherapy (sequential treatment FEC100 or EC100 then taxane, paclitaxel weekly for the most part) for a triple-negative CS between 2012 and 2018.

We have the microbiopsy of the primary tumor preserved in FFPE and the operating room preserved in FFPE.

We have all the clinical data for the diagnosis and monitoring of these patients, already entered into a database.

The search for a BRCA germline mutation is available in most patients if indicated for an oncogenetic consultation.

biomarkers analysis :

• TILS account according to Salgado et al. before and after neoadjuvant chemotherapy
• IHC CK5-6 and EGFR then RA if the first two are negative to characterize triple negative tumors in "basal-like" and "non-basal-like"
• IHC CD3 (labeling of T lymphocytes)
• IHC CD4, CD8 and FOXP3 before and after neoadjuvant chemotherapy
• PDL1, TIM3 and LAG3 multiplex IHC before and after neoadjuvant chemotherapy
• Labeling of tumor cells: AE1 / AE3
• Use of markings for exploratory analyzes: CD68 (macrophages), CD39 (marker of lymphocyte exhaust

Inclusion Criteria:

• Samples from triple negative BC patients, patients treated by neoadjuvant chemotherapy ( FEC or EC than taxanes) Patients consent to use their samples.

Exclusion Criteria:

• Samples not available before or after neoadjuvant chemotherapy