2342P - Single tumor cells are a novel prognostic criterion in breast cancer patients

Background

Single tumor cells (STCs) are a manifestation of intratumor morphological heterogeneity and most likely arise from multicellular tumor structures as a result of cancer invasion. In recent years, the appearance of STCs has been described as tumor budding in the invasive front. However, there are no clear data on the clinical significance of these cells in breast cancer patients.

Methods

The study included 230 patients diagnosed with invasive breast carcinoma of the nonspecific type, luminal molecular subtypes. H&E staining was used to detect STCs in breast tissue. STCs (or detached individual tumor cells) were detected in the entire tumor tissue in contrast to tumor buds located in the invasive front, and were defined as tumor cells located outside multicellular tumor structures but similar to them in cytological features. 7-color immunofluorescence analysis was used to study the population composition of the microenvironment (ME) of STCs. Laser microdissection of STCs ME and sequencing on NextSeq500 (Illumina, USA) was performed.

Results

Patients who had a STCs had a 5.8-fold increased risk (CI95% 2.4-14.1) of developing distant metastases compared to patients who did not have a STCs (p=0.0001). Patients who had no STCs had a better metastatic-free survival (91.8%) than patients who had a STCs (49.1) (p<0.0001). The relative risk of distant metastases in breast cancer patients where only Th2-like immune reaction is found in the ME is 2.37 (CI95% 1.25-4.42) times higher than in patients where only Th1-like immune reaction (p=0.0352). In addition, a Top 10 analysis of up- and downregulated genes in the STCs ME in breast cancer patients depending on the status of distant metastasis was performed. Decrease of CD52 (7-fold), NUDT3 (6-fold), TAP1 (6-fold) (p<0.001) genes expression and increase of LAMA5 (4-fold), LPCAT1 (5-fold), FLVCR1 (5-fold) (p<0.001) genes expression were detected in the STCs ME of breast cancer patients with distant metastases compared to those without.

Conclusions

A novel simple prognostic criterion for predicting breast cancer metastasis has been developed. The microenvironment has been shown to play an important role in the metastatic potential of a single tumour cells. Immunosignatures of the pro-tumour microenvironment have been identified.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Tomsk National Research Medical Center.

Funding

The study was supported by the Russian Science Foundation (grant #23-15-00135).

Disclosure

All authors have declared no conflicts of interest.