LAUSR

Background: Poor prognosis in TNBC can be predicted in the significant fraction of patients with large volume residual cancer burden (RCB-II/III) after neoadjuvant chemotherapy (NACT). Whilst residual disease has been characterised to identify “driver” mutations and copy number variations, the contribution of the immune response within its tumour microenvironment remains unclear. Here we aimed to: 1) assess the potential spatial heterogeneity of immune transcript related gene expression between areas of tumour approximately 1cm apart as might still occur with a radiologically guided biopsy through the residual disease; and 2) assess the immune stroma composition of the TNBC high metastatic risk RCB II/III disease. Method: 12 TNBC post NACT RCB II/III residual cases were identified from the KHP biobank. HE and 27% (3/11) displayed a >2-fold (range 2.03-3.16) difference in the TILS. When comparing the 770 gene expression profiles between sampling areas in the same tumour, we found little spatial heterogeneity with areas A/B clustering together in 10 out of 12 cases. Interestingly, the two cases that revealed spatial heterogeneity within the paired samples displayed little immune cell heterogeneity histologically (i.e. Conclusion: The findings that high metastatic risk residual disease can be further characterized as either “immunologically inert” or “immunologically enriched” at the level of extensive immunological transcript gene expression and by histological assessment of TILS requires further investigation; and is being validated in a larger sample set. Citation Format: Irshad S, Cheang M, Gazinka P, Naidoo K, Buus R, Pinder S, Dowsett M, Tutt A. Immune profiling of post neoadjuvant high metastatic risk (RCB-II/III) residual disease in patients with early triple negative breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-07.