Unfavourable tumour stromal immune cell infiltrates but not circulating immune cell profiles in Aboriginal women with breast cancer

Breast cancer (BrCa) in Aboriginal Australian women carries more than double the risk of death relative to non-Aboriginal Patients. This higher death is partially explained by factors such as higher stage at diagnosis, younger age, increased co-morbidities, remoteness, socioeconomic disadvantage, and access to culturally sensitive health services. Aboriginal women in a Western Australian cohort also more frequently had tumours with adverse biological features including high grade and luminal B or HER2-enriched phenotype. However, an unexplained detriment remained relative to non-Aboriginal women after accounting for these factors. The immune environment of a tumour as well as of the patient in general can impact on native tumour behaviour as well as response to treatment. Studies in many tumour types including meta-analyses in breast cancer correlate higher circulating neutrophil: lymphocyte ratios (NLR) and neutrophil:platelet ratios (NPR) with poorer outcome. Further to this, tumour infiltrating lymphocyte (TIL) levels also have prognostic significance, associating with improved outcome in triple negative and HER2 positive cancers receiving chemotherapy but with adverse outcomes in estrogen receptor positive (ER+) cancers, potentially through to links to anti-estrogen resistance. To further explore drivers of poor outcome in Aboriginal women we studied circulating NLRs and NPRs in a cohort of Indigenous women matched by remoteness of residence and age to non-Indigenous women in Western Australia. Considering the impact of incidental inflammatory conditions over time only levels from counts taken within 90 days either side of diagnosis were considered. Tissue sections where available were assessed for TILs by standard published methods. NLR was available on 214 patients. The median ratio for Indigenous patients (2.46) was not different to non-Indigenous patients (2.13). Considering patients with NLR \u003e 3.0, a cut-off noted to have poorer prognosis in meta-analysis (ref), there was a stronger trend to higher relapse in non-Indigenous (HR 2.14, p=0.07) than Indigenous patients (HR =1.38, p=0.43) for higher NLR. High NLR was not more common in Indigenous relative to non-Indigenous patients (32% v 25%, p=0.37). Considering very high NLR, significantly more Indigenous women had NLRs \u003e5.0 (4.8 v 6.3%, p=0.04). PLR was available on 225 patients. The median for Indigenous patients (126) was not different to non-Indigenous patients (130). Considering patients with PLR \u003e 185, a cut-off noted to have poorer prognosis in meta-analysis (ref), there were non-significant trends to higher relapse in both Indigenous (HR 1.94, p=0.1) and non-Indigenous patients (HR =1.67, p=0.26) for higher PLR. However, high PLR was not more common in Indigenous relative to non-Indigenous patients (15.4 v 21.6%, p=0.24). Stromal TILs were available on 86 patients. Mean % TIL count was significantly higher in Indigenous women (10.7 v 6.6%, p=0.003). This difference was significant for ER+ (9.6 v 3.5%, p=0.004) but not ER- tumours (20.0 v 21.6%, p=0.79). Significantly more Aboriginal patients with ER positive tumours had \u003e=10% TIL infiltrates (41.7 v 9.8%, p=0.0025) but not those with ER- cancers (70 v 40%, p=0.18). In summary, measured circulating immune or inflammatory profiles did not substantially differ between Aboriginal and non-Aboriginal breast cancer patients. In contrast, although numbers are small, ER+ tumours in Aboriginal women had a higher incidence of significant TIL infiltrates which may both contribute to poorer prognosis and predict for higher utility from immunotherapy. An expansion of the cohort is underway along with immune cell sub-typing and immune checkpoint molecule assessments. Citation Format: Andrew David Redfern, Jacinta J Fong, Lisa J Spalding, Sherene Loi, Benjamin Dessauvagie, Jennet Harvey, Katie Meehan. Unfavourable tumour stromal immune cell infiltrates but not circulating immune cell profiles in Aboriginal women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-18.