Abstract Breast cancer (BrCa) incidence is lower in Aboriginal Australian women but carries more than double the risk of death. However, rates of Aboriginal BrCa diagnosis are increasing, hypothesized to be due to lifestyle changes. Thus, with rising incidence and higher mortality, deaths due to BrCa are rising in absolute terms in Aboriginal women. Studies of this higher death rate thus far have been epidemiological, exploring factors such as higher stage at diagnosis, younger age, increased co-morbidities, remoteness, socioeconomic disadvantage, and access to culturally sensitive health services. Collectively, these factors do not fully explain this higher rate of death. However, no study has explored any aspect of tumour or host biology in Aboriginal BrCa. We have studied a cohort of 262 Aboriginal women identified from the WA Cancer Registry comprising all cases diagnosed with BrCa in Western Australia for the period 2001-2016. Remoteness, in the form of an Accessibility/Remoteness Index of Australia (ARIA) score, was calculated from address at the time of diagnosis for each patient. All participants were then matched 2:3 by remoteness of residence and age with non-Aboriginal patients. Mortality data including cause was collected through state Death Registry linkage. Basic tumour parameters as well as receptor expressions were extracted from routine pathology assessment data with extra sections scored for missing values when tissue was available. A BrCa sub-type was assigned to each participant based on a modified IHC4 method using tumour grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. A significant detriment was found for Indigenous BrCa mortality, univariate hazard ratio (HR)=4.19 (95% confidence interval (CI) 2.42 - 7.25, p<0.001) after matching for remoteness and age, multivariate HR=2.55 (95% CI 1.39 - 4.67, p=0.003) after further adjustment for lymph involvement and size.Supporting the hypothesis that Indigenous BrCa is more likely to be aggressive, substantially more tumours in Aboriginal women were greater than 2cm (51 v 23%, p<0.0001), grade 3 (45 v 26%, p<0.0001) and lymph node positive (56 v 33%, p=0.011). Considering individual receptors, HER2 positivity was substantially more common (21 v 12%, p=0.009) although ER and PR did not differ. Combining grade and receptor status revealed substantially higher proportions of the higher risk sub-types luminal B (29 v 16%) and HER2-enriched (11 v 5%), but no difference in triple negative cancers (15 v 15%), overall p=0.001 for sub-type differences. These biological differences explained part but not all of the survival detriment observed for Aboriginal women with attenuated survival detriment seen within each biological sub-type. Further studies on more detailed aspects of tumour biology are ongoing. Citation Format: Andrew David Redfern, Lisa J Spalding, Edward YC Lee, Connor F Redfern, Leanne Pilkington, Max Bulsara, Richard Trevithick, Katie Meehan. Aggressive tumour biology contributes to poor breast cancer outcomes for indigenous Australians [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 P2-10-09.
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