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Purpose Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. Methods The Mann–Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). Results 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360–9.691, p = 0.010) and 2.445 (95% CI 1.131–5.288, p = 0.023), respectively. Conclusion Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.

Background:Juvenile idiopathic arthritis (JIA) was thought to be the most common inflammatory arthritis in children (Shih et al., 2019). However an aggressive, erosive arthritis of little-known immunologic mechanism occurs 20 times more frequently in children with Down’s syndrome (Foley et al., 2019).Objectives:This study was undertaken to characterize immune cell responses and synovial fibroblast invasiveness in children with Down’s syndrome-associated arthritis (DA).Methods:Multiparametric flow cytometric analysis was used to examine peripheral blood T cell, B cell and monocyte populations. In addition, T cell cytokine responses and their metabolic profile in children with DA, JIA, Down’s Syndrome (trisomy 21 [T21]), and in healthy controls were assessed. The function of DA primary synovial fibroblasts (FLS) was assessed in response to stimulation with pro-inflammatory mediators alone and in combination (TNF-α, IL-17a, IFN-γ, GM-CSF). The two major energy pathways glycolysis (ECAR) and oxidative phosphorylation (OCR) were quantified by the Seahorse XFe96 Analyser. Migration, adhesion, invasion and cytokine/chemokine secretion were quantified by wound repair scratch assays, Transwell collagen invasion chambers, adhesion binding assays, and ELISAs.Results:T cell frequencies were higher in DA compared to JIA and T21 in contrast to B cell frequencies which were decreased. T cell responses in DA were characterized by increased frequencies of CD4+ and CD8+ TNF- α, IFN- γ and GM-CSF producing T cells. The frequency of T peripheral helper (Tph) cells were elevated in children with DA compared to all other groups. In parallel, an increase in their metabolic profile evident by higher phosphorylation of mTOR pathway components AKT, mTOR and S6. Comparison of DA and JIA FLS demonstrated that DA FLS display a more invasive/migratory capacity and are more metabolically active. Based on the increased cytokine responses in DA T cells, we next examined the effect T cell derived cytokines TNF-α, IL-17A, IFN-γ and GM-CSF alone and in combination on DA FLS function. TNF-α, IL-17a and IFN-γ induced IL-6, RANTES and MCP-1 secretion, with no effect observed for GM-CSF. Furthermore, TNF-α and IL-17A induced DA FLS migration and PBMC adhesion to DA FLS. Finally IL17A and IFN-γ potentiated the effect of TNF-α on IL-6 and MCP-1 secretion compared to stimulations alone.Conclusion:DA is a more common and aggressive form of arthritis compared to JIA. It is characterized by increased T cell responses and a more invasive FLS phenotype compared to that of JIA, with T cell derived cytokine alone and in combination further inducing DA FLS pathogenic mechanisms. These effects mirror the increased erosive disease observed clinically.References:[1]Foley, C. et al. (2019) ‘Increased T cell plasticity with dysregulation of T follicular helper, T peripheral helper and T regulatory cell responses in children with JIA and Down syndrome-associated arthritis’, Arthritis & Rheumatology, pp. 0–1. doi: 10.1002/art.41150.[2]Shih, Y. J. et al. (2019) ‘Enthesitis-related arthritis is the most common category of juvenile idiopathic arthritis in Taiwan and presents persistent active disease’, Pediatric Rheumatology. Pediatric Rheumatology. doi: 10.1186/s12969-019-0363-0.Disclosure of Interests:None declared.

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