Lipid-determined differences in response to chemotherapy between Black and White breast cancer patients

Summary

Targeted treatments for triple negative breast cancer (TNBC) are still not available despite this subtype disproportionately contributing to breast cancer (BCa) mortality and disproportionately affecting ethnic minority groups. Racial differences in lipid processing are unexplored in the context of explaining why Black women are significantly more likely to develop TNBC and why treatment is less efficacious than in White women. The objectives of this project are to understand lipidome differences in TNBC cells between chemotherapy responders and non-responders, and between Black and White patients. We hope this project will lead to a better understanding of why Black women are more likely to get TNBC than White women and why treatment is less efficacious.

Targeted treatments for triple negative breast cancer (TNBC) are still not available despite this subtype disproportionately contributing to breast cancer (BCa) mortality and disproportionately affecting ethnic minority groups. The role of lipids in severity TNBC and chemoresistance is emerging and beginning to inform understanding that may lead to therapeutic targeting of this pathway to help improve outcomes. Racial differences in lipid processing are unexplored in the context of explaining why Black women are significantly more likely to develop TNBC and why treatment is less efficacious than in White women. Chemotherapy efficacy in TNBC has emerged as particularly reliant on, and sensitive to, changes in lipid profile (e.g. omega-3s improve response to BCa therapy; oxysterols confer chemoresistance; obesity linked dyslipidaemia is prognostic for poor TNBC outcomes). Many lipid targeting therapies in clinical use for other diseases may therefore be appropriate in the TNBC setting. The mechanisms of how lipids alter TNBC chemoresponse to treatment are largely unknown and have not been systematically evaluated, thus limiting the potential application of lipid targeting nutritional and pharmacological interventions. The objectives of this project are to: characterise the lipid profile of tumours derived from Black and White TNBC patients; establish the balance and ratios of lipid content and proteome between tumours of TNBC patients who respond to chemotherapy compared to those who don’t; determine associations between nutritional status, lipid balance, and chemoresponse in breast cancer patients; compare proteomic changes in TNBC induced by lipids associated with chemoresponse or with lack of chemoresponse.

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