Prospective study of trace elements in breast cancer risk and treatment response

Background: Breast cancer (BC), the most common cancer in women, affects over 2M annually, with 500K+ deaths. BC risk in BRCA1 mutation carriers varies (49%-72%), suggesting environmental influences. Some studies have reported TE impact on BC risk/survival, with optimal levels improving outcomes, but data is limited to few European populations. Aim: To prospectively measure trace element (TE) Se, Cu, Zn, As, Pb and Cd plasma levels in 400 unselected BC cases at diagnosis, 400 healthy controls and 200 unaffected BRCA1/2 pathogenic variant (PV) carriers and to determine their association with BC risk and treatment outcomes. Endpoints: In BC group overall/BC-specific survival, event-free survival; pathological complete response after preoperative systemic therapy. In control group - cancer events. Hypothesis: Abnormal TE levels are significantly associated with BC risk and treatment outcome. Modulation: TE like Zn is lower, while Cu, Pb, Cd is higher in BC cases. Cd links to higher risk of distant metastasis. Optimal Se level may reduce BC risk. TE Mechanisms: TE cause oxidative damage, altering gene expression and cancer risk. Novelty: Prospective study in Latvia to confirm TE levels in BC and unaffected controls, including subgroup of BRCA1/2 PV carriers. Lifestyle/nutritional confounders will be addressed as a part of comprehensive analysis. Impact: Results could shift BC risk reduction/treatment globally, leveraging European project synergies.