Association between allostatic load and risk of breast carcinoma in situ in the UK biobank.

BACKGROUND

The association between allostatic load (AL) and breast carcinoma in situ (BCIS) remains unclear. We investigated this relationship in the UK Biobank while also assessing its role in invasive breast cancer (IDC) for comparison.

METHODS

Using data from the UK Biobank, we included 159,240 women (40-69 years). AL was derived from 12 biomarkers. Cox proportional hazards models, restricted cubic splines (RCS), and time-dependent ROC curves were used to assess associations with BCIS and IDC.

RESULTS

Over a median follow-up of 13.65 years, 1,320 BCIS and 7,197 IDC cases occurred. In fully adjusted models, AL was not associated with BCIS (HR per 1-point increase = 1.004; 95% CI: 0.966-1.042; p  = 0.854). RCS confirmed no non-linear relationship (p = 0.605). Conversely, AL was significantly associated with IDC (HR = 1.018; 95% CI: 1.002-1.035; p  = 0.026), indicating a 1.8% increased risk per unit increase. Predictive utility was minimal (AUC < 0.58), and sensitivity analyses using quintile-based AL scoring validated these findings.

CONCLUSION

While AL is an independent risk factor for IDC, it shows no association with BCIS. These findings suggest that the biological drivers of in-situ lesions differ from those of invasive progression, highlighting AL as an etiologic factor for malignancy rather than a screening tool for early-stage localization.