(P12-012-25) Insulinemic and Inflammatory Dietary Patterns and Breast Cancer Risk and Prognosis: Role of the PI3K/Akt/mTOR Pathway Among Black Women

Objectives: The Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) are obesogenic dietary patterns contributing to energy imbalance and associated with higher breast cancer (BrCa) risk; however, specific mechanisms of action have not been investigated. The phosphoinositide-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway, when overactivated by habitual energy imbalance, has been associated with increased BrCa risk, yet synergies between the pathway and dietary patterns have not been investigated.

Methods: Baseline dietary, hormone receptor, and immunohistochemical (IHC) biomarker (mTOR, p (phosphorylated)-mTOR, p-Akt, p70S6) data from 394 Black women in the Women’s Circle of Health and the Women’s Circle of Health Follow-up Study were included. Dietary scores for reversed EDIH (rEDIH) and rEDIP were calculated from food frequency questionnaire data. Multivariable-adjusted logistic regression was used to compute prevalence odds ratios for the associations of dietary patterns and BrCa outcomes by IHC biomarkers. All-cause and BrCa-specific mortality outcomes by IHC marker were also examined in multivariable-adjusted Cox regression analyses.

Results: A 1-standard deviation (sd) increment in rEDIH and rEDIP was associated with lower odds of breast tumor expression of pAkt in the nucleus, p70S6 and pmTOR in the cytoplasm. For example, a 1-sd increment in rEDIH was associated with 34% lower odds of breast tumors with p70S6 overexpression, OR=0.66 (95% CI: 0.48, 0.91; p=0.01). Similarly, the dietary patterns were associated with reduced risk of dying from breast tumors with high expression of nuclear pAkt and cytoplasmic p70S6 and pmTOR; e.g., a 1-sd increment in rEDIH was associated with 13% to 14% reduced risk of all-cause [HR, 0.87; (0.75, 1.00; p=0.05)] and BrCa-specific [HR, 0.86; (0.74, 0.97; p=0.01)] mortality among women with positive pmTOR cancers.

Conclusions: Low-insulinemic and anti-inflammatory dietary patterns may reduce BrCa mortality via regulation of the PI3K/Akt/mTOR pathway. Further studies are warranted to confirm these novel findings.

Funding Sources: This work was funded by grant NIH/NCI R37CA248371 (Dr. Cheng).