Prolonged Overnight Fasting as a Novel Intervention Strategy for Reducing Breast Cancer Risk

Background: This dissertation examined whether the length of the nightly fasting interval was (1) associated with metabolic biomarkers putatively associated with breast cancer risk; and (2) predictive of breast cancer prognosis among women with a history of breast cancer. These analyses were conducted using data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and the Women’s Healthy Eating and Living Study (WHEL). Methods: The NHANES sample included approximately 2000 non-diabetic women. Nightly fasting duration was calculated from one telephone-based dietary recall. Multivariable linear regression models were used to examine associations between the length of the nightly fasting interval and metabolic biomarkers putativelyassociated with breast cancer risk, including hemoglobin A1c (HbA1c) and C-reactive protein (CRP). The WHEL sample included 2413 non-diabetic breast cancer survivors. Usual nightly fasting duration was assessed from 3-4 recalls that were collected at multiple time-points (i.e., baseline, year 1, year 4). Multivariable linear regression models were used to examine associations between the nightly fasting interval and factors hypothesized to influence breast cancer outcomes: HbA1c, CRP, sleep duration, and BMI. Delayed-entry Cox proportional hazard models were used to assess the association of usual nightly fasting duration, modeled as a time-varying covariate, with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Results: In the NHANES sample of women, each 3-hour increase in nightly fasting duration was associated with significantly lower HbA1c and 2-hour post-prandial glucose measurements. In addition, nightly fasting duration was inversely associated with CRP concentrations among women who consumed <30% of their calories after 5 pm (p=0.01). Among WHEL breast cancer survivors, prolonged nightly fasting was associated with significantly lower HbA1c and longer sleep duration. Women who fasted <13 hours per night had a 36% increased risk of breast cancer recurrence compared to women who fasted ≥13 hours (HR: 1.36; 95% CI, 1.05 − 1.76). Nightly fasting duration was not associated with a statistically significant increased risk of breast cancer-specific or all-cause mortality.Conclusions: Findings suggest that increasing the length of the nightly fasting interval could be a simple, feasible, and novel dietary strategy to regulate metabolic biomarkers putatively associated with breast cancer risk and reduce the risk of breast cancer recurrence