Breast cancer survivors are at higher risk of death, cancer recurrence, and other comorbidities after diagnosis, as compared to cancer-free women. Dietary guidelines designed to improve prognosis, a lifestyle treatment strategy for newly diagnosed breast cancer patients, are primarily based on research findings related to breast cancer incidence, not survival. Due to post diagnostic factors such as altered physiology, cancer treatments, increased awareness of symptoms, and modified dietary and lifestyle behaviors, it is not likely that the mechanisms contributing to breast cancer etiology are the same as those that lead to recurrence and death. This dissertation provides critical and timely information to support or warrant modification of current dietary recommendations for breast cancer survivors, which will ultimately benefit the estimated 3.8 million women currently living with breast cancer in the United States.
The three analyses outlined in this dissertation leveraged data from the Pathways Study, a long-standing prospective cohort study of a diverse population of breast cancer survivors at Kaiser Permanente Northern California (KPNC), an integrated health care delivery system. Recruitment of study participants began in 2006 and continued through 2013, enrolling 4,505 breast cancer survivors within an average of 2 months after diagnosis. Surveys were administered to participants at enrollment (baseline), 6, 24 and 72 months. In addition to the surveys, these analyses utilized KPNC’s rich clinical and administrative databases, including both demographic and clinical characteristics such as tumor staging, tumor size, hormone receptor status, and treatment. These databases also provided ascertainment of both breast cancer recurrence and mortality.
In chapter 1, the relationship between four a priori dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis and breast cancer recurrence, cause-specific mortality, and all-cause mortality were evaluated. The dietary quality indices included an index based on the American Cancer Society nutrition guidelines (ACS), the alternate Mediterranean Diet Index (aMED), an index based on the Dietary Approaches to Stop Hypertension diet (DASH), and the 2015 Healthy Eating Index (HEI). Minimally and fully adjusted outcome models including each index were evaluated, and sub-analyses were also conducted to examine the independent associations between the individual food components from each index and all-cause mortality. Assessments of effect measure modification were also considered between the indices and select covariates. Overall, this analysis showed that participants who reported consuming diets that were more concordant with healthy eating patterns, were found to be at lower risk of non-breast cancer-specific and all-cause mortality. No clear patterns emerged when examining the associations between the dietary quality indices and breast cancer recurrence or breast cancer-specific mortality.
In chapter 2, the potential effects of interventions on diet quality and lifestyle factors on survival after a breast cancer diagnosis was examined using a causal inference approach. In this study, the parametric g-formula was applied to observational data from the Pathways Study to estimate the risk of all-cause mortality under several hypothetical interventions related to dietary quality, physical activity, and smoking. Each intervention was assumed to begin at the time of the breast cancer diagnosis and maintained over a 13-year follow-up period. Hypothetical interventions at modest levels of intensity were first considered and then interventions with progressively increased intensity to their maximum levels were pursued. Joint interventions on combinations of diet and lifestyle factors were evaluated, as well as the expected risks under no intervention (natural course). This analysis showed hypothetical interventions that increased diet quality, increased physical activity, and stopped participants from smoking, each reduced the risk of death among breast cancer survivors. It also showed that increasing the intensity of the intervention on diet and physical activity was directly related to the strength of the associations. Joint interventions on combinations of diet and lifestyle factors were also evaluated and conveyed the greatest reductions in risk.
In chapter 3, a hierarchical modelling approach was used to examine the relationship between survival and intake of multiple food items assessed at baseline, including whole grains, refined grains, dairy, vegetables, legumes, nuts, processed meat, red meat, poultry and added sugars. A second level model was specified to explain drivers of the food level effects via nutrients considered to be related to survival (e.g. carbohydrates, protein, fiber, calcium, iron, isoflavones, vitamin C, vitamin D, and others). This approach allowed estimation of the mutually adjusted associations between multiple food items on breast cancer survival, as well as the role of specific nutrients in these foods. This study showed a decreased risk in all-cause mortality with increased consumption of whole grains, soy products and nuts and seeds at baseline. Among the fixed effects, iron, isoflavone and fiber consumption were associated with a decreased risk of all-cause mortality, though the estimates for iron and fiber were most imprecise.
These analyses demonstrated that diet, whether evaluated in the context of an overall dietary pattern, or though hypothetical interventions in combination with other lifestyle factors, or examined as individual food items in conjunction with their associated nutrients, plays a critical role in survival after a breast cancer diagnosis. A clearer understanding of diet and its impact on breast cancer prognosis is an essential contribution to the development of guidelines specifically designed for woman surviving breast cancer.
