Grant Abstract: Infrastructure for Pathways, a Prospective Study of Breast Cancer Survivorship

Grant Number: 5U01CA195565-05
PI Name: Kushi
Project Title: Infrastructure for Pathways, a Prospective Study of Breast Cancer Survivorship

Abstract: Recent studies have shown potential harm of dietary supplement use during active breast cancer treatment. Despite these potential risks, use of dietary supplements by women during breast cancer treatment is very common. A major limitation of prior epidemiologic studies on the association between dietary supplement use and breast cancer outcomes is lack of access to detailed data on the dose and duration of specific dietary supplements and dose of specific forms of cancer treatments, including chemotherapies, endocrine therapies, biologic therapies, and radiation therapy. Metabolic and pharmacokinetic mechanisms of known treatment-supplement interactions affect the efficacy of multiple cancer treatment pathways, including mechanisms related to oxidative stress, estrogen metabolism, drug metabolism, platelet/coagulation function, inhibition of CYP450 enzymes, and hepatotoxicity. Some of these interactions may lead to poorer clinical outcomes. We will investigate the effects of specific cancer treatment-supplement interactions on long-term breast cancer clinical outcomes by enhancing data resources within the National Cancer Institute (NCI)-funded Pathways Study (R01CA105274, PI: Kushi; U01CA195565, MPI: Kushi, Ambrosone), a racially/ethnically diverse cohort of 4,505 stage I-IV breast cancer patients diagnosed within Kaiser Permanente Northern California (KPNC). Over 1,500 unique supplements and natural products have been reported to be used by study participants. In this Administrative Supplement, we will newly link data on specific dietary supplements used by Pathways Study participants to data from the Natural Medicines database, which includes detailed information on dietary supplement mechanisms of action and potential drug-supplement interactions for over 10,000 unique supplements. The Specific Aims and analytic goals of this proposal are focused on developing new data linkages and data analysis methods to examine drug-dietary supplement interactions for one specific chemotherapy drug, doxorubicin, which can be affected by five different drug-dietary supplement interaction pathways. Doxorubicin was used by 1,331, nearly one quarter (23.3%), of Pathways Study participants. Operational tasks are: 1) To describe the frequency of potential known interactions between doxorubicin and dietary supplements known to affect 5 different metabolic and pharmacokinetic pathways: antioxidant, antiplatelet, cytochrome P450 CYP3A4 and CYP2D6 enzyme inhibition, and P-glycoprotein (Pgp) inhibition; and 2) To explore the associations between use of dietary supplements known to interact with doxorubicin on the five pathways listed above and breast cancer recurrence and survival outcomes. These research activities will develop new methodologies and infrastructure to examine the long-term clinical effects of cancer treatment and dietary supplement interactions. Study results will also inform the design of a future R01 application to fully examine the effects of dietary supplement interactions on breast cancer clinical outcomes in the Pathways Study cohort.

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