Prospective Study of Breast Cancer Survivorship
Lawrence H. Kushi, Sc.D.
Kaiser Permanente
Division of Research
Oakland, Calif.
Funded since 2004
Despite substantial lifestyle changes, such as in diet or use of complementary
and alternative medicine (CAM) among women with breast cancer, few studies
have examined whether such factors improve prognosis. These factors also
may influence quality of life, which in turn, may influence prognosis.
How these factors influence prognosis may depend in part on molecular
characteristics, such as genetic polymorphisms that influence oxidative
damage or DNA repair, or aberrant DNA methylation which influences gene
expression. These markers may themselves influence prognosis or interact
with conventional therapies.
The investigators are addressing these gaps in knowledge by establishing
the largest prospective cohort study of women with breast cancer to date.
They are enrolling at least 5,021 women with breast cancer from Kaiser
Permanente of Northern California (KPNC). With extremely rapid case ascertainment
through computerized pathology reports, they will identify cases of breast
cancer as they are confirmed histologically and thus minimizing survival
bias. They will interview and send questionnaires to participants, and
extract data from medical charts and KPNC databases. Blood samples will
be collected prior to treatment in order to characterize genetic polymorphisms,
and tumor specimens will be obtained to examine aberrant DNA methylation.
Blood samples and breast tumor DNA also will be banked for future use.
This resource will enable study of the effects on recurrence and survival
of:
- lifestyle factors, including diet, physical activity, use of CAMs,
and quality of life; and
- host and tumor molecular characteristics, including genetic polymorphisms
(e.g., those involved in cyclophosphamide (CYP3A4, GSTP1, GSTA1) or
tamoxifen metabolism (SULTIA1); protection against oxidative damage
(MnSOD, CAT, GPX1, GSTM1, GSTT1); DNA repair (XRCC1, LIG4, XRCC3, XPD,
ERCC1, APE1); and aberrant DNA methylation of genes in breast tumors
(BRCA1, P161NK4a, E-Cadherin, glypican3, DUTT1, HIC1, TSLC1, DAP-kinase,
GSTP1).
Using proportional hazards regression, the investigators will examine
associations of lifestyle factors and molecular markers on risk of recurrence
and mortality. They estimate that at least 599 recurrences and 331 deaths
during the 5-year funding period. For survival, the investigators will
have power to detect a relative hazard of 1.64 comparing upper to lower
quartiles of continuous exposures, such as nutrient intake, and a relative
hazard of 159 for an exposure with prevalence of 0.10. This study will
provide some of the first information on these risk factors and breast
cancer prognosis.
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