Sage Gene Expression Profiles Characterizing Cure

摘要

The timing of breast cancer resection within the estrous cycle of the cycling C3H mouse and the menstrual cycle of the premenopausal woman determines to some extent whether the disease is cured in the mouse and the ten-year disease free survival of the woman. Two metaanalyses have demonstrated the positive effect of timing breast cancer resection as near to midcycle (early luteal phase) as possible. A third study has estimated this beneficial effect of surgery timing to be potentially more than two-fold greater than the positive effect of adjuvant chemotherapy. Recent editorial review demonstrates that established prognostic indicators including: tumor histopathologic grade, tumor cell proliferation markers, tumor cell estrogen and progesterone receptor content, tumor cell molecular characteristics associated with angiogenesis and tumor cell invasion and motility are more frequently ominous and more severely negative in tumors resected in the follicular as compared to the luteal phase of the patient's menstrual cycle. We hypothesize that there are characteristic patterns of tumor cell gene expression that change throughout the menstrual (estrous) cycle, and that a subset of these cycling genes are in part associated with, and responsible for the changes in curability of resected breast cancers. We used Serial Analysis of Gene Expression (SAGE) to identify hormone- responsive genes by performing comprehensive gene expression profiling of experimental mouse tumors resected during the estrus phase (when we observe a l00% cure rate) and the diestrus phase (when we observe a 35% cure rate).