http://breast-cancer-research.com/co...df/bcr2120.pdf
I know this can be tough reading, so, in an effort to help extract the information that is most meaningful to us, I direct your attention to pages 21 and 22 of the paper. The discussion focuses on the loss of PR function in ER+ bc, as well as the effect of Her2+:
" . . . oxident suppressed E/ER regulated genes identified from ER overexpressing MCF7, were suppresed in ER+/PR- tumors relative to ER+/PR+ tumors, suggesting that loss of PR expression might be a partial surrogate for increased oxidative stress. . . Recent evidence also indicates that ERBB2 overexpression is associated with loss of PR co-expression in ER+ breast cancers. Although suppression of oxidant-repressed genes was not shown to be associated with ERBB2 overexpression, there was an enrichment of oxidant-induced genes among ERBB2 overexpressing ER+ breast tumors, suggesting that elevated oxidative stress is associated with ERBB2 overexpression and may contribute to the loss of PR co-expression seen in ERBB2 overexpressing ER+ breast cancers. . . ER+/PR- breast cancers express significantly higher levels of proliferation genes relative to ER+/PR+ tumors. Proliferation genes were also expressed at higher levels in the ERBB2 overexpressing tumors relative to ERBB2-negative tumors. The observed associations between tumors bearing higher proliferation and oxidative stress signatures are consistent with numerous past observations that mitogenic signaling pathways generate and require increased ROS" (reactive oxygen species - critical mediators of growth factor receptor signaling and estrogen inducible cell proliferation).
Hopeful
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