The primary ER screen was performed using dsRNAs transcribed in vitro from a second generation RNAi library (HD2; [67]).
110 genes that were scored as positive, unclear or not determined in the primary ER screen were re-tested in a second screening set-up with the same dsRNAs that were used in the first screen (Figure 1; Table S1).
Hence, it is becoming clearer that PIK3CA mutations are associated with better outcomes in primary ER-positive disease.
Trial data show that the partial ER agonist tamoxifen and other ER modulators such as raloxifene [ 98] reduce the incidence of primary ER-positive breast cancer [ 3, 99].
This suggests that oxidative stress, and its effects on E/ER signaling, contributes to the development of an aggressive subset of primary ER-positive breast cancers.
However, about one-third of primary ER-positive breast tumors do not benefit from adjuvant tamoxifen treatment, resulting in disease recurrence [ 5].
Two examples of paired aCGH profiles are shown in Figure 2. In Figure 2A, both the primary ER positive tumor and the xenograft displayed a slightly altered profile.
We asked whether methylation of the NT5E CpG island in primary ER-positive cases was associated with loco-regional and/or distant metastatic relapse.
Taken together, these findings suggest that Sox2 expression in primary ER-positive tumours may be a clinical prognostic biomarker for tamoxifen resistance.
All patients were postmenopausal women presenting to the Edinburgh Breast Unit with large primary ER-rich (Allred score > 5) breast cancers but without evidence of distant metastatic disease.
