ER ER ER ER - Endocrine Reviews

overexpression of HER family receptors (EGFR and/or HER2 and/or HER3) and
tamoxifen outcome has recently been shown in two additional independent datasets of
patients treated with adjuvant tamoxifen (112, 113).
At present there are no clear outcome data related to HER2 status from adjuvant trials of
aromatase inhibitors. Data on the influence of HER2 status on the relative benefits of
tamoxifen and the AI letrozole as adjuvant therapy in the Breast International Group
(BIG) 1-98 trial (114, 115) are, therefore, of considerable interest. Both preliminary and
updated reports indicated that HER2-positive status was associated with significantly
higher relapse rate in the BIG 1-98 trial, regardless of whether letrozole or tamoxifen was
used. Additional studies are currently underway to determine the significance of HER2
status in the large randomized adjuvant ATAC trial comparing the AI anastrozole, the
SERM tamoxifen, and the combination (116).
Neoadjuvant trials conducted in women with locally advanced breast cancer prior to
surgery provide a unique opportunity to integrate the molecular determinants of response
and resistance with the clinical response of primary breast cancer to medical therapy.
Results in the neoadjuvant setting are less controversial and provide solid evidence for
the role of HER2 and to a lesser extent of EGFR in tamoxifen resistance (Table 1). Ellis
and associates, in a neoadjuvant study that randomized for treatment with the AI letrozole
vs. tamoxifen, provided a context to study in further detail the relationship between
EGFR and HER2 expression and response to aromatase inhibitors vs. tamoxifen (117). In
this report, biopsy-confirmed ER-positive and/or progesterone receptor (PgR)-positive
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