Abstract
9559 Background: Data from the ATAC & IES trials suggest that differences exist in the molecular profile of patients who response to early or delayed treatment with aromatase inhibitors. PR-ve patients derived greater benefit from initial aromatase inhibitor treatment compared to tamoxifen (ATAC) than those treated after 2–3 years tamoxifen (IES). We show that HER1–3 positive/PR negative patients are significantly more likely to relapse on tamoxifen treatment at an early stage but that HER/PR status has no impact on the likelihood of later recurrences. Methods: 402 ER+ve surgical patients treated between 1983–1999 who received adjuvant tamoxifen and adjuvant chemo/radiotherapy according to protocols at the time. IHC staining for EGFR, HER2 and HER3 & PR was performed and scored using the Herceptest or Histoscore method. Statistical calculations were performed using Kaplan-Meier log rank testing of breast cancer related relapse on tamoxifen over 2 time periods; throughout the duration of tamoxifen (ATAC) treatment or after 3 years of tamoxifen therapy (IES). Results: Both HER1–3+ve (28%) and PR-ve (37.9%) patients demonstrated increased relapse rates on tamoxifen (p=0.0060 and p=0.0017 respectively). Patients PR-ve and/or HER1–3+ve (53%) were significantly more likely to relapse on tamoxifen in univariate analysis (p<0.0001) and in Cox multivariate regression analysis, along with nodal status, grade and size (p=0.0026). However in patients who survived 3 years of tamoxifen (as in the IES study) no significant effect of PR/HER1–3 expression on recurrence rates in univariate (p=0.09) or multivariate analysis was observed p=0.2478). Conclusions: This data suggests that HER1–3 and PR are time dependent variables related to breast cancer recurrence. Critically, these results may be invoked to explain the observed differences in the predictive value of PR, and potentially HER1–3 expression between the ATAC and IES studies and to predict when to implement AI treatment. In ATAC ER+ve/PR-ve cases showed higher rates of relapse on tamoxifen vs AIs a finding not repeated in the IES study which randomised patients surviving 3 years tamoxifen. This hypothesis could be tested in the remodelled TEAM study in the near future. No significant financial relationships to disclose.
Published Version
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