Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included prospectively planned biomarker studies to identify prognostic and predictive biomarkers for patients receiving endocrine therapy. Quantitative IHC data for ER/PgR (Can Res 69:83S, SABCS2008), HER2, HER3 and Ki67 was available for the current analysis relative to outcome of estrogen receptor–positive (ER+) early postmenopausal breast cancer (BC) patients treated with exemestane versus tamoxifen.Patients & Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. Quantitative analysis of hormone receptors (HER2/3) by conventional IHC, and image analysis derived continuous scores for Ki67/ER/PgR were analyzed relative to disease-free survival and treatment on an intent to treat basis using survival data for the first 2.75 years of the TEAM trial. Data on HER2FISH and EGF Receptor IHC will be presented.Results: Of 4595 eligible cases samples received, 16 were excluded, 271 had incomplete biomarker data, leaving 4308 patients for the final biomarker analysis. 1275 (30%) cases were HER2/3 positive.A significant treatment by marker effect was observed for exemestane versus tamoxifen with HER2/3 negative cases deriving benefit from aromatase inhibitor treatment (HER2/3-ve HR=0.69 95%CI, 0.53-0.88; HER2/3 pos HR, 1.13; 95%CI, 0.82–1.55; p=0.016 for interaction in multivariate analysis). By conventional and STEPP analysis no predictive effect of Ki67 was observed. In multivariate regression analysis increased HER2 expression (P=0.0001) decreased PgR expression (P<0.0001) and increased percentage of Ki67 positive cells (P=0.004) as continuous IHC variables were independently prognostic as were size (P=0.0001), nodal status (P<0.0001), grade (P=0.03) and age (P<0.0001).Conclusion: Multiple biological parameters (HER2/PgR/Ki67) are independently prognostic in ER+ve early postmenopausal BC. Modelling will be explored to derive prognostic and potentially predictive biomarker signatures for application in BC. Preferential exemestane versus tamoxifen treatment benefit was seen in HER2/3 negative cases, whilst HER2/3 positive cases had a poor prognosis in this population receiving hormonal therapy (suggesting resistance to endocrine therapy), and no evidence of benefit from AIs versus tamoxifen. Type I receptor tyrosine kinases may identify breast cancers with relative resistance to all forms of endocrine therapy. Whilst Ki67 alone was not predictive of benefit from Ais, Ki67, HER2 and PgR were independent prognostic variables and modelling of predictive/prognostic effects may further inform treatment selection in early postmenopausal breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 75.
Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial identified quantitative relationships between ER/PgR (Can Res 69:83S) and patient prognosis, and suggested that high ER expression might be predictive for benefit from aromatase inhibitors. Conventional immunohistochemical assays, even when performed centrally, appear to be more variable than fluorescent immunohistochemical assays analysed by automated image analysis such as the AQUA system. However, output from the two systems may provide subtly different results for biomarkers. We have performed analysis of ER/PgR using AQUA technology in the TEAM pathology cohort and will present data on the full anlaysis of ER/PgR by central IHC and AQUA in 4600 cases. Preliminary data on ER (using a single TMA core) are included in the current analysis.Patients & Methods: TMAs from 4598 TEAM patients were analysed by AQUA and image analysis using established algorithms performed. Comparisons between IHC and AQUA were performed and outcome data will be analysed and presented.Results: Interim AQUA results from a single core were available from 2319 TEAM cases. Analysis of results suggested incremental increases in AQUA scores across conventional Allred categories (2-8). Regression analysis suggests that multiple cores may be required adequate representation of ER expression. PgR data will be presented.Conclusion: Initial comparison between AQUA and ER expression by central IHC suggests these methods are comparable. Further data is required to assess the potential value of AQUA scores and will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3045.
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