- Title
- HER2 status predicts for upfront AI benefit: a TRANS-AIOG meta-analysis of 12,129 patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2
- Creator
- Bartlett, John M. S.; Ahmed, Ikhlaaq; Brookes, Cassandra L.; Forbes, John F.; Viale, Giuseppe; Cuzick, Jack; Dowsett, Mitchell; Rea, Daniel W.; Regan, Meredith M.; Sestak, Ivana; Mallon, Elizabeth A.; Dell'Orto, Patrizia; Thürlimann, Beat; Seynaeve, Caroline; Putter, Hein; Van de Velde, Cornelis J. H.
- Relation
- European Journal of Cancer Vol. 79, Issue July, p. 129-138
- Publisher Link
- http://dx.doi.org/10.1016/j.ejca.2017.03.033
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2017
- Description
- Background: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. Methods: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs. Results: A prospectively planned, patient-level data meta-analysis across 3 trials demonstrated a significant treatment (AI versus tamoxifen) by marker (HER2) interaction in a multivariate analysis; (interaction hazard ratio [HR] = 1.61, 95% CI 1.01-2.57; p < 0.05). Heterogeneity between trials did not reach statistical significance. The HER2 negative (HER2-ve) group gained greater benefit from AI versus tamoxifen (HR = 0.70, 95% CI 0.56-0.87) than the HER2-positive (HER2+ve) group (HR = 1.13, 95% CI 0.75-1.71). However, the small number of HER2+ve cases (n = 1092 across the 3 trials) and distant recurrences (n = 111) may explain heterogeneity between trials. Conclusions: A patient-level data meta-analysis demonstrated a significant interaction between HER2 status and treatment with AI versus tamoxifen in the first 2-3 years of adjuvant endocrine therapy. Patients with HER2-ve cancers experienced improved outcomes (distant relapse) when treated with upfront AI rather than tamoxifen, whilst patients with HER2+ve cancers fared no better or slightly worse in the first 2-3 years. However, the small number of HER2+ve cancers/events may explain a large degree of heterogeneity in the HER2+ve groups across all 3 trials. Other causes, perhaps related to subtle differences between AIs, cannot be excluded and warrant further exploration.
- Subject
- breast cancer; HER2; prediction; aromatase inhibitor; meta-analysis
- Identifier
- http://hdl.handle.net/1959.13/1396636
- Identifier
- uon:34088
- Identifier
- ISSN:0959-8049
- Language
- eng
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