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

• Published in: European journal of cancer (1990) 2017-07, Vol.79, p.129-138
• Main Authors: Bartlett, John M.S, Ahmed, Ikhlaaq, Regan, Meredith M, Sestak, Ivana, Mallon, Elizabeth A, Dell'Orto, Patrizia, Thürlimann, Beat, Seynaeve, Caroline, Putter, Hein, Van de Velde, Cornelis J.H, Brookes, Cassandra L, Forbes, John F, Viale, Giuseppe, Cuzick, Jack, Dowsett, Mitchell, Rea, Daniel W
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents, Hormonal - therapeutic use; Aromatase; Aromatase inhibitor; Aromatase Inhibitors - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - surgery; Chemotherapy, Adjuvant - methods; Clinical trials; Clinical Trials, Phase III as Topic; Data analysis; Data processing; Drug Substitution; Endocrine therapy; ErbB-2 protein; Female; Fluorescence; Fluorescence in situ hybridization; Hematology, Oncology and Palliative Medicine; HER2; Heterogeneity; Humans; Immunohistochemistry; Mastectomy - statistics & numerical data; Meta-analysis; Middle Aged; Multicenter Studies as Topic; Multivariate analysis; Nitriles - therapeutic use; Patients; Prediction; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Statistical analysis; Statistics; Tamoxifen; Tamoxifen - therapeutic use; Therapy; Treatment Outcome; Triazoles - therapeutic use
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.03.033

Abstract 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