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Войти в исследования European journal of cancer (Oxford, England : 1990) · 2026
Body mass index in postmenopausal women with estrogen receptor-positive, HER2-negative early breast cancer: An exploratory analysis of the LORELEI trial.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Dauccia Chiara, Franzoi Maria Alice, Saura Cristina, Hlauschek Dominik, Sölkner Lidija, Gnant Michael, Dubsky Peter C, Helfgott Ruth, Zoppoli Gabriele, Oliveira Mafalda, Collet Laetitia, Fredrickson Jill, Wilson Timothy R, Arecco Luca, Agostinetto Elisa, de Azambuja Evandro
Аннотация
BACKGROUND: Phosphoinositide 3-kinase (PI3K) pathway, involved in obesity-related signalling, may influence efficacy and toxicity of PI3K inhibitors (PI3Ki). We explored associations between body mass index (BMI) and objective response rate (ORR), safety, molecular features, and breast density in the LORELEI trial.
METHODS: LORELEI (NCT02273973) was a randomized trial evaluating neoadjuvant PI3Ki taselisib plus letrozole vs placebo plus letrozole in patients with estrogen receptor-positive/HER2-negative early breast cancer. Patients were classified as normal weight (BMI 18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (≥30 kg/m²). Logistic regression tested BMI by treatment arm, adverse events were analysed descriptively by BMI category. Immune composition and gene expression profiles were evaluated by RNA sequencing.
RESULTS: Of 329 patients, 98 (29.8%) were classified as normal weight, 125 (38%) as overweight, and 106 (32.2%) as obese. In the placebo arm, higher BMI was associated with lower ORR [odds ratio (OR) 0.90, 95% CI 0.83-0.97]; no association was observed in the taselisib arm [OR 1.03, 95% CI 0.96-1.11; interaction p = 0.007 (unadjusted), p = 0.013 (adjusted)]. In patients with obesity the incidence of hyperglycaemia and diarrhoea was 15.1% and 24.5%, respectively. Higher levels of pS6, a downstream effector of the PI3K pathway, were associated with increased ORR in patients with obesity in the placebo arm (interaction p = 0.011). Patients with obesity had lower baseline breast density (p < 0.001), not associated with ORR. Obesity was associated with increased IL6 expression, immune cell infiltration, and fatty acid metabolism signature.
CONCLUSIONS: Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib.
METHODS: LORELEI (NCT02273973) was a randomized trial evaluating neoadjuvant PI3Ki taselisib plus letrozole vs placebo plus letrozole in patients with estrogen receptor-positive/HER2-negative early breast cancer. Patients were classified as normal weight (BMI 18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (≥30 kg/m²). Logistic regression tested BMI by treatment arm, adverse events were analysed descriptively by BMI category. Immune composition and gene expression profiles were evaluated by RNA sequencing.
RESULTS: Of 329 patients, 98 (29.8%) were classified as normal weight, 125 (38%) as overweight, and 106 (32.2%) as obese. In the placebo arm, higher BMI was associated with lower ORR [odds ratio (OR) 0.90, 95% CI 0.83-0.97]; no association was observed in the taselisib arm [OR 1.03, 95% CI 0.96-1.11; interaction p = 0.007 (unadjusted), p = 0.013 (adjusted)]. In patients with obesity the incidence of hyperglycaemia and diarrhoea was 15.1% and 24.5%, respectively. Higher levels of pS6, a downstream effector of the PI3K pathway, were associated with increased ORR in patients with obesity in the placebo arm (interaction p = 0.011). Patients with obesity had lower baseline breast density (p < 0.001), not associated with ORR. Obesity was associated with increased IL6 expression, immune cell infiltration, and fatty acid metabolism signature.
CONCLUSIONS: Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib.