Abstract

Abstract BACKGROUND Breast cancer patients treated with adjuvant endocrine therapy commonly experience weight gain, which has been associated with low adherence to therapy and worse breast cancer prognosis. Dietary interventions are the first-line treatment for weight management in breast cancer patients and have beneficial results. Yet, the ability to maintain these outcomes requires further research. Here, we aimed to assess whether a personalized postprandial glucose targeting (PPT) diet is beneficial for weight management and metabolic health as compared with the recommended Mediterranean (MED) diet in this population. DESIGN AND METHODS BREACPNT is a phase-2 randomized trial in HR+ patients with breast cancer, treated with adjuvant endocrine therapy. We randomly assigned participants to follow a MED diet or a PPT diet for a 6-month dietary intervention and additional 6-month follow-up. The PPT diet is based on a machine-learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGRs). During the intervention, participants were monthly followed by a registered dietitian, they were additionally connected to a 2-week continuous glucose monitoring (CGM) on 3-timepoints, provided stool and blood samples and self-reported dietary intake using a smartphone application. RESULTS Among 127 randomized patients (mean ± SD age 53 ± 10 years, BMI 28.6 ± 5 kg/m2), 103 (81%) completed the 6-month intervention period. A total of 94 participants provided 12-month follow-up data. Both interventions led to a significant weight loss. The PPT-diet showed numerically greater weight loss with median change of -1.45kg (IQR -3.75 – 0) compared to the MED-diet with median change of -1kg (IQR -3.2 - 0.1) , however this was not significant (p=0.9). Notably, at the 12-month time point , participants in the PPT arm were more likely to maintain the weight loss (median -1.2kg, IQR -4 - 0.1) compared to participants in the MED-arm (median -0.15kg , IQR -4.25 - 1.5), p=0.14) and had significantly improved waist circumference (median, IQR; -5 cm, -8-(-2) in the PPT arm, compared to -1cm, -6.5-3 in the MED arm, p=0.01). In terms of glucose metabolism the PPT-diet led to improved glycemic control as measured by CGM, with significant lower average postprandial glucose responses (PPGRs) and glucose coefficient of variation (CV) compared to the MED-diet arm (mean 6-month change in PPGR was 2.1 ± 7.5 mg/dL × h for MED and −3.4 ± 5.6 mg/dL × h for PPT, p< 0.001, and the 6-month mean change for CV was 0.15 ± 2.76 for MED and −1.37 ± 3.2 for PPT, p< 0.01). Within the entire cohort, participants who experienced the greatest weight loss (upper quartile) were more likely to be postmenopausal compared to participants in the lower quartile. Additionally, participants who did not achieve weight loss (lower quartile) were significantly more likely to be treated with tamoxifen than AI (p=0.015). CONCLUSIONS In this dietary intervention in HR+ breast cancer patients, both PPT diet and MED diet led to weight loss and improved food quality, with a slight advantage to PPT diet. PPT diet additionally improved glycemic features as compared to MED diet, which are linked to lower risk of obesity and disease recurrence, suggesting an advantage in a glucose targeting approach. Premenopausal and Tamoxifen treated patients were less likely to lose weight through the intervention. These findings may have implications for dietary advice in clinical practice. Citation Format: Michal Rein, Maya Dadiani, Anastasia Godneva, Michal Bakalenik-Gavry, Dana Morzaev-Sulzbach, Maya Lotan-Pompan, Adina Weinberger, Eran Segal, Einav Gal-Yam. BREAst Cancer Personalized NuTrition (BREACPNT): dietary intervention in HR+ breast cancer patients treated with endocrine therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-02.

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