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Impact of BMI on the Outcome of Metastatic Breast Cancer Patients Treated with Everolimus: a Retrospective Exploratory Analysis of the BALLET Study

Abstract

Introduction: Reliable biomarkers of response to mTOR inhibition are yet to be identified. As mTOR is heavily implicated in cell-metabolism, we investigated the relation between BMI variation and outcomes in metastatic breast cancer (mBC) patients treated with everolimus.

Results: we found a linear correlation between everolimus exposure duration and BMI/weight decrease. Patients exhibiting >2 kg weight loss or >3% BMI decrease from baseline at the end of treatment (EOT) had a statistically significant improvement in PFS. Interestingly, a similar BMI/weight decrease within the first 8 weeks of therapy identified patients at higher risk of progression.

Patients And Methods: we performed a retrospective analysis of patients enrolled in the BALLET trial who progressed during the study. Primary end-point was progression-free survival (PFS). Secondary end-point was the identification of other predictors of response.

Conclusion: A >3% weight loss at EOT is associated with better outcome in mBC patients treated with everolimus. On the contrary, a significant early weight loss represents a predictor of poor survival and could therefore be used as an early negative prognostic marker. As PI3K-inhibition also converges onto mTOR, these findings might extend to patients treated with selective PI3K inhibitors and warrant further investigation.

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References
1.
Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo H . Alpelisib for -Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019; 380(20):1929-1940. DOI: 10.1056/NEJMoa1813904. View

2.
Fox K, Brooks J, Gandra S, Markus R, Chiou C . Estimation of Cachexia among Cancer Patients Based on Four Definitions. J Oncol. 2009; 2009:693458. PMC: 2705834. DOI: 10.1155/2009/693458. View

3.
Martin L, Senesse P, Gioulbasanis I, Antoun S, Bozzetti F, Deans C . Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2014; 33(1):90-9. DOI: 10.1200/JCO.2014.56.1894. View

4.
Robert F, Mills J, Agenor A, Wang D, DiMarco S, Cencic R . Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival. Cancer Res. 2011; 72(3):747-56. DOI: 10.1158/0008-5472.CAN-11-2739. View

5.
Miller T, Hennessy B, Gonzalez-Angulo A, Fox E, Mills G, Chen H . Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010; 120(7):2406-13. PMC: 2898598. DOI: 10.1172/JCI41680. View