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ARTICLE

Bevacizumab and Paclitaxel in Advanced, Hormone Receptor-Positive Breast Cancer: Multifactor Dimensionality Reduction Methodology to Identify Best Overall Survival

Luigi Coltelli1,2,#, Paola Orlandi3,#, Chiara Finale1,4,#, Gianna Musettini1,4,#, Luna Chiara Masini1,4, Marco Scalese5, Giulia Soria1,4, Elena Sartori1,4, Ylenia Nodari1,4, Giada Arrighi1,2, Arianna Bandini3, Marta Banchi3, Costanza Tacchi3, Donghao Tang3, Barbara Salvadori6, Lucia Tanganelli1,7, Simona Giovannelli1,8, Mirco Pistelli9, Samanta Cupini1,4, Maurizio Lucchesi1,10, Alessandro Cosimi11, Giulia Lorenzini1,7, Elisa Biasco1,4, Chiara Caparello1,4, Giulia Acconci1,4,6, Eloise Fontana1,4, Eleonora Bona1,4, Azzurra Farnesi1,4, Antonio Pellino1,4, Andrea Marini1,4, Ermelinda De Maio1,4, Irene Stasi1,4, Cecilia Barbara1,4, En
1 Department of Oncology, Azienda USL Toscana Nord Ovest, Livorno, Italy
2 Division of Medical Oncology, Pontedera Hospital, Azienda USL Toscana Nord Ovest, Pontedera, Italy
3 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
4 Division of Medical Oncology, Livorno Hospital, Azienda USL Toscana Nord Ovest, Livorno, Italy
5 Institute of Clinical Physiology, Italian National Research Council—CNR, Pisa, Italy
6 Division of Medical Oncology II, Azienda Ospedaliero-Universitaria Pisana, S. Chiara Hospital, Pisa, Italy
7 Division of Medical Oncology, Versilia Hospital, Azienda Usl Toscana Nord Ovest, Lido di Camaiore, Italy
8 Division of Medical Oncology, San Luca Hospital, Azienda Usl Toscana Nord Ovest, Lucca, Italy
9 Division of Medical Oncology, Umberto I Salesi-Lancisi Hospital, Azienda Ospedaliero-Universitaria Umberto I, Ancona, Italy
10 Division of Medical Oncology, Apuane Hospital, Azienda Usl Toscana Nord Ovest, Massa e Carrara, Italy
11 SC Screening, Azienda USL Toscana Sud Est, Siena, Italy
12 Department of Internal Medicine, Azienda USL Toscana Nord Ovest, Livorno, Italy
13 Division of Internal Medicine, Livorno Hospital, Azienda USL Toscana Nord Ovest, Livorno, Italy
* Corresponding Author: Giacomo Allegrini. Email: email; Guido Bocci. Email: email
# These authors contributed equally to this work as the first author

Oncology Research https://doi.org/10.32604/or.2026.073799

Received 25 September 2025; Accepted 30 January 2026; Published online 13 February 2026

Abstract

Background: The treatment of advanced hormone receptor-positive (HR+) breast cancer has seen relevant changes in last years. However, bevacizumab remains an option when combined with paclitaxel, but no certified pharmacogenetic profiles are now usable for the prediction of its response in breast cancer patients. This study aimed to explore the pharmacogenetic interactions among single nucleotide polymorphisms (SNPs) of genes involved in the angiogenic process and their impact on progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+) metastatic breast cancer subjects administered with bevacizumab plus paclitaxel, or with paclitaxel alone (clinicaltrial.gov identifier NCT01935102). Methods: Germline DNA extracted from blood samples was analyzed using real-time polymerase chain reaction to investigate SNPs. The multifactor dimensionality reduction (MDR) analysis was employed to assess interactions between these genetic variants. A total of 168 eligible patients were analyzed. Among these, 106 patients received both paclitaxel and bevacizumab, while 62 received paclitaxel alone. Results: In the combination therapy group, MDR analysis identified two pharmacogenetic interaction profiles involving specific genotypes of vascular endothelial growth factor-A(VEGF-A) rs833061 and vascular endothelial growth factor receptor-2 (VEGFR-2) rs1870377. Patients with a favorable genetic profile had a median PFS (mPFS) of 22.9 months, compared to 8.7 months in those with an unfavorable profile (p = 0.001). Cox proportional hazards analysis displayed an adjusted hazard ratio of 0.443 (95% CI: 0.284–0.691; p < 0.0001). The median OS (mOS) was 50.2 months for the favorable profile vs. 23.5 months for the unfavorable (p = 0.003), with an adjusted hazard ratio (HR) of 0.404 (95% CI: 0.249–0.657; p < 0.0001). In the 62 subjects administered with just paclitaxel, no significant differences in PFS (p = 0.820) or OS (p = 0.143) were observed between favorable and unfavorable genetic profiles. Conclusions: The MDR analysis of VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes can detect a subgroup of bevacizumab-administered+ metastatic breast cancer patients with improved PFS and OS.

Keywords

Single nucleotide polymorphisms; vascular endothelial growth factor-A; VEGF receptor-2; bevacizumab; paclitaxel; advanced breast cancer; angiogenesis; pharmacogenetic interaction analysis

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