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Introduction <p>Taxanes are drugs commonly used in the treatment of breast cancer. Despite their proven therapeutic efficacy, they can induce severe toxicities, which can be investigated by pharmacogenomics. In this context, the aim of this study was to investigate 26 molecular biomarkers in 17 pharmacogenes (CYP2C8, ABCB1, CYP1A1, CYP1B1, CYP19A1, CYP3A5, ERCC1, ERBB2, VEGFA, ERCC2, MDM2, MTHFR, RAD51, SOD2, TP53, TANC1 and XRCC1), in women with Breast Cancer undergoing Taxane treatment in the Brazilian Amazon region.</p> Methods <p>This study was carried out with 279 women diagnosed with BC, undergoing antineoplastic chemotherapy treatment based on Taxanes (Docetaxel and Paclitaxel), in Brazilian Amazon region. 26 pharmacogenetic markers located in 17 genes involved in the metabolic pathway of Taxanes and related toxicities were selected. Single nucleotide variants were genotyped by allelic discrimination using TaqMan OpenArray Genotyping technology. </p> Results <p>The study population showed significant associations of Taxane toxicities with ten variants of nine genes: CYP1A1, CYP19A1, CYP3A5, ERCC1, VEGFA, ERCC2, MTHFR, TANC1 and XRCC1. Notably, variants in TANC1 and XRCC1, previously associated with radiotoxicity, were also implicated in Taxane-induced toxicities. The study demonstrated that novel biomarkers may be important for investigating Taxane-induced toxicities in breast cancer. </p> Conclusions <p>These findings represent a unique contribution to the field, potentially enabling more precise chemotherapy selection, particularly for populations such as Amazonian women.</p>

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Novel molecular biomarkers associated with Taxane-induced toxicities in women with breast cancer from the Brazilian Amazon

  • 期刊论文

  • 发表日期：

    2025年11月1日

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  • Marta Solange Camarinha Ramos Costa,
  • Ana Caroline Alves da Costa,
  • Esdras Edgar Batista Pereira,
  • Diana Feio da Veiga Borges Leal,
  • Antônio André Conde Modesto,
  • Elisa da Silva Menezes,
  • Rita de Cássia Calderaro Coelho,
  • Sidney Emanuel Batista dos Santos,
  • Marianne Rodrigues Fernandes,
  • Ney Pereira Carneiro dos Santos

摘要

Introduction

Taxanes are drugs commonly used in the treatment of breast cancer. Despite their proven therapeutic efficacy, they can induce severe toxicities, which can be investigated by pharmacogenomics. In this context, the aim of this study was to investigate 26 molecular biomarkers in 17 pharmacogenes (CYP2C8, ABCB1, CYP1A1, CYP1B1, CYP19A1, CYP3A5, ERCC1, ERBB2, VEGFA, ERCC2, MDM2, MTHFR, RAD51, SOD2, TP53, TANC1 and XRCC1), in women with Breast Cancer undergoing Taxane treatment in the Brazilian Amazon region.

Methods

This study was carried out with 279 women diagnosed with BC, undergoing antineoplastic chemotherapy treatment based on Taxanes (Docetaxel and Paclitaxel), in Brazilian Amazon region. 26 pharmacogenetic markers located in 17 genes involved in the metabolic pathway of Taxanes and related toxicities were selected. Single nucleotide variants were genotyped by allelic discrimination using TaqMan OpenArray Genotyping technology.

Results

The study population showed significant associations of Taxane toxicities with ten variants of nine genes: CYP1A1, CYP19A1, CYP3A5, ERCC1, VEGFA, ERCC2, MTHFR, TANC1 and XRCC1. Notably, variants in TANC1 and XRCC1, previously associated with radiotoxicity, were also implicated in Taxane-induced toxicities. The study demonstrated that novel biomarkers may be important for investigating Taxane-induced toxicities in breast cancer.

Conclusions

These findings represent a unique contribution to the field, potentially enabling more precise chemotherapy selection, particularly for populations such as Amazonian women.