Pharmacogenetic Approach to Toxicity in Breast Cancer Patients Treated with Taxanes

Silvia Angelini; Andrea Botticelli; Concetta Elisa Onesti; Raffaele Giusti; Valentina Sini; Valeria Durante; Lidia Strigari; Giovanna Gentile; Bruna Cerbelli; Patrizia Pellegrini; Valentina Sgroi; Mario Occhipinti; Francesca Romana DI Pietro; Alessandro Rossi; Maurizio Simmaco; Federica Mazzuca; Paolo Marchetti

doi:10.21873/anticanres.11610

Pharmacogenetic Approach to Toxicity in Breast Cancer Patients Treated with Taxanes

Anticancer Res. 2017 May;37(5):2633-2639. doi: 10.21873/anticanres.11610.

Authors

Silvia Angelini^{1

2}, Andrea Botticelli¹, Concetta Elisa Onesti^{3

2}, Raffaele Giusti², Valentina Sini^{1

4}, Valeria Durante^{1

2}, Lidia Strigari⁵, Giovanna Gentile⁶, Bruna Cerbelli⁷, Patrizia Pellegrini², Valentina Sgroi^{1

2}, Mario Occhipinti^{1

2}, Francesca Romana DI Pietro^{1

2}, Alessandro Rossi⁸, Maurizio Simmaco⁹, Federica Mazzuca^{1

2}, Paolo Marchetti^{1

2

6}

Affiliations

¹ Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
² Department of Medical Oncology, Sant'Andrea Hospital, Rome, Italy.
³ Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy elisaonesti@gmail.com.
⁴ Santo Spirito Hospital, Lungotevere in Saxia, Rome, Italy.
⁵ Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.
⁶ Dermopatic Institute of the Immacolata IDI-IRCSS, Rome, Italy.
⁷ Department of Radiological Oncological and Pathological Sciences, "Sapienza" University of Rome, Rome, Italy.
⁸ Faculty of Medicine and Psychology, Sapienza" University of Rome, Rome, Italy.
⁹ Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), "Sapienza" University of Rome, Rome, Italy.

PMID: 28476838
DOI: 10.21873/anticanres.11610

Abstract

Background: Taxanes are widely used to treat breast cancer patients. Taxanes are metabolized in human liver by the cytochrome CYP3A and are substrate of ATP-binding cassette multidrug transporters ABCB1. Single-nucleotide polymorphisms (SNPs) in genes involved in taxanes' metabolism could affect the inter-individual variability in reported toxicities.

Materials and methods: In this retrospective study, 152 women, affected by breast cancer and receiving a taxane-based chemotherapy, were enrolled. A peripheral blood sample was taken for genotyping the following polymorphisms: CYP3A4* 1B (A>G), CYP3A5 *3 (G>A) and ABCB1 (C1236T; C3435T).

Results: We observed an association between ABCB1 3435 T/T and lower grade of toxicities (p=0.05). No other association were found for CYP 3A4 *1B, 3A5*3 and ABCB1 C1236T.

Conclusion: ABCB1 3435 T/T seems to be associated to lower rate of toxicity in patients receiving taxanes. Further prospective and larger studies should be performed to clarify the role of this polymorphism.

Keywords: ABCB1; Breast cancer; P-gp; cytochrome P450; polymorphisms; taxanes.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
Adult
Aged
Aged, 80 and over
Antineoplastic Agents / adverse effects*
Antineoplastic Agents / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics*
Cytochrome P-450 CYP3A / genetics
Female
Genotype
Humans
Middle Aged
Pharmacogenetics
Polymorphism, Single Nucleotide
Taxoids / adverse effects*
Taxoids / therapeutic use

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
Antineoplastic Agents
Taxoids
CYP3A5 protein, human
Cytochrome P-450 CYP3A
CYP3A4 protein, human