Research article

Letrozole sensitizes breast cancer cells to ionizing radiation

David Azria^1*, Christel Larbouret², Severine Cunat³, Mahmut Ozsahin⁴, Sophie Gourgou⁵, Pierre Martineau⁶, Dean B Evans⁷, Gilles Romieu⁸, Pascal Pujol³ and Andre Pèlegrin²

• * Corresponding author: David Azria azria@valdorel.fnclcc.fr

Author Affiliations

¹ Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier, France

² INSERM EMI0227, CRLC Val d'Aurelle, Montpellier, France

³ INSERM U 540, Montpellier, France

⁴ Department of Radiation Oncology, Lausanne, Switzerland

⁵ Biostatistics Unit, CRLC Val d'Aurelle, Montpellier, France

⁶ Centre for Pharmacology and Health Biotechnology, CNRS, Montpellier, France

⁷ Novartis Pharma AG, Basel, Switzerland

⁸ Department of Medical Oncology, CRLC Val d'Aurelle, Montpellier, France

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Breast Cancer Res 2005, 7:R156-R163 doi:10.1186/bcr969

Published: 7 December 2004

Abstract

Introduction

Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene.

Methods

Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry.

Results

The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G₂ phase arrest and a decrease of cells in the S phase, with cell redistribution in the G₁ phase.

Conclusions

These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.