Abstract
IntroductionRadiotherapy (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.MethodsIrradiations 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.ResultsThe 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.ConclusionsThese radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.
Highlights
Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer
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 with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009)
These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer
Summary
Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. The aromatase inhibitor letrozole has been shown to be superior to tamoxifen (TAM) in the first-line treatment of metastatic breast cancer [1,2]. A randomized clinical trial comparing these two drugs in the adjuvant setting is currently ongoing, and should soon provide insight into the relative efficacy of letrozole and TAM. Another adjuvant trial, the MA. study, evaluated patients from the National Cancer Institute of Canada Clinical Trials Group who were disease-free after initially being treated with 5 years of TAM and being randomized to receive either 5 years of placebo or 5 years of letrozole treatment. The present study has examined this question in vitro, using
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