Letrozole sensitizes breast cancer cells to ionizing radiation.
BACKGROUND
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 microM) 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.
Azria
David
D
Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier, France. azria@valdorel.fnclcc.fr
Larbouret
Christel
C
Cunat
Severine
S
Ozsahin
Mahmut
M
Gourgou
Sophie
S
Martineau
Pierre
P
Evans
Dean B
DB
Romieu
Gilles
G
Pujol
Pascal
P
Pèlegrin
Andre
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018714:Radiotherapy, Adjuvant; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009570:Nitriles; D011838:Radiation-Sensitizing Agents; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase