Optimal combination of radiotherapy and endocrine drugs in breast cancer treatment.

PURPOSE: Breast cancer is the most common cancer in women. Radiotherapy is considered a standard treatment option after surgery and adjuvant endocrine therapy is also universally used. Tamoxifen and letrozole are the current first-line endocrine therapy drugs. However, information has been scarce about how best to sequence these therapies to maximize their effectiveness and keep toxic effects to a minimum. In this study, we observed the effect of different sequence combination of radiotherapy and endocrine drugs, tamoxifen or letrozole, to get the best treatment sequence.
MATERIALS AND METHODS: The combination effect of radiotherapy and tamoxifen was observed on breast tumour cell line MCF-7, radiotherapy and letrozole on aromatase-expressing breast tumour cell line MCF-7CA. Irradiation was performed with 6Gy, except for doses ranging from 0 to 8Gy for clone formation assay. Tamoxifen or letrozole was added before or after irradiation, respectively. Radiosensitivity was evaluated by clonogenic assay, cell viability by 3-(4,-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. To explore the potential mechanism, cell apoptosis was determined by DNA-binding dye 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) assay, the change of Bcl-2 and Bax expression was by western blot.
RESULTS: Although no significant statistical difference was observed between different sequence, tamoxifen and letrozole both increased radiosensitivity. Furthermore, the above inhibitory effect was related with apoptosis signaling pathway, especially Bcl-2 and Bax.
CONCLUSION: Taken together, these results suggested that endocrine drugs, such as tamoxifen and letrozole, have potential application with radiotherapy.