Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale?
Endocrine therapy is often given together with postoperative radiotherapy in patients with breast cancer and positive hormone-receptor status. However, few experimental or clinical studies address the combined effects of hormone and radiation therapy. Preclinical models have shown changes in tumour cell kinetics with the addition of tamoxifen, and some show reduced tumour cell death with concurrent anti-oestrogen treatment and radiotherapy. Although data from in-vitro studies support the notion of antagonistic effects of concurrent tamoxifen and radiotherapy on tumour cells, in-vivo research suggests a synergistic effect that could be attributable to micro-environmental changes in tumour responsiveness to ionising radiation and hormone therapy. Retrospective studies suggest that in practical application, concurrent administration of tamoxifen with radiotherapy does not compromise local control but might increase toxicity. Preliminary results from simultaneous treatment with aromatase inhibitors and radiation indicate that this combination of endocrine and radiation therapy could enhance cytotoxicity and improve tumour response. Further studies are needed to clarify the physiological mechanisms activated by oestrogens, which will allow a more thorough understanding of the complex interactions between 17beta-oestradiol and P53/P21(WAF1/CIP1)/Rb pathways and of the interaction between endocrine therapy and radiotherapy.
Chargari
Cyrus
C
Department of Radiotherapy, Institut Gustave Roussy, Villejuif, France.
Toillon
Robert Alain
RA
Macdermed
Dhara
D
Castadot
Pierre
P
Magné
Nicolas
N
D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D003131:Combined Modality Therapy; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D011836:Radiation Tolerance; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000502:physiology
D047072:Aromatase Inhibitors; D020845:Selective Estrogen Receptor Modulators; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D004958:Estradiol