Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer.
Breast cancer is the most common malignancy and the second most common cause of cancer-related death in women. Endocrine therapy has been used for more than a century to treat advanced-stage breast cancer. The results obtained with the third-generation aromatase inhibitor letrozole demonstrated an actual improvement in patient outcome compared with tamoxifen. This benefit translates into disease-free survival improvement for adjuvant treatment and overall survival in patients with metastatic disease. The present clinical situation of hormonal therapy is stable; however, recently, new anticancer agents (temsirolimus and everolimus) that inhibit mammalian target of rapamycin protein kinase have been developed and seem to be very promising because of their synergistic activity with letrozole. The phase II study of a combination of temsirolimus or everolimus with letrozole demonstrated a better progression-free survival in the combination arm than in the letrozole alone arm. Consequently, the results of ongoing phase III studies are eagerly awaited.
Chollet
Philippe
P
Centre Jean Perrin, Bureau de Recherche Clinique, 58 rue Montalembert, BP 392, 63011 Clermont Ferrand Cedex 1, France.
Abrial
Catherine
C
Tacca
Olivier
O
Mouret-Reynier
Marie-Ange
MA
Leheurteur
Marianne
M
Durando
Xavier
X
Curé
Hervé
H
D000970:Antineoplastic Agents / Q000145:classification / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D000068338:Everolimus; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D000068338:Everolimus; D000077289:Letrozole; D009570:Nitriles; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014230:Triazoles; C401859:temsirolimus; C546842:MTOR protein, human