title: Could exemestane affect insulin-like growth factors, interleukin 6 and bone metabolism in postmenopausal advanced breast cancer patients after failure on aminoglutethimide, anastrozole or letrozole?
abstract: Postmenopausal hormone-sensitive breast cancer is currently treated with either antioestrogens or aromatase inhibitors (AIs), due to the clinical efficacy and safety of these drugs. Today's challenge is the sequential use of AIs with different structure and no cross-resistance to improve the therapeutic outcome. The present study describes the biological action of the steroidal structure (SS)-AI exemestane (EXE), in patients progressing on aminoglutethimide (AG) or other non-steroidal structure (NSS)-AIs (letrozole or anastrozole). Thirteen patients were evaluated for serum insulin-like growth factor (IGF) components [total IGF-1, IGF-2 and IGF binding protein (IGFBP)-3], interleukin (IL)-6 system [IL-6 and soluble IL-6 receptor (sIL-6-R)] and bone metabolism markers [bone gla protein/osteocalcin (BGP), bone-specific isoform of alkaline phosphatase (BAP) and carboxy-telopeptide of type I procollagen (ICTP)]. IGF system components show a trend to increase both in patients progressing on AG and in patients progressing on other NSS-AIs. Such an increase depends on the wash-out length from the previous treatment and is strictly linked to the circulating oestrogen levels. Serum IL-6 and sIL-6-R are mainly related to the patients' clinical outcome. Bone formation (BGP and BAP) and bone resorption (ICTP) markers seem to be at equilibrium with oestrogen levels when starting EXE and do not appear to be uncoupled over treatment. The observed variations seem to be mainly linked to the circulating oestrogen levels rather than directly to the way of action of the AI employed.
authors.affiliation: Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, I-20133 Milano, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ferrari
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Antonia
authors.initials: A
authors.lastname: Martinetti
authors.forename: Luigi
authors.initials: L
authors.lastname: Celio
authors.forename: Raffaella
authors.initials: R
authors.lastname: Longarini
authors.forename: Ignazia
authors.initials: I
authors.lastname: La Torre
authors.forename: Roberto
authors.initials: R
authors.lastname: Buzzoni
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.forename: Ettore
authors.initials: E
authors.lastname: Seregni
authors.forename: Emilio
authors.initials: E
authors.lastname: Bombardieri
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015992:Body Mass Index; D001842:Bone and Bones / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014018:Tissue Distribution; D017211:Treatment Failure
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D015850:Interleukin-6; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C056516:exemestane