The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: effects on bone metabolism markers.
BACKGROUND
the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available.


OBJECTIVE
the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated.


METHODS
twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n=10, arm A) or in combination with formestane fortnightly (n=11, arm B). Blood samples were collected over a 3-month period.


RESULTS
serum PICP and PINP levels increased significantly over time (P=0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P=0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases.


CONCLUSIONS
it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.
Martinetti
A
A
Unit of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, via Venezian, 1-20133, Milan, Italy.
Ferrari
L
L
Celio
L
L
Mariani
L
L
Miceli
R
R
Zilembo
N
N
Di Bartolomeo
M
M
Toffolatti
L
L
Pozzi
P
P
Seregni
E
E
Bombardieri
E
E
Bajetta
E
E
D000328:Adult; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006133:Growth Substances / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D017697:Premenopause; D018709:Statistics, Nonparametric; D017329:Triptorelin Pamoate / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D015415:Biomarkers; D006133:Growth Substances; D015850:Interleukin-6; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D000735:Androstenedione; D004958:Estradiol; C014594:formestane