Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: effects on estrogens and bone metabolism.
BACKGROUND
To study the short-term biological effect of anastrozole on serum estrogens, androgens, 17-hydroxyprogesterone (17OH-PGR), gonadotrophins, sex hormone binding globulin (SHBG) and bone metabolism markers.


METHODS
Thirty-four consecutive patients with advanced breast cancer received anastrozole 1 mg/day. Blood samples were taken before commencement of treatment and at 2, 4, 8 and 12 weeks during treatment to measure serum levels of estrogens (E(1), E(2) and E(1)-S), androgens [androstenedione (Delta(4)), dihydrotestosterone (DHT), testosterone (TST), free TST, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S)], 17OH-PGR, SHBG and gonadotrophins. As an indicator of bone resorption, we measured serum levels of C-terminal telopeptide of type I collagen (ICTP) and the cross-linked N-telopeptide of type I collagen (NTx), and for osteoblastic activity, intact osteocalcin (BGP) and bone alkaline phosphatase (BAP).


RESULTS
After 2 weeks E(1 )and E(1)-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E(2) decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens or 17OH-PGR. There was a significant increase in gonadotrophins over time (P = 0.0001 for both luteinizing hormone and follicle-stimulating hormone), and a significant decrease in SHBG (P = 0.0001). A progressive significant increase in bone metabolism serum markers was detected in all patients: BAP, P = 0.039; BGP, P = 0.016; ICTP, P = 0.0021; and NTx, P = 0.0013. In particular, patients with bone metastases had a statistically significant increase of bone resorption markers (ICTP, P = 0.0019; NTx, P = 0.025) and borderline for bone formation markers. In patients without bone disease, BAP, BGP and ICTP remained unchanged, whereas serum NTx significantly increased (P = 0.019).


CONCLUSIONS
Anastrozole is a selective aromatase inhibitor as it does not modify serum levels of androgens and 17OH-PGR. In our experience no relationship was found in the short-term period between serum estrogen suppression and bone metabolism.
Bajetta
E
E
Medical Oncology Unit B and Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. bajetta@istitutotumori.mi.it
Martinetti
A
A
Zilembo
N
N
Pozzi
P
P
La Torre
I
I
Ferrari
L
L
Seregni
E
E
Longarini
R
R
Salvucci
G
G
Bombardieri
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000728:Androgens / Q000378:metabolism; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D017698:Postmenopause; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000728:Androgens; D015415:Biomarkers; D004967:Estrogens; D009570:Nitriles; D012738:Sex Hormone-Binding Globulin; D014230:Triazoles; D015675:Osteocalcin; D000077384:Anastrozole