Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer.
OBJECTIVE
To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer.


METHODS
Randomization was to 12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both orally. Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12 weeks.


RESULTS
Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and tamoxifen patients, respectively (P =.13). In the vorozole group, the correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes and clinical response at 12 weeks were not significant (P =.09) and marginally significant (P =.04), respectively. Serum lipids did not differ between groups. Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1 levels fell significantly with tamoxifen (P =.001) compared with the nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with tamoxifen (P =.006) and rose by 11% with vorozole (P =.15).


CONCLUSIONS
The correlation with vorozole of Ki67 with volume and clinical response supports this as an intermediate marker. The nonsignificant effects on bone and lipid metabolism by the aromatase inhibitor may be important to consider for adjuvant and potential prevention strategies.
Harper-Wynne
Catherine L
CL
Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom.
Sacks
Nigel P M
NP
Shenton
Karyn
K
MacNeill
Fiona A
FA
Sauven
Paul
P
Laidlaw
Ian J
IJ
Rayter
Zen
Z
Miall
Stephanie
S
Howes
Angela
A
Salter
Janine
J
Hills
Margaret J
MJ
Lowe
Frances M
FM
A'Hern
Roger
R
Nasiri
Nazar
N
Doody
Debbie
D
Iqbal
Jhangir
J
Dowsett
Mitchell
M
D000284:Administration, Oral; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D007986:Luteinizing Hormone / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; C060523:vorozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone