Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer

• Published in: Journal of clinical oncology Vol. 20; no. 4; pp. 1026 - 1035
• Main Authors: HARPER-WYNNE, Catherine L, SACKS, Nigel P. M, HILLS, Margaret J, LOWE, Frances M, A'HERN, Roger, NASIRI, Nazar, DOODY, Debbie, IQBAL, Jhangir, DOWSETT, Mitchell, SHENTON, Karyn, MACNEILL, Fiona A, SAUVEN, Paul, LAIDLAW, Ian J, RAYTER, Zen, MIALL, Stephanie, HOWES, Angela, SALTER, Janine
• Format: Journal Article
• Language: English
• Published: Baltimore, MD Lippincott Williams & Wilkins 15.02.2002
• Subjects: Administration, Oral; Aged; Antineoplastic agents; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - pharmacology; Biological and medical sciences; Biomarkers, Tumor - analysis; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Female; Follicle Stimulating Hormone - analysis; Hematologic and hematopoietic diseases; Humans; Ki-67 Antigen - analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Luteinizing Hormone - analysis; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Postmenopause; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Tamoxifen - administration & dosage; Tamoxifen - pharmacology; Triazoles - administration & dosage; Triazoles - pharmacology; Antineoplastic agent; Cell proliferation; Benzotriazole derivatives; Antiestrogen; Estrogen; Biological marker; Antihormone; Estrogen synthase; Glycoprotein hormone; Vorozole; Luteinizing hormone; Postmenopause; Mammary gland; Non steroid compound; Follicle stimulating hormone; Human; Enzyme; Treatment efficiency; Oral administration; Enzyme inhibitor; Gonadotropin; Malignant tumor; Insulin like growth factor 1; Ovarian hormone; Biological activity; Tamoxifene; Mammary gland diseases; Chemotherapy; Treatment; Adenohypophyseal hormone; Ki67 antigen; Sex steroid hormone; Comparative study
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2002.20.4.1026

To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer. 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. 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). 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.