In premenopausal women treated for breast cancer, endocrine therapy combining an aromatase inhibitor (AI) and a gonadotropin-releasing hormone (GnRH) agonist (GA) for ovarian suppression may be indicated in high-risk or in metastatic cancer.
Women diagnosed with breast cancer metastases within a period of 6 months and before the end of follow-up were matched (1:1) by age, index year, physician, type of hormonal therapy (tamoxifen or aromatase inhibitors) and follow-up time (in months) with women without metastases.
In the 135 assessable patients (93 % were receiving an aromatase inhibitor; biomarker assessment had been performed on primary tumors in 77 cases, on metastases in 23 and on both in 35), median TTP was 16 months (median follow-up 43 months).
Aromatase inhibitors have important roles in optimal management of postmenopausal patients with hormone-responsive metastases in both the adjuvant and advanced-disease settings.
We identified a subregion defined by microsatellite marker CYP19 (15q21.1) that showed significantly higher frequencies of allelic imbalance in metastases and recurrences (57.6%) when compared to primary carcinomas (8.9%; p<0.0001).
The basic carcinogenic processes are: (1) constitutive prostaglandin biosynthesis and formation of mutagenic oxygen and nitrogen free radicals responsible for tumor initiation; (2) PGE-2-induced expression of aromatase and constitutive estrogen biosynthesis which sustains mitogenesis and tumor promotion; and (3) PGE-2-induced expression of vascular endothelial growth factor which stimulates angiogenesis and tumor metastasis.