Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients

1994 ◽  
Vol 30 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Laurence M. Demers
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Aromatase Activity ◽  
Breast Cancer Patients ◽  
Cgs 20267

scholarly journals Local Aromatase Activity Alterations In Breast Cancer Tissues: A Potential Way Of Decision Support For Clinicians

2020 ◽  
Author(s):  
Mete Bora Tuzuner ◽  
Tulin Ozturk ◽  
Sennur Ilvan ◽  
Zeynep Hande Turna ◽  
Turkan Yurdun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Cancer Patients ◽  
Breast Tissue ◽  
Postmenopausal Breast Cancer ◽  
Activity Level ◽  
Aromatase Activity ◽  
Low Grade ◽  
Activity Levels ◽  
Breast Cancer Patients

Background and aims: It is becoming evident that local estrogen exposure is important in postmenopausal breast cancer patients. The microenvironment is established by breast stromal cells based on communication with tumor cells that is essential to cancer development, invasion, and metastasis. Here we investigated aromatase activity levels in both tumor and matched stromal tissues by showing their impact on the manufacturing of local estrogen and tumor progression in cases of invasive ductal carcinoma (IDC). Methods: Tumor (T) and tumor-associated stroma (TAS) neighboring tissues were acquired from each postmenopausal patient, diagnosed with IDC, and categorized as luminal A (n=20). The control group was formed from tumor-free breast tissue samples (N, n=12). A microsomal-based technique was created to compare breast tissue aromatase activities using liquid chromatography-mass spectrometry. Findings: We observed that the TAS tissues have the highest aromatase activities (p< 0.05). High progesterone receptor (PR) intensity levels were found to be decreasing the activity level in these tissues significantly (p<0.05). Tumor tissue specific aromatase activity levels of postmenopausal patients' were tend to be lower compared to healthy premenopausal subjects' (3 fold, p<0.001). In addition, low activity in tumor tissues were associated with low grade and late-stage cancers. Conclusions: Early detection and personalized therapy is essential for postmenopausal breast cancer patients. Together, our in-house tandem mass spectrometry technique has the potential for further development and standardization for the measurement of aromatase activity and may assist clinicians to decide on therapy policies for postmenopausal IDC patients which could be an invaluable asset for a precise and specific evaluation.

Genetic variation in CYP19A1 and response to exemestane: Survival in early breast cancer in the Dutch TEAM trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10518-10518
Author(s):  
Daniel Houtsma ◽  
Duveken Fontein ◽  
Judith A. M. Wessels ◽  
Caroline M. Seynaeve ◽  
Cock JH van De Velde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Proportional Hazards ◽  
Histological Grade ◽  
Cox Proportional Hazards ◽  
Aromatase Activity ◽  
Breast Cancer Patients ◽  
Tagging Snp ◽  
Cox Proportional Hazards Models

10518 Background: In patients with endocrine-sensitive breast cancer treated with adjuvant aromatase inhibitors (AI) it is unclear which patients will develop a recurrence and who will benefit from AI’s. Variations in the aromatase gene (CYP19A1) are associated with altered estrogen levels and altered aromatase activity. The aim of this study was to examine the effect of SNPs in the CYP19A1 gene on survival in a prospective cohort of breast cancer patients treated with adjuvant exemestane. Methods: Patients of whom tissue was available and who were treated with five years of exemestane were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. DNA was isolated from tumor samples and 30 SNPs were identified using a tagging SNP approach, aiming for 80% coverage of CYP19A1. Genotypes were determined with taqman assays. Primary endpoint of the study was relapse-free survival (RFS) and secondary endpoint was overall survival (OS). A Kaplan-Meier analysis was performed and Cox proportional hazards models assessed survival differences. Analyses were adjusted for age at diagnosis, tumor size, nodal status, histological grade, surgery, adjuvant radiotherapy and chemotherapy. Results: 807 patients were included in the analyses and genotypes were obtained in 722 cases. A significant association with worse RFS was found with two SNPs: rs7176005 and rs16964211, showing hazard ratios (HR) of 3.48 and 5.42 for the homozygeous variant types respectively. These SNPs, as well as a third SNP, rs6493497, were also significantly associated with OS (HR 5.87, 5.3 and 3.36 respectively). Conclusions: Germline variations in the CYP19A1 gene are related to a worse outcome in early breast cancer patients treated with exemestane. These findings may contribute to the individualization of hormonal therapy in breast cancer. The relation between RFS and SNP’s in CYP19A1. [Table: see text]

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