Aromatase Inhibitors and Inactivators for the Treatment of Postmenopausal Breast Cancer: A Review

Author(s):  
Jurgen Geisler
2020 ◽  
Vol 20 (17) ◽  
pp. 1994-2004 ◽  
Author(s):  
Pooja Ratre ◽  
Keerti Mishra ◽  
Amit Dubey ◽  
Amber Vyas ◽  
Akhlesh Jain ◽  
...  

Background: Estrogens are essential for the growth of breast cancer in the case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with an increase in age. Since the enzyme aromatase catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third-generation AIs have been approved by the FDA. The third-generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. Methods: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: ‘aromatase’, ‘aromatase inhibitors’, ‘breast cancer’, ‘steroidal aromatase inhibitors’, ‘non-steroidal inhibitors’ and ‘generations of aromatase inhibitors’. Results: In the current scenario of breast cancer chemotherapy, AIs are the most widely used agents which reveal optimum efficacy along with the least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its role in the biosynthesis of estrogen, biochemistry, gene expression, 3D-structure, and information of reported AIs along with their role in breast cancer treatment. Conclusion: AIs are the mainstream solution of the ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of a healthy life of women suffering from breast cancer.


2004 ◽  
Vol 11 (2) ◽  
pp. 179-189 ◽  
Author(s):  
P E L√∏nning

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.


2015 ◽  
Vol 86 (7) ◽  
pp. 906-916 ◽  
Author(s):  
L. Susan Taichman ◽  
Marita R. Inglehart ◽  
William V. Giannobile ◽  
Thomas Braun ◽  
Giselle Kolenic ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
pp. 11
Author(s):  
Reham M. Faheim ◽  
Eman A. El-Shaarawy ◽  
Dina A. Salem ◽  
Rehab G. Shaaban

Background: Aromatase inhibitors (AIs) represent an effective endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients with early stage or metastatic disease.Objective: Assessment of Cardiotoxicity in Hormone positive Postmenopausal Breast Cancer Patients receiving AIs (upfront orswitch therapy).Methods: This cross sectional study included 123 postmenopausal breast cancer patients presented to the Clinical Oncology Department, Ain Shams University (Cairo, Egypt) in the interval from August 2016 to June 2017 with hormone receptor positive receiving Aromatase Inhibitors, To assess cardiotoxicity in these patients, they were subjected to blood pressure and lipid profile measurement, electrocardiography (ECG), and electrocardiography (ECHO) and classified into patients had Nolvadex then A.I (arm 1) and others had upfront A.I (arm 2).Results: The age of patients ranged from 41 years to 85 years with mean age of 61 years. Seventy one patients (57.7%) showed cardiotoxicity as assessed by ECHO. They showed significant correlation with rising age above 62 years, IHD, history of HTN and DM (p value: .001, .001, .017 and 0.035 respectively). However, correlation between cardiotoxity and blood pressure changes, lipid profile changes and ECG findings and ECHO changes in switch therapy and upfront A.I were not statistically significant (p value = .275, .116, .081 and .761 respectively).Conclusion: Assessment of cardiotoxicity in hormone positive postmenopausal breast cancer patients receiving Aromatase Inhibitors showed evidence of cardiotoxicity in half the patients (57.7%) as detected by ECHO only. They showed statistically non significant correlations either recievied switch therapy or upfront A.I.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11020-e11020 ◽  
Author(s):  
Ugur Sahin ◽  
Ibrahim Petekkaya ◽  
Cagatay Arslan ◽  
Saim Furkan Sarici ◽  
Mustafa Solak ◽  
...  

e11020 Background: Aromatase inhibitors (AIs), anastrozole (ANA) and letrozole (LET), have been shown to be more effective than tamoxifen in the adjuvant treatment of postmenopausal hormone receptor positive breast cancer. However, data from preclinical studies and subgroup analyses of some major clinical trials suggest differring efficacy among AIs. Yet the best clinical choice is still not very clear. This retrospective study aims at comparing the results of treatment with either AI among different subgroups of patients, especially among the obese patients. Methods: Between 2006-2011, 335 women with stage I to IIIC hormone receptor positive postmenopausal breast cancer treated with either ANA or LET as adjuvant treatment were included. Body mass index (BMI), estrogen and progesterone receptor (ER and PR) and HER-2 status at the time of diagnosis were recorded. Patients were grouped as BMI ≤ 30 and BMI > 30. The Kaplan-Meier survival estimates were calculated. Subgroups were compared with the log rank test. A 5 % type-I error was used to infer statistical significance. Results: The percentage of patients receiving ANA or LET were 47.2% and 57.8%, respectively. Median age at diagnosis was 58 (42-84) and lower in the ANA group (p=0.04). Stage II to IIIC disease was present in 76.8 % and the distribution was similar between ANA and LET (p=0.84). Median time of follow-up was 29 months (6-124) and median duration of hormonotherapy was 29 months (3-68) and similar between two groups (p=0.52 and p=0.55, respectively). Of the patients 41.2 % had a BMI of > 30. There was no significant difference in overall (OS) and progression-free (PFS) survivals between ANA and LET (p=0.08 and p=0.94, respectively). However, among patients with a BMI of > 30 a statistically insignificant benefit in PFS was observed with LET (p=0.1). ER, PR and HER2 status had no significant impact on OS and PFS. Conclusions: In a median follow-up of 29 months letrozole and anastrozole yielded similar OS and PFS. However, among patients with a BMI of > 30, LET might bring about a PFS advantage. In selected obese patients LET might be a reasonable choice in this setting. Larger studies with long term follow-up are needed to reach an exact conclusion.


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