Canadian Journal of Applied Sciences


ISSN: 1925-7430
Short Key Title: Can J App Sci
DOI: http://dx.doi.org/10.21065/19257430
Start Year: 2011

RESPONSE EVALUATION OF TAMOXIFEN VS AROMATASE INHIBITORS
Saba Mazhar, Mariam Nawaz, Muhammad Tahir Aziz, Sidrah Andleeb
Department of Pharmaceutical Services, SKMCH&RC, Lahore, Pakistan
Keywords: Tamoxifen, aromatase inhibitor, breast cancer
Abstract

Objective:The study was conducted to evaluate the accuracy of use of aromatase inhibitors (AI) and tamoxifen treatment in pre-menopausal and post-menopausal breast cancer patients. Method: The prescription data of 143 patients was reviewed for evaluation of letrozole, anastrazole and tamoxifen utilization between years 2006-2013 at SKMCH&RC. Use was analyzed against pre-menopausal and post-menopausal status of the patients using hospital information software (HIS) for data collection. NCCN Breast Cancer Guidelines were used as reference. Results:Tamoxifen upfront use in pre-menopausal women with breast cancer was 93.3%, while that of Aromatase inhibitor was 6.7%. Tamoxifen was used as second line therapy in pre-menopausal women in 6.7% while aromatase inhibitor was used as second line therapy in pre-menopausal women in 93.3%. Tamoxifen upfront in post-menopausal was 18.6%, aromatase inhibitor upfront in post-menopausal was 81.4%. Conclusion:Tamoxifen is used as first line therapy in majority of pre-menopausal breast cancer patients while aromatase inhibitors are used as second line. In case of post-menopausal breast cancer patients aromatase inhibitors are used as first line in majority of patients while tamoxifen is used as second line.

Article Information

Identifiers and Pagination:
Year:2014
Volume:4
First Page:100
Last Page:104
Publisher Id:CanJAppSci (2014 ). 4. 100-104
Article History:
Received:June 28, 2014
Accepted:September 5, 2014
Collection year:2014
First Published:October 3, 2014

INTRODUCTION

Despiteprogresses in breast cancer therapy, there is still an increased number of patients with diagnosed metastatic diseases. Early identification and timely treatment of women with breast cancer can surely decrease the mortality associated with the disease(1).Etiology of breast cancer is still unknown but factors responsiblemay include hereditary predisposition, late menarche, early menopause, obesity, late child birth, oral contraceptives use, high fat diet, age, alcohol, smoking, toxins, exposure to radiographs and even high socioeconomic status (1).

Estrogen helps in promoting the growth of normal and cancerous epithelial cells of breast. It does so by activation of estrogen receptors which in turn activate gene promoters. These gene promoters then activate several genes which play role in inhibiting cell death, promoting cell division, formation of new blood vessels and protease activity (3).Aromatase (cytochrome P-450 [CYP] 19) is the enzyme which catalyzes the rate limiting step (conversion of steroidal C-19 androgens to C-18 estrogens) of estrogen formation. It is the last step in the formation of estrogen and considered important for the inhibition of steroid formation (4)

Letrozole is third generation non-steroidal aromatase inhibitor. It has proven efficacy in hormone sensitive postmenopausal breast cancer (5).Letrozoleacts by hindering the final step of the estrogen biosynthetic pathway.  Randomized controlled trials conducted in postmenopausal women showed that Letrozole is more effective than tamoxifen (6).Anastrazole is another third generation non-steroidal aromatase inhibitor and is used in breast cancer patients with positive hormone receptor test (7). Studies have shown thatanastrazole is more effective in postmenopausal women with breast cancer than tamoxifen(8-9).

Tamoxifen is non-steroidal drug having anti-estrogen properties used in cases with positive estrogen receptor (ER) test. It inhibits prostaglandin synthetase and has effects similar to anti-estrogen drugs. Target organs include endometrium, bones and blood lipids. It has very low affinity for androgen receptors (10). National Surgical Adjuvant Breast and Bowel Project (NSABP) did study on 13388 high risk patients who were more than 35 years of age.  It was seen that patients who were given tamoxifen had significant less occurrence of breast cancer than the patients who were given placebo (11).Tamoxifen has very good tolerability profile for breast cancer patients and effective both in pre-menopausal and post-menopausal patients. These characteristics make tamoxifenmaintain its position in treatment of estrogen receptor positive breast cancer patients (12).It is one of the most commonly used FDA approved medicine for prevention of breast cancer (13). In clinically high risk patients e.g. patients with two first degree relatives with diagnosed breast cancer, history of atypical hyperplasia or history of in-situ lobular carcinoma, tamoxifen is recommended specially if risk is more than 5% and benefit outweighs harms. Duration of therapy in such patients should be 5 years (14)

Complexity of tamoxifen is also explained in another paper as an anti-estrogen with complex pharmacology encompassing variable species-, tissue-, cell-, gene-, age- and duration of administration-specific effects, from estrogen-like agonist actions to complete blockade of estrogen action. This complexity is consistent with various, and sometimes paradoxical, effects that have been associated with tamoxifen administration in animals and humans (15).

According to ASCO guidelines Update 2014, women diagnosed with ER positive in pre-menopausal and peri-menopausal stage should be treated with Tamoxifen and adjuvant endocrine therapy for 5 years, and after that, any additional therapy can be recommended. In pre-menopausal women Tamoxifen is recommended as a treatment for first 10 years and in post-menopausal women either Tamoxifen or aromatase inhibitor up to 10 years can be given with adjuvant endocrine therapy (16)

However, in case of post-menopausal women it is reported that aromatase inhibitors is preferred as first line therapy and Tamoxifen is preferred second line (17, 18). Nabholtzet al. concluded that there was lower incidence of vaginal bleeding and thromboembolic events that is the reason why anastrazole is preferred over Tamoxifen in post-menopausal women with breast cancer (19). According to another study aromatase inhibitor use in post-menopausal women reduced the chances of reoccurrence (20).Itexplains why aromatase inhibitors are preferred over anti-estrogen medicine like tamoxifen in post-menopausal breast cancer patients.

Among the treatments given to breast cancer patients, tamoxifen (non-steroidal anti-estrogen) and aromatase inhibitors (letrozole and anastrazole) are widely used. However, tamoxifen is preferred medicine in premenopausal women while aromatase inhibitors are preferred in post-menopausal women.  ASCO guidelines recommend that tamoxifen should be given to pre-menopausal women for 10 years while in post-menopausal women both therapies are recommended.

 

MATERIAL AND METHODS

The prescription data of 143 patients (2006-2013) was reviewed for evaluation of letrozole, anastrazole and tamoxifen utilization. Clinical performa was utilized for data collection regarding MR number, name, age and gender of each individual. Their treatment history was checked forTamoxifen vs. AI use.   Hormonal status of patients was checked and recorded by checking estrogen receptor (ER) test, Progesterone receptor (PR) test andHuman epidermal growth factor receptor (HER2Neu) test. Menstrual history of patients was also recorded and they were labeled as either in pre-menopausal stage, post-menopausal stage. It was also enquired that whether endocrine therapy was recommended before aromatase inhibitors or not and if yes, was it already given before aromatase inhibitor use or not? Duration of Tamoxifen therapy before aromatase inhibitors were introduced was also checked. Use of the drugs was compared against latest NCCN guidelines. Switching between letrozole to anastrazole and anastrazole to letrozole was also monitored.  After getting all the data prescribing trends were checked and utilization evaluation was done. Hospital information system software (HIS) was used for data collection.

 

RESULTS& DISCUSSION

Tamoxifen upfront use in pre-menopausal women with breast cancer was 93.3%, while that of AI was 6.7%. Tamoxifen was used as second line therapy in pre-menopausal women in 6.7% while aromatase inhibitor was used as second line therapy in pre-menopausal women in 93.3%. Tamoxifen upfront use in post-menopausal cases was 18.6%. Aromatase inhibitor upfront use in post-menopausal cases was 81.4%.

The institute majorly complies with the latest guidelines of oral chemo use in breast cancer. In a few cases, physicians prefer to use AI over tamoxifen to avoid tamoxifen related adverse effects of hot flashes, decreased bone density and thrombo-embolic events.

 

Table 1: AI use trend in breast cancer patients (2006-2013)

Total (92)


Pre-menopausal

Post-menopausal

Unknown

AI used upfront

1

90

1

AI as second
line therapy

1

89

1





 

Table 2: Tamoxifen use trend in Breast Cancer patients (2006-2013)


Total  (52)


Pre-menopausal

Post-menopausal


29

23

Tamoxifen upfront

28

20

Tamoxifen upfront

97%

87%

Table 3: Tamoxifen vs. AI use trend in breast cancer patients (2006-2013)

Total 144


Pre-menopausal

%age

Post-menopausal

%age

Unknown


30


113


1

Tamoxifen Upfront

28

93.3

21

18.6


AI used upfront

2

6.7

92

81.4

1

Tamoxifen used as 2nd Line therapy

2

6.7

92

81.4


AI used as 2nd Line therapy

28

93.3

21

18.6








 

CONCLUSION

With few exceptions, tamoxifen is the treatment of first choice for pre-menopausal breast cancer cases, while Aromatase inhibitors are the preferred treatment in post-menopausal cases at the institute.

 

REFERENCES

1.       Njiaju UO, OlopadeOI.Genetic determinants of breast cancer risk: a review of current literature and issues pertaining to clinical application. Breast J. 2012 Sep;18(5):436-42. doi: 10.1111/j.1524-4741.2012.01274.x. athttp://www.ncbi.nlm.nih.gov/pubmed/22957996

2.       C. M. Mansfield. A review of the etiology of breast cancer.JNatl Med Assoc. Mar 1993; 85(3): 217–221. At http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571884/?page=1

3.       C J Fabian. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J ClinPract. Dec 2007; 61(12): 2051–2063. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/

4.       Ajay S. Bhatnagar. The discovery and mechanism of action of letrozole.Breast Cancer Res Treat. Oct 2007; 105(Suppl 1): 7–17. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001216/

5.       Simpson D, Curran MP, Perry CM. Letrozole: a review of its use in postmenopausal women with breast cancer. Drugs. 2004;64(11):1213-30. http://www.ncbi.nlm.nih.gov/pubmed/15161328

6.       Dunn C, Keam SJ. Letrozole: a pharmacoeconomic review of its use in postmenopausal women with breast cancer. Pharmacoeconomics. 2006;24(5):495-517 http://www.ncbi.nlm.nih.gov/pubmed/16706574

7.       Kelly CM, Buzdar AU. Anastrozole.ExpertOpin Drug Saf. 2010 Nov;9(6):995-1003. http://www.ncbi.nlm.nih.gov/pubmed/20923259

8.       Rocchi A, Verma S. Anastrozole is cost-effective vstamoxifen as initial adjuvant therapy in early breast cancer: Canadian perspectives on the ATAC completed-treatment analysis.Support Care Cancer. 2006 Sep;14(9):917-27. Epub 2006 Apr 5. http://www.ncbi.nlm.nih.gov/pubmed/16596419

9.       Simons WR, Jones D, Buzdar A. Cost-effectiveness of anastrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer.ClinTher. 2003 Nov;25(11):2972-87. http://www.ncbi.nlm.nih.gov/pubmed/14693319

10.   Eric Wooltorton. Tamoxifen for breast cancer prevention: safety warning. CMAJ. Aug 20, 2002; 167(4): 378–379. At http://www.ncbi.nlm.nih.gov/pmc/articles/PMC117858/

11.   Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371-88 at http://www.ncbi.nlm.nih.gov/pubmed/9747868

12.   Clemons M, Danson S, Howell A. Tamoxifen ("Nolvadex"): a review. Cancer Treat Rev. 2002 Aug;28(4):165-80. http://www.ncbi.nlm.nih.gov/pubmed/12363457

13.   Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, Forbes JF, Glaus A, Howell A, von Minckwitz G, Vogel V, ZwierzinaH.Preventive therapy for breast cancer: a consensus statement. Lancet Oncol. 2011 May;12(5):496-503. doi: 10.1016/S1470-2045(11)70030-4. At http://www.ncbi.nlm.nih.gov/pubmed/21441069

14.   Levine M, Moutquin JM, Walton R, FeightnerJ;Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative's Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. CMAJ. 2001 Jun 12;164(12):1681-90. At http://www.ncbi.nlm.nih.gov/pubmed/11450210/

15.   Paolo Bruzzi, Head. Tamoxifen for the prevention of breast cancer.BMJ. Apr 18, 1998; 316(7139): 1181–1182. At http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1112979/

16.   ASCO guidelines – 2014

17.   Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M, von Euler M.Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J ClinOncol. 2000 Nov 15;18(22):3748-57. At http://www.ncbi.nlm.nih.gov/pubmed/11078487

18.   Nabholtz JM, Bonneterre J, Buzdar A, Robertson JF, ThürlimannB.Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer. 2003 Aug;39(12):1684-9. At http://www.ncbi.nlm.nih.gov/pubmed/12888362

19.   Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M.Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J ClinOncol. 2000 Nov 15;18(22):3758-67. At http://www.ncbi.nlm.nih.gov/pubmed/11078488

20.   de Cremoux P, Diéras V, Poupon MF, Magdelénat H, Sigal-Zafrani B, Fourquet A, Pierga JY. Tamoxifen and aromatase inhibitors in the treatment of breast cancer in menopausal women: pharmacological and clinical aspects Bull Cancer. 2004 Dec;91(12):917-27. At http://www.ncbi.nlm.nih.gov/pubmed/15634633


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Dr. Xianghui Qi is working as Professor in the School of Food & Biological Engineering, Jiangsu University, China. His research interests: Biosynthesis of high value-added chemicals by microbes and engineered strains; Discovery of novel genes, enzymes and new strains; Rational & Irrational design of microbial enzymes; Isolation, identification and evolution of microbes; Metabolic engineering & Pathway engineering of functional microbes, and biotransformation; Metabolic regulation based on the research of microbial omics; Application of high value-added products including functional sugar alcohols by biosynthesis and biotransformation based on microbial engineered strains.

Journal Highlights
Abbreviation: Can J Appl Sci
doi: http://dx.doi.org/10.21065/19257430
Frequency: Annual
Current Volume: 7 (2017)
Next scheduled volume: December, 2018  
Back volumes: 1-7
Starting year: 2011
Nature: Online
Submission: Online
Language: English

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