Evaluation of Aromatase Inhibitors’ Side Effects in Clinical and Experimental Studies
Authors:
P. Kubatka; M. Péč
Authors‘ workplace:
Ústav lekárskej biológie, Jesseniova lekárska fakulta Univerzity Komenského, Martin
Published in:
Klin Onkol 2009; 22(3): 89-93
Category:
Reviews
Overview
Aromatase inhibitors are now the first choice endocrine therapy in the metastatic setting for postmenopausal women. These endocrine agents also seem likely to soon become the standard adjuvant therapy for postmenopausal patients with hormone-responsive breast cancer, either alone or in sequence with tamoxifen. In the treatment with aromatase inhibitors, the incidence of some adverse effects such as endometrial cancer, stroke or pulmonary tromboembolism treatment associated with tamoxifen is reduced. Questions remain about the long term side-effects and safety profile of aromatase inhibitors – monitoring and handling of bone loss associated with their application are essential and are being addressed in ongoing trials. Further studies with longer follow up are required to clarify the effects of aromatase inhibitors on lipid metabolism and cardiovascular health.
Key words:
aromatase inhibitors – adverse effects – lipid metabolism – bone – urogenital system
Sources
1. Bonneterre J, Thürliman B, Robertson JF et al. Anastrozole versus tamoxifen as first line therapy for advanced breast cancer in 668 postmenopausal women: results of Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol 2000; 18: 3748–3757.
2. Thürlimann B, Hess D, Koberle D et al. Anastrozole (‘Arimidex’) versus tamoxifen as first line therapy in postmenopausal women with advanced breast cancer: Results of the double-blind cross-over SAKK trial 21/95 – a sub study of the TARGET (Tamoxifen or ‘Arimidex’ Randomized Group Efficacy and Tolerability) trial. Breast Cancer Res Treat 2004; 85: 247–254.
3. Mouridsen H, Gershanovich M, Sun Y. Phase III study of letrozole versus tamoxifen as first line therapy of advanced breast cancer in postmenopausal women: analysis of survival and updates of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 2003; 21: 2101–2119.
4. Paridaens R, Therasse P, Dirix L et al. First line hormonal treatment (HT) for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients – A randomized phase III trial of the EORTC Breast Group. Proc Am Soc Clin Oncol 2004; 22: 14.
5. Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365: 60–62.
6. Jakesz R, Jonat W, Gnant M et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after two years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005; 366: 455–462.
7. Thürlimann BJ, Keshaviah A, Mouridsen H et al. BIG 1-98: randomized double-blind phase III study to evaluate letrozole versus tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Proc Am Soc Clin Oncol 2005; 23: 16.
8. Goss PE, Ingle JN, Martino S et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005; 97: 1262–1271.
9. Coombes RC, Hall E, Gibson LJ et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004; 350: 1081–1092.
10. Kubatka P, Sadloňová V, Kajo K et al. Chemopreventive effects of anastrozole in a premenopausal breast cancer model. Anticancer Res 2008; 28: 2819–2823.
11. Kubatka P, Sadloňová V, Kajo K et al. Preventive effects of letrozole in the model of premenopausal mammary carcinogenesis. Neoplasma 2008; 55: 42–46.
12. Kubatka P, Sadloňová V, Kajo K et al. Neoplastic effects of exemestane in premenopausal breast cancer model. Neoplasma 2008; 55: 538–543.
13. Wasan KM, Goss PE, Pritchard PH et al. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L). Ann Oncol 2005; 16: 707–715.
14. Goss PE, Qi S, Cheung AM et al. Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats. Clin Cancer Res 2004; 10: 5717–5723.
15. Goss PE, Qi S, Josse RG et al. The steroidal aromatase inhibitor exemestane prevents bone loss in ovariectomized rats. Bone 2004; 34: 384–392.
16. Hodis HN, Mack WJ, Azen SP et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med 2003; 349: 535–345.
17. Anderson GL, Limacher M, Assaf AR et al. Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy – the women’s health initiative randomized controlled trial. JAMA 2004; 291: 1701–1712.
18. Krag L, Geisler J, Lønning PE et al. Lipid and coagulation profile in postmenopausal women with early breast cancer at low risk treated with exemestane: a randomized, placebo-controlled study. Am Soc Clin Oncol 2004; 23: 39.
19. Coates AS, Keshaviah A, Thürlimann B et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrinereponsive early breast postmenopausal women with endocrine-reponsive early breast cancer: update of study BIG 1-98. J Clin Oncol 2007; 25: 486–492.
20. Coombes RC, Kilburn LS, Snowdon CF et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369: 559–570.
21. Markopoulos C, Polychronis A, Zobolas V et al. The effect of exemestane on the lipidemic profile of postmenopausal early breast cancer patients: preliminary results of the TEAM Greek sub study. Breast Cancer Res Treat 2005; 93: 61–66.
22. Elisaf MS, Bairaktari ET, Nicolaides C et al. Effect of letrozole on the lipid profile in postmenopausal women with breast cancer. Eur J Cancer 2001; 37: 1510–1513.
23. Dewar J, Nabholtz JM, Bonneterre J et al. The effect of anastrozole (Arimidex) on plasma lipids – data from a randomized comparison of anastrozole versus tamoxifen in postmenopausal women with advanced breast cancer. Breast Cancer Res Treat 2000; 64: 51.
24. Wojtacki J, Kruszewski W, Sliwinska M et al. Effect of non steroidal aromatase inhibitors on serum lipids profile in patients with breast cancer: preliminary report. Eur J Cancer 2000; 36: 71.
25. McCloskey E, Eastell R, Lakner G et al. Initial results from the LEAP study: the first direct comparison of safety parameters between aromatase inhibitors in healthy postmenopausal women. San Antonio Breast Cancer Symposium 2005. Abstract 2052.
26. McCloskey E. Effects of third-generation aromatase inhibitors on bone. Eur J Cancer 2006; 42: 1044–1051.
27. Goss PE, Hadji P, Subar M et al. Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 2007; 9: R52.
28. Geisler J, Lønning PE, Krag LE et al. Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: a randomised, placebo-controlled study. Eur J Cancer 2006; 42: 2968–2975.
29. Hillner BE, Ingle JN, Chlebowski RT et al. American society of clinical oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003; 21: 4042–4057.
30. Garuti G, Cellani F, Centinaio G et al. Prospective endometrial assessment of breast cancer patients treated with third generation aromatase inhibitors. Gyn Oncol 2006; 103: 599–603.
31. Li HZ, Chen XN, Qiao J. Letrozole as primary therapy for endometrial hyperplasia in young women. Int J Gyn Obst 2008; 100: 10–12.
32. Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fert Steril 2006; 85: 1307–1318.
33. Cortinez A, De Carvalho I, Vantman D et al. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fert Steril 2005; 83: 110–115.
34. Bhatnagar AS, Batzl C, Hausler A et al. The role of estrogen in the feedback-regulation of follicle-stimulating-hormone secretion in the female rat. J Steroid Biochem Mol Biol 1993; 47: 161–166.
35. Sinha S, Kaseta J, Santner SJ et al. Effect of CGS 20267 on ovarian aromatase and gonadotropin levels in the rat. Breast Cancer Res Treat 1998; 48(1): 45–51.
36. Muratori A, Lippi A, Mancina R et al. Pharmacological profile of MEN11066, a novel potent and selective aromatase inhibitor. J Steroid Biochem Mol Biol 2003; 84: 503–512.
37. Iino Y, Karakida T, Sugamata N et al. Antitumor effects of SEF19, a new nonsteroidal aromatase inhibitor, on 7,12-dimethylbenz(a)anthracene induced mammary tumors in rats. Anticancer Res 1998; 18: 171–176.
38. Pelleymounter MA, Baker MB, McCaleb M. Does estradiol mediate leptin‘s effects on adiposity and body weight? Am J Physiol 1999; 276: E955–E963.
39. Varma M, Chai JK, Meguid MM et al. Effect of estradiol and progesterone on daily rhythm in food intake and feeding patterns in Fischer rats. Physiol Behav 1999; 68: 99–107.
40. Di Salle E, Zaccheo T, Rossi R et al. Chemopreventive effect of the aromatase inactivator exemestane in the dimethylbenzanthracene (DMBA) induced mammary tumors in rats. J Clin Oncol 2004; 22(14S): 3108.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2009 Issue 3
Most read in this issue
- Evaluation of Aromatase Inhibitors’ Side Effects in Clinical and Experimental Studies
- Clostridium Difficile Associated Diarrhoea –Problem of Oncological Patient?
- Use of PET/CT Examination in Head and Neck Cancer Radiotherapy Planning
- New Radiopharmaceuticals and Positron-emission Tomography Applications at the Masaryk Memorial Cancer Institute in Brno