Circulating Levels of Estradiol in Breast Cancer Patients Treated with Aromatase Inhibitors and Their Clinical Implications
Authors:
K. Petrakova 1,2; M. Krásenská 1; D. Valík 3,4; M. Holánek 1; M. Palacova 1; R. Demlová 4,5
Authors‘ workplace:
Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
1; Lékařská fakulta MU, Brno
2; Oddělení laboratorní medicíny, Masarykův onkologický ústav, Brno
3; RECAMO, Masarykův onkologický ústav, Brno
4; Oddělení klinických hodnocení, Masarykův onkologický ústav, Brno
5
Published in:
Klin Onkol 2016; 29(Supplementum 3): 50-57
Category:
Review
doi:
https://doi.org/10.14735/amko20163S50
Overview
Adjuvant treatment with aromatase inhibitors improves outcomes in postmenopausal women with hormone-sensitive early breast cancer; however, they should not be used in premenopausal women. Menopausal status is the most important factor in the choice of the hormonal treatment. There is no direct correlation between amenorrhea and ovarian function, as even the patients with amenorrhea may present with premenopausal plasma estradiol levels. The evaluation of hormonal status becomes more complicated in patients taking tamoxifen, which might lead to further increase of plasma estradiol levels. Therefore, its evaluation before and during the treatment with aromatase inhibitors is clinically important. There is a considerable caution needed when indicating aromatase inhibitors in patients with menopause caused by previous adjuvant chemotherapy, while recovery of ovarian function may appear after a certain period. This could take from 4 to 59 months (12 months on average) and it might not be accompanied by menses. This happens typically in women younger than 40 years, who should, therefore, not be treated by aromatase inhibitors alone. This supports the notion that monitoring of plasma estradiol levels is crucial in women from 40 to 50 years of age, especially before the start of aromatase inhibitors treatment.
Key words:
breast cancer – premenopause – postmenopause – perimenopause – estradiol – aromatase inhibitors
This work was supported by MEYS – NPS I – LO1413 for RECAMO.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
18. 2. 2016
Accepted:
29. 6. 2016
Sources
1. Van Bogaert LJ, Van Craynest MP, Abarca-Quinones J. Direct influence of the three natural estrogens on human mammary gland in vitro. Horm Metab Res 1982; 14 (11): 598–601.
2. Miller WR. Aromatase and its inhibitors: new biology and clinical perspectives. Endocr Relat Cancer 1999; 6 (2): 127–130.
3. Vermulen A. The hormonal activity of the postmenopausal ovary. J Clin Endocrinol Metabol 1976; 42 (2): 247–253.
4. Southern A, Louis OJ, Gordon GG et al. The conversion of androgens to estrogens in hyperthyroidism. J Clin Endocrinol Metab 1974; 38 (2): 207–214.
5. Lonning PE, Haynes PB, Straume HA et al. Exploring breast cancer estrogen disposition: the basis for endocrine manipulation. Clin Cancer Res 2011; 17 (15): 4948–4958. doi: 10.1158/1078-0432.CCR-11-0043.
6. Dunbier KA, Anderson H, Ghazoui Z et al. Relationship between plasma estradiol levels and estrogen-responsive gene expression in estrogen receptor-positive breast cancer in postmenopausal women. J Clin Oncol 2010; 28 (7): 1161–1167. doi: 10.1200/JCO.2009.23. 9616.
7. Svod.cz [internetová stránka]. Český národní webový portál epidemiologie nádorů. Masarykova univerzita, Česká republika; c2006. Dostupné z: www.svod.cz.
8. Goldhirsch A, Winer EP, Coates AS et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24 (9): 2206–2223. doi: 10.1093/annonc/mdt303.
9. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378 (9793): 771–784. doi: 10.1016/S0140-6736 (11) 60993-8.
10. Groom GV, Griffiths K. Effect of the anti-oestrogen tamoxifen on plasma levels of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol and progesterone in normal pre-menopausal women. J Endocrinol 1976; 70 (3): 421–428.
11. Smith IE, Dowsett M, Zap YS et al. Adjuvant aromatase inhibitors for early breast cancer after chemotherapy-induced amenorrhoea: caution and suggested guidelines. J Clin Oncol 2006; 24 (16): 2444–2447.
12. Mitwally M, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fert Steril 2001; 75 (2): 305–309.
13. Thurliman B, Keshaviah A, Coates AS et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005; 353 (26): 2747–2757.
14. Burger HG, Hale GE, Robertson DM et al. A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women‘s Midlife Health Project. Hum Reprod Update 2007; 13 (6): 559–565.
15. Moú.cz [homepage on the Internet]. Oddělení laboratorní medicíny. Dostupné z: https: //www.mou.cz/oddeleni-laboratorni-mediciny-olm/d115#chapter=1.
16. Henrich JB, Hughes JP, Kaufman SC et al. Limitations of follicle-stimulating hormone in assessing menopause status: findings from the National Health and Nutrition Examination Survey (NHANES 1999–2000). Menopause 2006; 13 (2): 171–177.
17. Smith IE, Dowsett M, Yap YS et al. Adjuvant aromatase inhibitors for early breast cancer after chemotherapy-induced amenorrhoea: caution and suggested guidelines. J Clin Oncol 2006; 24 (16): 2444–2447.
18. Folferd EJ, Lonning PE, Dowsett M. Interpreting plasma estrogen levels in breast cancer: caution needed. J Clin Oncol 2014; 32 (14): 1396–1400. doi: 10.1200/JCO.2013.53.9411.
19. Ganz PA, Land SR, Geyer CE et al. Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial. J Clin Oncol 2011; 29 (9): 1110–1116. doi: 10.1200/JCO.2010.29.7689.
20. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14 (5): 1718–1729.
21. Forbes JF, Cuzick J, Buzdar A et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9 (1): 45–53.
22. Trinkaus M, Chin S, Wolfman W et al. Should urogenital atrophy in breast cancer survivors be treated with topical estrogens? Oncologist 2008; 13 (3): 222–231. doi: 10.1634/theoncologist.2007-0234.
23. Kendall A, Dowsett M, Folkerd E et al. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 2006; 17 (4): 584–587.
24. LHRH-agonists in Early Breast Cancer Overview group, Cuzik J, Ambroisine L et al. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 2007; 369 (9574): 1711–1723.
25. Bellet M, Gray KP, Francis PA et al. Twelve-month estrogen levels in premenopausal women with hormone receptor-positive breast cancer receiving adjuvant triptorelin plus exemestane or tamoxifen in the Suppression of Ovarian Function Trial (SOFT): the SOFT-EST substudy. J Clin Oncol 2016; 34 (14): 1584–1593. doi: 10.1200/JCO.2015.61.2259.
26. Lonning PE, Johanssen DC, Lien EA et al. Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. J Steroid Biochem Mol Biol 1995; 52 (5): 491–496.
27. Dowsett M, Cuzick J, Ingle J et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 2010; 28 (3): 509–518. doi: 10.1200/JCO.2009.23.1274.
28. Ortmann O, Pagani O, Jones A et al. Which factors should be taken into account in perimenopausal women with early breast cancer who may become eligible for an aromatase inhibitor? Recommendations of an expert panel. Cancer Treat Rev 2011; 37 (2) : 97–104. doi: 10.1016/j.ctrv.2010.05.005.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2016 Issue Supplementum 3
Most read in this issue
- Treatment with Aromatase Inhibitors in Postmenopausal Women with Breast Cancer and the Possibility of Influencing Side Effects
- Breast Cancer – Specifics of Gynecological Care and Counseling
- Circulating Levels of Estradiol in Breast Cancer Patients Treated with Aromatase Inhibitors and Their Clinical Implications
- Pregnancy after Treatment of Breast Cancer