Main Article Content
Breast cancer, Finasteride, Implant, Intrauterine device, Medroxyprogesterone, Spironolactone
Background: The effect of exogenous sex hormones on the risk of breast cancer has been shown for some compounds but for other compounds it is under detailed investigation. This study, as part of a quadruple of articles reviewing the consequences of using sex hormones in women with various breast conditions, discusses the prescription of non-oral hormonal contraceptives and miscellaneous exogenous steroid hormones.
Methods: We browsed international clinical guidelines and carried out a comprehensive search in the literature by relevant keywords in order to extract data about the effects of hormone-releasing intrauterine devices, injectable depot-medroxyprogesterone acetate, contraceptive implants, cyproterone acetate, finasteride, and spironolactone on the breast.
Results: Studies are scarce for most of these compounds, and information comes mainly from researches about oral contraceptives and hormone replacement therapy. Although none is recommended for use in patients with breast cancer, administration in benign disorders of the breast, women with positive family history of breast cancer and general women is acceptable with minor risks.
Conclusions: Most non-oral hormonal methods of contraception and miscellaneous available hormone compounds prescribed for the treatment of hormonal disorders are safe for temporary use, except for women with breast cancer. For them, analogues of gonadotropin-releasing hormones may be considered a safe hormonal prescription.
2. Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1998; 90:1292-9.
3. Clemons M, Goss P. Estrogen and the risk of breast cancer. New England Journal of Medicine. 2001; 344:276-85.
4. Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. New England Journal of Medicine. 2006; 354:270-82.
5. Pizot C, Boniol M, Mullie P, Koechlin A, Boniol M, Boyle P, et al. Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies. European Journal of Cancer. 2016; 52:138-54.
6. Wang K, Li F, Chen L, Lai YM, Zhang X, Li HY. Change in risk of breast cancer after receiving hormone replacement therapy by considering effect-modifiers: a systematic review and dose-response meta-analysis of prospective studies. Oncotarget. 2017; 8:81109-24.
7. Eskandari A, Alipour S. Hormone Replacement Therapy and Breast Diseases: A Matter of Concern for the Gynecologist. Archives of Breast Cancer. 2019; 6:113-9.
8. Alipour S, Eskandari A. Prescribing Oral Contraceptives in Women With Breast Diseases: A Matter of Concern for the Gynecologist. Archives of Breast Cancer. 2019; 6:55-68.
9. Humans IWGotEoCRt, Cancer IAfRo, Organization WH. Hormonal contraception and post-menopausal hormonal therapy: World Health Organization; 1999.
10. Paul C, Skegg D, Spears G. Depot medroxypro-gesterone (Depo-Provera) and risk of breast cancer. Bmj. 1989; 299:759-62.
11. Li CI, Beaber EF, Tang MTC, Porter PL, Daling JR, Malone KE. Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20 to 44 years of age. Cancer research. 2012; 72:2028-35.
12. Greenspan A, Hatcher R, Moore M, Rosenberg M, Ory H. The association of depo-medroxyprogesterone acetate and breast cancer. Contraception. 1980; 21:563-9.
13. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB. Depot medroxyprog-esterone acetate and breast cancer: a pooled analysis of the World Health Organization and New Zealand studies. Jama. 1995; 273:799-804.
14. Strom BL, Berlin JA, Weber AL, Norman SA, Bernstein L, Burkman RT, et al. Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception. 2004; 69:353-60.
15. Curtis KM, Jatlaoui TC, Tepper NK, Zapata LB, Horton LG, Jamieson DJ, et al. US selected practice recommendations for contraceptive use, 2016. 2016.
16. Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. US medical eligibility criteria for contraceptive use, 2016. 2016.
17. Nelson AL. Contraindications to IUD and IUS use. Contraception. 2007; 75:S76-S81.
18.Dinger J, Bardenheuer K, Do Minh T. Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer. Contraception. 2011; 83:211-7.
19. Trinh XB, Tjalma WA, Makar AP, Buytaert G, Weyler J, Van Dam PA. Use of the levonorgestrel-releasing intrauterine system in breast cancer patients. Fertility and sterility. 2008; 90:17-22.
20. Jareid M, Thalabard J-C, Aarflot M, Bøvelstad HM, Lund E, Braaten T. Levonorgestrel-releasing intrauterine system use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer. Results from the NOWAC Study. Gynecologic oncology. 2018; 149:127-32.
21. Backman T, Rauramo I, Jaakkola K, Inki P, Vaahtera K, Launonen A, et al. Use of the levonorgestrel-releasing intrauterine system and breast cancer. Obstetrics & Gynecology. 2005; 106:813-7.
22. Soini T, Hurskainen R, Grénman S, Mäenpää J, Paavonen J, Pukkala E. Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland. Obstetrics & Gynecology. 2014; 124:292-9.
23. Schwarz EB, Hess R, Trussell J. Contraception for cancer survivors. Journal of general internal medicine. 2009; 24:401-6.
24. Patel A, Schwarz E. Society of Family Planning. Cancer and contraception. Release date May 2012. SFP Guideline# 20121. Contraception. 2012; 86:191-8.
25. Shi Q, Li J, Li M, Wu J, Yao Q, Xing A. The role of levonorgestrel-releasing intrauterine system for endometrial protection in women with breast cancer taking tamoxifen. European journal of gynaecological oncology. 2014; 35:492-8.
26. Bucciero M, Parda-Chlebowicz M. Contrac-eption: Overview. Ambulatory Gynecology: Springer; 2018. p. 33-57.
27. Hohmann H, Creinin MD. The contraceptive implant. Clinical obstetrics and gynecology. 2007; 50:907-17.
28. Sweeney C, Giuliano AR, Baumgartner KB, Byers T, Herrick JS, Edwards SL, et al. Oral, injected and implanted contraceptives and breast cancer risk among US Hispanic and non?Hispanic white women. International journal of cancer. 2007; 121:2517-23.
29. Tchekmedyian NS, Tait N, Moody M, Greco FA, Aisner J, editors. Appetite stimulation with megestrol acetate in cachectic cancer patients. Seminars in oncology; 1986.
30. Loprinzi CL, Ellison NM, Schaid DJ, Krook JE, Athmann LM, Dose AM, et al. Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. JNCI: Journal of the National Cancer Institute. 1990; 82:1127-32.
31. Kornblith AB, Hollis DR, Zuckerman E, Lyss AP, Canellos GP, Cooper MR, et al. Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B. Journal of clinical oncology. 1993; 11:2081-9.
32. Quella SK, Loprinzi CL, Sloan JA, Vaught NL, DeKrey WL, Fischer T, et al. Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes. Cancer: Interdisciplinary International Journal of the American Cancer Society. 1998; 82:1784-8.
33. Goodwin JW, Green SJ, Moinpour CM, Bearden III JD, Giguere JK, Jiang CS, et al. Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: Southwest Oncology Group Study 9626. Journal of clinical oncology. 2008; 26:1650-6.
34. Warren MP. Is megestrol acetate a suitable option for treatment of hot flashes in women with breast cancer? Nature clinical practice Endocrinology & metabolism. 2008; 4:650-1.
35. Schindler AE, Henkel A, Christensen B, Oettel M, Moore C. Dienogest and the breast. Gynecol Endocrinol. 2009; 25:472-4.
36. Beex L, Pieters G, Smals A, Koenders A, Benraad T, Kloppenborg P. Tamoxifen versus ethinyl estradiol in the treatment of postmenopausal women with advanced breast cancer. Cancer treatment reports. 1981; 65:179-85.
37. Iwase H, Yamamoto Y, Yamamoto-Ibusuki M, Murakami K, Okumura Y, Tomita S, et al. Ethinylestradiol is beneficial for postmenopausal patients with heavily pre-treated metastatic breast cancer after prior aromatase inhibitor treatment: a prospective study. British journal of cancer. 2013; 109:1537.
38. Goto H, Inao T, Nakano M, Ibusuki M, Murakami K, Yamamoto Y, et al. [A case of estrogen receptor-positive metastatic breast cancer in a postmenopausal woman treated with ethinyl estradiol]. Gan to kagaku ryoho Cancer & chemotherapy. 2013; 40:2569-71.
39. Rohan TE, McMichael AJ. Non-contraceptive exogenous oestrogen therapy and breast cancer. The Medical journal of Australia. 1988; 148:217-21.
40. Pellegrini A, Massidda B, Mascia V, Ionta MT, Lippi MG, Muggiano A, et al. Ethinyl estradiol and medroxyprogesterone treatment in advanced breast cancer: a pilot study. Cancer Treat Rep. 1981; 65:135-6.
41.Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric : the journal of the International Menopause Society. 2005; 8:3-63.
42. Neumann F. Pharmacology and potential use of cyproterone acetate. Hormone and metabolic research. 1977; 9:1-13.
43. Bulun S. Physiology and Pathology of the Female Reproductive Axis In: Melmed S, Polonsky K, Larsen PR, Kronenberg H, editors. Williams Textbook of Endocrinology. (Thirteenth Edition) ed: Elsevier; 2016. p. 590-663.
44. Goldenberg S, Bruchovsky N. Use of cyproterone acetate in prostate cancer. The Urologic Clinics of North America. 1991; 18:111-22.
45. Cremoncini C, Vignati E, Libroia A. Treatment of hirsutism and acne in women with two combinations of cyproterone acetate and ethinylestradiol. Acta Europaea Fertilitatis. 1976; 7:299-314.
46. Willemse P, Dikkeschei L, Mulder N, Van Der Ploeg E, Sleijfer DT, De Vries E. Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer. European Journal of Cancer and Clinical Oncology. 1988; 24:417-21.
47. Lopez M. Cyproterone acetate in the treatment of metastatic cancer of the male breast. Cancer. 1985; 55:2334-6.
48. Lopez M, Barduagni A. Cyproterone acetate in advanced male breast cancer. Cancer. 1982; 49:9-11.
49.Green L, Wysowski DK, Fourcroy JL. Gynecomastia and breast cancer during finasteride therapy. New England Journal of Medicine. 1996; 335:823-.
50. Lee SC, Ellis RJ. Male breast cancer during finasteride therapy. Journal of the National Cancer Institute. 2004; 96:338-9.
51. Duijnhoven RG, Straus SM, Souverein PC, de Boer A, Bosch JR, Hoes AW, et al. Long-term use of 5?-reductase inhibitors and the risk of male breast cancer. Cancer Causes & Control. 2014; 25:1577-82.
52. Bird ST, Brophy JM, Hartzema AG, Delaney JA, Etminan M. Male breast cancer and 5?-reductase inhibitors finasteride and dutasteride. The Journal of urology. 2013; 190:1811-4.
53.Loube S. Breast cancer associated with administration of spironolactone. Lancet. 1975; 28:1428-9.
54. Stierer M, Spoula H, Rosen H. Breast cancer in the male--a retrospective analysis of 15 cases. Onkologie. 1990; 13:128-31.
55. Mackenzie IS, MacDonald TM, Thompson A, Morant S, Wei L. Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ. 2012; 345:e4447.
56. Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M. Spironolactone use and the risk of breast and gynecologic cancers. Cancer epidemiology. 2013; 37:870-5.
57. Roy SN, Bhattacharya S. Benefits and risks of pharmacological agents used for the treatment of menorrhagia. Drug safety. 2004; 27:75-90.
58. Kessel B. Premenstrual syndrome: Advances in diagnosis and treatment. Obstetrics and gynecology clinics of North America. 2000; 27:625-39.
59.Panay N. Management of premenstrual syndrome. BMJ Sexual & Reproductive Health. 2009; 35:187-94.
60. Dr?g?nescu M, Carmocan C. Hormone Therapy in Breast Cancer. Chirurgia (Bucharest, Romania: 1990). 2017; 112:413-7.
61. Kendzierski DC, Schneider BP, Kiel PJ. Efficacy of Different Leuprolide Administration Schedules in Premenopausal Breast Cancer: A Retrospective Review. Clinical breast cancer. 2018; 18:e939-e42.
62. Wang C, Chen M, Fu F, Huang M. Gonadotropin-releasing hormone analog cotreatment for the preservation of ovarian function during gonadotoxic chemotherapy for breast cancer: a meta-analysis. PloS one. 2013; 8:e66360.
63. Leonard R, Adamson D, Bertelli G, Mansi J, Yellowlees A, Dunlop J, et al. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial. Annals of Oncology. 2017; 28:1811-6.