Abstract
This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents +breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women’s health.

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References
Siegel RL, Miller KD, Jemal A (2015) Cancer Statistics, 2015. CA Cancer J Clin 65(1):5–29
Dunn BK, Wickerham DL, Ford LG (2005) Prevention of hormone-related cancers: breast Cancer. J Clin Oncol 23(2):357–367
Murphy E (2011) Estrogen signaling and cardiovascular disease. Circ Res 109(6):687–696
Wells B, DiPiro J, Schwinghammer T, DiPiro C (2008) Pharmacotherapy handbook, seventh edition, 7th edn. McGraw-Hill Medical, New York
Adami H-O, Hunter D, Trichopoulos D (2008) Textbook of Cancer Epidemiology, vol 2. Oxford University Press, New York
NCHS Data Briefs: Current Contraceptive Status Among Women Aged 15–44: United States, 2011–2013 [Internet]. 2014 Dec [cited 2015 Apr 4]. Report No.: 173. http://www.cdc.gov/nchs/data/databriefs/db173.htm
Family Planning—United Nations Population Division Department of Economic and Social Affairs [Internet]. [cited 28 Mar 2015]. http://www.un.org/en/development/desa/population/theme/family-planning/index.shtml
Löwy I, Weisz G (2005) French hormones: progestins and therapeutic variation in France. Soc Sci Med 60(11):2609–2622
Warren MP, Shantha S (1999) Uses of progesterone in clinical practice. Int J Fertil Womens Med 44(2):96–103
Dumeaux V, Alsaker E, Lund E (2003) Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study. Int J Cancer 105(6):844–850
Beaber EF, Malone KE, Tang M-TC, Barlow WE, Porter PL, Daling JR et al (2014) Oral contraceptives and breast cancer risk overall and by molecular subtype among young women. Cancer Epidemiol Biomark Prev 23(5):755–764
Hormonal Contraceptives, Progestogens Only. In: Hormonal contraception and post-menopausal hormonal therapy: IARC monographs on the evaluation of carcinogenic risks to humans [Internet]. 1999. http://monographs.iarc.fr/ENG/Monographs/vol72/
Pasqualini JR (2007) Progestins and breast cancer. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 23(Suppl 1):32–41
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2007) Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 335(7624):806–808
Marchbanks PA, McDonald JA, Wilson HG, Folger SG, Mandel MG, Daling JR et al (2002) Oral contraceptives and the risk of breast cancer. N Engl J Med 346(26):2025–2032
Shapiro S, Rosenberg L, Hoffman M, Truter H, Cooper D, Rao S et al (2000) Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives. Am J Epidemiol 151(4):396–403
Strom BL, Berlin JA, Weber AL, Norman SA, Bernstein L, Burkman RT et al (2004) Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception. 69(5):353–360
Backman T, Rauramo I, Jaakkola K, Inki P, Vaahtera K, Launonen A et al (2005) Use of the levonorgestrel-releasing intrauterine system and breast cancer. Obstet Gynecol 106(4):813–817
Fabre A, Fournier A, Mesrine S, Desreux J, Gompel A, Boutron-Ruault M-C et al (2007) Oral progestagens before menopause and breast cancer risk. Br J Cancer 96(5):841–844
Kumle M, Weiderpass E, Braaten T, Persson I, Adami H-O, Lund E (2002) Use of oral contraceptives and breast cancer risk: the Norwegian–Swedish women’s lifestyle and health cohort study. Cancer Epidemiol Biomark Prev 11(11):1375–1381
Collaborative Group on Hormonal Factors in Breast Cancer (1996) Breast cancer and hormonal contraceptives: further results. Contraception 54(3 (Suppl)):1S–106S
Faculty of sexual & reproductive healthcare clinical guidance: Combined Hormonal Contraception Clinical Effectiveness Unit [Internet]. England: Faculty of Sexual and Reproductive Healthcare; pp 1–19. http://www.fsrh.org/pdfs/CEUGuidanceProgestogenOnlyPill09.pdf
Mantha S, Karp R, Raghavan V, Terrin N, Bauer KA, Zwicker JI (2012) Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis. BMJ 7(345):e4944
de Melo NR (2010) Estrogen-free oral hormonal contraception: benefits of the progestin-only pill. Womens Health 5:721
Faculty of Sexual & Reproductive Healthcare Clinical Guidance: Progestogen-only Pills Clinical Effectiveness Unit [Internet]. England: Faculty of Sexual and Reproductive Healthcare; pp 1–19. http://www.fsrh.org/pdfs/CEUGuidanceProgestogenOnlyPill09.pdf
Sitruk-Ware R (2006) New progestagens for contraceptive use. Hum Reprod Update 12(2):169–178
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This publication was made possible in part by Grant Number T32-GM081740 from NIH-NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH.
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Samson, M., Porter, N., Orekoya, O. et al. Progestin and breast cancer risk: a systematic review. Breast Cancer Res Treat 155, 3–12 (2016). https://doi.org/10.1007/s10549-015-3663-1
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DOI: https://doi.org/10.1007/s10549-015-3663-1