Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed.

1.
Glass AG, Lacey JV Jr, Carreon JD, Hoover RN: Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 2007;99:1152-1161.
2.
Miller BA, Feuer EJ, Hankey BF: Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin 1993;43:27-41.
3.
Trichopoulos D: Hypothesis: does breast cancer originate in utero? Lancet 1990;335:939-940.
4.
Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A: Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J Nutr 2002;132:552S-558S.
5.
Whitsett TG Jr, Lamartiniere CA: Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat. Expert Rev Anticancer Ther 2006;6:1699-1706.
6.
MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S: Age at first birth and breast cancer risk. Bull World Health Organ 1970;43:209-221.
7.
Hunt SC, Williams RR, Skolnick MH, Lyon JL, Smart CR: Breast cancer and reproductive history from genealogical data. J Natl Cancer Inst 1980;64:1047-1053.
8.
Santucci-Pereira J, George C, Armiss D, Russo IH, Vanegas JE, Sheriff F, de Cicco RL, Su Y, Russo PA, Bidinotto LT, Russo J: Mimicking pregnancy as a strategy for breast cancer prevention. Breast Cancer Manag 2013;2:283-294.
9.
Hickey M, Hart R, Keelan JA: The relationship between umbilical cord estrogens and perinatal characteristics. Cancer Epidemiol Biomarkers Prev 2014;23:946-952.
10.
Xue F, Michels KB: Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 2007;8:1088-1100.
11.
Park SK, Kang D, McGlynn KA, Garcia-Closas M, Kim Y, Yoo KY, Brinton LA: Intrauterine environments and breast cancer risk: meta-analysis and systematic review. Breast Cancer Res 2008;10:R8.
12.
Hilakivi-Clarke L: Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters. Breast Cancer Res 2014;16:208.
13.
Boylan ES, Calhoon RE: Transplacental action of diethylstilbestrol on mammary carcinogenesis in female rats given one or two doses of 7,12-dimethylbenz(a)anthracene. Cancer Res 1983;43:4879-4884.
14.
Soto AM, Brisken C, Schaeberle C, Sonnenschein C: Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. J Mammary Gland Biol Neoplasia 2013;18:199-208.
15.
Körner W, Hanf V, Schuller W, Kempter C, Metzger J, Hagenmaier H: Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents. Sci Total Environ 1999;225:33-48.
16.
Henneberg A, Bender K, Blaha L, Giebner S, Kuch B, Kohler HR, Maier D, Oehlmann J, Richter D, Scheurer M, Schulte-Oehlmann U, Sieratowicz A, Ziebart S, Triebskorn R: Are in vitro methods for the detection of endocrine potentials in the aquatic environment predictive for in vivo effects? Outcomes of the Projects SchussenAktiv and SchussenAktivplus in the Lake Constance Area, Germany. PloS One 2014;9:e98307.
17.
Troisi R, Grotmol T, Jacobsen J, Tretli S, Toft-Sorensen H, Gissler M, Kaaja R, Potischman N, Ekbom A, R NH, Stephansson O: Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population-based study. J Dev Orig Health Dis 2013;4:35-41.
18.
Hardefeldt PJ, Edirimanne S, Eslick GD: Diabetes increases the risk of breast cancer: a meta-analysis. Endocr Relat Cancer 2012;19:793-803.
19.
Taylor AP, Leon E, Goldenberg DM: Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement. Br J Cancer 2010;103:82-89.
20.
Ekbom A, Hsieh CC, Lipworth L, Adami HQ, Trichopoulos D: Intrauterine environment and breast cancer risk in women: a population-based study. J Natl Cancer Inst 1997;89:71-76.
21.
Douple EB, Mabuchi K, Cullings HM, Preston DL, Kodama K, Shimizu Y, Fujiwara S, Shore RE: Long-term radiation-related health effects in a unique human population: lessons learned from the atomic bomb survivors of Hiroshima and Nagasaki. Disaster Med Public Health Prep 2011;5(suppl 1):S122-133.
22.
Goto H, Watanabe T, Miyao M, Fukuda H, Sato Y, Oshida Y: Cancer mortality among atomic bomb survivors exposed as children. Environ Health Prev Med 2012;17:228-234.
23.
Gierisch JM, Coeytaux RR, Urrutia RP, Havrilesky LJ, Moorman PG, Lowery WJ, Dinan M, McBroom AJ, Hasselblad V, Sanders GD, Myers ER: Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 2013;22:1931-1943.
24.
Beaber EF, Buist DS, Barlow WE, Malone KE, Reed SD, Li CI: Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age. Cancer Res 2014;74:4078-4089.
25.
Obr AE, Edwards DP: The biology of progesterone receptor in the normal mammary gland and in breast cancer. Mol Cell Endocrinol 2012;357:4-17.
26.
Gurney EP, Nachtigall MJ, Nachtigall LE, Naftolin F: The women's health initiative trial and related studies: 10 years later: a clinician's view. J Steroid Biochem Mol Biol 2014;142:4-11.
27.
Imkampe AK, Bates T: Correlation of age at oral contraceptive pill start with age at breast cancer diagnosis. Breast J 2012;18:35-40.
28.
Beral V, Bull D, Doll R, Peto R, Reeves G: Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83,000 women with breast cancer from 16 countries. Lancet 2004;363:1007-1016.
29.
Wu JQ, Li YY, Ren JC, Zhao R, Zhou Y, Gao ES: Induced abortion and breast cancer: results from a population-based case control study in china. Asian Pac J Cancer Prev 2014;15:3635-3640.
30.
Barry JA, Azizia MM, Hardiman PJ: Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2014;20:748-758.
31.
Zreik TG, Mazloom A, Chen Y, Vannucci M, Pinnix CC, Fulton S, Hadziahmetovic M, Asmar N, Munkarah AR, Ayoub CM, Shihadeh F, Berjawi G, Hannoun A, Zalloua P, Wogan C, Dabaja B: Fertility drugs and the risk of breast cancer: a meta-analysis and review. Breast Cancer Res Treat 2010;124:13-26.
32.
Brinton LA, Scoccia B, Moghissi KS, Westhoff CL, Niwa S, Ruggieri D, Trabert B, Lamb EJ: Long-term relationship of ovulation-stimulating drugs to breast cancer risk. Cancer Epidemiol Biomarkers Prev 2014;23:584-593.
33.
Sergentanis TN, Diamantaras AA, Perlepe C, Kanavidis P, Skalkidou A, Petridou ET: IVF and breast cancer: a systematic review and meta-analysis. Hum Reprod Update 2014;20:106-123.
34.
Horn J, Opdahl S, Engstrom MJ, Romundstad PR, Tretli S, Haugen OA, Bofin AM, Vatten LJ, Asvold BO: Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women. Cancer Causes Control 2014;25:881-889.
35.
Kim JS, Kang EJ, Woo OH, Park KH, Woo SU, Yang DS, Kim AR, Lee JB, Kim YH, Kim JS, Seo JH: The relationship between preeclampsia, pregnancy-induced hypertension and maternal risk of breast cancer: a meta-analysis. Acta Oncol 2013;52:1643-1648.
36.
Kim HS, Woo OH, Park KH, Woo SU, Yang DS, Kim AR, Lee ES, Lee JB, Kim YH, Kim JS, Seo JH: The relationship between twin births and maternal risk of breast cancer: a meta-analysis. Breast Cancer Res Treat 2012;131:671-677.
37.
Tong GX, Cheng J, Chai J, Geng QQ, Chen PL, Shen XR, Liang H, Wang DB: Association between gestational diabetes mellitus and subsequent risk of cancer: a systematic review of epidemiological studies. Asian Pac J Cancer Prev 2014;15:4265-4269.
38.
Innes KE, Byers TE: First pregnancy characteristics and subsequent breast cancer risk among young women. Int J Cancer 2004;112:306-311.
39.
Collaborative Group on Hormonal Factors in Breast Cancer: Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. Lancet 2002;360:187-195.
40.
Faupel-Badger JM, Arcaro KF, Balkam JJ, Eliassen AH, Hassiotou F, Lebrilla CB, Michels KB, Palmer JR, Schedin P, Stuebe AM, Watson CJ, Sherman ME: Postpartum remodeling, lactation, and breast cancer risk: summary of a national cancer institute-sponsored workshop. J Natl Cancer Inst 2013;105:166-174.
41.
Jäger S, Jacobs S, Kroger J, Fritsche A, Schienkiewitz A, Rubin D, Boeing H, Schulze MB: Breast-feeding and maternal risk of type 2 diabetes: a prospective study and meta-analysis. Diabetologia 2014;57:1355-1365.
42.
Onitilo AA, Stankowski RV, Berg RL, Engel JM, Glurich I, Williams GM, Doi SA: Type 2 diabetes mellitus, glycemic control, and cancer risk. Eur J Cancer Prev 2014;23:134-140.
43.
Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA: Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone 2014;66:146-154.
44.
Palafox M, Ferrer I, Pellegrini P, Vila S, Hernandez-Ortega S, Urruticoechea A, Climent F, Soler MT, Munoz P, Vinals F, Tometsko M, Branstetter D, Dougall WC, Gonzalez-Suarez E: RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res 2012;72:2879-2888.
45.
Hanf V, Kreienberg R: (Breast cancer: importance of environmental factors in its formation). Med Monatsschr Pharm 1998;21:265-274.
46.
Kreuzer PE, Csanady GA, Baur C, Kessler W, Papke O, Greim H, Filser JG: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch Toxicol 1997;71:383-400.
47.
Wise LA, Titus-Ernstoff L: Exposure to breast milk in infancy and risk of adult breast cancer: more scientific data are needed. J Epidemiol Community Health 2010;64:745-746.
48.
Wise LA, Titus-Ernstoff L, Newcomb PA, Trentham-Dietz A, Trichopoulos D, Hampton JM, Egan KM: Exposure to breast milk in infancy and risk of breast cancer. Cancer Causes Control 2009;20:1083-1090.
49.
Innes KE, Byers TE: Smoking during pregnancy and breast cancer risk in very young women (United States). Cancer Causes Control 2001;12:179-185.
50.
Silva Idos S, De Stavola B, McCormack V: Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies. PLoS Med 2008;5:e193.
51.
Stephansson O, Granath F, Ekbom A, Michels KB: Risk of breast cancer among daughters of mothers with diabetes: a population-based cohort study. Breast Cancer Res 2010;12:R14.
52.
Choi JY, Lee KM, Park SK, Noh DY, Ahn SH, Yoo KY, Kang D: Association of paternal age at birth and the risk of breast cancer in offspring: a case control study. BMC Cancer 2005;5:143.
53.
Wilson KM, Willett WC, Michels KB: Mothers' pre-pregnancy BMI and weight gain during pregnancy and risk of breast cancer in daughters. Breast Cancer Res Treat 2011;130:273-279.
54.
Yuen J, Ekbom A, Trichopoulos D, Hsieh CC, Adami HO: Season of birth and breast cancer risk in Sweden. Br J Cancer 1994;70:564-568.
55.
Stocks P: Social status in relation to carcinoma of the breast. Schweiz Z Pathol Bakteriol 1955;18:706-717.
56.
Brasky TM, Li Y, Jaworowicz DJ Jr, Potischman N, Ambrosone CB, Hutson AD, Nie J, Shields PG, Trevisan M, Rudra CB, Edge SB, Freudenheim JL: Pregnancy-related characteristics and breast cancer risk. Cancer Causes Control 2013;24:1675-1685.
57.
Bukowski R, Davis KE, Wilson PW: Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease. PloS One 2012;7:e33047.
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