Abstract
This review presents an atlas of the histology of the normal physiological states of the human breast including prenatal, prepubertal, and pubertal development, adult resting gland, pregnancy, lactation, and postinvolution. The aim is to produce a pictorial overview of the main stages in development and the common findings in the adult that are considered to be within the range of normality. Unlike inbred strains of animals, in humans it is clear that the chronology of ductal and lobular development is not predictable, either in the fetus, the infant, the peripubertal breast, or the adult. This is probably due to the individual variation in hormone levels both in utero and after birth. For many of the developmental time points there are very little data available. In this review we indicate the current state of knowledge of human breast development and some of the main similarities and differences with the rodent, the main animal model. The major phases of growth and development are described and accompanied by photographs that are representative of each stage. Stress is placed on terminology as there is confusion in the literature. This article is written as an accessory to the companion review on breast cancer.
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REFERENCE
T. Sakakura (1987). Mammary embryogenesis. In M. C. Neville and C. W. Daniel (eds.), The Mammary Gland: Development Regulation and Function, Plenum Press, New York, pp. 37–66.
G. W. Robinson, A. B. Karpf, and K. Kratochwil (1999). Regulation of mammary gland development by tissue interaction. J. Mammary Gland Biol. Neoplasia 4:9–19.
G. Chepko and G. H. Smith (1999). Mammary epithelial stem cells: Our current understanding. J. Mammary Gland Biol. Neoplasia 4:35–52.
I. Thesleff, A. Vaahtokari, and A. M. Partanen (1995). Regulation of organogenesis. Int. J. Dev. Biol. 39:35–50.
C. Tickle (1995). Vertebrate limb development. Curr. Opin. Genet. Dev. 5:478–484.
R. L. Johnson and C. J. Tabin (1997). Molecular models for vertebrate limb development. Cell 90:979–990.
J. W. R. Schwabe, C. Rodriguez-Esteban, and J. C. I. Belmonte (1998). Limbs are moving: Where are they going? Trends Genet. 14:229–235.
L. Niswander (1997). Limb mutants: What can they tell us about normal limb development. Curr. Opin. Genet. Dev. 7:530–536.
H. Peters and R. Balling (1999). Teeth. Where and how to make them. Trends Genet. 15:59–65.
I. Thesleff and P. Nieminen (1996). Tooth morphogenesis and cell differentiation. Curr. Opin. Cell Biol. 8:844–850.
J. F. Wiesen, P. Young, Z. Werb, and G. R. Cunha (1999). Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 126:335–344.
M. E. Dunbar, P. Young, J. P. Zhang, J. McCaughern-Carucci, B. Lanske, J. J. Orloff, A. Karaplis, G. Cunha, and J. J. Wysolmerski (1998). Stromal cells are critical targets in the regulation of mammary ductal morphogenesis by parathyroid hormone-related protein. Dev. Biol. 203:75–89.
J. Sebastian, R. G. Richards, M. P. Walker, J. F. Wiesen, Z. Werb, R. Derynck, Y. K. Hom, G. R. Cunha, and R. P. DiAugustine (1998). Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth Differ. 9:777–785.
L. Hennighausen and G. W. Robinson (1998). Think globally, act locally: The making of a mouse mammary gland. Genes Dev. 12:449–455.
R. D. Cardiff and S. R. Wellings (1999). The comparative pathology of human and mouse mammary glands. J. Mammary Gland Biol. Neoplasia 4:105–122.
H. Vorherr (1974). The Breast: Morphology, Physiology, and Lactation. Academic Press, New York.
E. S. R. Hughes (1949). The development of the mammary gland. Ann. R. Coll. Surg. Engl. 6:99–119.
E. K. Dawson (1934). A histological study of the normal mamma in relation to tumour growth. 1—Early development to maturity. Edinburgh Med. J. 41:653–682.
D. J. Laurence, P. Monaghan, and B. A. Gusterson (1991). The development of the normal human breast. Oxf. Rev. Reprod. Biol. 13:149–174.
J. Russo and I. H. Russo (1987). Development of the human mammary gland. In M. C. Neville and C. W. Daniel (eds.), The Mammary Gland: Development Regulation and Function, Plenum Press, New York, pp. 67–93.
R. R. Gates (1946). Inheritance of various sexual and intersexual conditions, Human Genetics, Macmillan, New York.
J. Dixon (1995). ABC of Breast Diseases, BMJ, London.
L. E. Hughes, R. E. Mansel, and D. J. T. Webster (1989). Benign Disorders and Diseases of the Breast: Concepts and Clinical Management, Baillière Tindall, London.
F. C. Fraser (1956). Dominant Inheritance of Absent Nipples and Breasts, Instituto Gregorio Mendel, Rome.
H. Goldenring and E. S. Crelin (1961). Mother and daughter with bilateral congenital amastia. Yale J. Biol. Med. 33:466–467.
G. H. Klinkerfuss (1924). Four generations of polymastia. JAMA 82:1247–1248.
M. Bamshad, R. C. Lin, D. J. Jaw, W. S. Watkins, P. A. Krakowiak, M. E. Moore, P. Franceschini, R. Lala, L. B. Holmes, T. C. Gebuhr, B. G. Bruneau, A. Schinzel, C. E. Seidman, and L. B. Jorde (1997). Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat. Genet. 16:311–315.
H. van Bokhoven, M. Jung, A. P. Smits, S. van Beersum, R. S. F. M. van Steensel, M. Veenstra, J. H. Tuerlings, E. C. Mariman, H. G. Brunner, T. F. Wienker, A. Reis, H. H. Ropers, and B. C. Hamel (1999). Limb mammary syndrome: A new genetic disorder with mammary hypoplasia, ectrodactyly, and other hand/foot anomalies maps to human chromosome 3q27. Am. J. Hum. Genet. 64:538–546.
E. F. Scanlon (1986). Benign diseases of the breast. In R. J. McKenna and G. P. Murphy (eds.), Fundamentals of Surgical Oncology, Macmillan, New York, pp. 548–556.
B. Staats, U. Bonk, S. Wanschura, P. Hanisch, E. F. Schoenmakers, W. J. Van de Ven, S. Bartnitzke, and J. Bullerdiek (1996). A fibroadenoma with a t(4;12) (q27;q15) affecting the HMGI-C gene, a member of the high mobility group protein gene family. Breast Cancer Res. Treat. 38:299–303.
P. P. Osin, R. Anbazhagan, J. Bartkova, B. Nathan, and B. A. Gusterson (1998). Breast development gives insights into breast disease. Histopathology 33:275–283.
R. Anbazhagan (1993). Foetal and infant breast development. In Pathology, University of London, London, p. 292.
R. Anbazhagan, P. P. Osin, J. Bartkova, B. Nathan, E. B. Lane, and B. A. Gusterson (1998). The development of epithelial phenotypes in the human fetal and infant breast. J. Pathol. 184:197–206.
P. Monaghan, N. P. Perusinghe, P. Cowen, and B. A. Gusterson (1990). Peripubertal human breast development. Anat. Rec. 226:501–508.
R. Anbazhagan, B. Nathan, and B. A. Gusterson (1992). Prenatal influences and breast cancer [letter; comment]. Lancet 340:1477–1478.
R. Anbazhagan and B. A. Gusterson (1992). Reversed cerebral asymmetry and breast cancer [letter; comment]. Lancet 339:1056.
R. Anbazhagan and B. A. Gusterson (1994). Prenatal factors may influence predisposition to breast cancer. Eur. J. Cancer 1:1–3.
J. F. Meckel (1820). Handbuch der menschlichen Anatomie, Halle, Germany.
C. Langer (1850). Milchdruse. Idenkschr. Akad. Wiss. Wien.
M. Huss (1873). Entwicklungsgeschichte der Milchdrusen. Jena Z. Naturw. 7:176.
A. Kolliker (1879). Brustdruse. Verh. Med.-Physik. Ges. Wurzb. 14:198–202.
G. Rein (1896). Hyperthelie menschlichen Embryonen. Anat. Anz. 11:702.
M. C. Alvarez Sanz, J. M. Liu, H. H. Huang, and E. J. Hawrylewicz (1986). Effect of dietary protein on morphologic development of rat mammary gland. J. Natl. Cancer Inst. 77:477–487.
H. Salazar, H. Tobon, and J. B. Josimovich (1975). Developmental, gestational and postgestational modifications of the human breast. Clin. Obstet. Gynecol. 18:113–137.
P. Kellokumpu-Lehtinen, R. M. Johansson, and L. J. Pelliniemi (1987). Ultrastructure of human fetal mammary gland. Anat. Rec. 218:66–72.
B. L. Hogan (1999). Morphogenesis. Cell 96:225–233.
K. Kratochwil (1971). In vitro analysis of the hormonal basis for sexual dimorphism in the embryonic development of the mouse mammary gland. J. Embryol. Exp. Morphol. 25:141–153.
R. Anbazhagan, J. Bartek, P. Monaghan, and B. A. Gusterson (1991). Growth and development of the human infant breast. Am. J. Anat. 192:407–417.
K. Kratochwil and P. Schwartz (1976). Tissue interaction in androgen response of embryonic mammary rudiment of the mouse: Identification of target tissue for testosterone. Proc. Natl. Acad. Sci. USA 73:4041–4044.
C. W. Turner (1931). The anatomy of the mammary gland in cattle. II. Fetal development. Missouri Agric. Exp. Sta. Res. Bull. 160:5–39.
C. W. Turner (1930). The anatomy of the mammary gland of cattle. I. Embryonic development. Missouri Agric. Exp. Sta. Res. Bull. 140:3–34.
B. Nathan, R. Anbazhagan, P. Clarkson, J. Bartkova, and B. Gusterson (1994). Expression of BCL-2 in the developing human fetal and infant breast. Histopathology 24:73–76.
J. Hiba, E. D. Pozo, A. Genazzani, E. Pusterla, I. Lancranjan, D. Sidiropoulos, and J. Gunti (1977). Hormonal mechanism of milk secretion in the newborn. J. Clin. Endocrinol. Metab. 44:973–976.
A. J. Atherton, M. J. Warburton, M. J. O'Hare, P. Monaghan, D. Schuppan, and B. A. Gusterson (1998). Differential expression of type IV collagen/undulin by human mammary gland intralobular and interlobular fibroblasts. Cell Tiss. Res. 291:507–511.
A. J. Atherton, P. Monaghan, M. J. Warburton, D. Robertson, A. J. Kenny, and B. A. Gusterson (1992). Dipeptidyl peptidase IV expression identifies a functional subpopulation of breast fibroblasts. Int. J. Cancer 50:15–19.
A. J. Atherton, P. Monaghan, M. J. Warburton, and B. A. Gusterson (1992). Immunocytochemical localization of the ectoenzyme aminopeptidase N in the human breast. J. Histochem. Cytochem. 40:705–710.
R. Anbazhagan, J. Bartkova, G. Stamp, M. Pignatelli, B. Gusterson, and J. Bartek (1995). Expression of integrin subunits in the human infant breast correlates with morphogenesis and differentiation. J. Pathol. 176:227–232; Erratum (1996), J. Pathol. 178(2):235.
J. W. Keeling, G. King, and F. Walker (1998). Oestrogen and progesterone receptors in fetal, infant and childhood mammary tissue. J. Pathol. 186:21A.
S. A. Bartow (1998). Use of the autopsy to study ontogeny and expression of the estrogen receptor gene in human breast. J. Mammary Gland Biol. Neoplasia 3:37–48.
A. Dabelow (1957). Die Milchdruse. In A. Benninghoff et al. (eds.), Handbuch der mikroskopischen Anatomie des Menschen, Springer-Verlag, Berlin, pp. 277–512.
K. C. Richardson. (1947). The structural features of the mammary tissues. Br. Med. Bull. 5:123–129.
J. O. Drife (1986). Breast development in puberty. Ann. N.Y. Acad. Sci. 464:58–65.
J. Fraser (1929). The breast in health and disease. Edinburgh Med. J. 36:217–241.
D. L. Page and T. J. Anderson (1987). Diagnostic Histopathology of the Breast, Churchill Livingstone, Edinburgh.
H. Hamperl (1970). The myothelia (myoepithelial cells). Normal state; regressive changes; hyperplasia; tumors. Curr. Top. Pathol. 53:161–220.
C. A. Smith, P. Monaghan, and A. M. Neville (1984). Basal clear cells of the normal human breast. Virchows Arch. A Pathol. Anat. Histopathol. 402:319–329.
T. Kamalati, B. Niranjan, A. Atherton, R. Anbazhaghan, and B. Gusterson (1996). Differentiation antigens in stromal and epithelial cells of the breast. Cancer Treat. Res. 83:227–242.
C. Pechoux, T. Gudjonsson, L. Ronnov-Jessen, M. J. Bissell, and O. W. Petersen (1999). Human mammary luminal epithelial cells contain progenitors to myoepithelial cells. Dev. Biol. 206:88–99.
B. P. Eyden, R. J. Watson, M. Harris, and A. Howell (1986). Intralobular stromal fibroblasts in the resting human mammary gland: Ultrastructural properties and intercellular relationships. J. Submicrosc. Cytol. 18:397–408.
A. J. Atherton, R. Anbazhagan, P. Monaghan, J. Bartek, and B. A. Gusterson (1994). Immunolocalisation of cell surface peptidases in the developing human breast. Differentiation 56:101–106.
J. R. Harris (1996). Diseases of the Breast. Lippincott-Raven, Philadelphia.
W. M. Kramer and B. F. Rush, Jr. (1973). Mammary duct proliferation in the elderly. A histopathologic study. Cancer 31:130–137.
E. Mallon, P. Osin, N. Nasiri, I. Blain, B. Howard, and B. Gusterson (2000). The basic pathology of human breast cancer. J. Mammary Gland Biol. Neoplasia, this issue.
W. Bateson (1894). Materials for the Study of Variation, Macmillan, London.
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Howard, B.A., Gusterson, B.A. Human Breast Development. J Mammary Gland Biol Neoplasia 5, 119–137 (2000). https://doi.org/10.1023/A:1026487120779
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DOI: https://doi.org/10.1023/A:1026487120779