Integumentary System - Mammary Gland Development

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Adult female mammary anatomy cartoon

The mammary gland is the functional structure of the female breast and develops initially as a skin specialization. Breast growth and appearance in male and female children are virtually identical prior to puberty.

Postnatally at puberty female mammary glands under the influence of mainly sex hormone signaling, undergo a series of growth changes that can be defined anatomically by a series of "Tanner Stages". The bilayered mammary epithelium initially forms ducts that extend and branch.

In pregnancy, an additional series of signals leads to further changes in breast structure, differentiating into milk-producing alveoli. The key function of this process is to prepare the maternal breast for lactation and providing nutrition through milk to the newborn. (More? Normal Development - Milk)

Molecular signals identified as involved in this process include multiple Wnt ligands and β-catenin’s transcriptional activity for developmental processes and also for mammary stem cell self renewal.

At menopause, changes in sex hormone secretion can once again alter breast structure.

The breast also associated with oncogenesis (breast cancer). Research in this area has been aided by the discovery in 1994 of the two breast cancer susceptibility genes (BRCA1, BRCA2). There is some developing evidence that modification of stem cells (progenitor cells) that exist in the mammary gland may also contribute to neoplasms (cancer).

Integumentary Links: Introduction | Lecture | Hair | Tooth | Nail | Gland | Mammary Gland | Eyelid | Outer Ear | Melanocyte | Touch | Histology | Abnormalities | Category:Integumentary
Historic Embryology  
1910 Manual of Human Embryology | 1914 Integumentary | 1923 Head Subcutaneous Plexus | 1921 Text-Book of Embryology | 1924 Developmental Anatomy | 1941 Skin Sensory | Historic Disclaimer

Normal Development - Milk

Some Recent Findings

  • Characterization of the correlation between ages at entry into breast and pubic hair development [1] "Among 3938 participants, estimated mean ages at entry into Tanner stage 2 for breast and pubic hair development were 10.19 and 10.95, respectively."
  • Elevated Circulating IGF-I Promotes Mammary Gland Development and Proliferation[2]"Animal studies have shown that Insulin-like growth factor 1 (IGF-1, somatomedin-C) is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. "
  • Editorial: The Mammary Stroma in Normal Development and Function[3] "Many lines of evidence have evolved to reinforce the notion that mammary epithelial cell growth, differentiation, lactation and progression to cancer involves bidirectional interactions between the epithelial population and its surrounding stroma. ...the stromal environment constitutes and supports a critical vasculature that supplies nutrients and endocrine cues, a lymphatic system that not only removes metabolites but also provides an intimate interface with the immune system, and an extracellular matrix scaffold in which epithelial cells grow, differentiate and regress."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Mammary Embryology

Kun Wang, Zhiyan Shan, Lian Duan, Tiantian Gong, Feng Liu, Yue Zhang, Zhendong Wang, Jingling Shen, Lei Lei iTRAQ-based quantitative proteomic analysis of Yamanaka factors reprogrammed breast cancer cells. Oncotarget: 2017; PubMed 28423718

Marta Santos, Patrícia Dias-Pereira, Christina Williams, Carlos Lopes, Matthew Breen Malignant canine mammary tumours: Preliminary genomic insights using oligonucleotide array comparative genomic hybridisation analysis. Vet. J.: 2017; PubMed 28392153

Maria Panagopoulou, Maria Lambropoulou, Ioanna Balgkouranidou, Evangelia Nena, Makrina Karaglani, Christina Nicolaidou, Anthi Asimaki, Theocharis Konstantinidis, Theodoros C Constantinidis, George Kolios, Stylianos Kakolyris, Theodoros Agorastos, Ekaterini Chatzaki Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer. Tumour Biol.: 2017, 39(4);1010428317697557 PubMed 28381193

Shi-Wen Jiang, Siliang Xu, Haibin Chen, Jiayin Liu, Ping Duan Oncogenic role of SET/I2PP2A for gynecologic cancers. Curr Drug Targets: 2017; PubMed 28356029

Yuki Otsuki, Koichi Ueda, Chisei Satoh, Ryuta Maekawa, Koh-Ichiro Yoshiura, Sachiko Iseki Intermediate Phenotype between ADULT Syndrome and EEC Syndrome Caused by R243Q Mutation in TP63. Plast Reconstr Surg Glob Open: 2016, 4(12);e1185 PubMed 28293528


  • Human Embryology (2nd ed.) Larson Chapter 14 p443-455
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 20: P513-529
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 21: P481-496
  • Essentials of Human Embryology Larson Chapter 14: P303-315
  • Human Embryology, Fitzgerald and Fitzgerald
  • Color Atlas of Clinical Embryology Moore Persaud and Shiota Chapter 15: p231-236

Development Overview

  • week 6 epidermis downgrowth into dermis, modified sweat glands
    • epithelia/mesenchyme inductive interaction, mesenchyme forms connective tissue and fat
  • mammary ridges - mammary bud formation, pair of ventral regions axilla to inguinal
    • pectoral regions generate breasts
  • buds branch to form lactiferous ducts, only main duct formed at birth
  • mammary pit - forms fetal period
  • areola - depressed region at gland, proliferation of connective tissue postnatally
  • prior to puberty male and female glands the same


The mamma consists of gland tissue; of fibrous tissue, connecting its lobes; and of fatty tissue in the intervals between the lobes. The gland tissue, when freed from fibrous tissue and fat, is of a pale reddish color, firm in texture, flattened from before backward and thicker in the center than at the circumference.

The subcutaneous surface of the mamma presents numerous irregular processes which project toward the skin and are joined to it by bands of connective tissue. It consists of numerous lobes, and these are composed of lobules, connected together by areolar tissue, blood vessels, and ducts.

The smallest lobules consist of a cluster of rounded alveoli, which open into the smallest branches of the lactiferous ducts; these ducts unite to form larger ducts, and these end in a single canal, corresponding with one of the chief subdivisions of the gland. The number of excretory ducts varies from fifteen to twenty; they are termed the tubuli lactiferi.

(from Gray's Anatomy)

Adult female mammary anatomy cartoon


  • sex hormone estrogen stimulate growth, full development approx 20 years
  • growth also influenced by other hormones - progereterone, prolactin, corticoids, growth hormone
  • mainly fat and connective tissue deposition

Tanner Mammary Development Stages

In 1976 Tanner and Whitehouse established a series of descriptive stages for primary and secondary sexual characteristic development at puberty. The female secondary sex characteristics of breast development were divided into five numbered (I - V) "Tanner Stages".[4]

Tanner Stages
Tanner Stage Genitals (male) Breasts (female) Pubic hair (male and female)
prepubertal (testis volume < 1.5 ml
small penis (3 cm or less)
(age 9 and younger)
no glandular tissue
areola follows the skin contours of the chest (prepubertal)
(age 10 and younger)
no pubic hair at all (prepubertal state)
(age 10 and younger)
testis volume 1.6 to 6 ml
skin on scrotum thins, reddens and enlarges
penis length unchanged
(age 9–11)
breast bud forms
with small area of surrounding glandular tissue
areola begins to widen
(age 10–11.5)
small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females)
(age 10–11.5)
testis volume 6 to 12 ml
scrotum enlarges further
penis begins to lengthen to about 6 cm
(age 11–12.5)
breast begins to become more elevated
and extends beyond the borders of the areola, which continues to widen but remains in contour with surrounding breast
(age 11.5–13)
hair becomes more coarse and curly
begins to extend laterally
(age 11.5–13)
testis volume 12 to 20 ml
scrotum enlarges further and darkens
penis increases in length to 10 cm and circumference
(age 12.5–14)
increased breast size and elevation
areola and papilla form a secondary mound projecting from the contour of the surrounding breast
(age 13–15)
adult–like hair quality
extending across pubis but sparing medial thighs
(age 13–15)
testis volume > 20 ml
adult scrotum and penis of 15 cm in length
(age 14+)
breast reaches final adult size
areola returns to contour of the surrounding breast
with a projecting central papilla
(age 15+)
hair extends to medial surface of the thighs
(age 15+)
Links: Puberty Development | Genital System Development | Female | Male
Note that while typical ages are shown in brackets within the table, this is not a system for determining age.
Based upon W.A. Marshall and J.M. Tanner, published stages for girls (1969 [5]) and boys (1970 [6]).

Mammary Glands Pregnancy

During pregnancy raised estrogens and progesterone stimulate gland development, secretory alveolar structures form and differentiate, leading to milk production in late pregnancy and milk secretion during lactation. Breasts are hemispherical in shape due to fat deposition. After birth, neonatal lactation supports further growth/development.

Mammary Glands Weaning

After the infant ceases breast feeding, weaning, the mammary gland milk-producing epithelial cells undergo a process called "involution", that requires cell apoptosis.

Mammary involution.jpg

Mammary involution[7]


Adult female mammary anatomy cartoon

The mammary glands are modified glands of the skin and their development is similar to that of sweat glands.

  • compound branched alveolar glands, secretory unit is the alveolus
  • consist of 15-25 lobes separated by dense interlobar connective tissue and fat.
  • each lobe contains an individual gland.
  • lactiferous duct - excretory duct of each lobe with own opening on the nipple.


  • inner layer of cuboidal secretory epithelial cells
    • merocrine secretion, protein micelles are release by exocytosis.
  • outer layer of myoepithelial cells
    • located between the secretory cells and the surrounding basal lamina.
    • contraction helps force the milk from the secretory alveoli into the ducts.

Note - plasma cells in the stroma also secrete antibodies (dimeric IgA) and released into the milk, to provides passive immunity to the suckling young.

lactiferous duct lactating mammary gland
Lactiferous duct 01.jpg Mammary gland 01.jpg

Mouse Mammary

Mouse mammary gland development (E14.5)[8]

E10 - milk line first formed by a slight thickening and stratification of the surface ectoderm.

E10.5 - expression of Wnt10b in mammary lines on the trunk between the limbs and in axillary and inguinal streaks.

E11.5 - the milk line breaks up into individual placodes and the underlying mammary mesenchyme begins to condense.

E15.5 - mammary epithelium begins to proliferate at the tip and the primary sprout pushes through the mammary mesenchyme towards the underlying fat pad.

E18.5 - elongating duct has now grown into the fat pad and has branched into a small ductal system. Cells of the mammary mesenchyme have formed the nipple, which is made of specialized epidermal cells.

Timeline data from review[9]

Related Mouse Mammary Images: E10/11 | E11 | E12 | E13 | E14.5

Wnt Signaling

Canonical Wnt signals are transduced through a Frizzled receptor and the LRP5 or LRP6 co-receptor. Loss of Lrp6 compromises Wnt/beta-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis.[10]

Non-canonical receptor Ror2 along with its ligand Wnt5b (expressed in both the basal and luminal cell layers) regulates the branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium.[11]

Links: Wnt Signaling | Mouse Timeline Detailed


Abnormalities occur in approximately 1% of female population and include in both sexes:

  • polymastia - extra breast
  • polytheli - extra nipple
  • supernumerary nipple (relatively common in males)
  • gynecomastia (Greek, gyne = woman, mastos = breast) is the excessive development of the male breast, which can occur transiently in puberty or due to other (hormonal) abnormalities.

International Classification of Diseases

Q83 Congenital malformations of breast

Excl.: absence of pectoral muscle (Q79.8)

  • Q83.0 Congenital absence of breast with absent nipple
  • Q83.1 Accessory breast Supernumerary breast
  • Q83.2 Absent nipple
  • Q83.3 Accessory nipple Supernumerary nipple
  • Q83.8 Other congenital malformations of breast Hypoplasia of breast
  • Q83.9 Congenital malformation of breast, unspecified
ICD-10 Code: Q83 Congenital malformations of breast

Breast Cancer

In 1994, two breast cancer susceptibility genes were identified BRCA1 on chromosome 17 and BRCA2 on chromosome 13.

When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth. (text modified from: NCBI genes and disease)

BRAC1 and more recently BRIP1 (BRCA1-interacting protein 1) appear to be statistically the more common cancer genes associated with breast cancer.


Australia - Breast cancer in young women

New cases of breast cancer by histology type and age group (Australia, 2009)

26 Oct 2015 Key facts about breast cancer in women in their 20s and 30s[12]

  • In 2015, it is projected that 795 young women will be diagnosed with breast cancer and 65 will die from this disease.
    • On average, this is more than 2 breast cancers diagnosed every day and more than 1 death every week.
  • most commonly diagnosed cancer for women aged 20 to 39 and is associated with poorer survival outcomes.
    • for women aged 40 and over, 40 new cases per day and 57 deaths per week-breast cancer.
  • Overall, 5-year relative survival is significantly lower in younger women, who had an 88% chance of surviving for 5 years in 2007-2011 compared with the 5-year relative survival rate for women aged 40 and over of 90%. However, the 5-year relative survival rate has improved for young women, from 72% in 1982-1986 to 88% in 2007-2011.
Links: Australian Statistics


  1. Krista Yorita Christensen, Mildred Maisonet, Carol Rubin, W Dana Flanders, Carolyn Drews-Botsch, Celia Dominguez, Michael A McGeehin, Michele Marcus Characterization of the correlation between ages at entry into breast and pubic hair development. Ann Epidemiol: 2010, 20(5);405-8 PubMed 20382343
  2. Dara Cannata, Danielle Lann, Yingjie Wu, Sebastien Elis, Hui Sun, Shoshana Yakar, Deborah A Lazzarino, Teresa L Wood, Derek Leroith Elevated circulating IGF-I promotes mammary gland development and proliferation. Endocrinology: 2010, 151(12);5751-61 PubMed 20926579
  3. Pepper Schedin, Russell C Hovey Editorial: The mammary stroma in normal development and function. J Mammary Gland Biol Neoplasia: 2010, 15(3);275-7 PubMed 20824491
  4. J M Tanner, R H Whitehouse Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch. Dis. Child.: 1976, 51(3);170-9 PubMed 952550
  5. W A Marshall, J M Tanner Variations in pattern of pubertal changes in girls. Arch. Dis. Child.: 1969, 44(235);291-303 PubMed 5785179
  6. W A Marshall, J M Tanner Variations in the pattern of pubertal changes in boys. Arch. Dis. Child.: 1970, 45(239);13-23 PubMed 5440182
  7. Christine J Watson Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ. Breast Cancer Res.: 2006, 8(2);203 PubMed 16677411 | Breast Cancer Res.
  8. Beatrice Howard, Alan Ashworth Signalling pathways implicated in early mammary gland morphogenesis and breast cancer. PLoS Genet.: 2006, 2(8);e112 PubMed 16933995 | PLoS Genet.
  9. Gertraud W Robinson Cooperation of signalling pathways in embryonic mammary gland development. Nat. Rev. Genet.: 2007, 8(12);963-72 PubMed 18007652
  10. Charlotta Lindvall, Cassandra R Zylstra, Nicole Evans, Richard A West, Karl Dykema, Kyle A Furge, Bart O Williams The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS ONE: 2009, 4(6);e5813 PubMed 19503830
  11. Kevin Roarty, Amy N Shore, Chad J Creighton, Jeffrey M Rosen Ror2 regulates branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium. J. Cell Biol.: 2015; PubMed 25624393 | J Cell Biol.
  12. AIHW 2015. Breast cancer in young women: key facts about breast cancer in women in their 20s and 30s. Cancer series no. 96. Cat. no. CAN 94. Canberra: AIHW.



Christophe M Lefèvre, Julie A Sharp, Kevin R Nicholas Evolution of lactation: ancient origin and extreme adaptations of the lactation system. Annu Rev Genomics Hum Genet: 2010, 11;219-38 PubMed 20565255

Pamela Cowin, John Wysolmerski Molecular mechanisms guiding embryonic mammary gland development. Cold Spring Harb Perspect Biol: 2010, 2(6);a003251 PubMed 20484386

Constantine Dimitrakakis, Carolyn Bondy Androgens and the breast. Breast Cancer Res.: 2009, 11(5);212 PubMed 19889198

Anne M Rowzee, Deborah A Lazzarino, Lauren Rota, Zhaoyu Sun, Teresa L Wood IGF ligand and receptor regulation of mammary development. J Mammary Gland Biol Neoplasia: 2008, 13(4);361-70 PubMed 19020961

Heather L LaMarca, Jeffrey M Rosen Minireview: hormones and mammary cell fate--what will I become when I grow up? Endocrinology: 2008, 149(9);4317-21 PubMed 18556345

M M Richert, K L Schwertfeger, J W Ryder, S M Anderson An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia: 2000, 5(2);227-41 PubMed 11149575


Radhika Nair, Simon Junankar, Sandra O'Toole, Jaynish Shah, Alexander D Borowsky, J Michael Bishop, Alexander Swarbrick Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development. PLoS ONE: 2010, 5(8);e11947 PubMed 20689821

Thomas W Owens, Fiona M Foster, Jolanta Tanianis-Hughes, Julia Y Cheung, Lisa Brackenbury, Charles H Streuli Analysis of inhibitor of apoptosis protein family expression during mammary gland development. BMC Dev. Biol.: 2010, 10;71 PubMed 20584313

Nicholas McCormick, Vanessa Velasquez, Lydia Finney, Stefan Vogt, Shannon L Kelleher X-ray fluorescence microscopy reveals accumulation and secretion of discrete intracellular zinc pools in the lactating mouse mammary gland. PLoS ONE: 2010, 5(6);e11078 PubMed 20552032

| PLoS One. Holly E Barker, Gordon K Smyth, James Wettenhall, Teresa A Ward, Mary L Bath, Geoffrey J Lindeman, Jane E Visvader Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland. BMC Dev. Biol.: 2008, 8;94 PubMed 18826651

D T Ramsay, J C Kent, R A Hartmann, P E Hartmann Anatomy of the lactating human breast redefined with ultrasound imaging. J. Anat.: 2005, 206(6);525-34 PubMed 15960763

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