Lecture 28: Development, Anatomy and Physiology of Breast

Question 1

What is the leading cause of cancer for women?

Answer 1

Breast cancer

Question 2

What is mammogenesis?

Answer 2

Process by which breast develops

Question 3

What is lactogenesis?

Answer 3

Process by which milk is produced

Question 4

What is the primary function of the mammary gland?

Answer 4

Lactation

• provides nourishment to dependent offspring
• transfers passive immunity to the young
• facilitates bonding between mother and offspring
• promotes postpartum uterine involution

Question 5

What lymph nodes do you biopsy for breast cancer?

Answer 5

Axillary lymph nodes

Question 6

What are the components of breast tissue architecture?

Answer 6

1. Epithelial component (ectoderm)
   
   • 20%
   • ducts
   • lobules (acini, alvelolar epithelial cells)
2. Stromal/mesenchymal component (mesoderm)
   
   • fibrous connective tissue (fibroblast)
   • adipose tissue (adipocytes)

Question 7

What is TDLU?

Answer 7

Terminal Ductal Lubular Unit

Question 8

What are the two types of connective tissue in the breast?

Answer 8

1. Intralobular stroma

2. INTERlobular stroma (extralobular stroma)

Question 9

What are the stages of mammary gland development?

Answer 9

1. fetal
2. puberty
3. pregnancy
4. lactation
5. post-lactational involution
6. menopause

Question 10

What are the multipotent progenitors that forms the cells of the mammary glands?

Answer 10

1. Myoepithelial progenitor
2. Ductal progenitor
3. Alveolar progenitor

Question 11

What are the hormonal requirements for breast development in puberty?

Answer 11

Estrogen
Ductal morphogenesis (building the the tree)
Ductal elongation

Question 12

What are the hormonal requirements in preganancy?

Answer 12

Lobuloalveolar development (expanding leaves of tree

1. Progesterone
2. Prolactin

Question 13

What are the hormonal requirements in lactation?

Answer 13

1. Prolactin (cortisol)

2. Insulin

Question 14

What is colostrum?

Answer 14

The first secretion from the mammary glands after giving birth, rich in antibodies

Question 15

What is the milk streak or a milk line?

Answer 15

Precursors to mammary glands and nipples

Question 16

What are the characteristics of fetal mammary development?

Answer 16

1. Hormone independent events
   Milk streak  mammary buds  primordial ductal tree
2. Hormone dependent events
   -canalization of ducts
   -colostrum formation, parenchymal differentioation
3. No sexual dimorphism prior to puberty

Question 17

What is hormone independent in fetus?

Answer 17

Development of ductal tree

Question 18

What is hormone dependent in fetus?

Answer 18

Canalization of ducts

Colustrum formation

Question 19

When is the mitotic rate of glandular epithelial cells greatest?

Answer 19

During the luteal phase

Estrogen and progesterone are more mitogenic than E2 alone

Question 20

What are the changes in volume, nodularity and sensitivity in the breast in the luteal phase due to?

Answer 20

Due to tissue edema and hyperemia

Luteal phase

Question 21

What are the hormonal changes seen in pregnancy?

Answer 21

Progesterone, estrogen and prolactin
Progesterone and prolactin inhibit lactogenic action of prolactin
Lobuloalveolar development

Question 22

Are ovaries required for lactation?

Answer 22

No

Question 23

What is required for continued lactation?

Answer 23

1. Regular removal of milk
2. Intact HPA axis
3. Adequate diet and nutrition

Question 24

What are the breast changes for lactation?

Answer 24

1. Terminal differentiation of alveolar epithelial cells
2. High prolactin levels in setting of LOW E2 AND P LEVELS
3. Milk production/ejection controlled by neural reflex arcs

Question 25

What are the neural reflex arcs for milk production and ejection?

Answer 25

1. Stimuli associated with nursing stimulates oxytocin release - oxytocin will lead to milk ejection (myoepithelial contraction) 2. Suckling lead to prolactin release which leads to milk production - transcription of milk genes - induction of enzymes for lactose synthesis - induction of differentiation

Question 26

What do dopamine agonists like Bromocriptine do?

Answer 26

Inhibits lactogenesis

Question 27

Why do you have amenorrhea during lactation?

Answer 27

Hyperprolactinemia-induced inhibition of gonadotropin secretion

Question 28

What are the characteristics of postlactational involution?

Answer 28

At weaning -prolactin and oxytocin release not stimulated -unremoved milk leads to increased acinar pressure Lactation ceases within 10 days 80% of epithelium dies Involution takes 3-4 months and involves remodeling of tissues -parity leads to permanent change in breast

Question 29

What is parity?

Answer 29

A technical term that refers to number of times a female has given birth

Question 30

What are the characteristics of breast devo during menopause?

Answer 30

1. Decreased estrogen/progesterone secretion 2. Progression involution of ductal and glandular elements of the breast 3. Changes make aging breast more amenable to mammography

Question 31

What are potential disorders of breast development?

Answer 31

1. Hypoplasia/Amastia | 2. Supernumerary nipples polymastia

Question 32

What are the characteristics of hypoplasia/amastia?

Answer 32

1. Asymmtery common 2. Underdevelopment common 3. Secondary to biopsy, chest wall trauma, thoracic radiation as a kid

Question 33

What is amastia?

Answer 33

When breast tissue, nipple and areola is absent

Question 34

What are the characteristics of supernumerary nipples/polymastia?

Answer 34

Secondary to incomplete regression of milk streak

Question 35

What is important about the endocrine pathophysiology of breast?

Answer 35

``` Breast is hormonally responsive Alterations in breast accompanied by endocrine disturbances Indicative of i. Turner ii. precocious puberty (PCOS?) ```

Question 36

What are the characteristics of galactorrhea?

Answer 36

1. Persistent discharge of milk in the absence of parturition -discharge in the non-nursing mother over 6 months postpartum 2. Associated with hyperprolactinemia, amenorrhea Caused by Prolactinoma and drugs 3. Normoprolactinemia, regular menses can be present as well -this is caused by excess sensitivity of breast to prolactin

Question 37

What is Sheehan’s Syndrome?

Answer 37

Infarction of pituitary during labor and delivery Pituitary particularly susceptible to decreased blood flow due to increased size during pregnancy Lack of postpartum milk production

Question 38

What does lack of postpartum milk production make you think of?

Answer 38

Sheehan’s syndrome | Infarction of pituitary during labor

Question 39

What causes gynecomastia?

Answer 39

Decreased androgen:estrogen ratio

Question 40

What are the characteristics of gynecomastia?

Answer 40

1. Excessive development of male mammary gland 2. Physiological gynecomastia - transient gynecomastia of newborn - transient breast enlargement at puberty/elderly 3. Pathological gynecomastia - reduced androgen/estrogen production or action