Anat, Physio, and Devo of Breast

Question 1

What are 2 “mosts” that breast cancer holds?

Answer 1

Causes most mortality of any cancer worldwide.

Most common cancer in women in the US.

Question 2

Other than nourishment for the baby, what are 3 functions of lactation?

Answer 2

1) Passive immunity (IgA)
2) Maternal-child bonding.
3) Promotes post-partum uterine involution.

Question 3

Layers of breast organization from origin to end?

Answer 3

Acinii -> lobules -> ducts -> nipple.

Question 4

What is the blood supply to the breast? What fraction of the blood supply does each contribute, approximately?

Answer 4

2/3 medial from internal mammary a.

1/3 lateral from lateral thoracic a.

Question 5

What is the lymphatic drainage of the breast like? Implication?

Answer 5

95% goes lateral up into the axilla. This is where you must biopsy lymph nodes to check for spread.

Small % drains medially through internal mammary nodes

Question 6

What are the 2 major divisions of epithelium in breast tissue? What cells types are in each?

Answer 6

1) Ducts (cuboidal epithelial cells and myoepithelial cells)

2) Lobules (acini/ alveolar epithelial cells that make the milk)

Question 7

What are the 2 major divisions of stroma in the breast? What cell types are in each?

Answer 7

1) Connective tissue (fibroblasts / fibrous connective tissue.
2) Fat (sdipocytes)

Question 8

What are the 2 types of stroma in the TDLU of the breast? How do they contrast histologically?

Answer 8

1) Intralobular: fibrous, relatively cellular

2) Extralobular (aka interlobular): lots of collagen, few cells, appear as DENSE BANDS and can see whorls of collagen

Question 9

What type of cells surround the ducts to help them expel milk?

Answer 9

Myoepithelial cells.

Question 10

6 stages of breast development / change?

Answer 10

Fetal, Puberty, Pregnancy, Lactation, Post-lactational involution, Menopause.

Controlled by hormones and growth factors

Question 11

What are 4 cells that “ER +/- Multipotent Progenitors” can give rise to?

Answer 11

Ductal myoepithelial cells
Ductal luminal cells
Secretory alveolar luminal cells
Alveolar myoepithelial cells
(more importantly... multipotent progenitors give rise to all the different epithelial cells)

Question 12

What part of breast development occurs during puberty? What drives it?

Answer 12

Ductal morphogenesis, esp. elongation, driven by ESTROGEN

Requires normal pituitary function

Question 13

What part of breast development occurs during pregnancy? What drives it? (2 things)

Answer 13

Lobuloalveolar development, driven by progesterone and prolactin.

Question 14

What drives lactation? (1 major thing, 2 maybe things)

Answer 14

Prolactin

cortisol and insulin are added in parentheses

Question 15

What breast structures’ development in embryogenesis is horomone-independent?

Answer 15

Milk streak -> mammary bud -> primordial ductal tree.

If this goes awry- can result in extra nipples or breast tissue!

Question 16

What two events in breast development do placental sex steroids drive?

Answer 16

Canalization of ducts.

Parenchymal differentiation–> colostrum (first milk) formation… .

Question 17

During what phase of the menstrual cycle is the mitotic rate of glandular breast tissue the greatest?

Answer 17

The luteal phase

E and P together are more mitogenic than E alone!

Question 18

What causes changes in breast volume, nodularity, and sensitivity during luteal phase?

Answer 18

Tissue edema and hyperemia.

I.e. these symptoms don’t have anything to do with the ducts/ epithelial development, though the ducts are changing

Question 19

Why don’t women start lactating until after birth?

Answer 19

Progesterone and estrogens inhibit lactogenic action of prolactin.
After birth, placenta is no longer there cranking out hormones, and thus lactation can start.

Question 20

Gene expression changes in breasts during pregnancy?

Answer 20

Genes for cell proliferation are upregulated.

Question 21

Pharmaceuticals that affect lactation?

Answer 21

Dopamine agonists inhibit lactogenesis.

Dopamine antagonists cause lactogenesis (recall this side effect of some antipsychotics).

Question 22

2 neural reflex arcs involved in milk production and letdown?

Answer 22

Stimuli associated with nursing (eg. baby crying) -> oxytocin -> myoepithelial contraction -> milk ejection.
Suckling -> prolactin release -> milk production.

Question 23

3 things you need for lactation, and one thing you don’t.

Answer 23

1) Regular removal of milk
(Stimuli and nursing results in continued prolactin release)
2) Intact HPA axis.
3) Adequate nutrition.

You don’t need ovaries to lactate (e.g. post-menopausal breast-feeding).

Question 24

Take home point about lactation-induced amenorrhea?

Answer 24

It has an effect on fertility at the population level, but it’s not an effective form of contraception.

Question 25

What 2 things happen after breast feeding stops?

Answer 25

1) Lactation ceases within 7-10 days.
2) Involution (apoptosis of 80% of epithelium) happens over the course of 3-4 months and results in permanent breast tissue remodeling

Question 26

Breast changes in menopause? (3 things)

Answer 26

1) Involution of ductal and glandular elements.
2) Decreased density of stroma (more amenable to mammography).
3) Decreased estrogen/progesterone

Question 27

What are 2 disorders of breast development? (causes)

Answer 27

1) Hypoplasia/amastia - (biopsy/trauma, radiotherapy)

2) Supernumerary nipples/polymasia (milk streak doesn’t completely regress)

Question 28

Two syndromes involving sexual differentiation that can cause breast development problems?

Answer 28

1) Turner syndrome
2) Precocious puberty

These disorders can give you information about the underlying endocrine disturbance!

Question 29

Definition of galactorrhea?

Answer 29

Milk discharge in absence of partuition, or discharge >6mo post-partum if not nursing.

Question 30

What can cause galactorrhea? (3 things)

Answer 30

Hyperprolactinemia (from prolactinoma or drugs)

Breasts more sensitive to prolactin.

Question 31

What is Sheehan’s syndrome? What is often the first presenting sign?

Answer 31

Infarct of pituitary during labor/delivery (due to hypotension)
No lactation may be first sign.

Question 32

What’s the cause of gynecomastia common to different etiologies?

Answer 32

Reduced androgen:estrogen ratio.

Question 33

What causes terminal differentiation of alveolar epithelial cells?

Answer 33

• Neural arc reflex of LACTATION leads to…
  1) Transcription of milk protein genes
  2) Induction of enzymes for lactose synthesis
  3) Induction of cell differentiation

Question 34

What two events does weaning induce in the breast (that leads to involution)?

Answer 34

1) Prolactin and oxytocin release no longer stimulated

2) Un removed milk leads to increase of acinar pressure

Question 35

What are some etiologies of gynecomastia in men?

Answer 35

• Transient imbalance in hormones during puberty

- Obesity (fat–> estrogen)

Question 36

What are some major risk factors for breast cancer ? (REVIEW)

Answer 36

Obesity in postmenopausal women

• For evert 25 pound increase, increase your risk 80%
• Early 1st period, late menopause

Question 37

What are some protective factors against breast cancer?

Answer 37

• Being SUPER young at 1st birth (under 18)

- Ovariectomy