Anat, Physio, and Devo of Breast Flashcards
What are 2 “mosts” that breast cancer holds?
Causes most mortality of any cancer worldwide.
Most common cancer in women in the US.
Other than nourishment for the baby, what are 3 functions of lactation?
1) Passive immunity (IgA)
2) Maternal-child bonding.
3) Promotes post-partum uterine involution.
Layers of breast organization from origin to end?
Acinii -> lobules -> ducts -> nipple.
What is the blood supply to the breast? What fraction of the blood supply does each contribute, approximately?
2/3 medial from internal mammary a.
1/3 lateral from lateral thoracic a.
What is the lymphatic drainage of the breast like? Implication?
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
What are the 2 major divisions of epithelium in breast tissue? What cells types are in each?
1) Ducts (cuboidal epithelial cells and myoepithelial cells)
2) Lobules (acini/ alveolar epithelial cells that make the milk)
What are the 2 major divisions of stroma in the breast? What cell types are in each?
1) Connective tissue (fibroblasts / fibrous connective tissue.
2) Fat (sdipocytes)
What are the 2 types of stroma in the TDLU of the breast? How do they contrast histologically?
1) Intralobular: fibrous, relatively cellular
2) Extralobular (aka interlobular): lots of collagen, few cells, appear as DENSE BANDS and can see whorls of collagen
What type of cells surround the ducts to help them expel milk?
Myoepithelial cells.
6 stages of breast development / change?
Fetal, Puberty, Pregnancy, Lactation, Post-lactational involution, Menopause.
Controlled by hormones and growth factors
What are 4 cells that “ER +/- Multipotent Progenitors” can give rise to?
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)
What part of breast development occurs during puberty? What drives it?
Ductal morphogenesis, esp. elongation, driven by ESTROGEN
Requires normal pituitary function
What part of breast development occurs during pregnancy? What drives it? (2 things)
Lobuloalveolar development, driven by progesterone and prolactin.
What drives lactation? (1 major thing, 2 maybe things)
Prolactin
cortisol and insulin are added in parentheses
What breast structures’ development in embryogenesis is horomone-independent?
Milk streak -> mammary bud -> primordial ductal tree.
If this goes awry- can result in extra nipples or breast tissue!
What two events in breast development do placental sex steroids drive?
Canalization of ducts.
Parenchymal differentiation–> colostrum (first milk) formation… .
During what phase of the menstrual cycle is the mitotic rate of glandular breast tissue the greatest?
The luteal phase
E and P together are more mitogenic than E alone!
What causes changes in breast volume, nodularity, and sensitivity during luteal phase?
Tissue edema and hyperemia.
I.e. these symptoms don’t have anything to do with the ducts/ epithelial development, though the ducts are changing
Why don’t women start lactating until after birth?
Progesterone and estrogens inhibit lactogenic action of prolactin.
After birth, placenta is no longer there cranking out hormones, and thus lactation can start.
Gene expression changes in breasts during pregnancy?
Genes for cell proliferation are upregulated.
Pharmaceuticals that affect lactation?
Dopamine agonists inhibit lactogenesis.
Dopamine antagonists cause lactogenesis (recall this side effect of some antipsychotics).
2 neural reflex arcs involved in milk production and letdown?
Stimuli associated with nursing (eg. baby crying) -> oxytocin -> myoepithelial contraction -> milk ejection.
Suckling -> prolactin release -> milk production.
3 things you need for lactation, and one thing you don’t.
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).
Take home point about lactation-induced amenorrhea?
It has an effect on fertility at the population level, but it’s not an effective form of contraception.
What 2 things happen after breast feeding stops?
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
Breast changes in menopause? (3 things)
1) Involution of ductal and glandular elements.
2) Decreased density of stroma (more amenable to mammography).
3) Decreased estrogen/progesterone
What are 2 disorders of breast development? (causes)
1) Hypoplasia/amastia - (biopsy/trauma, radiotherapy)
2) Supernumerary nipples/polymasia (milk streak doesn’t completely regress)
Two syndromes involving sexual differentiation that can cause breast development problems?
1) Turner syndrome
2) Precocious puberty
These disorders can give you information about the underlying endocrine disturbance!
Definition of galactorrhea?
Milk discharge in absence of partuition, or discharge >6mo post-partum if not nursing.
What can cause galactorrhea? (3 things)
Hyperprolactinemia (from prolactinoma or drugs)
Breasts more sensitive to prolactin.
What is Sheehan’s syndrome? What is often the first presenting sign?
Infarct of pituitary during labor/delivery (due to hypotension)
No lactation may be first sign.
What’s the cause of gynecomastia common to different etiologies?
Reduced androgen:estrogen ratio.
What causes terminal differentiation of alveolar epithelial cells?
- 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
What two events does weaning induce in the breast (that leads to involution)?
1) Prolactin and oxytocin release no longer stimulated
2) Un removed milk leads to increase of acinar pressure
What are some etiologies of gynecomastia in men?
- Transient imbalance in hormones during puberty
- Obesity (fat–> estrogen)
What are some major risk factors for breast cancer ? (REVIEW)
Obesity in postmenopausal women
- For evert 25 pound increase, increase your risk 80%
- Early 1st period, late menopause
What are some protective factors against breast cancer?
- Being SUPER young at 1st birth (under 18)
- Ovariectomy
