Breast (Week 7--Pregler and Metten)

Question 1

Breast cancer

Answer 1

Most common cancer in women in the US

180,000 cases diagnosed every year

Question 2

Breast embryology

Answer 2

Week 5-6 of fetal development, 2 ventral bands of ectoderm (milk lines) form from axilla to groin, then disappear

Mammary glands develop as ingrowth of ectoderm, budding into underlying mesenchyme

Primary bud initiates 15-20 secondary buds

Epithelial cords develop from buds, extend into connective tissue of chest wall; Lumina develop in buds to form lactiferous ducts

At birth, lactiferous ducts open into shallow epithelial depression called mammary pit (elevates during infancy due to mesenchymal proliferation to become nipple)

Question 3

Breast developmental anomalies

Answer 3

1) Inverted nipple if mammary pit doesn’t elevate above skin level (2-4% of patients)
2) Accessory of supernumerary nipples may develop along the milk line (0.5-1% of patients)

Question 4

Complications of breast cancer surgery

Answer 4

1) Lymphedema: swelling of arm can occur if take out too many lymph nodes and thus bad drainage
2) Numbness, burning breast/axilla/arm: if damage to nerve (lateral branch of 2nd intercostal for medial arm and axilla)

Question 5

Treatment of breast cancer

Answer 5

1) Lumpectomy with radiation (do sentinal node sampling with axillary node dissection if positive)
2) Modified radical mastectomy (removal of breast and removal of pectoralis minor to allow access to level III nodes)

Question 6

Anatomy of the breast

Answer 6

Between superficial fascia of anterior thoracic wall and fascia of pectoral muscle

From rib 2/3 to rib 6/7, and lateral sternum to midaxillary line

Axillary tail of Spence extends superolaterally into anterior axillary fold

Upper outer quadrant of breast contains most breast tissue (THIS is why there’s more breast cancer there–just because there’s more tissue there)

Question 7

Arterial blood supply in breast

Answer 7

Internal mammary artery: perforating branches

Posterior intercostal arteries: lateral branches

Axillary artery branches: highest thoracic, lateral thoracic (branches to serratus anterior, pectoralis major/minor and subscapularis muscles also), pectoral branches of thoracoacromial artery

Question 8

Lymphatic and venous drainage of the breast

Answer 8

Primary venous drainage is toward axilla: internal thoracic vein perforating branches, axillary vein tributaries, posterior intercostal ven perforating branches

Lymphatic drainage usually parallels venous drainage

Batson’s plexus: vertebral venous tributaries that invest vertebrae, could explain common pattern of breast metastases to vertebrae, skull, pelvic bones, CNS

Question 9

Is breast cancer metastasis to bone dangerous?

Answer 9

Actually, not really–very controllable and patients can live over 20 years

Bisphosphonate (used for osteoporosis!) drugs IV and high dose are very effective at controlling metastatic breast cancer to bone

Question 10

Innervation of the breast

Answer 10

Supraclavicular nerve from cervical plexus–anterior and medial branches–innervate skin over upper portion of breast

4, 5, 6 intercostal nerves provide sensory innervation (lateral mammary branches are cutaneous, exit through serratus anterior

Note: lateral branch of 2nd intercostal nerve (intercostal brachial nerve) must be visualized during surgical dissection of axilla because if resected, sensation lost from upper medial aspect of arm and axilla

Question 11

Three levels of lymph nodes

Answer 11

Level I: lateral to pectoralis minor (receive most drainage from upper extremity; where sentinal node usually is)

Level II: deep to pectoralis minor

Level III: medial to pectoralis minor (subclavicular lymph nodes)

Question 12

What is protective against breast cancer?

Answer 12

Early full-term pregnancy

(maybe something about fully developed tissue that is resistant to oncogenic changes)

Question 13

Breast development over life stages

Answer 13

Nulliparous (no pregnancies): conical, flattening above nipple

Parity: larger, more pendulous, increased volume and density

Aging: flattened, flacid, decreased volume, tissue replaced by fat

Question 14

Why is mammography not good for younger women?

Answer 14

Because younger women’s breast tissue is very dense and looks white like a tumor

Question 15

What causes breast glandular tissue to proliferate at puberty?

Answer 15

Estrogen and progesterone

Note: glandular tissue not completely developed until pregnancy occurs, and at delivery intralobular ducts form buds and then alveoli

Question 16

Anatomy (micro) of the breast

Answer 16

15-20 irregular lobes of branched tubuloalveolar glands that terminate in lactiferous duct, then goes into dilated portion just under areola, lactiferous sinus

Question 17

Glands throughout menstrual cycle

Answer 17

Before and after ovulation, ductal elements lined with squamous epithelium

At ovulation with estrogen stimulation, secretory cells increase in height, lumina appear, small volume of secretions accumulate

Question 18

Breast during pregnancy

Answer 18

Breast enlarges in response to hormonal simulation

Lymphocytes, plasma cells, eosinophils infiltrate connective tissue

Glandular tissues divide, branching ductules and develop prominent alveoli

Question 19

Breast at delivery

Answer 19

Proliferation declines

Initially secrete colostrum, high in IgA, lymphocytes and plasma cells that infiltrate stroma during pregnancy

Breasts continue to enlarge via hypertrophy of alveolar cells and accumulation of secretory products in ductules (protein synthesized in ER, lipid as free droplets in cytoplasm)

Question 20

What does prolactin do to the HPG axis?

Answer 20

Prolactin inhibits GnRH secretion from the hypothalamus so shuts off HPG axis

Abnormal prolactin secretion can cause amenorrhea, infertility, osteoporosis

However, prolactin during pregnancy is good because you don’t want to ovulate during pregnancy!

Question 21

What happens to hormones post-partum?

Answer 21

After placenta is delivered, estrogen and progesterone diminish, and this ALLOWS prolactin to stimulate the breast to lactate

Question 22

What causes prolactin to stay high after delivery?

Answer 22

Suckling of baby controls neural arc that originates in the nerve endings in the nipple-areolar complex and this keeps prolactin high

Note: if you don’t keep breastfeeding, or don’t do it at night, prolactin will decrease!

Question 23

What does oxytocin do?

Answer 23

Oxytocin iniates contraction of smooth muscle in myoepithelial cells surrounding alveoli, causing expulsion of milk into lactiferous sinuses (milk let-down)

Oxytocin release can result from stimuli related to nursing (even hearing other babies crying!)

Involved in other kinds of human bonding also

Question 24

What would a dopamine blocker drug (like metaclopramide) do?

Answer 24

Could cause prolactin secretion since dopamine usually inhibits prolactin secretion

Too much prolactin will inhibit GnRH and shut down HPG axis so can have amenorrhea, osteoporosis

Question 25

What can progestin-only pills do?

Answer 25

Can shut down HPG axis and block estrogen release so these women at more risk for osteoporosis

Question 26

What happens after you stop breasfeeding?

Answer 26

Breast returns to inactive nonsecretory state

Prolactin and oxytocin release decrease

Unremoved milk increases pressure within ductal and alveolar structures, lobular structures atrophy and secretory cells degenerate (note: wean slowly so less pain)

Question 27

Most common breast lumps

Answer 27

Cyst (fluid filled sac; on US is round with no internal echos)

Fibroadenoma (rubbery firm; most common mass in women under 35)

Cancer

Question 28

Causes of neonatal jaundice

Answer 28

Increased production of bilirubin, decreased clearance of bilirubin, increased enterohepatic circulation

UGT enzymes conjugate bilirubin and are already only 1% active in newborns but UGT gene mutation can decrease activity even more (esp in Asians!)

Question 29

How can breast milk cause jaundice?

Answer 29

A substance in breast milk may inhibit UGT

Question 30

Pathological causes of decreased clearance due to UGT problem

Answer 30

1) Crigler-Nager type 1 (no UGT activity)
2) Crigler-Nager type 2 (low UGT activity and usually responds to phenobarbitol treatment)
3) Gilbert’s Syndrome (mutation in promoter region of UGT so reduced UGT but enough for normal function)

Question 31

Why might normal infants have jaundice?

Answer 31

Fewer intestinal bacteria (which normally reduce bilirubin to urobilinogen) so get buildup of bilirubin

Beta-glucuronidase activity increased so get greater hydrolysis of conjugated to unconjugated blirubin and thus greater absorption (?)

Question 32

What is increased enterohepatic circulation?

Answer 32

If breastfeeding fails baby gets less calories and increases enterohepatic circulation

Low volume of stool output increases bilirubin absorption

Question 33

Core needle biopsy

Answer 33

Can be looked at/interpreted like excisional biopsy but doesn’t leave a scar on the mammogram like excisional biopsy does

Question 34

Where does the majority of breast cancer arise from?

Answer 34

Terminal ducts of the TDLU (terminal ductal lobular unit)

Note that TDLU contains both terminal ducts and acini

Question 35

How to describe where a breast mass is

Answer 35

Left/Right, Upper/Lower, Inner/Outer

Clock face

Cm out from nipple

Question 36

What do you do if you find a palpable mass?

Answer 36

Woman under 30 do ultrasound

Woman over 30 do mammogram

Question 37

Fine needle aspiration (FNA)

Answer 37

Smaller needle to look at cells

(can diagnose fibroadenoma just by FNA)

Question 38

Does intraductal hyperplasia/carcinoma require treatment?

Answer 38

No!

Question 39

Does ductal cell carcinoma in situ require treatment?

Answer 39

Yes!

But it is not an invasive carcinoma (just in situ)

Question 40

TDLU

Answer 40

Develops after first menses

Terminal duct + acini

TDLU is on the end of a ductule then to lactiferous duct!

Question 41

How many TDLUs on the end on ONE lactiferous duct?

Answer 41

A TON!

One lactiferous duct and all its associated TDLUs is considered a lobe of the mammary gland

Question 42

Breasts at puberty

Answer 42

E and P during each menstrual cycle stimulate lactiferous ducts to branch and form lobules

E promotes adipocyte differentiation so breasts just get fatter