Most common cancer in women in the US
180,000 cases diagnosed every year
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)
Breast developmental anomalies
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)
Complications of breast cancer surgery
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)
Treatment of breast cancer
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)
Anatomy of the breast
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)
Arterial blood supply in breast
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
Lymphatic and venous drainage of the breast
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
Is breast cancer metastasis to bone dangerous?
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
Innervation of the breast
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
Three levels of lymph nodes
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)
What is protective against breast cancer?
Early full-term pregnancy
(maybe something about fully developed tissue that is resistant to oncogenic changes)
Breast development over life stages
Nulliparous (no pregnancies): conical, flattening above nipple
Parity: larger, more pendulous, increased volume and density
Aging: flattened, flacid, decreased volume, tissue replaced by fat
Why is mammography not good for younger women?
Because younger women's breast tissue is very dense and looks white like a tumor
What causes breast glandular tissue to proliferate at puberty?
Estrogen and progesterone
Note: glandular tissue not completely developed until pregnancy occurs, and at delivery intralobular ducts form buds and then alveoli
Anatomy (micro) of the breast
15-20 irregular lobes of branched tubuloalveolar glands that terminate in lactiferous duct, then goes into dilated portion just under areola, lactiferous sinus
Glands throughout menstrual cycle
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
Breast during pregnancy
Breast enlarges in response to hormonal simulation
Lymphocytes, plasma cells, eosinophils infiltrate connective tissue
Glandular tissues divide, branching ductules and develop prominent alveoli
Breast at delivery
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)
What does prolactin do to the HPG axis?
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!
What happens to hormones post-partum?
After placenta is delivered, estrogen and progesterone diminish, and this ALLOWS prolactin to stimulate the breast to lactate
What causes prolactin to stay high after delivery?
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!
What does oxytocin do?
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
What would a dopamine blocker drug (like metaclopramide) do?
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
What can progestin-only pills do?
Can shut down HPG axis and block estrogen release so these women at more risk for osteoporosis
What happens after you stop breasfeeding?
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)
Most common breast lumps
Cyst (fluid filled sac; on US is round with no internal echos)
Fibroadenoma (rubbery firm; most common mass in women under 35)
Causes of neonatal jaundice
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!)
How can breast milk cause jaundice?
A substance in breast milk may inhibit UGT
Pathological causes of decreased clearance due to UGT problem
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)
Why might normal infants have jaundice?
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 (?)
What is increased enterohepatic circulation?
If breastfeeding fails baby gets less calories and increases enterohepatic circulation
Low volume of stool output increases bilirubin absorption
Core needle biopsy
Can be looked at/interpreted like excisional biopsy but doesn't leave a scar on the mammogram like excisional biopsy does
Where does the majority of breast cancer arise from?
Terminal ducts of the TDLU (terminal ductal lobular unit)
Note that TDLU contains both terminal ducts and acini
How to describe where a breast mass is
Left/Right, Upper/Lower, Inner/Outer
Cm out from nipple
What do you do if you find a palpable mass?
Woman under 30 do ultrasound
Woman over 30 do mammogram
Fine needle aspiration (FNA)
Smaller needle to look at cells
(can diagnose fibroadenoma just by FNA)
Does intraductal hyperplasia/carcinoma require treatment?
Does ductal cell carcinoma in situ require treatment?
But it is not an invasive carcinoma (just in situ)
Develops after first menses
Terminal duct + acini
TDLU is on the end of a ductule then to lactiferous duct!
How many TDLUs on the end on ONE lactiferous duct?
One lactiferous duct and all its associated TDLUs is considered a lobe of the mammary gland
Breasts at puberty
E and P during each menstrual cycle stimulate lactiferous ducts to branch and form lobules
E promotes adipocyte differentiation so breasts just get fatter