LC Exam 2 Breast Flashcards
Risk factor for breast cancer with relation to pregnancy
Age at/after pregnancy
Increased age increases risk and delay until protection
AAP recommendation for breast feeding
Advantages for baby
Advantages for mom
6 months
Reduces many disease risks in preterm infants (meningitis, nec enterocolitis, ears, UTIs etc)
Decreased risk of SIDS, diabetes, cancer, etc etc
Mom: decreased menstrual bleeding, increased child spacing, faster return to pre-preg weight
Anatomy of human breast
7 lobes
Secretory epithelial cells and myoepithelial cells (lobuloalveolar unit)
Lactating vs. non-lactating breast composition
Lactating: Glandular = 62%, intraglandular fat = 7%
Non-lac: Glandular = 20%, intraglandular fat = 49%
Subq and retro fat remain the same
Breast development cycles
Embryogenesis (establish gland) Puberty Mature Pregnancy Lactation cycle (and menstrual cycle, like mini lactation cycle)
Embryogenesis of breast
Ectoderm invades mesenchyme
Mesenchyme differentiates into fat pad (mammary mesenchyme)
Driven by PTHrP
No PTHrP = Blomstrands chrondroplasia (amastia)
Neonatal breast tissue can secret under right maternal hormonal conditions
Menstrual cycle changes in breast tissue
More ducts with LH/E2 spike
More alveoli with prog (luteal phase)
In preg= alveoli differentiation/side branches are a result of progesterone and PRL secretion by placenta
Pubertal breast changes
Glandular expansion driven by E2 and progesterone
E2 + GH induce IGF-1 secretion from stromal cells (TEB)
Progesterone during menstrual phase = side branches (TDLU) development -> regress at end of luteal unless pregnancy
TEB = terminal end bud
TDLU = terminal ductual lobular unit
Initial pregnancy breast changes
Lactogenesis I
Differentiation:
Increased lobulation
Alveolar cell differentiation
Inhibition of milk secretion (by high levels of progesterone)
Hormones: E2, prog, placental lactogen, PRL
Later pregnancy breast changes
Lasctogenesis II
Removal of placenta (progesterone) -> milk secretion
Elevated PRL levels from pituitary required to maintain
Retained placenta can inhibit breastfeeding
Lactation post-delivery
PRL: maintains lactation and inhibits reproductive fxn
OXY: assists milk letdown
Breastfeeding nutrition for infants
Maternal igs (mostly IgA)
Macrophages
Lymphocytes
Exclusively breastfed infants require vitamin D supplementation
Breastfeeding decreases risk of which disease for baby
Infections Asthma Allergies DM Obesity Bonding
Breastfeeding decreases risk of which cancers for mom
OXY release -> decrease pp hemorrhage More rapid return to prepartum weight Breast cancer Ovarian cancer Bonding
Milk secretion factors vs. milk letdown factors
Secretion: PRL and milk removal
Letdown/ejection: Oxytocin and suckling
Suckling also inhibits dopamine from hypothalamus ->
Stimulates PRL release from anterior pit
Operant conditioning can also stimulate hypothalamus
Other factors affecting breastfeeding
Stress Delayed initiation Pituitary damage Excessive weight -> (inhibits initiation, duration, PRL response to suckling, reduced ability to modify metabolic demand)
Human vs. bovine milk
Human contains necessary oligosacchrides
Milk composition/volume with days postpartum
Composition changes with volume Volume increases Tight junctions close IgA secretion rises then falls Leukocytes falls Increased nutrition and decreased immunity with days postpartum
Role of milk removal in breastfeeing
Removal of milk is required to maintain tight junction closure in glandular system
Prior pregnancy affect on breastfeeding
Prior pregnancy primes glandular system for new round of breastfeeding
Colostrum
Milk produced following birth
Yellow
High in IgA, lactoferrin (anti-infection)
High protein, low fat/lactose
Facilitates lactobacillus and passage of meconium
Transitional milk (2-14 days)
Igs and proteins decrease
Lactose, fat, and calories increase
Vitamin changes
Mature milk
Water: main component
Lipids: 50% calories, content varies with time
Proteins: Casein and whey, lactoferrin (inhibits Fe dependent bacterial growth in GI tract)
IgA/microbal factors
CHO, iron, zinc, vitamins (need vit D supplementation)
Variation during feeding
Foremilk: more liquidy, less dense
Hindmilk: more dense
Malnourished mothers
Same proportion of macromolecules
Less amount
Maternal contraindications to breastfeeding
Medications
Untreated EtOH or drug abuse
Infections (TB, HIV in developed countries)
Undeveloped countries: HIV okay unless have access to clean water and formula
Takeaways from 10 step Baby Friendly Hospital Inititave
Written breastfeeding policy Help initiate within 30 min of birth No other food or drink unless medically indicated Mom and baby stay together Feed on demand, no pacifiers
The Golden Hour (not sunrise/sunset, but the first hour after birth)
Feed within 30 min (baby gets sleepy)
Skin to skin (thermoregulation)
Breastfeeding crawl (not done but she said it was super “cool”, which is odd)
Feeding in the first 1-3 days
Colostrum is low volume, high fat/protein/Ig
Glycogen stores provide 12 hours
Lipogenesis keeps baby going, low volume is enough
Milk comes in day 3-4 (later in 1st birth and C-section)
Infant weight
Expected to lose 5-7% of birth weight (lipogenesis while milk comes in)
Losses stop typically around day 5
Regain of BW by day 7-14
Common problems
Pain/damage leads to engorgement, harder to pass milk, more often feedings, more pain/damage (cycle)
Primary lactation failure (rare)
Insufficient milk syndrome (inadequate removal leading to inadequate production)
Alternatives to breastfeeding
Formula
1st line: Cow base (modified for casein:whey ratio)
2nd: Soy
Formula generally has more total protein (9 vs 15g)
Risks with formula
Increased risk of atopy (developing allergies)
Increased risk of T1DM via autoimmune against bovine?
Increased risk of obesity (easier to get milk out, try and finish bottle - inhibits self regulation, leading to early/rapid weight gain)
Infant growth
Same for first 3 months
After: formula fed gain more weight
Biggest difference: around 6 months
Known for a while, now a concern for later obesity
Use WHO growth charts 0-2 yrs of age (not CDC)
Galactorrhea causes
- Excessive nipple stimulation
- Prolactinoma
- Drugs
Inflammatory breast pathologies
Acute mastitis Chronic mastitis Periductal mastitis Mammary duct ectasia Fat necrosis
Ductal system basics:
Epithelium
Stroma
Lobules male vs. female
Fxnal unit = terminal duct lobular unit
Two layered epithelium: epi cells and myoepi cells
>2 layers and loss of myoepi = pathologic
Interlobular stroma is regular fibrous tissue
Intralobular stroma is specialized and responsive to hormones
No lobules in male breast (or female prior to menarche)
Changes in breast composition with:
Lactation
Age
Lactation: increased lobular size and space, less stroma
Age: decreased interlobular stroma (more fat, less fibrous)
Potentially developmental abnormalities of the breast
Accessory breast tissue or increased nipples (anywhere along milk line - inguinal to axilla, most commonly axilla)
Congenital inverted/retracted nipples (careful of cancer)
Juvenille hypertrophy
Gynecomastia
Increased ducts and stroma (mostly stromal)
Unilateral or bilateral
Increase in E2
Many causes
Acute mastitis
Young female, just started lactating
Irritation, infection (staph/strep)
Tx: continued drainage and abx (diclox)
Close follow up warranted (inflammatory carcinoma)
Chronic mastitis
Perimenopausal most common
Duct ectasia
Obstruction due to thickened secretions
Fibrosis and irregular mass formation
Recurrent subareolar abcess periductal mastitis
Squamous metaplasia leading to closure and abscess
Common in smokers
Fat necrosis
Related to trauma
Mass with calcifications (saponification)
Early: necrotic fat, PMN’s
Late: macs, giant cells, fibrosis, Ca2+cation
Benign neoplasm of breast
Fibroadenoma
Lactating adenoma
Phyllodes tumor
Papilloma
Fibroadenoma
Premenopausal women
Origin: TDLU, fibrous tissue and ductal tissue
Well-circumscribed, mobile
E2 sensitive
No increased risk of carcinoma (as long as no epithelial hyperplasia)
Lactating adenoma
Presents during preg/lactation
Circumscribed, soft mass
Proliferation of small tubular structures with lactational changes
Phyllodes tumor
Fibroadeonma like- increased fibrous component pushing out to from leaves in cystic spaces
Can be benign, low grade (recur), high grade (mets)
Epi is benign, stroma can be malignant
Papilloma
Proliferation of epithelium (finger like projections with 2 cell layer)
Present as small mass with bloody discharge
Must r/o carcinoma (lack of myo or more than 2 layers)
Breast cancer etiologies
- Sporadic (70-80%)
- Hereditary (10-15%) - BRCA positive
- Familial (20-25%) - FHx but BRCA negative
(CHEK2, other tumor suppressor genes)
Syndromes associated with hereditary breast cancer and mutations
Li Fraumeni: p53
Cowden: PTEN
Peutz-Jeghers: STK11/LKB1
3 causes for increased incidence of breast cancer in western countries
- Delayed first pregnancy
- Fewer pregnancies
- Adoption of western diet/lifestyle
Atypical breast hyperplasia
Can be ductal or lobular
On spectrum in between in-situ and hyperplasia
Increased risk of invasive carcinoma
Ductal carcinoma in situ: Characteristics S/Sx Tx Low vs high grade
Proliferation of cells in ducts with no BM invasion
Calcification on mammography, no mass on exam
E-Cadherin POSITIVE
Risk of invasive
Excision usually cures
Low grade: often hormone receptor mutation (ER, PR)
High grade: often HER2/NEU overexpression
DCIS: subtypes and grade
In general, increasing cells in the ducts
Cribiform variant
Papillary variant
Solid variant
Micropapillary (no fibrovascular core, hobnail cells)
Comedo: high grade
Paget disease of the breast/nipple
Ulcerated nipple (often confused with eczema)
Associated with underlying carcinoma
Acanthosis (often confused with melanoma)
Lobular carcinoma in situ
Usually only solid No mass or calcifications, often incidental finding Often multifocal and bilateral E-cadherin NEGATIVE Increased bilateral invasive risk
Invasive carcinoma of the breast
Mass forming
Locally advanced disease: fixation and dimpling
Most commonly upper, outer quadrand
Mets first to axillary LN
Inflammatory carcinoma (invasive ductual)
Inflammed swollen breast
Lymph drainage block, diffuse dermal LN involvement
Looks like acute mastitis (fail abx)
Poor prognosis
Invasive ductal carcinoma
Well to poorly differentiated
Most common type of invasive carcinoma
Mets to lungs and pleura
Invasive lobular carcinoma
Loss of E-cadherin Express hormone receptors No HER2/Nau overexpression Single-file pattern Mets to CSF, GI, ovaries
Tubular carcinoma
Really good prognosis, so need to be sure
Well differentiated tubules that lack myoepithelial cells
Types of invasive ductal carcinoma
Tubular
Mucinous
Medullary
Inflammatory
Mucinous carcinoma
carcinoma with tumor cells floating in mucus Well circumscribed Older age group Good prognosis Hormone receptors and BRCA1 positive No HER/Neu over-expression
Medullary carcinoma
Large, high grade cells in sheets with lymphs and plasma cells
Triple negative, BRCA1
Good prognosis
Metaplastic carcinoma
Non-glandular growth
Usually ER/PR negative
Fast growing
No differentiation, ugly, high mitotic activity, squamoid
Stromal breast tumors
Angiosarcoma
Angiosarcoma
Spindle cells
Extravasation of blood vessels
Mixed stromal/epithelial
Phyllodes tumor
Phyllodes tumor
Fibroadenoma like, but can be malignant
Much higher fibrous/stromal component
Lymphoid breast tumors
Mantle cell lymphoma
CLL
Diffuse Large B cell
Pathogenesis: ER positive
ER positive, HER2 negative (50-65%)
Gain of 1q, loss of 16q, PIK3 activating
Associated with lower grade, better prognosis
Molecular pathways of pathogenesis
ER positive, HER2 negative (50-65%) HER2 positive (20%) Triple negative (15%) - BRCA1 associated, worst prog
Pathogenesis: HER2 positive
Associated with Li Fraumeni
Amplification of HER2 on 17q
Associated with higher grade
Biomarkers and response to therapy
ER/PR mutation = tamoxifen
HER2 = Herceptin
Triple negative = poor prog
Male breast cancer
Subareolar mass, involve chest wall and skin
Assoc with BRCA2 and Klinefelter
Stage for stage/grade for grade equal to females
Often present at later stage
