Lecture 9: Breast Disorders (Updated with supplemental) Flashcards
What derm layer do breasts arise from?
Ectoderm
What is most of the breast composed of?
Adipose tissue
What is responsible for keeping the breast upright?
Cooper’s ligaments
Where does breast lymph eventually drain to?
Axillary lymph nodes
What is the most common site of breast cancer metastases?
Axillary lymph nodes
Sentinel nodes
Most lymph drains through them.
During what period does the primordial breast arise from the basal layer of the epidermis?
Fetal period
During what period does extensive branching of the ductal system and lobule development occur?
Ages 10-13
Estrogen & progesterone
What happens to nipple sensitivity during puberty?
Increased
During what phase in the premenstrual period do breast epithelial cells proliferate?
Luteal phase
Increased size/fullness/tenderness 1 week before menses
What occurs to breast epithelial cells in the postmenstrual phase at the end of the luteal phase?
Programmed cell death
Decreased size/turgor, number, size, diameter
When is final breast tissue fully differentiated?
At the first-term pregnancy
What two hormones modulate final breast differentiation?
Progesterone & Prolactin
What 6 things characterize final breast tissue differentation?
- Marked increase in breast size and turgidity
- Deeping pigmentation of the nipple-areolar complex
- Nipple enlargement
- Areolar widening with increased number and size of lubricating glands
- Branching and widening of breast ducts
- Increased acini
breasts, nipples, areolar enlarge
In late pregnancy, what is fatty tissue replaced by?
Cellular breast parenchyma
What triggers the onset of milk production?
Drop of progesterone
What regulates milk production?
Prolactin
How is breast tissue affected by the postmenopausal decreases of estrogen and progesterone?
Atrophy and involution of the breast.
During what period is fluid most likely to be expressed from the nipple?
Within 2 years of lactation
What might green nipple discharge suggest?
Cholesterol diepoxides
What is considered physiologic nipple discharge?
Manual pressure required but no blood.
Non-spontaneous = good sign
When is further evaluation warranted for nipple discharge?
- Spontaneous
- Single-duct
Normal is multi-duct
What is the MCC of pathologic nipple discharge?
Intraductal papillomas
Others: carcinoma or fibrocystic changes
Incredibly Popular
In general, what medication class can induce galactorrhea?
Psychiatric medications/nervous system
What is the classic presentation of galactorrhea?
Bilateral multiductal milky discharge in a non-lactating patient
What is the classic presentation of pathologic nipple discharge?
Unilateral, spontaneous serous or sersanguinous discharge from a single duct.
What might bloody nipple discharge suggest?
Cancer, but could also be a benign papilloma
What is the issue with cytology of nipple discharge?
Does not rule out cancer.
What is the definitive dx and tx for pathologic nipple discharge?
Subareolar duct excision (microductectomy)
What drug is MC associated with gynecomastia?
Anabolic steroids/Androgens
SPIRONOLACTONE
What is the additional layer seen in gynecomasta?
Glandular tissue
What does true gynecomastia feel like?
Central, more tender
How does pubertal gynecomastia present?
Tender 2-3 cm discoid enlargement of glandular tissue beneath areola
If a boy has pubertal gynecomastia, what should you recommend?
Reassurance; 60% resolves in a year on its own.
What features might suggest cancerous gynecomastia? (5)
- Asymmetry
- Enlargement not beneath the areola
- Unusual firmness
- Nipple retraction
- Bleeding or discharge
What does elevated b-HCG in a male probably suggest?
Testicular cancer
What does low testosterone + high LH suggest in a male? High testosterone + high LH?
- Low testosterone + high LH = primary hypogondanism
- High testosterone + high LH = androgen resistance
What procedure might we recommend for suspicious gynecomastia?
Needle bx with cytology
How do you treat true gynecomastia not caused by medications and non-resolving? (5)
SERMs:
- Raloxifene PO QD
- Tamoxifen PO QD
Aromatase inhibitors: (not recommended in teens d/t risk of osteoporosis)
- Anastrazole 1mg PO QD
Testosterone therapy if hypogonadism
Radiation therapy (Prophylaxis if you have prostate cx + antiandrogen tx)
Surgery last resort
Who is mastitis MC seen in?
Lactating/nursing
If not this population, check for breast cx.
What is the MCC of mastitis?
Staph Aureus
What is the presentation of mastitis? (3)
- Classic: Painful, erythematous lobules in the outer quadrant of breast, esp during 2nd-3rd week of puerperium
- S/S of systemic infection
- Abscess
Puerperium = 6 weeks after childbirth
What finding within milk might suggest mastitis?
Antibody-coated bacteria in milk.
Non-Rx Tx of mastitis (4)
- Avoid milk stasis (keep breastfeeding!)
- Warm compresses
- Well-fitted bra
- Acetaminophen or ibuprofen
Baby is unlikely to be infected.
ABX for mastitis
- Dicloxacillin or keflex
- Alt: Clinda or Bactrim DS
- Severe: IV Vanco + rocephin/zosyn
10-14d
When must bactrim be avoided in treatment of mastitis? (2)
- BFeeding infant is < 1 month old
- Hx of G6PD, jaundice, or prematurity.
What causes a subareolar breast abscess?
Keratin-plugged milk ducts behind the nipple
How is a subareolar breast abscess treated?
Subareolar duct excision and removal of sinus tracts.
Also need to biopsy abscess wall to r/o cx
How can you differentiate fat necrosis from breast cancer on exam?
You can’t
You need US and mammograms
How do you manage fat necrosis?
Only biopsy it if it doesn’t go away after a few weeks.
What is the MCC of Cyclic breast pain or mastalgia in reproductive aged women?
Fibrocystic breast change
MC age = 30-50
Why is cyclic breast pain rare after menopause UNLESS on HRT?
Estrogen and progesterone cause the cyclic changes, so breast shouldn’t really change cyclically after.
What is the main potential risk factor for fibrocystic breast changes?
Drinking alcohol while 18-22
When are fibrocystic breast changes most painful?
During premenstrual period (days 12-14, 21-28)
What substance may worsen the S/S of fibrocystic breast changes?
Caffeine
What are the S/S of fibrocystic breast changes? (4)
- Pain/tenderness associated with a mass
- Fluctuations in size
- Multiplicity of lesions
- Nonbloody green/brown discharge
When is a mammogram not indicated for evaluating fibrocystic breast changes?
< 30 y
You should use US instead.
If a dominant fibrocystic mass is seen on the breast, what procedure should you do?
Biopsy
Checking if it is a fibroadenoma
What is the first thing you should tell a patient with fibrocystic breast changes?
Its not cancer
When do fibrocystic breast changes tend to resolve?
After menopause
Who is fibroadenoma MC in?
Young women (within 20 years of puberty)
What is a fibroadenoma?
Focal abnormality of breast lobule that is common & benign.
What is the classic presentation of a fibroadenoma?
- Round, firm, discrete, relatively mobile, nontender mass that is 1-5cm.
- On US: well-defined solid mass with benign features.
Usually found accidentaly.
How is a fibroadenoma definitively diagnosed?
Core needle biopsy or mass excision
What tumor seems similar to a fibroadenoma but has a higher chance of malignancy? How do you check it?
Phyllodes tumor, which can be checked via mammogram/US
How do you treat unclear dx or rapid growth fibroadenoma?
Surgery: excision with margins of normal tissue
Phyllodes is same but wider margins
How do you tx an asymptomatic fibroadenoma? (2)
- Monitor via US/breast exam every 3-6m
- Can do core needle bx to confirm
Image of Fibrocystic changes vs fibroadenoma
What is the MCC cancer in women?
Skin cancer, then breast cancer.
What is the MCC of death due to Cx in women?
Lung cancer, then breast cancer
What is the average age of breast cx diagnosis?
60-61
What is the lifetime risk of developing invasive breast cancer for any female patient?
1 in 8
Why do we screen breast cx so thoroughly?
50% of women who get it have no identifiable RFs for it.
What gene mutations are associated with increased breast cx risk?
BRCA1 and BRCA2 (autosomal dominant)
BRCA1 is the worse of the two
Also tied to ovarian cx
What is the greatest RF for breast Cx?
Personal hx of breast cx
What are the RFs for breast cx?
- Nulliparity
- First full term pregnancy after 30
- Early menarche (b4 12)
- Late natural menopause (after 50)
- Postmenopausal combinattion HRT
- Hx of uterine cx
- PERSONAL HX of Breast Cx
More menstrual cycles = more cell turnover = higher cx risk
How is the majority of breast cancer diagnosed?
Mammogram
What labs should you check in initial eval of breast cx? (3)
- CBC
- LFTs (or CMP)
- ALP
Checking for signs of early metastases
How does breast cancer usually present?
Painless breast mass in the upper outer quadrant
Tail of spence
What findings might suggest metastases of breast cancer? (3)
- Axillary mass or swelling of arm
- Bone pain or back pain
- Wt Loss
What are the concerning findings for breast cancer on exam? (3)
- Change in breast size/contour
- Nipple or skin retraction
- Edema or erythema
What features make a lymph node suspicious?
- Firmness or nodes > 5 mm
- Matted or fixed axillary => locally advanced
But 40% can be clinically negative
What swollen lymph nodes might suggest distant metastases of breast cx?
- Supraclavicular
- Infraclavicular
What is the usual finding on exam for breast cancer?
Nontender, firm, or hard lump with poorly delineated margins generally caused by local infiltration
What findings suggest advanced breast cancer? (4)
- Appearance changes
- LAN (esp axillary or supra/infraclavicular)
- Edema of ipsilateral arm
- Large primary tumor > 5 cm
What is paget’s carcinoma?
Eczematoid eruption and ulceration
Associated with underlying carcinoma
Kinda like a burnt appearance
What is the usual presentation of paget’s disease of the breast?
Pain, itching or burning of breast along with superficial erosion or ulceration.
How do you dx paget’s disease of the breast?
Full-thickness biopsy
How do you tx paget’s disease of the breast?
Mastectomy
What is the characteristic description of inflammatory breast carcinoma?
Orange peel skin
What is inflammatory carcinoma?
Diffuse, brawny edema of skin with an erysipeloid border due to tumor emboli.
When do you biopsy for inflammatory carcinoma?
1-2 weeks of non-responsiveness for suspected mastitis
The condition it can be mistaken for.
How do you tx inflammatory carcinoma?
- Chemo
- Surgery
- Radiation
How accurate is a mammogram?
90% of the time, and does it 2 yrs before its even palpable.
Both a high sens and high spec test.
Still do a CBE!
How do you definitively dx breast cx?
Bx (preferably core needle)
What is the least invasive method of bx for breast cx?
FNA
Also the least helpful
What is the recommendation regarding CBE?
You can do it if you want
What is the general consensus regarding mammogram screening frequency?
Q2 years by 50, and continue past 75 if pt has good life expectancy (> 10y)
At least once every 2 years!
What are the two primary components in breasts that become cancerous?
- Ductal
- Lobular
Epithelium
What is the majority of breast cancer receptive to in terms of hormones?
Estrogen
Where does ER(-) breast cx tend to metastasize to?
- Liver
- Lungs
- Brain
LLB
Where does ER/PR/HER2+ breast cx tend to metastasize to?
- Bone
- Soft tissue
- Genital organs
Balls & Bones
What are surgery options for breast cx?
- Radical mastectomy
- Modified radical mastectomy (same efficacy as radical but looks better)
- Breast conservation therapy (All the non-radical mastectomies, but limited to mainly stage 1-2)
What drug treats ER/PR/HER2+ breast cx?
Tamoxifen/raloxifene (SERMs) or Anastrazole (aromatase inhibitors)
What drug may be used as an adjuvant for negative ER/PR/HER2 breast cx?
Pembrolizumab (keytruda)
What is the difference between tamoxifen and raloxifene in terms of estrogen modulation?
- Tamoxifen: Blocks in breast, mimics in uterus & bone.
- Raloxifene: Blocks in breast & uterus, only mimics in bone.
Raloxifene has less SE.
MC SE of SERMs? (6)
- Hot flashes
- Nausea
- Muscle aches/cramps
- Hair thinning
- HA
- Paresthesias
Main DDI for SERMs?
QT-prolongation
Who can aromatase inhibitors NOT be used in?
Pregnant women
On average, what is the median time to recurrence to breast cx?
4 years
What kind of breast cx is more likely to recur?
Hormone receptor negative
What are fulvestrant and elacestrant primarily used in?
Antineoplastics
ER/PR+ but HER- breast cx.
Blows up estrogen receptors.
Used for metastatic breast cancer
After breast cancer tx, how soon do you followup in the first 2 years for PEs?
PE Q4mo for 2 years
What drugs cannot be used with Aromatase inhibitors?
- Estrogen
- Immunomodulating drugs
- Hormone-modulating anti-CA therapy
Describe the views used for a Screening mammogram.
- Craniocaudal (CC): compression of breasts from above/horizontally.
- Mediolateral oblique (MLO): compression of breasts from the side/vertically.
What is the additional view that a diagnostic mammogram can add?
Spot compression view
What are the 3 types of soft tissue/architecture abnormalities on mammogram that are considered significant?
- Spiculated focal mass: MOST SPECIFIC FEATURE OF BREAST CANCER
- Irregularly shaped mass
- Architectural distortion: change in normal lay of breast tissue
What is more suspicious of breast cancer: High-density or low-denisty masses?
High-density
What kind of clustered microcalcifications are most suspicious of breast cancer?
0.1-1 mm calcium particles grouped as > 4-5 per cubic centimeter
Linear branching microcalcifications
Granular can also be sus; Linear Branching Micro = Looks Bad Man
What kind of clustered microcalcifications are least suspicious of breast cancer?
0.1-1 mm calcium particles grouped as > 4-5 per cubic centimeter
- Vascular
- Skin
- Rim-like
- Large & coarse
- Smooth round/oval
What are the 4 categories to rank breast density?
- Predominantly fatty (0-25)
- Scattered fibroglandular densities (26-50)
- Heterogenously dense (51-75)
- Dense (76+)
Predominant quadrant for breast cancer
Outer Upper Quadrant
What does BI-RADS 0 mean?
Not enough info to be conclusive.
Need more scanning or rescan
What do BI-RADS 1 and 2 mean?
- 1 is negative, routine f/u only
- 2 is benign, routine f/u only
Usually fibroadenomas or vascular calcifications
What does BI-RADS 3 mean and f/u frequency?
- Probably benign (< 2% risk of cancer)
- Screening recommendations: Diagnostic mammo/US every 6 months x1 year, then annually for x2 years.
Can downgrade during these scans.
What does BI-RADS 4 mean?
- Suspicious abnormality; biopsy should be considered.
- Chance of cancer is 2-94%
- Rated A-C.
4A = 2-9% risk
4B = 10-49% risk
4C = 50-94% risk
What does BI-RADS 5 mean?
Highly suggestive of malignancy; appropriate action should be taken (95-100% cancer)
Spiculated, sus calcifications, skin retraction
What does BI-RADS 6 mean?
- Biopsy proven malignancy.
- Yet to be surgically excised.
My summary of BI-RADS
- 0 = not enough info, poor scan
- 1 = negative, just routine f/u. (Q1-2 years)
- 2 = benign, just routine f/u (Q1-2 years)
- 3 = tiny chance of cancer, f/u (Q6 mo)
- 4ABC = wide range, could be cancer
- 5 = very sus!
- 6 = yea you have cancer
KNOCKERS Mnemonic
- Ketoconazole
- Nifedipine
- Omeprazole
- Cimetidine
- Ketoconazole (again)
- Estrogens
- Recreational drugs + alcohol
- Spironolactone
Gynecomastia etiologies
Cirrhosis for dz since ascites is tx’d with spironolactone.
High yield mastitis
- Painful, erythematous
- Signs of infection
- MCC: Staph aureus
- Tx: Dicloxacillin/keflex for 10-14 days + Continue BFeeding
- Tylenol or advil for pain
High yield breast abscess
- FLUCTUANT, palpable mass
- Probably had mastitis prior
- Tx: I&D first, then tx same as mastitis: dicloxacillin/keflex 10-14 days + continue BFeeding
- Need subareolar duct excision + tract removal
Cram the pance said FNA i think
High yield fibroadenoma
- ROUND, MOBILE, NON-tender mass 1-5 cm in diameter
- Painless
- Occurs in YOUNG women, so use US > mammo
- Definitive dx: core biopsy or mass excision
Usually just monitor.
High yield fibrocystic breast changes
- PAINFUL AF
- 30+ USUALLY
- Commonly WORSE PRIOR to menstruation, then less afterwards
- Multiple lesions, HYPOechoic (dark)
- Mammo for > 30y
- Tx is primarily analgesics, but can use danazol/tamoxifen.
- Usually ok post-menopause
High yield gynecomastia
- Pubertal boys
- Generally self-resolving, but tx underlying condition if secondary gynecomastia
- Spironolactone or KNOCKERS mnemonic
- Described as central, tender < 0.5cm diameter under areola
- Pseudogynecomastia is in large BMI
- GLANDULAR TISSUE
- Only use testosterone if cause is hypogonadism
Testosterone in excess gets converted to estradiol
