Breast Disorders Flashcards
3 components of the female breast
- Glands and ducts (organized
- into lobes)
- Stroma (fibrous tissue) to bind lobes together
- Adipose tissue within and between lobes
each breast is made up of how many lobes?
12-20 lobes
which part of the breast contains major excretory duct for the lobe
apex of the breast
Each lobe has a group of lobules that have several ducts which unite to form the ?
major duct for the lobe
Each major duct widens to form ____ and then narrows at its individual opening in the nipple
an ampulla
Areola also contains sebaceous glands (______ ______) which may be visible as punctate prominences
Montgomery glands
what % of a normla breast is composed of adipose tissue?
80-85%
difference in breast in Nonpregnant, nonlactating; pregnant; lactation
- Nonpregnant, nonlactating - small, tightly packed alveoli
- Pregnant - alveoli hypertrophy and lining cells proliferate
- Lactation - alveolar cells secrete lipids and proteins (milk)
Deep surface of breast lies on what structure
fascia of chest wall muscles
Fascia is condensed into multiple bands - _____ _____ - support breast in upright position
Cooper’s ligaments
lymphatic drainage Ultimately drains into where?
axillary lymph nodes
receive most lymphatic drainage and therefore are the most common site of breast cancer metastases
AXillary nodes - sentinel nodes
alt pathways of lymphatic drainage
internal mammary, supraclavicular, epitrochlear, contralateral axillary and abdominal lymph nodes
development of fetal nipple and prepubertal breast?
- Fetal - Primordial breast arises from basal layer of epidermis
- Prepubertal - breast is rudimentary bud
- Few branching ducts
- Ducts are capped with alveolar buds, end buds, or small lobules
at what age do the breast begin to grow?
what hormone affects breast tissue?
age 10-13
- estrogen/progesterone affect breast tissue
- Communication between epithelial and mesenchymal cells
- Extensive branching of ductal system and lobule development
what structures change during overall breast growth
increased:
- acinar tissue
- ductal size & branching
- adipose
Premenstrual - breast epithelial cells proliferate during the _____ phase when estrogen and progesterone are increased
what other changes happen?
luteal
- Acinar cells increase in number and size
- Ductal lumens widen
- Overall increased breast size, turgor/fullness, and tenderness - 1 week before menses
Postmenstrual - breast epithelial cells undergo _______ at the end of the luteal phase when estrogen and progesterone levels decline
what other changes happen?
programmed cell death
- Decreased size and turgor (may still be tender)
- Reduced number and size of breast acini
- Decreased diameter of ducts
Final breast tissue differentiation occurs under the influence of _____ and _____ and is not complete until first full-term pregnancy
progesterone
prolactin
changes to the breast during pregnancy
- Marked increase in breast size and turgidity
- Deepening 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
changes to breast during late pregnancy (~34 wks)
fatty tissues are almost completely replaced by cellular breast parenchyma
Drop in what hormone triggers onset of milk production
progesterone
what is main regulator of milk production
Prolactin
menopausal changes to breast?
Decrease in estrogen and progesterone
- atrophy and involution
- Decr # and size of ducts and acini
- regresses to almost infantile state
- Adipose tissue may or may not atrophy
- Parenchymal elements are lost
Fluid can be expressed from ducts in who?
- 40% of premenopausal women
- 55% of parous women
- 75% of women who have lactated within 2 years
green nipple discharge is related to ?
cholesterol diepoxides
what presentation of nipple discharge is more physiologic?
which one needs further eval?
-
Multiduct discharge elicited only following manual pressure with no blood
- Physiologic - no further evaluation needed
- May see bloody multiduct discharge in pregnancy - Spontaneous or single duct discharge - needs evaluation
causes of abnml nipple discharge
- Normal lactation
- Galactorrhea
- Benign physiologic nipple discharge
- Pathologic nipple discharge
- MCC: intraductal papillomas
- Other causes - carcinoma, fibrocystic change
- Usually unilateral and single-duct discharge - Can be serous, bloody, or serosanguineous
important questions to ask about abnml nipple discharge
- +/- breast mass
- Location of discharge - Unilateral or bilateral; Single or multiple ducts
- Qualities of discharge - Spontaneous or must be expressed; Constant or intermittent; Elicited by pressure at a single site or general pressure
- Menses/Hormonal - Timing in relation to menstrual cycle; Pre- or post-menopausal; History of hormone use (contraception, HRT)
causes of galactorrhea
- Idiopathic
- Physiologic - pregnancy, postpartum, breast stimulation, neonatal
- Meds - antipsychotics, methyldopa, imipramine, amphetamine, metoclopramide, OCPs, herbals
- Neoplasm - lung, renal, lymphoma, pituitary, hypothalamic
- Diseases - CKD, sarcoidosis, Cushing’s, hypothyroidism, acromegaly
- CNS lesions - pituitary adenoma, empty sella, head trauma
- Chest wall irritation - clothing, burns, VZV, eczema, esophagitis, surgery
bilateral multiductal milky discharge in nonlactating patient
dx?
W/u if PE otherwise normal, negative imaging and multiductal discharge?
- galactorrhea
- Pregnancy test, prolactin, renal function, thyroid function, endocrinology consult
- unilateral, spontaneous serous or serosanguineous discharge from single duct
- Intraductal papilloma or intraductal malignancy
- Palpable mass may not be present
dx?
Bloody discharge - more suggestive of ?
- pathologic discharge
- cancer but usually due to benign papilloma
w/u for pathologic discharge?
- Cytology rarely helpful - negative doesn’t r/o cancer
- Mammography or US - may reveal underlying abnormalities in duct
- Ductography - may show intraductal filling defect
- Ductoscopy - endoscopic evaluation of ducts
definitive and tx for pathologic discharge
subareolar duct excision (microductectomy)
- Palpable glandular breast tissue in males
- Pubertal - 60% of boys - Usually resolves spontaneously in 1 year
- Palpate carefully to determine true (glandular) gynecomastia from fatty pseudogynecomastia - Compare subareolar tissue to nearby adipose; Fatty tissue - diffuse, nontender; True glandular enlargement - central, may be tender
- Grade findings according to severity - Higher number = more severe
- Pubertal - tender 2-3 cm discoid enlargement of glandular tissue beneath areola
dx?
Gynecomastia
50% of athletes who abuse what substances that can cause Gynecomastia
androgens or anabolic steroids
50% of athletes who abuse what substances that can cause Gynecomastia
Gynecomastia s/s suggestive of CA
- Asymmetry
- Enlargement not beneath areola
- Unusual firmness
- Nipple retraction
- Bleeding or discharge
w/u for gynecomastia
-
Serum prolactin & hCG
- + beta-hCG usually 2o testicular tumor or other CA (i.e., lung or liver) - may see mildly elevated hCG in pts with primary hypogonadism and high LH -
Serum free testosterone & LH
- Low testosterone & high LH - primary hypogonadism
- High testosterone & high LH - androgen resistance -
Serum estradiol
- Increased - testicular tumors, elevated hCG, liver disease, obesity, adrenal tumor, hermaphroditism, aromatase gene mutations - Serum TSH & FT4
- Karyotype (for Klinefelter syndrome)
- CXR - search for metastatic or bronchogenic carcinoma - If suspicious/unclear diagnosis
- Needle bx with cytology -If suspicious enlargement
tx for pubertal & med-induced gynecomastia
- usually resolves spontaneously in 1-2 years
- Medication-induced - stops after d/c offending drug
tx for painful or persistent gynecomastia
treat for 9-12 mo
-
SERM - for true glandular gynecomastia
- raloxifine (Evista) 60 mg orally daily (more effective)
- tamoxifen 10-20 mg orally daily -
Aromatase inhibitor
- anastrozole (Arimidex) 1 mg orally daily
- Causes decreased serum estradiol and increased testosterone - Testosterone therapy - For men with hypogonadism - may improve or worsen
-
Radiation therapy
- Prophylactic - men with prostate CA receiving antiandrogen tx
- Reduces incidence 52% to 85% - Surgery - persistent or severe
what gyneomastia tx is not recommended for Teens long-term?
what are the risks?
- aromatase inhibitor
- Risk of osteoporosis, delayed epiphyseal fusion
- MC with lactation and nursing
- primiparous nursing patients
- Rare prior to 5th day postpartum - Uncommon if pt is not nursing and no other obvious cause (i.e., radiation tx for CA)
- Should prompt work-up (imaging, bx) to exclude inflammatory breast CA
dx?
MCC?
- mastitis
- Staph aureus
- painful erythematous lobule in outer quadrant of breast noted during 2nd or 3rd week of puerperium
- Systemic signs of infection - F, malaise, myalgias, leukocytosis
- Do not ascribe high fever to simple breast engorgement - Abscess - pitting edema and fluctuation
- Antibody-coated bacteria in milk supports dx
dx?
- Mastitis
tx for mastitis
- Avoid milk stasis - Continue breastfeeding or use breast pump; warm compresses; Well-fitted bra; Instruct on proper breastfeeding techniques; Analgesics - acetaminophen or ibuprofen
- Abx x 10-14 d; Dicloxacillin / cephalexin (500 mg QID); Alt - clinda, bactrim
- Severe - inpatient IV Vancomycin + ceftriaxone OR pip-taz
mastitis - avoid bactrim if infant is how old/has what?
if breastfeeding infant is < 1 month old or has hx of G6PD deficiency, jaundice, or prematurity
what may arise arise from pre-existing mastitis
Redness, tenderness, induration
Palpable mass or fluctuance
breast abscess
difference between peripheral vs subareolar breast abcess?
tx for each?
Non-puerperal - peripheral or subareolar
-
Peripheral - skin infections (folliculitis, infected epidermal cyst)
- I&D + abx as for mastitis -
Subareolar - keratin-plugged milk ducts behind nipple
- Often fistulas between multiple abscesses
- Simple I&D - 40% recurrence rate
- Needs subareolar duct excision and complete removal of sinus tracts
- Bx of abscess wall to rule out breast CA
- Mass, often accompanied by skin or nipple retraction
- +/- ecchymosis, tenderness
- Clinically indistinguishable from breast CA - Trauma, radiation or surgery - presumed etiology
- Only ~50% of pts recall hx of trauma
dx?
w/u?
mgmt?
Fat Necrosis
- May use US or mammo to help with dx
- If untreated, mass gradually disappears
- If no resolution after several weeks - bx
- No need to excise unless persistent or unclear dx
MCC of cyclic breast pain or mastalgia in reproductive age women
Fibrocystic Breast Changes
- MC age - 30-50 yrs
- Rare after menopause unless pt is on HRT
Benign changes in breast epithelium
cause of Fibrocystic Breast Changes?
- Thought to be due to hormonal imbalance that may produce asymptomatic breast lumps on palpation
- Estrogen considered a causative factor
fibrocystic breast changes may be increased risk in women who consume what?
drink alcohol
especially ages 18-22
-
Pain or tenderness associated with a mass
- Pain 2o proliferation of normal glandular tissue
- Estrogen stimulates ducts, progesterone stimulates stroma
- Change in pain/tenderness over the course of menstrual cycle - Usually present or worse during premenstrual phase - Fluctuations in size
- Multiplicity of lesions
- +/- Nonbloody green or brown nipple discharge
- Caffeine may worsen sx
dx?
w/u?
tx?
- fibrocystic breast
- US/mammo (no mammo if < 30yo); US +/- aspiration useful if cystic vs mass; bx for dominant mass
- reassurance; avoid trauma; good bra; CAM; OTC analgesics; drainage if large
Things that may be helpful: Abstaining from caffeine, coffee, chocolate; Low-fat diets may help
options of CAM for fibrocystic breast
efficacy controversial
- Evening primrose oil - 44-58% of users report relief
- Vitamin E 400 IU daily
mgmt for severe pain in fibrocystic breast?
refractory severe cases?
- danazol, tamoxifen have been used - limited by SE
- surgery
prognosis for fibrocystic breast
- Exacerbations may occur at any time until menopause
- sx usually resolve following menopause
- Single nonproliferative lesions (fibrocystic changes) = no increased risk of breast CA
- proliferative or atypical - may have higher CA risk
- Common, benign neoplasm - Focal abnormality of breast lobule
- Usually in young women (within 20 yrs of puberty)
- More frequent and earlier age of onset in black women
dx?
Fibroadenoma
cause of Fibroadenoma
Etiology unknown - suspected possible hormonal link
- Increase in size during pregnancy and with estrogen therapy
- Decrease in size after menopause
Classic - round, firm, discrete, relatively mobile, nontender mass
1-5 cm in diameter
Usually discovered by accident
dx?
w/u? findings? definitive dx?
- Fibroadenoma
- MC clinical; US - well-defined solid mass with benign features
- Definitive dx - core biopsy or mass excision
- Unclear or rapid growth - surgery; asx - monitor (Core needle bx OR repeat US & breast exam in 3-6 mo)
T/F: Simple fibroadenomas are benign; do not increase risk of breast cancer
T
fibroadenomas may be confused with a ____, a fibroepithelial tumor that clinically resembles fibroadenomas and has a small chance of becoming malignant
Phyllodes tumor
- MCC of cancer in women other than nonmelanoma skin cancers
- MCC cancer (after skin CA) in all ethnic groups - highest incidence among white pts
- 2nd MCC CA death in women (#1 lung CA)
breast cancer
Incidence and mortality slowly decreasing due to improved screening and treatment
chances of developing breast CA increases with?
age
Avg age - 60-61 years
Main cause of death in women 40-59
Risk of developing invasive breast cancer in a lifetime?
1 in 8
lifetime risk for female pts
Over ?% of women who develop breast CA do not have significant identifiable risks
50
RF severity of +FHx of breast cancer?
- 1 first degree relative (mother/sister) - 2x risk
- 2 first degree relatives - nearly 3x risk
- Younger age of family at dx = higher risk
- However - only 15-20% of pts with breast CA report (+) family hx
what specific genetic mutation is a RF for breast CA?
- BRCA1 and BRCA 2 - 5% of breast cancers
- Autosomal dominant
which genetic mutation has significantly increased lifetime risk by age 70?
- BRCA 1 - breast CA 57%; ovarian CA 40%
- Cumulative risk by age 70 for BRCA 2 - breast CA 49%; ovarian CA 18%
- Men with BRCA 1/BRCA 2 also at higher risk
RF for breast cancer? greatest RF?
- FHx
- genetic mutations
- age
- Nulliparity
- First full term pregnancy after age 30
- Early menarche (before age 12) - Late menarche - decreased risk
- Late natural menopause (after age 50) - Early or artificial menopause - decreased risk
- Postmenopausal combination HRT
- Hx of uterine cancer
- Greatest RF - personal h/o breast cancer - Increased risk in both same and in contralateral breast
initial eval and labs of breast CA
- Most dx after abnormal mammogram, instead of discovery of a breast mass - >90% dx by mammogram
- Initial eval - CBE and assessment of lesion, bilateral mammo (if not already done) and breast US if indicated
- Initial labs - CBC, LFTs, alkaline phosphatase
- painless breast mass
- Usually hard, fixed, irregular margins, nonmobile
- in the upper outer quadrant
- regional LNs
- possible initial findings: Axillary mass or swelling of arm; Bone pain or back pain; wt loss
- less common: pain, nipple discharge, erosion, retraction, enlargement/shrinking, itching, redness, generalized hardness
dx?
concerning findings? (3)
- Breast Cancer
- Change in breast size/contour; Nipple or skin retraction; Edema or erythema
possible palpations of regional LN for breast CA?
which is MC?
- axillary, pectoral, supraclavicular, infraclavicular, subscapular, epitrochlear and lateral chain
- Axillary nodes - >85% of breast lymph drainage
description of high sus for breast CA vs not but frequently present?
- Firm nodes or nodes >5 mm - highly suspicious
- 1-2 mobile, nontender, not overly firm - frequently present, not suspicious
Microscopic metastases in ?% of pts with clinically negative nodes
40
LNs found in these 2 locations have strong possibility of distant metastases
breast CA
+ supraclavicular or infraclavicular nodes
what type of carcinoma may only see small (1-2 mm) nipple erosions
Paget’s carcinoma
Appearance Changes suggestive of advanced cancer
- Edema
- Redness
- Nodularity
- Ulceration of skin
- Fixation to chest wall
- Enlargement or shrinkage of breast
- Retraction of breast
Findings suggestive of advanced cancer
- LAD - Marked axillary LAD; Supraclavicular or infraclavicular LAD
- Edema of ipsilateral arm
- Large primary tumor (>5 cm)
- Eczematoid eruption and ulceration
- Arises from nipple - can spread to areola - 1% of all breast cancers
- Often mistaken for dermatitis or infection
- Associated with underlying carcinoma
- pain, itching or burning of breast along with superficial erosion or ulceration
- May see bloody nipple discharge, retracted nipple
dx?
w/u?
tx?
- Paget’s Disease of the Breast
- full-thickness bx
- Mastectomy is traditional therapy; excision of nipple, areola and local mass; in situ dz do not need axillary eval - only if palpable mass, invasive cancer or mastectomy
Diffuse, brawny edema of skin with erysipeloid border
Blocked dermal lymphatics by tumor emboli → lymphedema, hyperemia
“Peau d’orange” (orange peel skin) possible
Usually no palpable underlying mass
aggressive but rare - Nearly 35% have metastasis at dx
dx?
w/u?
mgmt?
- Inflammatory Carcinoma
- If suspected mastitis does not respond (1-2 wks) to abx - bx needed
- multiple rounds of chemo, followed by surgery and radiation
Breast imaging modality of choice
May detect CA 2 yrs before CA is palpable
False +/- possible - however correct in about 90% of cases
General sensitivity 70-90%, specificity >90%
which type of imaging?
mammo
w/u for Breast CA
- mammo
- US and MRI not recommended for general population - consider adding if very high risk
- Up to 15% of CA detected on CBE not seen on mammogram - Bx should still be done if dominant or suspicious mass
- Biopsy - definitive dx - MC lesions are benign on bx when thought to be CA (30%) - Cytology - helpful on some occasions - cyst fluid, nipple discharge
- Labs - CBC, LFTs, beta-HCG, alkaline phosphatase
- imaging - limit for high pretest probability of distant metastasis
types of bx done for breast CA
- FNA - simple; can’t distinguish invasive or noninvasive
- Core needle - more definitive dx, less chance of inadequate samples, determine invasive from noninvasive
- Open surgical - if core needle bx cannot be done
screenings for breast CA
- CBE - not a replacement for imaging
- Genetic testing - high risk families, genetic counseling needed before and after
General consensus for mammogram screenings
at least once every 2 years among women 50-74
- ACS/ACOG/ACR - Q 1 yr starting 40-45, may transition to Q2 yrs at 55
- USPSTF/WHO/AAFP - Q 2 yrs ages 50-75
- If 75+ - continue screening if estimated 10 years life expectancy
> 95% of breast CA are what part of the breast?
epithelial components
- Ductal - large or intermediate sized ducts
- Lobular - epithelium of terminal ducts of lobules
2 subtype of breast CA
invasive or be carcinoma-in-situ (CIS)
- Most arise from intermediate ducts and are invasive
- Ductal CIS - associated invasive cancers present in 1-3%
- Lobular CIS - 25-30% will develop invasive ductal cancer later
Most cancers have what type of hormone receptor site?
- 80% - ER + and/or PR +
- 23% - HER2 + (human epidermal growth factor receptor 2)
- 13% - no hormone receptors
- which hormone receptors metastasize to bone, soft tissue, and genital organs?
- which one metastasizes to liver, lung and brain?
- ER/PR/HER2 + - metastasize to bone, soft tissue, genital organs
- No Receptors - metastasize to liver, lung, brain
en bloc removal of breast, pectoral muscles, axillary lymph nodes
Rarely indicated or performed currently
which type of surgery
Radical Mastectomy
what is the modified radical mastectomy?
- removal of breast and underlying pectoralis major fascia with evaluation of select axillary nodes
- Better cosmetic and functional result than radical mastectomy
- No difference in survival or disease free rates
what is breast conservation therapy?
what stage of CA is indicated?
excision of tumor mass with negative margin, axillary evaluation and postoperative irradiation
Includes segmental mastectomy, partial mastectomy, quadrantectomy
For stage I and II and certain stage III cancers
Gaining increasing acceptance
adjuvant tx If positive for ER/PR/HER2?
If negative for those receptors?
hormonal therapy indicated
- Regardless of age, menopausal status, LN involvement or tumor size
- Historically - 5 y of tamoxifen; Increased risk of endometrial Ca and VTE
- Recently - aromatase inhibitors (anastrozole) thought to be equally or more effective
If negative for ER/PR/HER2 - may consider adjuvant; pembrolizumab (Keytruda)
which adjuvant tx reduces occult metastases?
systemic chemotherapy - Polychemotherapy for 3-6 months or 4-6 cycles
- which med binds to estrogen receptors; block estrogen in some (not all) tissues?
- Which ones are MC used for breast CA?
- Selective Estrogen Receptor Modulators - SERMs
- tamoxifen (Nolvadex), raloxifene (Evista)
- May be used for chemoprevention of breast CA in some high-risk women
- May be used off-label to treat other estrogen-sensitive neoplasms
which SERM blocks in breasts; mimics in uterus, bone?
which one blocks breasts, uterus; mimics in bone?
- tamoxifen
- raloxifene - Less potent estrogen blockade - smaller reduction in new cancer; Less estrogenic SE (endometrial CA, VTE)
SERM SE
- Common - hot flashes, nausea, muscle aches and cramps, hair thinning, headache, paresthesias
-
Estrogenic - increased risk of thrombosis, fatty liver, endometrial cancer
- Improves bone density and lipid profiles - Impaired cognition
- False thyroid function studies
DDI SERMs
- Not for use with other hormone-modulating anti-CA therapy
- SSRIs, cimetidine can reduce efficacy
- Avoid with QT-prolonging agents
- Used for breast CA
- inhibit aromatase (enzyme that produces estrogen)
- May be slightly more effective at reducing recurrence of breast CA
- May be less effective than tamoxifen at initial chemoprevention
- used alone, combo with GnRH blockers, or before/following SERMs
- used off-label to treat other estrogen-sensitive CA or reduce risk of breast CA in high-risk postmenopausal pts
what med?
Aromatase Inhibitors - anastrazole (Arimidex), exemestane (Aromasin), letrozole (Femara)
letrozole also used for ovulation induction
SE of Aromatase Inhibitor? CI?
- Common - hot flashes, GI upset, muscle weakness, joint pain, HA, worsened IHD
- Hypercholesterolemia
- Insomnia, impaired cognition, fatigue, mood changes
- Thinning hair
- CI: established pregnancy
DDI aromatase inhibitor
- Caution with, or do not use with, other hormone-modulating anti-CA therapy
- May increase serum concentration of methadone or L-methadone
- Do not use with estrogen or immunomodulating drugs
3 other antibeoplastics
- Fulvestrant (Faslodex), elacestrant (Orserdu)
- GnRH agonists/antagonists
- Pembrolizumab (Keytruda)
- used for metastatic breast cancer and ER or PR+, HER- cancers
- SERD - attach to and cause destruction of estrogen receptors
- does not mimic effects of estrogen
which antineoplastic?
Fulvestrant (Faslodex), elacestrant (Orserdu)
f/u for breast CA?
median time to recurrence?
- PE Q 4 mo x 2 yrs, then Q 6 mo x 3 yrs, then yearly; Mammo 6 mo after radiation, then yearly; Routine laboratory tests
- 4 years
what type of breast CA has a higher chance of recurrence
Hormone receptor negative cancers
