General Surgery Breast Flashcards
What is the typical lymphatic drainage of the breast
> 75% of lymphatic drainage of breast superiorly and laterally to axillary lymph nodes
Mostly from lateral breast (upper and lower outer quadrants)
What are the 3 levels of axillary lymph nodes
Level 1 - lateral to pectoral minor
Level 2 - deep to pectoral minor
Level 3 - medial to pectoral minor
What level of lymph node has worst prognosis
High level of involvement has worse prognosis
Where does the majority of the lymphatic drainage of breast to para-sternal (aka internal mammary) lymph nodes comes from
<25% of lymphatic drainage of breast to para-sternal (aka internal mammary) lymph nodes (mostly from medial (upper and lower inner quadrants) breast)
Where can the breast lymph drain to
Axillary lymph nodes
Internal mammary lymph nodes
Opposite breast
Inferior phrenic nodes
Galactorrhea definition
galactorrhea usually bilateral milky discharge
What are physiologic causes of galactorrhea
pregnancy, lactation, stress
What are pathologic causes of galactorrhea
Medication
Hyper-prolactinemia
What is the most common cause of spontaneous unilateral nipple discharge
Intraductal papilloma
Provoked nipple discharge usually suggests
Physiologic etiology
Differential for nipple discharge
benign ductal disorder: intra-ductal papilloma, mammary duct ectasia, fibrocystic changes
malignancy: breast cancer most often intra-ductal carcinoma or invasive ductal carcinoma
(nipple discharge is an uncommon symptom (10%) of breast cancer)
infection: abscess, mastitis
What are medications that can cause nipple dicharge
The following cause prolactin release:
Oral contraceptive
Anti-hypertensive meds
Anti-histamine
Opioids
Dopamine antagonist
How to differentiate glactorrhea and nipple discharge
nipple discharge usually unilateral
galactorrhea is bilateral milky nipple discharge
What is cyclic mastalgia
cyclic mastalgia is bilateral intense soreness or heaviness a few days before menses, usually due to hormonal changes in menstrual cycle
causes include
physiologic: breast pain due to hormonal changes in menstrual cycle
Non-cyclical breast pain definition
non-cyclical breast pain describes a variety of pain that does not fit definition of cyclical mastalgia, which usually due to breast or chest wall lesion
Differential diagnosis of non-cyclical breast pain
Intra-mammary (pathology inside breast)
structural: large pendulous breast, macro cyst
normal breast: diet, lifestyle, pregnancy
trauma
infection: mastitis, breast abscess
inflammatory: ductal ectasia, hidradenitis suppurative, thrombophlebitis
iatrogenic: hormone replacement therapy, other medications
malignancy: inflammatory breast cancer
mastalgia is an uncommon symptoms (~5%) of breast cancer
B) Extra-mammary
Breast pain investigations
if benign history and physical exam consistent with cyclical mastalgia, then no investigations required
if patient age <30 with no risk factor, then breast ultrasound
if patient age >30, mammogram and targeted ultrasound
if mass on physical exam, mammogram
Symptomatic treatment of mastalgia
lifestyle modification: sports bra for relief, restriction of caffeine / chocolate
warm or cold compresses
analgesics (acetaminophen or NSAID) for pain
if severe, Danazol can be used but have sginificant androgenic side effects
Mastitis/breast abscess epidemiology
common in breast feeding women
risk factors: smoking
Mastitis/breast abscess pathophysiology
infection and inflammation of breast tissue, caused by bacterial infection entry through duct system (Staphylococcus aureus, Enterococcus, anaerobic Streptococci, bacteroids
app)
infection of breast tissue may be complicated by formation of an abscess
non-lactational mastitis usually due to peri-ductal (sub-areolar) mastitis
Mastitis/breast abscess clinical presentation
breast symptoms: unilateral localized pain, may have sub-areolar mass (abscess), nipple discharge, nipple inversion
constitutional symptoms: fever, chills, malaise
breast exam: inflamed breast skin (erythema, swelling, tenderness, warmth), may have palpable fluctuant mass (abscess)
Mastitis/breast abscess investigations
breast ultrasound, which can differentiate abscess from tumor and other lesions
if unresponsive to treatment, then follow up investigations include mammogram and breast biopsy to rule out breast cancer
after resolution, follow up with repeat breast ultrasound and mammogram to rule out pathological breast lesions that predispose to infection
labs: CBC (leukocytosis)
any nipple discharge, milk or drained pus from abscess can be sent for culture and sensitivity (C&S)
consider blood culture if systemically unwell
Mastitis/breast abscess diagnosis
diagnosis usually made by physical exam of signs of inflammation confirmed on breast ultrasound
Treatment of mastitis
symptomatic management with hot / cold compresses, analgesia medication
antibiotic therapy
1) lactational mastitis: narrow coverage mainly for Staphylococcus aureus such as Dicloxacillin PO or Cephalexin PO or Erythromycin PO
2) non-lactational mastitis: same as lactational mastitis or consider broader coverage with Amoxicillin-Clavulanate
if lactating, continue breast feeding or using breast pump for complete emptying of breast, unless there is a breast abscess or purulent nipple discharge
Breast abscess treatment
consider IV antibiotics
abscess drainage by needle aspiration or incision & drainage (I & D)
Potential locations of a breast mass
premammary, intramammary, retromammary
Differential diagnosis for breast mass
benign breast mass more likely in younger premenopausal women
malignant breast mass more likely in older post menopausal women
usually differential diagnosis listed below are differentially diagnosed based on pathology of breast biopsy of lesion
1) Benign
structural: cyst, fibrocystic breast disease, fibrosis, adenosis, galactocele, epithelial related calcification
infection: abscess, granulomatous mastitis, papilloma
benign tumor: lipoma, lactational adenoma, papillary aprocrine change, mild hyperplasia of usual type, neurofibroma
pre-malignant tumor
proliferative without atypia (relative risk of ~2 for future breast malignancy): ductal hyperplasia of usual type, intra-ductal papilloma, sclerosing adenosis, fibroadenoma
atypical hyperplasia (relative risk of ~4 for future breast malignancy): atypical ductal hyperplasia, atypical lobular hyperplasia
iatrogenic: silicone implant
other: papillary apocrine change, epithelial related calcification, fat necrosis
2) Malignant
lobular carcinoma in situ, invasive lobular carcinoma
ductal carcinoma in situ, invasive ductal carcinoma (with subtypes)
connective and epithelial: phyllodes tumor, carcinosarcoma, angiosarcoma
Risk factors for breast malignancy
older age
post-menopausal
early menarche, late menopause
hormone use
null-parity
first live birth
Characteristics of benign and malignant breast lesions
characteristics of benign lesion: small (<2cm) superficial, smooth, round, rubbery, mobile with well defined border
characteristics of malignant lesion: large (>2cm), hard, irregularly bordered, non-mobile, fixed to skin or chest wall and with less well defined borders
Breast mass investigations
mammography = 1st imaging study for almost all breast mass
breast ultrasound = usually in pre-menopausal women age <30 for fibroadenoma and cyst; may be follow-up imaging after mammography
breast biopsy (can be guided by imaging including ultrasound, mammogram or MRI) for definitive diagnosis and rule out malignancy
Diagnostic work-up for breast mass for young pre-menopausal women
if malignant features on clinical exam, then mammogram followed by biopsy to rule out malignancy and for definitive diagnosis
if no malignant features on clinical exam, proceed with mammogram + ultrasound
if cystic changes on ultrasound, then aspirate for diagnosis
if lesion visualized, then core biopsy
if not visualized on mammogram and ultrasound, then consider CT or MRI of breast
Diagnostic work-up for breast mass for post-menopausal olderwomen
Mammogram with biopsy to confirm diagnosis and rule out breast malignancy for all cases
Screening mammogram purpose and sensitivity
purpose is to find cancer that is clinically undetectable (i.e. not detected on breast self exam nor clinical breast exam)
sensitivity of screening mammography is 75-90%
Diagnostic mammogram purpose
purpose is to follow up on a positive breast finding on mammography screen, symptoms or clinical finding
symptoms: pain, nipple discharge, skin change, nipple inversion, shrinking breast, enlarging breast
clinical finding: palpable lump
Screening mammography guidelines
in asymptomatic women <40 years of age, mammogram is not recommended
in asymptomatic women 40-49 years of age, annual screening mammogram can be done at discretion of physician
in asymptomatic women 50-74 years of age, mammogram screening every 1-2 years is recommended, which is evidence based and generally accepted
mammogram every year if recommended by radiologist, personal history of breast cancer, strong family history of breast / ovarian cancer or increased breast density
in asymptomatic women >74, mammogram screening every 1-2 years is recommended if she is in good health condition
mammogram and MRI sometimes recommended for screening in very high risk groups such as BRCA mutation carriers
Mammogram findings
main abnormal mammogram findings include microcalficiation, architectural distortion, mass and asymmetry
90% breast cancer present as micro calcification and / or mass
10% breast cancer present with uncommon signs of architectural distortion and asymmetry
What is Breast Imaging, Reporting & Data System
BIRADS is a standardized system for reporting mammography for uniformity and improve utility
BIRADS applies to all imaging including mammography, ultrasound and MRI
BIRADS 0 - further imaging is required
further imaging usually ultrasound or cones down mammography view
usually any abnormality on any single imaging will be BIRADS 0 until further imaging is done
BIRADS 1 - normal
BIRADS 2 - benign (e.g. cyst, fibroadenoma)
BIRADS 3 - probably benign with very low chance (2%) of malignancy where follow-up imaging is recommended (usually in 6 months)
presence of malignancy features such as non-calcified circumscribed solid mass, focal asymmetry, cluster of round punctate calcification
BIRADS 4 - suspicious abnormality with 2-95% chance of malignancy, where biopsy is recommended
BIRADS 4a have lower chance of malignancy than 4b
BIRADS 5 - likely to be cancer (>95% chance of malignancy), so a biopsy and surgical consultation is recommended
BIRADS 6 - confirmed malignancy with biopsy
BIRADS follow-up
BIRADS 0 requires further imaging (usually coned compression & magnification view mammogram and ultrasound)
usually, any lesion detected on mammogram is BIRADS 0 until further imaging is done
BIRADS 1 and 2 require no further work-up
BIRADS 3 requires follow-up imaging in 6 months
BIRADS 4 and 5 requires biopsy
BIRADS 6 is post-biopsy
Work-up of abnormal lesion on mammogram
based on standard 2 view mammography alone, it is not possible to definitively diagnose benign vs. malignant
any lesion detected on standard 2 view mammography alone is classified as BIRAD 0 until further imaging is done
workup of abnormal lesion comprised of 2 steps:
1) localization of lesion on initial mammogram on CC and MLO views
2) follow-up imaging, which may include combination of additional mammogram view (coned compression & magnification view), ultrasound and / or MRI
any lesion detected on mammogram need to be followed up with additional imaging (additional mammographic view, ultrasound or MRI) for correlation, in order to give BIRAD >0
in general, additional mammogram views and ultrasound are always done for all abnormalities
in women age >35 years, always start with additional mammogram views and then followed by ultrasound
indication for MRI of breast include
a) high risk screening: BRCA 1 or 2 mutation, >25% lifetime risk of developing breast cancer, radiotherapy to anterior chest wall
b) complex cases e.g. palpable lump not visualized on mammogram nor ultrasound
c) local staging of diagnosed breast cancer
d) assess response to chemotherapy
3) further work-up based on BIRAD score after follow-up imaging
BIRADS 1 and 2 require no further work-up
BIRADS 3 requires follow-up imaging in 6 months
BIRADS 4 and 5 requires biopsy
Role of breast biopsy
usually, breast biopsy follows imaging work up with a BIRAD of 4 or 5
breast biopsy is mandatory for diagnosis of breast cancer
Breast biopsy procedure
breast biopsy is done by radiologist
biopsy is usually guided by the imaging on which the lesion is best visualized
1) ultrasound guided biopsy
1st line except when lesion cannot be visualized on ultrasound
ultrasound guided is in real time, fast and cheap
good for solid and complex solid cystic mass
2) stereotactic (i.e. mammogram guided) biopsy
good for biopsying microcalcification seen on mammogram
good for asymmetry on mammogram that is absent on ultrasound
use X, Y and Z coordinates based on mammogram
3) MRI guided biopsy
2nd last line, usually when lesion cannot be seen on ultrasound nor mammogram
4) excisional biopsy based on palpation clinically
last line, usually when all imaging fails and lesion is palpable on clinical exam
biopsy needle can be fine needle, core needle or vacuum assisted
fine needle aspiration (FNA) is used for lymph node or cyst biopsy, where it produces the smallest amount of sample
core needle biopsy (CNB) is usually used only with some exceptions
vacuum assisted device (VAD) biopsy is used for microcalcification or diffuse lesion or under MRI guidance, where it produces the largest amount of sample
post biopsy
if biopsying for calcification, view biopsy under X-ray to ensure that the calcification is in the biopsy
deploy marker clip at site of biopsy to mark area of original lesion in case of surgery afterwards
Breast cancer epidemiology
most common cancer in women (1 in 9 women will develop breast cancer during her lifetime; 1 in 29 women will die from it)
2nd most common cause of cancer death in women
most of cancer (~90%) are sporadic
only minority of cancer (5-10%) are hereditary (e.g. BRCA 1 or 2 mutation)
5 year survival rate for breast cancer is ~90% for women and ~80% for men
Breast cancer risk factors
demographics
female gender
older age, where incidence steadily increase after age 30 and peak at age 80
female gender and age are the most significant risk factor for breast cancer
medical history personal history of breast cancer increased breast density on mammogram prior biopsy for breast abnormalities pre-malignant breast lesion including atypical ductal or lobular hyperplasia on biopsy radiation to chest wall for lymphoma
family history of breast cancer
breast or ovarian cancer in 1st degree relatives including mother, sister, daughter
unopposed estrogen early menarche (age <12) late menopause (age >55) long term (>5 years) hormone replacement therapy (for menopause) nulliparity or first birth after age 30 no breast feeding
modifiable lifestyle risk factors
alcohol
obesity, especially after menopause
physical inactivity
other possible factors
smoking
Breast cancer risk calculation
age
medical history or breast cancer, ductal carcinoma in situ, lobular carcinoma
genetic syndrome associated with increased risk of breast cancer (BRCA 1, BRCA 2)
age of menarche
nulliparity, age of first live birth
family history of breast cancer
prior breast biopsy
race / ethnicity
any high risk (lifetime breast cancer risk >20%) is refered to breast high risk clinic
in high risk patients, selective estrogen receptor modulators (SERMS) such as tamoxifen and raloxifene decrease breast cancer risk
Classification of primary breast cancer
Non-invasive epithelial cancers
Invasive epithelial cancer
Mixed connective and epithelial tumours
Definition non-invasive in breast
atypical hyperplasia confined in basement membrane and duct
Types of non-invasive epithelial cancers
lobular carcinoma in situ (LCIS), which is a marker of developing breast cancer in either breast
ductal carcinoma in situ (DCIS) with 5 subtypes of DCIS from least to most aggressive: intra-ductal, papillary, cribriform, solid, comedo
DCIS is a marker of developing breast cancer in that breast and not the other breast
Types of invasive epithelial cancer
invasive lobular carcinoma (~10% of invasive cancer)
invasive ductal carcinoma (~90% of invasive cancer), which have many subtypes not otherwise specified (50-70% of invasive ductal carcinoma) medullary carcinoma (5%) tubular carcinoma (3%) mucinous or colloid carcinoma (3%) invasive cribiform carcinoma (3%) invasive papillary carcinoma (2%) adenoid cystic carcinoma (1%) metaplastic carcinoma (1%)
Invasive definition in breast
invasion beyond the basement membrane and duct
Mixed connective and epithelial tumor types
phyllodes tumors, which can be benign or malignant
carcinosarcoma
angiosarcoma, which is usually due to radiotherapy to chest wall or post mastectomy
Breast cancer clinical presentation
cancer can be in any breast quadrant: 50% in upper outer quadrant; 20% around areola; 15% in upper inner quadrant; 10% in lower outer quadrant; 5% in lower inner quadrant
most breast cancers are asymptomatic and detected by screening
breast cancer usually present as lump in breast
other symptoms / signs: nipple charge or discharge (clear or bloody fluid), change in breast skin colour or texture, skin dimpling, skin inversion, axillary lymphadenopathy
Paget’s disease of breast (malignancy involving nipple of breast spreading to areola): eczema of areola (flaky, scaly) which may have nipple discharge, burning sensation or inversion;
usually no breast mass and no mammogram abnormality; diagnosed by pathology of punch biopsy or full thickness biopsy of nipple
inflammatory breast cancer (diffuse tumor involving lymphatic channel within breast and overlying skin): peau d’orange (thickening skin, erythema, edema and warmth of firm breast due
to lymphatic obstruction); typically requiring neo-adjuvant chemotherapy followed by surgical mastectomy
inflammatory breast cancer (diffuse tumor involving lymphatic channel within breast and overlying skin): peau d’orange (thickening skin, erythema, edema and warmth of firm breast due
to lymphatic obstruction); typically requiring neo-adjuvant chemotherapy followed by surgical mastectomy
lobular carcinoma: classically in elderly women presenting as bilateral and multifocal lesions with high recurrence rate (ductal or lobular) in contralateral breast; metastasis to meninges,
pleura, GI series and urinary series; usually ER+ and PR+; requires mastectomy
metastasis: most commonly to axillary lymph nodes, bone, lung and liver; may metastasis to pleural, pericardium and abdominal cavity
bone metastasis have better prognosis than other metastases
Breast cancer staging work-up
mammogram and ultrasound to visualize lesion and guide biopsy
biopsy to confirm malignancy and for tumor staging
MRI to better visualize lesion, rule out multicentric (multiple tumor sites in >1 quadrant) or multifocal lesion (multiple tumor sites within 1 quadrant) and surgical planning
chest X-ray, liver ultrasound to rule out metastasis
other imaging as indicated by symptoms
bone scan for bone metastasis if bone pain or high alkaline phosphatase
brain CT for brain metastasis if CNS symptoms such as confusion, fall, ataxia
chest CT for lung metastasis if pulmonary symptoms
abdomen and pelvis CT for metastases to bone, liver or GI tract if high alkaline phosphatase, abnormal liver function test, abdominal symptoms or signs
Breast cancer prognostic factors
TNM staging
Pathological staging (microscopic features for prognosis):
Tumour size, focality, margin
Tumour grade (Nottingham histologic score) based on architectural tubular formation, atypia and mitosis
Lymph node status
Receptor (ER, PR, HER2) status
Hormone receptor status
What information does hormone receptor status give you
hormone receptors are tested from excised tumor biopsy, which inform chemotherapy and prognosis
hormone receptors include estrogen receptor (ER), progesterone receptor (PR) and HER2 neu overexpression (HER2)
ER+, PR+ are associated with better prognosis and can be treated with hormone therapy
HER2+ can be treated with herceptin
PR- associated with more aggresive cancer
ER- PR- have a worse prognosis
3 most important factors affecting breast cancer treatment and prognosis
- TNM staging
- receptor status (ER and HER2)
- women’s age and menopausal status
Breast cancer surgical procedures
a) lumpectomy (aka breast conservative surgery)
procedure = removal of lump with some surrounding healthy tissue (wide local excision), combined with radiotherapy
indication: stage 1 and 2 breast cancer
contraindication: high risk of local recurrence (extensive malignant calcification on mammogram, lobular carcinoma, multi-focal tumor, failure to obtain tumour free margin after
excision); contraindication to radiotherapy (see below); inflammatory chest cancer; lobular carcinoma
b) mastectomy
radical mastectomy = removal of entire breast, skin, pectoralis muscle and axillary nodes
modified radical mastectomy = removal of entire breast, skin and axillary nodes
simple mastectomy = removal of entire breast and skin
indication: invasive lobular carcinoma; multi centric or multifocal breast cancer
complication: skin necrosis
following lumpectomy or mastectomy, breast and nipple can be reconstructed with TRAM flaps or implants under pectoralis muscle
decision of lumpectomy vs. mastectomy depend on size / location / number of tumor, patient decision and cosmesis
c) sentinel lymph node biopsy = biopsy of first lymph node that drains the cancer
procedure = injection of radioisotope (Technetium-99) and blue dye near cancer which is drained by lymph, where lymph node that take up dye and radioisotope are dissected
and sent to pathology for examination
if sentinel lymph node is free of cancer, then no lymph node involvement
if sentinel lymph node contain cancer, then lymph node dissection
d) lymph node dissection
procedure: complete excision of all lymph nodes in axilla
indication: positive lymph node on fine needle aspiration biopsy; positive sentinel lymph node biopsy
complication: injury to brachial plexus nerves (decreased arm sensation, shoulder pain); lymphedema (10-15% risk)
Breast cancer surgical options
effectiveness of lumpectomy + radiotherapy is equivalent to mastectomy
lumpectomy with sentinel lymph node biopsy, followed by radiation
lumpectomy with sentinel lymph node biopsy -> axillary lymph node dissection followed by radiation
mastectomy with sentinel lymph node biopsy
modified radical mastectomy (mastectomy + axillary lymph node dissection)
Breast cancer radiotherapy procedure, indications and contraindications
procedure = external beam radiotherapy
indication: radiotherapy always follow lumpectomy to reduce risk of recurrence
radiotherapy usually not required in mastectomy especially with lymph node dissection
contraindication: pregnancy; previous chest radiotherapy; collagen vascular disease (scleroderma, lupus)
Breast cancer medical treatment role
neoadjuvant chemotherapy given before surgery to shrink aggressive tumor followed by surgical resection
adjuvant systemic chemotherapy given post surgery to reduce risk of recurrence and prolong survival
Breast cancer systemic chemotherapy
chemotherapy based on comprehensive risk assessment of cancer stage, receptor status, pathological stage and other features
all breast cancer can be treated with any of the chemotherapies below:
anthracyclines (topoisomerase 2 inhibitor): doxorubicin, epirubicin
taxanes (microtubule inhibitor): docetaxel and paclitaxel
platinums: cisplatin, carboplatin
alkylating agent: cyclophosphamide
antimetabolite: 5-FU
chemotherapy regimen include
FEC (fluorouracil, epirubicin, cyclophosphamide
Breast cancer hormonal therapy treatment
hormone or targeted therapy based on ER and HER2 status
ER+ and HER2-, treat with hormone therapy
ER- and HER2+, treat with herceptin
ER+ and HER2+, treat with hormonal therapy and herceptin
ER- and HER2-, no hormone receptor specific treatment, associated with poor outcome
a) Hormone therapy
selective estrogen modulator for pre-menopausal women: Tamoxifen
aromatase inhibitor for post-menopausal women: Anastrozole, Letrozole
complication: osteoporosis -> risk of fragility fracture
in pre-menopausal women, ovarian ablation or suppression is also a way to lower estrogen level
b) Herceptin
indication: HER2+ breast cancer
General breast cancer management guidelines according to stage
Stage 0 Breast Cancer
a) lumpectomy + radiotherapy
b) lumpectomy alone if negative margin >1cm and low nuclear grade breast cancer
c) simple mastectomy +/- sentinel lymph node biopsy
Stage 1 Breast Cancer
a) lumpectomy and axillary node dissection + radiotherapy
b) simple mastectomy + (axillary node dissection or sentinel lymph node biopsy)
adjuvant chemotherapy or hormonal therapy after discussion of risk and benefit
Stage 2 Breast Cancer
a) lumpectomy and axillary node dissection + radiotherapy + adjuvant chemotherapy (and hormonal therapy if applicable)
b) simple mastectomy + (axillary node dissection or sentinel lymph node biopsy) + adjuvant chemotherapy (and hormonal therapy if applicable)
Stage 3 Breast Cancer
a) if operable, modified radical mastectomy + radiotherapy + adjuvant chemotherapy (and hormonal therapy if applicable)
b) if inoperable, neoadjuvant chemotherapy (and hormonal therapy if applicable) or radiotherapy -> modified radical mastectomy + radiotherapy + adjuvant systemic
treatment
Stage 4 Breast Cancer
slow disease progression with systemic chemothrapy (and hormonal therapy if applicable)
palliative surgery and / or radiotherapy
