Transcript Document

What I thought I knew about
Breast Cancer
William C. Dooley, M.D.,
F.A.C.S.
The G. Rainey Williams
Professor of Surgical
Oncology
Surgery - Breast Diseases
• Evaluation
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Diagnostic steps
Decision to Bx
Types of bx
Pros/cons Bx Tech.
F/U common
problems
• Benign Lesions
– pathophysiology
– presentations
• Malignant Lesions
– W/U and Dx
– Therapeutic
alternatives
– common pit-falls
– primary vs. adjuvant
Rx
– pathology
– prognostication
– F/U and therapeutic
efficacy
Evaluation
• No hard and fast rules on screening mammo
– all symptomatic women >30yo
– within 10 yrs of first degree relative family hx
– all fatty infiltrated breasts annually >40
• Other radiographic screening limited to
– US in palpable abnormalities not clinically
distinct in young women
– W/U palp or mammo soft finding; especially in
those with established risk factors
Self Breast Exam
Women are empowered to pay
attention to breast health issues
by BSE
“Just another way for male
physicians to blame women for
not finding cancer soon
enough.”
No study shows decrease of size
at dx greater than 2.5 cm down
to 1.8 cmneed to get size <1.0 cm for
survival benefit
Evaluation
• Clinical history
– delineate pts risk early - use Gail Model
• http://bcra.nci.nih.gov/brc/start.htm
• Menarche, preg hx, breast feeding hx, family hx,
hormone use
• lesion characteristics
– menstrual changes, dietary influences, wt loss or gain
• prior breast disease hx
– pt and relatives - pay close attention to proliferative
– 69% successful malpractice is in + fam hx
– 80% pt found lump - Remember Osler!!
Evaluation
• PE
– Pennypacker technique of palpation
• three fingers; vertical strips
• include axillae and lower 1/2 neck
– Observation of skin
• sheer curtain -fluid motion
– Ck for nipple D/C
• hemoccult if present; single vs. mult duct
» Wait any fluid (esp. spontaneous) increases risk
– mobility
Clinical Breast Exam
• Why do it?
– Purpose and goals
• Breast Cancer is a common problem
• Screening of pre-menopausal women poor and death
rate high
• Post-menopausal still 15% felt before seen on
mammo
• 60% diagnosed breast cancers felt before ever sent
for imaging
• we need to reduce size at dx to increase survival
Clinical Breast Exam
• How to do it?
– The mechanics
• we are feeling to detect cancer - both sensitive and
specific
• dependant on scirrhous nature of most breast
cancers
• optimize conditions to detect differences in density
• use subtle signs that imply differences in scar
activity in the breast
Clinical Breast Exam
Clinical Breast Exam
Thin out the breast tissue to
less than 1” thick
Close attention to
mammographic miss
locales - UIQ and LOQ
In the skin, look for peau d’orange
look for nipple excoriation/ Paget’s
lymphatic engorgement or
Cooper’s ligament shortening
Move the breast and look
for differences in texture or
mobility of skin relative to
gland
Oops decreasing evidence it works
to reduce death rates
Evaluation
• Every abnormality charted and scaled
– O’clock and distance to nipple
• any unclear area submit to alternative exam
• any suspicious on 1 exam or unclear on 2
different exams (modality or temporal)
needs diagnostic evaluation - i.e.. Bx if
cannot find a good reason not to.
• level of suspicion based on fam hx. and
other cumulative risk factors
Diagnostic evaluation
• when unclear - Bx.
• never follow more than 12 weeks without a
clear commitment
• Bx method depends on :
– way in which lesion most crisply seen
– tolerable sampling bias based on clinical
situation
New Technologies
Digital Mammo
Ultrasound improvements
MRI
Nuclear medicine
Emerging technologies
Digital Mammography
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Technology
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Pixel size not yet equivalent to silver
grain size
GE diagnostic unit cautiously approved
for screening
Will allow very accurate SCBx
May allow new pattern recognition to
standardize reading (CAD)
However post-menopause only 1/2 of
unrecognized Ca B/O inaccurate
reading; premenopausal Ca not detected
40% of time by mammo alone
Post menopausal
Film=Digital
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Film found mor3e solid masses
Digital better with cals
Fewer call backs with digital
Pre-menopausal
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Digital is better
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NEJM 2005
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49528 pts both D+F
0.5% + D &F
Inv CA
» 25% D&F
» 10.4% F
» 11.3%D
» 21.8% never seen
DCIS
» 10.7% D&F
» 5.1% F
» 7.5% D
» 7.5% not seen
Ultrasound
• Very good in W/U of
cystic lesions
• Ability to differentiate
solid lesions
improving
• Left, however, with
high false + and false rates for solid lesions
MRI
• Costly technology
• New coils allow SCB or
localization
• True sensitivity and specificity
?
• BRCA 1 (&2) have higher
incidence of breast cancers not
seen on mammo and MRI saves
lives here.
• Can find 25-28% caners have
MF disease – no effect on
survival or eventual therapy
• Most insurers skeptical
Nuclear Medicine
• New isotopes hold promise such as FDG,
sestamibi, and C-11 thymidine
• Imaging with resolution is problematic
– must detect routinely @ < 10mm
• More costly than MRI
• New Contact and PET detectors increasing
accuracy dramatically and ? Cheaper than
MRI at finding MF disease
Experimental/ Emerging
Techniques
• Genetic Screening- may assess risk but not direct
diagnostic efforts in individuals
• Electrical Biophysical - uses properties of ionic
concentration unique in normal epithelial surfaces
• Ductal Based Screening and Treatment - ductal lavage
and ROBE or breast endoscopy – still limited by
pathology accuracy and recent data shows random
PAFNA superior at identifying epithelial proliferative
disease in chemoprevention (celebrex trial)
– New scope and hypermethylation mapping
– Lavage of non-fluid producing ducts in PAFNA +
Ductoscopy
Common Problems
• Mastodynia/Mastalgia
– cyclical
• interfere with effects of hormones on breasts or changes
menstrual hormonal pattern
– non-cyclical
• look for breast “mapped” causes, rx fluid retention
• rx with non-steroidals
– R/O non breast causes
• Tietze’s syndrome, Poland’s syndrome, etc.
– UCLA Study – (The Breast Journal 2005)
• 86 pts eval with mammo and US for breast pain
• 100% negative predictive value
Common Problems
• Fibrocystic disease
– 40% of all women in 30-50 range carry dx
– cyclical lumpiness &/or tenderness
– mega-cystic variant - chronic premenstrual
rapidly filling cysts
– fibrosis variant - multiple FA or pseudo-tumors
– Beware when ca risks higher and FCD
• very careful to do detailed screening
Common Problems
• Fibroadenoma family
– FA
• low risk except if ductal proliferative changes in
young
• juvenile variant in Orientals & Blacks
• 10-15% recurrence risk with excision
• Lactating adenoma issues
– Benign Phylloides tumors
• more aggressive in local failure only
Common Problems
– Cystosarcoma phylloides
• unclear benign/malignant border
• best considered a special variant of fibrosarcoma
• risk for local recurrence best predicted by mitotic
activity or ? Ki67
– >10 mitoses/30 HPF =Very malignant behavior
– like sarcoma spread is to next capillary filter station
• Rx
– lumpectomy only for lowest mitotic rates
– wide excision(TM) for all others & indeterminants
Common Problems
• Nipple D/C
– single duct, heme+ - 7-9% ca chance
• Bx - gold standard microductectomy
– galactogram pre or intra-op
– nipple to 1 cm beyond obstruction
– recent data suggests that routine use of breast endoscopy
or galactography will double the cancer detection rate in
these patients
– single duct , heme• Bx only if persistent - papilloma likely
– Multiple duct, heme+
• culture and rx antibiotics x1-3 mos; bx if not response
– Multiple duct, heme• w/u prolactin axis
Common Problems
• Infections
– difficult to cure with antibiotics
– acne type flora, prolonged rx stills gives
failures
• lactating - nurse or pump through Ab Rx
• non-lactating - look for ductal blocking lesions
– both pre and post Rx
• Post-conservation red breast syndrome
– radiation mastitis vs. anaerobic step infection
Common Problems
• Abcess
– any infection that fails to respond clinically in 3
days
• w/u with US, aspirate or drain all collections
– Clinical abscesses
• I&D – or Aspirate, irrigate, antibiotics
• W/U for ductal lesions within 1 mo of successful Rx
– Peri-ductal mastitis
• recurrent infection in large lactiferous ducts
• may require excision to control
Common Problems
• The funny nipple
– odd crusting, asymmetric reddening, red area
erupting from one of the major duct orifices
• consider Paget’s until two consecutive negative bx
taken of nipple-areolar complex
– Inversion
• only important if new and not associated with recent
hormone administration
– Montgomery gland problems
• common inclusion cysts, hidradenitis like fungal
infections
Breast Masses
• OU 4 yr study of 414 pts presenting as
breast mass primary c/o – min 6 mo f/u
• No effect of family hx or risk factors on
future ca dx
• Probability of ca dx
– 11.3% if pt found
– 6.9% if physician found
– 1.9% nurse/phy extender
Breast Masses
Clinical Impression of SO exam
ca
cyst
fcd
nipple d/c
pain
cancers
% diagnosed as cancer
31
0
0
3
0
100.00%
0.00%
0.00%
10.71%
0.00%
mass
ax adenopathy
7
0
3.61%
0.00%
mammogram abn
2
11.76%
Biopsy decisions
• How to find it?
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palpation - gold std.
mammo
US
Miralumma
MRI
Thermography
the latest hottest
research tool
• How big a piece do I
need?
– surgical excision - gold
– surgical incisional
– needle incisional
• Mammotome, MIBB
• ABBI
• Cassi - cryocore
– Needle core
• 14G, 16G, 18G
– FNA
Biopsy decisions
• commit yourself to a narrow list of acceptable
diagnoses before bx
• if pre-op dx important, use best single or combo of
non-surgical methods first
• if dx is irrelevant to excision plans, use surgical
excision first
• if Dx not on acceptable list, re-assess your choices
- fall back on remaining best list to minimize
sampling error
• Don’t Forget surgical Bx
Gynecomastia
• common in young and old
• risk factors
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liver disease or decreased steroid clearance
Dopamine blockers - Haldol
Dopamine del. agents-reserpine & L dopa
H2 blockers
AIDS drugs
• unilateral vs bilateral
• Rx - symptomatic or discreet asymmetry in
gland
Breast Cancer
• 200-230K per year; stable invasive
incidence – Oops increasing to 485K/yr 2017
• 40K deaths per year; 11K preventable with
annual >50 screening
• another 45K DCIS/yr
• probably 120K - LCIS, ALH, ADH, or other
significant proliferative risk lesions
• probably accounts for >30% of all Ca
survivors
Breast Cancer
Types of invasive
• Ductal-70 %
– classic scirrhus
– mammo/sono size
within 20% of path
size
– prognosis very grade
sensitive
• Lobular - 10-12%
– may be considerably
larger than clinically or
radiographically
suspected
• Minor forms
– tubular
• very well diff. ductal
– medullary
• angry
histopathologically but
benign course if small
N0
• “bloody cyst” and Rad
Rx
– adenoid cystic
– colloid/mucinous
• tumor mass tiny relative
to mucus
Breast Cancer
• Other minor forms
– all sweat gland
derivative types except
cystosarcoma family
– all treated the same
– subtype may only
effect interpretation of
future systemic or
contra-lateral risk
• Inflammatory
– looks like infection
– paucity of systemic
symptoms; min Left shift on
WBC
– High sed rate
– underlying breast mass
– Bx skin, nipple, cores
• may need immunohistochem
to correctly differentiate
tumor from lymphocytes
Breast Cancer
• Presentations
– Lumps
• ductal if hard
• soft lobular,colloid,tubular,
medullary, DCIS
– Firm patches
• ductal in tissue
• lobular
– Stellate mammo
• ductal or old lobular
– Calcifications
• ductal/ DCIS
• older with necrosis
– Nipple D/C
• bloody
• single duct
– Pagets disease
• subareolar DCIS or
invasive with
centripetal ductal spread
– Inflammatory
Current State of the Art in
Breast Cancer Screening and Rx
• 1930-1996 no change in
age adjusted death rate in
US from Breast Cancer
• 1997-2000 an 18%
decrease in death rate
accounted for >95% by
earlier stage at diagnosis
• Rx successes in clinical
trials not appreciated as
well in nation-wide
reviews
• Best Rx results seen with
rigid evidence based
• The Mammo glass ceiling of
1/3 in situ to 2/3 invasive
• Still in best situations mammo
leaves 2/3 of patients at risk for
cancer death
• Mammo findings late
– calcifications usually represent
obstructed ducts with a 600%
increase in cross-sectional area
– densities depend on
immunologic reaction of host
to invasion with a scirrhous
reaction
Breast Cancer Prevention
• Increased menses = increased breast cancer risk
• Breast feeding is very important to breast health
– decreases pre-menopausal breast cancer frequency
without affecting lifetime risk
• Low fat diet, EtOH, and hormone risks??
• NSABP P-01 SERM as “THE prevention agent”
– Tamoxifen - proven
– Evista (raloxifen) - suspected but checkered oncologic
history - poor head-to-head against Tam for therapy
– Peripheral Aromatase Inhibitors - promising data from
ATAC trial
Palpable Mass
Palpable Mass [PM]
patient or physician
Intake info including
Gail Model risk data
and
Turbo doc history form
Mammo scheduled if not in last 6 mo. if >30
Physician exam scheduled on all
US scheduled (>80% probability)
Obtain all mammo films last 3 years
Diagnostic W/U @ first visit
needle Bx likely if solid lesion
Very Suspicious [PMVS]
schedule SO appt pending path
Review appt need when path returns
Moderate Suspicion [PMMS]
Gail Risk >1.7
Schedule risk eval appt./ poss. SO
Moderate suspicion [PMDS]
Gail risk <1.7
Short term Mammo f/u
pending path
Low Suspicion [PMLS]
schedule regular mammo CBE f/u
Nipple Discharge
Nipple Discharge [ND]
patient or physician
Intake info including
Gail Model risk data
and
Turbo doc history form
Mammo scheduled if not in last 6 mo. if >30
Physician exam scheduled on all
US scheduled (>80% probability)
Obtain all mammo films last 3 years
Diagnostic W/U @ first visit
Hemoccult of d/c fluid
Positive Hemoccult [NDP]
refer for SO - ? ductal lavage/endoscopy
Negative Hemoccult with negative diag mammo [NDN]
3 month f/u if persists
repeat hemoccult
persistent >6 months - refer for ductal lavage
Mammo abnormality
Outside mammo [OMA]
physician record faxed
Inside Mammo [IMA]
Intake info including
Gail Model risk data
and
Turbo doc history form
Mammo scheduled if not in last 6 mo. if >30
Physician exam scheduled on all
US scheduled
Obtain all mammo films last 3 years
Diagnostic W/U @ first visit
needle Bx likely if solid lesion
vacuum assisted core if calcs
Very suspicious
schedule SO appt pending path
Review appt need when path returns
Moderate suspicion
Gail Risk >1.7
Schedule risk eval appt./ poss. SO
Moderate suspicion
Gail risk <1.7
Short term Mammo f/u
pending path
Low suspicion
schedule regular mammo CBE f/u
Painful breast / FCD
Painful breast or FCD
patient or physician
Intake info including
Gail Model risk data
and
Turbo doc history form
Mammo scheduled if not in last 6 mo. if >30
Physician exam scheduled on all
US scheduled
Obtain all mammo films last 3 years
Diagnostic W/U @ first visit
needle Bx likely if solid lesion
Very suspicious
schedule SO appt pending path
Review appt need when path returns
Moderate suspicion
Gail Risk >1.7
Schedule risk eval appt./ poss. SO
pending bx result
Moderate suspicion
Gail risk <1.7
Short term Mammo / CBE f/u
unlikely bx unless persists
Low suspicion
schedule regular mammo CBE f/u
SO referral if pain persists for
consideration of hormonal manipulation
LCIS
Lcis Bx on core
Wide surgical excision to R/O missed invasive ca
+ invasive go to Stage 1 protocol
negative for invasive ca
Consider Tamoxifen
with High risk F/U protocol
Level of evidence - B for excision; A for tam/C for high risk f/u
ADH/ALH
ADH/ALH Bx on core
Wide surgical excision to R/O missed invasive ca
+ invasive go to Stage 1 protocol
negative for invasive ca
Consider Tamoxifen
with High risk F/U protocol
Level of evidence - B for excision; B for tam/C for high risk f/u
DCIS
DCIS Bx on core
Wide surgical excision to R/O missed invasive ca
+ invasive go to Stage 1 protocol
Lumpectomy
requires negative margin
to reasonable pathologic doubt
if low Van Nuys (3-4)
consider no radiation
Full breast irradiation
external beam
High risk f/u
consider Tamoxifen
High risk f/u
consider Tamoxifen
negative for invasive ca
Total Mastectomy
TM with reconstruction
High risk f/u
consider Tamoxifen
High risk f/u
consider Tamoxifen
Level of evidence - A for L+R and TM; B for L alone/C for high risk f/u
Clinical Stage 1 or 2A
Biopsy proven Clinical
0.1-50mm mass; no nodes
Lumpectomy with axillary sampling
and Radiation
(sentinel node may suffice for smaller tumors)
(multifocality beyond 1 quadrant is contra-indication)
If limited life expectancy
radiation maybe forfeited
if low grade with large margins
margins require
negative beyond reasonable doubt
Modified Radical Mastectomy
(Total Mastectomy with axillary sampling)
98% breast removed
delayed reconstruction after oncologic rx can be considered
Modified Radical Mastectomy with Reconstruction
implant/expander or tissue (TRAM or DIEP)
reserved for good prognosis as immediate procedure
Radiation considered when
node + (esp. >4 N+)
or
Close margins in large tumors
All Patients with tumors >10mm and tumors 5-10mm high grade or
pathologic + nodes referred for systemic rx options (I.e. hormonal or
chemotherapy)
Level of evidence - A for L+R and MRM; B for MRM + recon; C for no radiation in
limited life expectancy; A for adjuvant systemic treatment
Pathologic Stage 1 or 2A
Pathologically proven by
LumpAx or MRM
with path including Er, PR, Ki-67, IHC Her2neu
CXR, EKG, and LFT's pre-op
<5mm & N0
routine high risk f/u
5-10mm & N0
discuss at multi-disciplinary conf. for systemic risk
Adjuvant chemo/hormonal for lowest risk/benefit ratio only
N+ & N0 >10mm
Adjuvant chemo with 4 cycles AC
Tam for receptor +/+, +/-, or -/+
waive systemic rx if high risk/benefit or limited non-cancer life expectancy
All Patients referred for BHI f/u as high risk and no routine lab tests;
symptomatic screening only for metastasis by ASCO guidelines
All Patients with clinical indications for radiation ( LumpAx) and
pathologic indications (+ or close margins; apical nodes +, etc.) referred
post chemo. Benefit of Herceptin in node + cases her-2 +. Molecular
testing may direct future chemo choices – NSABP retrospective .
Level of evidence - A for adjuvant systemic treatment and radiation treatment; B for
F/U
Clinical Stage 2B or 3A
Biopsy proven Clinical
+ or suspicious nodes and/or >5cm
no skin or true chest wall involvement
Maybe considered for neoadjuvant therapy research protocols
to increase breast conservation
Lumpectomy with axillary sampling
and Radiation
(sentinel node may suffice for smaller tumors)
(multifocality beyond 1 quadrant is contra-indication)
margins require
negative beyond reasonable doubt
Modified Radical Mastectomy
(Total Mastectomy with axillary sampling)
98% breast removed
delayed reconstruction after oncologic rx can be considered
Modified Radical Mastectomy with Reconstruction
implant/expander or tissue (TRAM or DIEP)
reserved for good prognosis as immediate procedure
Radiation considered when
node + (esp. >4 N+)
or
Close margins in large tumors
All Patients referred for systemic rx options (I.e. hormonal or chemotherapy)
Level of evidence - A for L+R and MRM; B for MRM + recon; A for adjuvant
systemic treatment; A for radiation post mastectomy for indications listed
Pathologic Stage 2B or 3A
Pathologically proven by
LumpAx or MRM
with path including ER, PR, Ki-67, IHC Her2neu
CXR, EKG, and LFT's pre-op
Adjuvant chemo with 4 cycles AC
Tam for receptor +/+, +/-, or -/+
All Patients referred for BHI f/u as high risk and no routine lab tests;
symptomatic screening only for metastasis by ASCO guidelines
All Patients with clinical indications for radiation ( LumpAx) and
pathologic indications (+ or close margins; apical nodes +, etc.) referred
post chemo.
Level of evidence - A for adjuvant systemic treatment; A for radiation indications
listed ; B for f/u recommendations
Clinical and Pathologic Stage 3B
Biopsy proven Clinical Stage 3B
Stage with Ct chest/abd and bone scan
+ skin or true chest wall involvement
neoadjuvant therapy or research protocols
Modified Radical Mastectomy
(Total Mastectomy with axillary sampling)
98% breast removed
delayed reconstruction after oncologic rx can be considered
Radiation
chest wall
and
supra-clav
All Patients referred for systemic rx options (I.e. hormonal or chemotherapy)
Level of evidence - A for MRM, Chemo, and Radiation
Clinical and Pathologic Stage 4
Biopsy proven Clinical Stage 4
document extent of disease with Ct chest/abd and bone scan
palliative therapy
Modified Radical Mastectomy
if patient has excellent responce to initial treatment
and > 1 yr life expectancy
Radiation
chest wall and supra-clav
if prolonged life expectancy
Level of evidence - D for MRM, Chemo, and Radiation
High Risk F/U
Defined risk
Gail/Claus Model or Ca personal hx
Annual Mammogram
with CBE
Risk counselling
at any event changing
risk pattern
additional testing as indicated
not limited to:
US, miraluma, MRI for symtoms
ductal lavage for risk stratification
Level of evidence: A for mammo/CBE, C for risk counselling, A for
chemoprevention consideration, A-C for additional tests
Summary
• Benign breast disease is common and its largest
impact is confounding Ca dx
• To make a REAL Difference for patients- we
must detect Ca @ <1.0 cm routinely
• Current Screening of young women poor
• Genetic screening will assist in risk eval.
• The Gail model and SERMs to change this
disease enormously in the next decade
• We Need Radically Different Approaches
– functional screening, new bx techniques, etc.
BREAST CANCER
“... THE REAL HOPE FOR
IMPROVEMENT DOES NOT REST
ON AN EXTENSION OF OPERATIVE
PROCEDURES, BUT AN EARLY
RECOGNITION AND EARLIER
EXTIRPATION OF THE FOCUS OF
INVASION...”
W.S. HALSTED, 12/1894