Transcript The Breast: an Overview

The Breast: an Overview
Lisa S. Dresner, MD, FACS
Associate Professor of Surgery
SUNY Downstate
Prevalence/Incidence

200,000 new cases in USA / year
 Incidence
– 121 / 100,000 white women
– 99 / 100,000 black women

Stage
– Increased numbers of early and non-invasive
cancers
– Stable or slightly decreased number of advanced

Rates: vary geographically and ethnically
 Rates vary greatly by age
Risk of Breast Cancer
Current
age
+10 yrs
+20 yrs
+30 yrs
Eventually
0
0.00
0.00
0.05
13.22
10
0.00
0.05
0.48
13.37
20
0.05
0.48
1.92
13.40
30
0.44
1.88
4.49
13.41
40
1.46
4.11
7.56
13.14
50
2.73
6.30
9.64
12.06
60
3.82
7.40
9.52
9.99
Lifetime risk of dx: 13.22 %
Lifetime risk of dying: 2.96 %
Anatomy
Anatomy
Structural Anatomy
Physiology
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Cell Regulation:
– Growth development and function under hormone
control
– Binding of hormone to specific cell receptors
trigger effects

Estrogens:
– important in development, growth and
differentiation. Normal and most malignant breast
cells contain ER receptors.
– E-ER complex binds with nuclear chromatin and
influences protein production including
progesterone receptor (PR)
History:
– Complaint, ask about SBE
– Timing and nature of previous breast
surgery (atypia, cancer etc)
– Family history of breast or ovarian cancer
– Use of hormones
– Reproductive history
– Radiation exposure
Physical Exam
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Best/easiest during week after menses
 Palpate supraclavicular, cervical and axillary
nodes
 Skin changes: dimpling, edema, nipple
change
 With patient supine with hand over head
examine breast in a systematic way against
the chest wall
Evaluation of Breast Mass

In women under 30 ultrasound
 In women over 30 mammo±ultrasound
 As a rule all except obviously benign masses
should have pathological diagnosis
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Open biopsy
Core biopsy
FNA
Ultrasound guided core biopsy (highly sensitive
and specific)
If the mass is indeterminate by your exam
consider ultrasound to confirm
 If mass not palpable stereotactic core biopsy
Ultrasound guided biopsy
Screening:

No controversy: all women aged 50 and
older should have a mammogram every 1-2
years as well as an annual clinical breast
exam (CBE)
 Women 40-50: guidelines ACS mammogram
every 1-2 years as well as an annual clinical
breast exam (CBE)
 High Risk: earlier mammography.
Mammogram: ACR Classification
Standardized way of reporting mammogram results.
BioRads Assessment
Category 0
Needs Additional Imaging Evaluation
Category 1
Negative (5/10,000 risk of breast cancer)
Category 2
Benign Finding (5/10,000 risk of breast cancer)
Category 3
Probably Benign Finding: Short Interval Follow up Suggested
(generally 6 months)
Category 4
Suspicious Abnormality-Biopsy Should be considered (risk
cancer 25-50%)
Category 5
Highly suggestive of malignancy- Appropriate Action should be
taken (obvious cancer: 75-100%risk)
Masses:
Circumscribed
Round
Microlobulated
Oval
Obscured
Lobulated
Ill-defined
Irregular
Spiculated
Infiltrating Carcinoma
Microcalcifications: Concerning
Microcalcs:
Benign
Cluster of irregular microcalcs.
Management of Non-Palpable
Mammographic abnormalities

Ultrasound: is there a mass?
– Ultrasound guided core biopsy may be diagnostic
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Stereotactic core biopsy
– Mammographic abnormalities

Mammotome (mammo-guided very big core;
may be excisional)
 Needle localization biopsy
– Mammo or ultrasound guided open biopsy

Cryoablation: for bx proven benign
MRI for evaluation of the breast
Highly sensative but high false postive
rate
 Useful for screening BRCA patients
 May be useful in staging known breast
cancer
 May become an important screening
modality
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Stereotactic core biopsy
Other imaging modalities
Tc99m sestamibi scan (Miraluma)
 Tomosynthesis (variation of
mammogram)

MRI
– Extremely sensitive (?high false
positives?)
– May be useful in staging
– May be useful in high risk patients with
difficult mammograms
– Not yet approved for screening
Benign Breast Disorders:
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1
Fibrocystic “disease”
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Nodular, lumpy, tender breasts:
Mastodynia
Clear/milky nipple discharge
Within the range of normal

Confirm benign-ness, Reassurance,
symptomatic relief. Encourage BSE
 Fibrocystic features
– Adenosis, cysts, fibrosis (not increased risk)
– Ductal and lobular hyperplasia with or without
atypia (with increased risk)
Breast cysts:

A palpable mass could be a cyst
– Simple cysts need no treatment
• Needle aspiration to confirm, or for pain relief
• Ultrasound (conclusive)
– Complex cysts, bloody cysts deserve
evaluation and biopsy (open or ultrasound
guided core)
• Excision if diagnosis is in doubt after minimal
invasive biopsy
Breast cyst
Fibroadenoma
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May present at any age but most common
women 16-24.
Rubbery, mobile, well defined
Confirm by core, excision, FNA, or
ultrasound, and/or short interval observation
by ultrasound
Giant fibroadenomas: may be very large and
grow rapidly (late teens and perimenopause):
RX: enucleation
Actual pathology may be adenoma,
fibroadenoma,etc
Phylloides Tumor

Old name cystosarcoma phylloides
 Mesenchymal tumor: leaf like masses, cellular with
necrosis and hemorrhage
 May occur in adolescent (generally benign) or
premenopausal woman (may be malignant)
 Treated with excision with margins
 25% risk of local recurrence in 10 years even with
‘benign” path
 Mitotic figure count is one predictor of malignancy
 Metastasis even in “malignant” tumors are rare
 Younger: more likely benign, older women more likely
malignant
Phylloides tumor:
Other benign breast masses
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Sclerosing adenosis
Radial scar
Fat necrosis
Ductal ectasia
Lactational mastitis and galactocele
Mondor’s disease
Intraductal papilloma
Lactating adenoma
Mastodynia
– Cyclical or continuous. May be referred to axilla,
upper arm, may improve with menopause
– Rarely associated with malignancy
– Continuous: may be related to a large
cyst,infection or inflammation
– Reassurance, NSAIDS, well fitted brassiere,
caffeine reduction, evening primrose oil, cessation
of tobacco use (takes months)
– Danazol, bromocriptine and tamoxifen (side
effects prohibitive)
– ?SSRI
Nipple Discharge
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–
–
–
–
Most common after lactation (as long as 2 years)
Subareolar infection (increased risk in smokers)
Galactorrhea (bilateral, milky) prolactin excess
Fibrocystic: green, yellow, brown (guiac)
Bloody: intraductal papilloma (benign), Cancer
should be ruled out. Ductogram (galactogram)
may be helpful
Hyperplasias: not malignant but not
really benign either
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Ductal hyperplasias
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–
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Mild
Moderate
Florid
Atypical Ductal hyperplasia (ADH)
(Ductal carcinoma in-situ- DCIS*)
Lobular hyperplasias
– Lobular hyperplasia
– Lobular carcinoma in-situ
Lobular Carcinoma In-situ LCIS
Bystander lesion- marker of risk

Commonly occurs in 4th decade of life, 2/3 are
premenopausal
 Lobular tumors are more likely ER/PR positive
 Diagnosis incidental on biopsy of other pathology
 Significant life time risk of breast cancer (5.9 to 12
times higher) but the risk is in both breasts
 Risk is greater 15-20 years after diagnosis than the
immediate post diagnostic period
Lobular Carcinoma
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Clinical features, epidemiology and risk
factors and treatment not different
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Doesn’t form microcalcifications and is
extensively infiltrative so may be
mammographically occult
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May present as “architectural distortion on
mamography
Invasive Ductal Carcinoma

Most common tumor: from ductal elements
 Invasion of nerves, vessels, lymphatics in the
breast parenchyma at edge of lesions may be
present and carries a poorer prognosis
 May have all or partial characteristics of other
types (colloid, tubular, medullary)
Breast Cancer
Breast Cancer Risk Factors

Greatly increased risk RR>4.0
– Inherited genetic mutations for breast
cancer
– ≥ 2 first degree relatives with breast cancer
diagnosed at early age
– Personal history of breast cancer
– Age >65 (increasing risk with increasing
age to 80)
Breast Cancer Risk Factors
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Moderately increased risk factors RR
2.1-4.0
– One first degree relative with breast cancer
– Nodular densities on mammogram (>75%
of volume)
– Atypical hyperplasia on breast biopsy
– High dose ionizing radiation to chest
Breast Cancer Risk Factors 3
Low increased risk: RR 1.1-2
High socioeconomic status, urban residence, Northern USA
Early menarche (<12), late menopause (>55)
No full term pregnancy, late (>30) first term pregnancy
Never breast fed
Postmenopausal obesity
Etoh,consumption
HRT, recent oca use
Tall
Personal history of ca endometrium, ovary or colon
Jewish heritage, mammographically dense breasts
Inherited Breast Cancer
Syndromes
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1. Li-Fraumeni syndrome: p53 mutation
2. Mutation on the sht arm of chromosome 2
3. BRCA-1 long arm chromosome 17
(associated with breast and ovarian cancer)
4. BRCA-2 small region of 13q12-13
Recommendations vary from bilateral
salpingo-oophorectomy and prophylactic
mastectomy to increased surveillance
Value of SERM (tamoxifen) unclear as most
hereditary-linked breast cancers are ER/PR
negative
Estimating Risk

Gail Model
– calculates risk using 6 key risk factors
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Age
Age menarche
Age first birth
Family history (1° female relative)
Number of previous breast biopsies
Number of biopsies with atypical hyperplasia
http://bcra.nci.nih.gov/brc/
Inflammatory breast cancer
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Diagnosis: clinical findings of inflamed breast
with underlying malignancy.
35% have obvious mets at time of diagnosis
Mammogram: edema
Dermal or core biopsy
Treatment is neoadjuvant chemotherapy first
then mastectomy plus RT
Inflammatory Breast Cancer
Inflammatory Breast Cancer
Staging

Primary tumor
– Tis: Carcinoma in-situ
– T1 : 2 cm or less
– T2 : >2 but not more than 5 cm
– T3 : >5 cm
– T4 : any size with chest wall extension,
skin involvement, skin nodules, or
inflammatory breast cancer
Staging
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Nodes
– N0 no involved nodes
– N1 mets to ipsilateral nodes (movable)
– N2 mets to ipsilateral nodes matted/fixed
– N3 ipsilateral internal mammary nodes
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Metastasis
– M0, M1
Stage Groups
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Stage 0
Stage 1
Stage IIA
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Stage IIB
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Stage IIIA
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Stage IIIB
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Stage IV
Tis, N0, M0
T1, N0, M0
T0-1, N1,M0
T2 , N0, M0
T2, N1, M0
T3, N0, M0
T0-2, N2, M0
T3, N1-2, M0
T4, N1-2, M0
Any T, N3, M0
Any T, Any N, M1
Tumor related prognostic factors
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Size
ER and PR status
Margins
Histologic type
Pathologic prognostic features
– Nuclear grade, angiolymphatic invasion,
lymphocytic response
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Invasivion: DCIS vs infiltrating intraductal I
– invasion of basement membrane
– Often both on same specimen
Breast Cancer:Treatment Options
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Local control:
– Lumpectomy with irradiation
– Mastectomy ± reconstruction
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Regional Control
– Axillary lymph node dissection
– Regional RT
Neoadjuvant Chemotherapy
Recommended for Stage IV, and some
III and IIb patients
 May allow breast conservation therapy
in women by downstaging tumor.
 Unclear yet that it improves survival but
good response is a good prognostic
sign
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Sentinal node biopsy
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New standard for clinically negative axilla
Avoids full axillary dissection and its
complications in patients with small tumors
and negative node status
blue dye plus nuclear medicine
Axillary node evaluation done to identify
node positive patients so as to guide
adjuvant therapy
“Proven” benefit in women with T1 tumors
(where axillary node infrequently involved)
Breast Conservation
Quality of results improved by
increasing facility with autologous flaps
and use of tissue expanders
 Improved quality of result with advent of
skin sparing mastectomy
 Options include flaps (Tram, latissimus),
free flaps, and implants.
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Skin sparing mastectomy
Adjuvant therapy
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Chemotherapy
– Decreases rate of distant recurrence
– Recommended for stage stage II breast cancers
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Hormonal therapy
– Effect in ER/PR positive breast cancers similar to
chemotherapy
– New agents (aromatase inhibitors) may supplant
Tamoxifen in the next few years in post
menopausal patients
Adjuvant Therapy
Recommendations for Adjuvant therapy n
i stage I and II Breast Cancer
Premenopausal
Postmenopausal
Tumor
ER positive
ER-Negativ e
ER positive
ER-Negativ e
<1 cm, negativ e
nodes
³ 1 cm, negative
nodes
Positive Nodes
¿
¿
¿
¿
Tam ± chemo
Chemo
Tam
Chemo
Chemo
Chemo
Tam
Chemo
On the horizon
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Ductal Lavage and FNA
Digital mammography Bone marrow biopsy
and staging
Sentinal node biopsy
? Axillary node dissection?
Aromatase therapy will supplant Tamoxifen
Increasing number of women with low
stage tumors receiving chemotherapy
Life long treatment with aromatase
inhibitors
Prevention:

Bilateral mastectomy
– Bilateral mastectomy decreases the risk of breast
cancer by 90%
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Salpingo-oophorectomy
– Recent study demonstrated significant decrease in
new breast cancer risk in BRCA carrier women
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Chemoprevention
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Tamoxifen
?Raloxifen: trials ongoing
?Aromatase inhibitors?
Chemoprevention is less likely to be effective in
BRCA1 tumors (greater # receptor negative
tumors)
Internet resources:
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Susan B Komen Foundation:
http://www.komen.org/
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National Cancer Institute
http://www.nci.nih.gov/cancertopics/type
s/breast
Mechanism of Action of Aromatase Inhibitors and Tamoxifen
Aromatase Inhibitors
Lower circulating estrogens by
preventing peripheral production of
estrogens
 anastrazole = Arimidex
 letrozole = Femara
 exemestane = Aromasin
 Each has been studies in different
clinical circumstances
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