Breast Cancer

November 3, 2017
 Introduction
Most common female cancer
Accounts for 32% of all female cancer
211,300 new cases yearly and rising
40,000 deaths yearly
Gross Anatomy

Sappys plexus lymphatics under areolar complex

75% of lymphatics flow to axilla
 Microscopic Anatomy
Stromal tissue
Connective tissue, capillaries, lymphocytes, etc.
Adipose tissue
Ductal tissue
Squamous epithelium
Columnar or cuboidal

epithelium
Lobular tissue
 Presentation
Breast lump
Abnormal mammogram
Axillary lympadenopathy
Metastatic disease
 Familial Breast Cancer
Cause 5-10% of all cancer and 25% in women
<30 y/o
BRCA2
Causes 40% of familial breast CA
50-70% - breast
15-45% - ovarian
Increased risk for prostate, colon
BRCA1
50-70% - breast
20-30% - ovarian
Increased risk for prostate, pancreatic, laryngeal,
 Screening Mammography
Recommendations
Biannually or annually in 40-49 y/o
Annually in >50 y/o
15% relative risk reduction
Birads
0 - Incomplete assessment; need additional imaging evaluation
1 - Negative; routine mammogram in 1 year recommended
2 - Benign finding; routine mammogram in 1 year recommended
3 - Probably benign finding; short-term follow-up suggested (3%)
4 - Suspicious abnormality; biopsy should be considered (30%)
5 - Highly suggestive of malignancy; appropriate action should be
taken (94%)
 Biopsy techniques
FNA
Diagnostic and therapeutic in cystic lesions
Core needle
U/S guided or sterotatic
90% effective in establishing diagnosis
Atypia need excision
Sterotatic
Needle localization
Excision biopsy
Risk of Future Invasive Breast Carcinoma
Based on Histologic Diagnosis from Breast
Biopsies
No Increase
Adenosis
Apocrine metaplasia
Cysts, small or large
Mild hyperplasia (>2 but <5 cells deep)
Duct ectasia
Fibroadenoma
Fibrosis
Mastitis, inflammatory
Periductal mastitis
Squamous metaplasia

Slightly Increased (relative risk, 1.52)

Moderate or florid hyperplasia, solid or papillary
Duct papilloma with fibrovascular core
Sclerosing adenosis, well-developed

Moderately Increased (relative risk, 45)

Atypical hyperplasia, ductal or lobular
 Benign Breast Masses
Cysts
Fibroadenoma
Hamartoma/Adenoma
Abscess
Papillomas Papilloma
Sclerosing adenosis
Radial scar
Fat necrosis
 Maligant Breast Masses
Ductal carcinoma
DCIS
Invasive
Lobular carcinoma
LCIS
Invasive
Inflammatory carcinoma
Pagets disease
Phyllodes tumor
Angiosarcoma
Ductal carcinoma
 DCIS
Ductal carcinoma in situ (DCIS)
1. Solid type*
2. Cribiform type

3. Papillary type

4. Comedo type*
Lobular carcinoma
 Invasive
Histology
A. Ductal NOS
B. Lobular
C. Mucinous
D. Tubular
E. Medullary
 Staging
Tumor
Tis: in situ
T1: <2cm
T2: 2-5cm
T3: >5cm
T4: invasion of skin or chest wall
Node
N1: 1-3 axillary nodes or int mam node
N2: 4-9 axillary nodes or palpalbe int mam node
N3: >10 nodes or combo of axillary and int mam nodes
{mic micoroscopic posivitiy, mol molecular posiivity
Metastasis
Staging
 Modified Radical Mastectomy
Entire breast tissue and Level I & II nodes
Survival at 10 yrs
Negative nodes 82% (5% local recurrence)
Positive nodes 48% (5% local recurrence)

Simple mastectomy Modified radical

 Breast Treatment Trials

NSABP (1971 with B-04

update in 2002)
Compared radical, vs modified
radical +/- radiation
No survival diff for node neg or
pos between three arms
75% of recurrences occur in 5
years
Tumor location not important
 Breast Treatment Trials
Ontario study
All pts got lumpectomy, randomized to radiation or no radiation
25% failure rate without radiation, 5% with
NSABP B-06
Mastecomy vs lumpectomy vs lumpectomy with radiation
No difference in survival
39% recur with lumpectomy, reduced to 14% with radiation, 3-4%
with mastectomy
0.5-1% per year recurrence rate for life with BCT and radiation
2-5% complication rate with radiation (rib fx, pericarditis, cosmesis)
 Radiation after mastectomy?
2 Danish studies and one Britsh study
Recommend in: >3 nodes positive,
aggressive/large tumors or extranodal invasion
Decreased local or regional recurrence

+/- survival benefit

 Sentinel node biopsy
Contraindications:
Clinically positive nodes, pregnant or nursing, prior axillary
surgery, locally advanced disease
False negative rate 3.1%
Macrometases (>0.2cm) so recommended pathology cuts are
0.2 cm
Micrometases (IHC staining) 37% death rate vs 50% of those
with macrometases
If sentinel node positive 43% will have other nodes positive and
24% will have >4 nodes positive
NSABP (B-32) in progress
 Treatment of DCIS
600% increase after mammography
Options
Mastectomy 1% breast ca mortality
Large tumors, multicentric, positive margins after
reexcision,
Lumpectomy and radiation
Radiation decreases local recurrence by 50%
Of those that recur 50/50 DCIS vs Invasive
0-3% chance of dying of maligant breast ca for all
DCIS
 Treatment of DCIS
Nodal involvement
3.6% of DCIS pts have positive nodes in
mastectomy specimins
By definition DCIS has no access to lymphatics
Size may matter (111 DCIS tumors evaluated)
<45mm 0% microinvasion
45-55mm 17% microinvasion
>55mm 48% microinvasion
 Tamoxifen in DCIS
NSABP (B-24)
Determine benefit of tamoxifen in lumpectomy plus
radiation pts
31% decrease in ipsilateral, 47% in contralateral,
31% decrease all together
Retrospectively looked at ER status
75% of DCIS is ER+
59% reduction in ER+ pts
No significant reduction in ER-
Treatment for invasive breast ca
Locally advanced is likely already metastatic in
most
Surgery and radiation alone make no difference on survival
Chemotherapy & +/- Tamoxifen
Neoadjuvant chemotherapy
7 randomized trials
No survival benefit
50-80% response
May allow for BCT in large tumors
Sentinel node before chemo
 Tamoxifen
Indications
ER + breast ca
LCIS
BRCA1/2
Increased overall risk

Benefits
Decreases risk of ca in other breast by 47-80%

Draw backs
Increases endometrial ca risk by 2.5, PE 3.0, DVT 1.7
Source: NSABP P-1 trial
 Chemotherapy
Early Breast Cancer Trialists Collaborative
Group
Decreases recurrence (12%) and death (11%) regardless of
nodal status
Indications
All patients except node negative, <10mm tumors
Regimens
Multidrug combination chemotherapy
Tamoxifen or aromatse inhibitor - ER positive tumors
Herceptin (trastuzumab) HER2/neu positive tumors
NSABP B-31 33% reduction in risk of death
 Other breast cancers
Inflammatory ca
Carcinoma invading lymphatic ducts
Chemotherapy, mastectomy, radiation

50% survival at 5 years

 Other breast cancers
Pagets disease
Intraepithelial extesion of ductal ca
Excision with nipple-areolar complex

Sentinel node if invasive ca

Mastectomy
 Other breast cancers
Phyllodes tumor
<1% of breast tumors
Age 30-45
Similar in appearance to fibroadenoma
4% recurrence after excision
0.9% axillary spread
Radiation, chemotherapy, tamoxifen ??

Phyllodes tumor Fibroadenoma

Angiosarcoma
Risk factors
Radiation
Lymphedema
Treatment
Excision, radiation
 Male breast cancer
90% are invasive at time of diagnosis
80% ER+, 75% PR+, 30% HER2/neu
More invade into pectoralis
Treatment same as for female ca