Transcript Local Management of Invasive Breast Cancer

Local
Management of
Invasive Breast
Cancer
By Steven Jones, MD
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Connecting with the patient is the best
part of medicine.
We’re artists, not engineers
Pathological Variables
Luminal A
HER2-Positive (IHC)
12
ER-Positive(IHC)
96
Grade III
19
Tumor size> 2 cm
53
Node- positive
52
Pathological Variables
Luminal B (%)
HER2-Positive (IHC)
20
ER-Positive(IHC)
97
Grade III
53
Tumor size> 2 cm
69
Node- positive
65
Pathological Variables
HER2-like (%)
HER2-Positive (IHC)
100
ER-Positive(IHC)
46
Grade III
74
Tumor size> 2 cm
74
Node- positive
66
Pathological Variables
Basil-like (%)
HER2-Positive (IHC)
10
ER-Positive(IHC)
12
Grade III
84
Tumor size> 2 cm
75
Node- positive
40
Epidemiology of Breast Cancer
 232,340 American
women diagnosed each
year.
 39,620 die each year from the disease
 Lifetime risk through age 85 is 1 in 8, or
12.5%
 2nd leading cause of cancer deaths among US
women, after lung cancer
 Leading cause of death among women age 4055
Staging Recommendation prior to
primary therapy
1.
2.
3.
History and physical
Liver function tests
Breast imaging: ipsilateral and contralateral
breasts
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4.
Mammogram
U/S
MRI
Axillary imaging
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U/S
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MRI
MRI for Local-regional Staging
Pros:
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Changes surgery 20%
Multifocal- 3.6%
Multicentric – 4.4%
Contralateral – 1.8%
Cons:
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With adjuvant therapy
local failure low – 6%
Too many
mastectomies
Some data demonstrate
no difference in local
failure rates
MRI Pre-op
 Diagnostic
dilemma
 BRCA 1 / 2 known or
suspected carriers
wishing BCT
 Occult malignancy
presenting with axillary
mets
Staging Recommendation Prior to
Primary Therapy
Diagnosis of Primary Breast Cancer
Clinical Staging
Hx, PE, Mammography LFT's
Locally Advance Disease
Abnormal LFT's
Symptoms
Clinical Stage I-IIIA
Asymptomatic
Normal LFT's
Pre-op Staging
Surgical Staging
Bone Scan
CXR
CT or U/S
Low Risk
no further staging
High risk
Bone Scan
CXR
CT or U/S
CRITERIA FOR REFERRAL FOR GENETIC
COUNSELING OF INDIVIDUALS AT INCREASED
RISKFOR BRCA1/2-ASSOCIATED HEREDITARY
BREAST CANCERa,b
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Personal history of breast cancer diagnosed≤ 40
Personal history of breast cancer diagnosed≤ 50 and
Ashkenazi Jewish ancestry
Personal history of breast cancer diagnosed≤ 50 and
at least one first- or second-degree relative with
breast cancer ≤50and/or epithelial ovarian cancer
aClose
relatives of individuals with the history mentioned in the table
are appropriate candidates for genetic counseling. It is optimal to
initiate testing in an individual with breast or ovarian cancer prior to
testing at-risk relatives.
bCriteria modified from NCCN (109)
Continued….
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Personal history of breast cancer and two or more
relatives on the same side of the family with breast
cancer and/or epithelial ovarian cancer
Personal history of epithelial ovarian cancer,
diagnosed at any age, particularly if Ashkenazi
Jewish
Personal history of male breast cancer particularly
if at least one first- or second-degree relative with
breast cancer and/or epithelial ovarian cancer
Relatives of individuals with a deleterious
BRCA1/2mutation
Evolution of Breast
Cancer
“Cancer of the breast
spreads centrifugally.
It disseminates to bone by
way of the lymphatics, not
by blood vessels.”
Halsted, WS. The results
of radical operations for
the cure of carcinoma of
the breast. Ann Surg
1907; 66:1
Halstedian concept
did not apply
o
More extensive
surgical procedures
did not reduce risk of
distant metastasis
o
Identification of small
breast cancer by
mammography
National Surgical Adjuvant Breast
Project
 Radical
mastectomy
vs
 Simple mastectomy with axillary irradiation
vs
 Simple mastectomy with delayed axillary
dissection
Started in 1971, 1665 patients enrolled, 25 year follow up
No difference in disease free or overall survival
Breast Cancer Multifocality
Holland et al.
 Only
37% of cancers are confined to the primary
tumor.
 20% have additional cancer within 2 cms.
 43% have additional cancer beyond 2 cms.
Holland R, Veling S, Mravunac M, et al. Histologic
multifocality of Tis, T1-2 breast carcinomas: implications for
clinical trials of breast-conserving treatment. Cancer 1985;
56: 979
NSABP B-06
 Total
mastectomy vs lumpectomy vs lumpectomy
plus irradiation
 No significant difference in survival
 14.3% recurrence in lumpectomy plus radiation
group at 25 years
 39.2% recurrence in lumpectomy without radiation
group at 25 years
Conclusion NSABP B-06
 Lumpectomy
followed by breast irradiation is the
appropriate therapy for women with breast cancer,
provided that the margins of resected specimens
are free of tumor and an acceptable cosmetic result
can be obtained.
Contraindications for Breast
Conserving Therapy
 Absolute:
 Prior
radiation to the breast or chest wall
 Pregnancy
 Muticentric disease
 Diffuse, malignant appearing microcalcifications
Relative Contraindications for
BCT
 History
of collagen vascular disease
 Very large tumor > 5cms
 Very large breasts
Margins
 Clear:
tumor not touching the ink
< 1mm – may be a problem with young or
extensive intraductal component
 Close:
ALGORITHM FOR ADJUVANT SYSTEMIC
THERAPY FOR BREAST CANCER
ER- and/or PR-Positive
ER- and PR-Negative
ERBB2 negativea
Endocrine therapy±
chemotherapy
depending on risk
Chemotherapy
ERBB2 positive
Endocrine therapy+
chemotherapy+
trastuzumab
chemotherapy+
trastuzumab
ER, estrogen receptor; PR, progesterone receptor
aFormerly HER-2
Radiation Therapy
 Whole
breast with boost to tumor bed standard
 Accelerated partial breast irradiation
 Balloon
( Mammosite)
 Interstitial brachytherapy
 External beam limited RT
 Intraoperative limited RT
Post-mastectomy Radiation
 Early
studies showed increased mortality
 Recent studies show substantial decrease in
locoregional recurrence
 Recent trials show survival benefit 5-8% at > 10
years.
Indications for Post-mastectomy
Radiation
 T3
or T4 tumors
 Tumors invading skin or muscle
 4 or more pos. axillary nodes
 (Some recommend for 1-3 nodes, depending)
Breast Reconstruction
– skin sparing
 Delayed immediate – skin sparing
 Delayed
 Immediate
Skin Sparing Mastectomy
 Includes
areolar (nipple
sparing controversial)
 Excise biopsy incision
 Radiate positive
margins
Axillary Biopsy and Control
1. Staging
In the absence of distant mets number of positive
lymph nodes is the most important prognostic factor.
2. Regional Control
In clinically negative axilla, axillary dissection
reduces local occurrence from 20% to 3%
3. Small survival advantage (3-5%)
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Sentinel Lymph Node
 Technetium
labeled
sulfur colloid
 Isosulfan blue
(lymphazurin 1%)
 Combined – 97%
ID’ed; 6% false
negative
 1% anaphylactic
reaction to blue dye
Locally Advanced Cancer
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Large primary tumors
(>5cm) especially with
pos. nodes
Tumors with skin or
chest wall involvement
Tumors with fixed or
matted axillary nodes or
ipsilateral subclavian or
supraclavicular lymph
nodes
Most have been present
for months or years but
treatment has been
delayed
Inflammatory Breast Cancer
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Rapid onset and
progression over weeks
to months
Skin often discolored red
to purple
Skin thickened or peau d’
orange
Induration
Invasion of dermal
lymphatics is a common
feature but not required
or sufficient for a
diagnosis
1-5% of breast cancers
Neoadjuvant Chemotherapy
aka
Preoperative Systemic
Therapy
aka
Primary Chemotherapy
NSABP B-18
 Started
1988; 1523 pts, 4 cycles AC
 80% overall response
 13% pathologic complete response
 No difference in overall survival
 Only 3% had progression of disease
 25% downstaging at axilla
 30% of women will downsize to allow
conversion from mastectomy to BCS
Indications
 To
downsize women with large tumors that cannot
undergo BCS with good cosmetic result – 30% of
women will downsize.
 Early
initiation of systemic treatment
 In vivo assessment of response, good biological
model
 Less radical surgery needed
Pre-operative Endocrine Therapy
 Best
for large low grade ER pos. tumors in post
menopausal women
 Response times 3 months or longer
 Greater response with aromatase inhibitors
compared with tamoxifen
 Under-utilized in the US
Tulane surgery:“ tough
as the marines except the
marines get to eat”