Local

Management of
Invasive Breast
Cancer
By Steven Jones, MD
• 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 40-
55
Staging Recommendation prior to
primary therapy
1. History and physical
2. Liver function tests
3. Breast imaging: ipsilateral and contralateral
breasts
• Mammogram
• U/S
• MRI
4. Axillary imaging
• U/S
• MRI
MRI for Local-regional Staging
Pros: Cons:

• Changes surgery 20% • With adjuvant therapy

• Multifocal- 3.6% local failure low – 6%
• Multicentric – 4.4% • Too many
• Contralateral – 1.8% 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 Clinical Stage I-IIIA

Abnormal LFT's Asymptomatic
Symptoms Normal LFT's

Pre-op Staging Surgical Staging

Bone Scan Low Risk High risk

CXR no further staging Bone Scan
CT or U/S CXR
CT or U/S
 CRITERIA FOR REFERRAL FOR GENETIC
COUNSELING OF INDIVIDUALS AT INCREASED
RISKFOR BRCA1/2-ASSOCIATED HEREDITARY
BREAST CANCERa,b
 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….
 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:
 Priorradiation 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

 Close: < 1mm – may be a problem with young or

extensive intraductal component
ALGORITHM FOR ADJUVANT SYSTEMIC
THERAPY FOR BREAST CANCER
ER- and/or PR-Positive ER- and PR-Negative

ERBB2 negativea Endocrine therapy± Chemotherapy

chemotherapy
depending on risk

ERBB2 positive Endocrine therapy+ chemotherapy+

chemotherapy+ trastuzumab
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
 Immediate – skin sparing
 Delayed immediate – skin sparing
 Delayed
 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%)
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
 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
 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
 Started1988; 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
 Bestfor 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”