Local Management of Invasive Breast CancerBy Steven Jones, MD
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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 therapy1. History and physical2. Liver function tests3. Breast imaging: ipsilateral and contralateral
breasts• Mammogram• U/S• MRI
4. Axillary imaging• U/S• MRI
MRI for Local-regional Staging
Pros:
• Changes surgery 20%• Multifocal- 3.6%• Multicentric – 4.4%• Contralateral – 1.8%
Cons:
• 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
B o ne S canC X R
C T o r U /S
P re-o p S tag ing
L o ca lly A dva n ce D ise a seA b n o rm a l L F T 's
S ym pto m s
L o w R iskn o fu rthe r s tag ing
H ig h ris kB o ne S can
C X RC T o r U /S
S u rg ica l S ta g ing
C lin ica l S ta ge I-II IAA sym pto m a ticN o rm a l L F T 's
C lin ica l S ta g ingH x , P E , M a m m o g ra p hy L F T 's
D ia g n os is o f P rim a ry B re a s t C a n cer
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 applyo 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 MultifocalityHolland 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
Close: < 1mm – may be a problem with young or extensive intraductal component
ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST
CANCER
ER, estrogen receptor; PR, progesterone receptoraFormerly 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
Includes areolar (nipple sparing controversial)
Excise biopsy incision Radiate positive
margins
Skin Sparing Mastectomy
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 Chemotherapyaka
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”
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