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Breast Cancer
Kristi McIntyre M.D.
Resident’s lecture
Breast cancer
Risk factors
Hereditary breast cancer
Detection
Staging
Surgical intervention
Prognostic factors
Management of early stage breast cancer
Breast cancer risk factors
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Age/race
Reproductive issues/Estrogen-related
factors
Breast histology
Life style factors
Family history/Genetic factors
Breast Cancer Risk Factors
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Breast Cancer Incidence
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Race/Ethnicity and Breast Cancer Risk
Annual incidence
Caucasian
137
African Americans
120
Hispanic
82
Asian
93
American Indian
59
SEER results: age adjusted only
Jemal CA:Cancer J.Clin ;2003,53:5
Race/Ethnicity and Breast Cancer Risk
“Adjusted Hazard Ratios”
0.4
0.6
African American
0.8
1.0
1.2
.72
Hispanics
American Indian
Asian
Only African Americans had lower breast cancer
risk (p=o.oo6) than Caucasians
Cheblowski JNCI ;March 2005
Race/Ethnicity and Breast Cancer Risk
Combined Grade III and ER negative by race
100
90
80
70
60
50
40
30
20
10
0
%
white
AA
Hispanic
Asian
Cheblowski JNCI ;March 2005
Race/Ethnicity and Breast Cancer Risk
o
o
o
Differences in breast cancer incidence rates
between most ethnic groups can largely be
explained by control of risk factors
African American women are at significantly
reduced risk
African American women have a higher
proportion of unfavorable features suggesting
cause for higher mortality rates
Cheblowski JNCI ;March 2005
Reproductive Factors and Breast Cancer
Menarche < 16
Menopause >50
Menarche <16
OR 1.2
Menopause >50
OR 1.5
Null parity
OR 2.0
Breastfeeding 4.3% decrease risk/yr
First live birth<20
OR 0.5
First live birth >35
OR 1.5
WHI Trial of Estrogen plus Progestin
E+P
Invasive Breast cancers
SEER high stage
Abnormal Mammograms
199
25%
716
placebo
150
16%
395
p-value
0.003
0.041
0.0001
More breast cancers diagnosed at more advanced
stage and increased abnormal mammograms
M
o
Chlebowski JAMA 2003;289. 3243
r
Breast histology and breast cancer risk
Benign breast disease
Fibrocystic disease
Atypical ductal hyperplasia
Atypical ductal hyperplasia and
family history
RR
0
4.3
11.0
Risk Factors for Breast Cancer
Family History
First Degree relative
•Premenopausal diagnosis
•Bilateral disease
•Premenopausal diagnosis and bilateral disease
•Postmenopausal diagnosis
Second Degree relative
•Premenopausal diagnosis
•Postmenopausal diagnosis
Risk
3.0
5.0
9.0
1.5
1.2
0
Hereditary
Family history and breast cancer risk
Most hereditary breast cancers arise from mutations
in BRCA1 and BRCA2
Autosomal dominant , tumor suppressor gene
BRCA mutations and lifetime cancer risk
50-85% breast cancer
50% Second breast cancers
15-45% ovarian cancer risk
Other malignancies:
prostrate
pancreatic
male breast cancer
Founder mutations and Breast cancer
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Ethnic background should be considered in risk
assessment for breast cancer
“ Founder” gene mutations discovered in
individuals of Ashkenazi Jewish descent
50-90 % have gene susceptibility with positive
family history
Founder mutations have been found in
populations of Iceland,Finland, France, Holland ,
Russia,and Sweden
Models for risk assessment
Gail model
Claus model
http://bcra.nci.nih.gov/brc
Age
Age first live birth
Age first menses
FH-maternal only; no age
# prior breast biopsies/ADH
race
Family history
Age at diagnosis
Both models inadequate : not useful for mutation
carriers or individual risk
www3.utsouthwestern.edu/cancergene/
Lifestyle factors and breast cancer risk
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Body mass index: postmenopausal women >30%
excess BMI increased risk
Dietary fat intake: increased risk
NSAID use: decreases risk
Physical activity: 1.25 to 2.5/hrs week brisk
walking had 18 % decrease risk
Smoking : increased risk
Alcohol use: increased (dose dependent)
Risk Reduction Strategies
Average Risk
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Early childbirth
Exercise
Maintain normal weight
Avoid smoking/alcohol
Avoid prolonged HRT
Moderate Risk
•Chemoprevention
Most breast cancers are
non palpable masses
discovered only on
screening mammograms
Malignant breast
densities
have irregular borders,
are stellate and
distort surrounding
architecture
Breast Cancer Detection
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United States Preventive Services Task Force
•Mammogram every 1-2 years for female age 4049(average risk)
•Age > 50 annual mammography and
clinical exam
•Age > 70 debatable
Mammography detects only 85% of biopsy proven
breast cancer hence not a substitute for tissue sampling
of palpable mass
Breast Cancer Screening
There is almost universal agreement
that randomized controlled trials of
screening have demonstrated death
rate from breast cancer can be
reduced by periodic screening with
mammography
MRI Breast
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Implant evaluation
Axillary adenopathy ?occult primary
Breast cancer patients (extent of disease,
response to neoadjuvant therapy)
Screening evaluation for high risk patient
Further evaluation of mammographic
abnormality
Staging of breast cancer
Estimate extent
of disease
Determine
prognosis
Guide
therapy
Staging of breast cancer
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Stage 0 (DCIS)
Stage I node negative
Stage II node positive
Stage III advanced node
Stage IV distant metastasis
2003 AJCC staging
change
•Distinction between
micrometastasis and isolated
tumor cells
•Identifiers for sentinel nodes
•#number of positive LN
Pathobiologic Events Associated with Ductal Carcinoma in Situ
Burstein, H. J. et al. N Engl J Med 2004;350:1430-1441
Management of Early stage breast cancer
1950 Halsted “radical mastectomy”
“breast cancer spreads in an
orderly fashion”
12%
10 year
survival
20-30% node negative breast cancer patients will
develop metastatic disease
Micrometastatic disease paradigm
Management of Early stage breast cancer
Radical Mastectomy
Lumpectomy
Whole breast
radiation
Partial breast radiation
Axillary dissection
Sentinel node biopsy
MORE
LESS
Surgical intervention for Breast Cancer
NSABP B-04
Total Mastectomy
+
Axillary dissection
Lumpectomy
+
Breast radiation
Lumpectomy
alone
No difference in Overall Survival or
Disease Free Survival
(20 year follow-up) Fisher et al.NEJM2002;347:1456-61
Surgical Intervention of Breast Cancer
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39% 
14%
NSABP B-04
Cumulative incidence
of ipsilateral breast
cancer
Standard of care:
lumpectomy+ Xrt
Surgical intervention for Breast Cancer
NSABP B-04
Fisher,et al.NEJM(2002):347;1454-61
Surgical Staging of Axilla
Axillary dissection= removal of level I and
Level II lymph nodes
Morbidity : wound infection
motion restriction
arm stiffness
pain
lymphedema
Sentinel node mapping
Chemotherapy for early stage breast cancer
Prognostic factors in Breast cancer
Recognized Factors
Potential factors
Nodal status
Tumor size
Histologic type
ER/PR
Proliferative index
Tumor grade
Vascular invasion
Her- 2
Gene microarray
Prognostic factors in Breast cancer
The most significant prognostic indicator for
patients with early stage breast cancer is the
presence or absence of axillary lymph node
involvement.
Prognostic factors in Breast cancer
Recognized Factors
Potential factors
Nodal status
Tumor size
Histologic type
ER/PR
Proliferative index
Tumor grade
Vascular invasion
Her- 2
Gene microarray
Prognostic factors in breast cancer
Multigene assay:
Paik et al.NEJM 2004;351:2817-26
Gene Microarray
Multigene assay to predict recurrence in node
negative breast cancer
HER- 2/neu
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Her-2/neu oncogene encodes for
transmembrane receptor belonging to
EGFR family
Amplified in 25-30% breast cancer
Overexpression associated with tumor
aggressiveness and increased rates of
recurrence
Her-2/neu
Basis for molecular targeted therapy with Herceptin
NCI clinical alert –April 25,2005
NSABP B-31
Operable breast cancer
Her 2 +, node +
Randomization
AC x4cycles
Taxol x4 cycles
AC x4cycles
Taxol x4 cycles
+
Herceptin
52%
decrease in
disease
recurrence
Thank you !