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Module 1: Breast Cancer
Instructor
Sheryl G. A. Gabram MD MBA FACS
Professor of Surgery, Emory University
Director Avon Comprehensive Breast Center at Grady
Unit 3: Major Cancers, Prevention, & Staging
Objectives
To discuss breast screening recommendations
To identify and provide recommendations for high
risk and symptomatic breast patients
To learn about current Surgical Care
Less is More
To become familiar with Medical Oncology
Targeted Therapy
To understand the role of Radiation Oncology
Options for Treatment
Unit 3: Major Cancers, Prevention, & Staging
Introduction: Breast Cancer
Unit 3: Major Cancers, Prevention, & Staging
Breast Cancer Staging
AJCC 7th edition
Breast Cancer
Localized
Regional Distant
Stage present
60%
33%
5%
Survival
98.3%
83.5%
23.3%
Surveillance Epidemiology and End Results
Summary statistics 2000
Improvement in survival…
Improvement in survival due to….

Earlier detection
 Identification
and referral for breast symptoms
 Increased use of screening mammography
 Intense surveillance of high risk patients

Targeted therapy

Hormonal, chemotherapeutic, biologic therapy
Allows for less surgery and possibly less
radiotherapy—impact on morbidity
ACS recommendations
for Early Breast Cancer Detection





No baseline mammography
Starting screening annually at age 40 as long as in
good health
CBE start in 20s-30s every 3 years, asymptomatic
preferably annually >40 (prior to mammography)
Beginning in 20s ♀ should be told +/- of BSE,
report breast changes promptly to MD
Women at ↑risk should talk to MD about more
frequent exams/novel imaging at younger age
Established Breast Cancer Risk Factors


Reproductive: age at menarche,

parity, age at 1st full-term
pregnancy, age at menopause

Endogenous hormone levels:

BMI, post-menopausal weight
gain
estradiol, androgens, prolactin,
insulin, ?melatonin



Diet: caloric intake, fat intake
Physical activity
Body habitus: height, weight,
Exogenous hormone exposure:

HRT

Mammographic breast density
Atypical hyperplasia & lobular
carcinoma in situ

Alcohol intake
Prior chest wall irradiation
Family history of breast or
ovarian cancer
Modified Gail Risk: Questions






Age
Age of menses
Age of first live birth
Number of 1st degree relatives breast cancer
Breast biopsy and if yes, ADH?
Ethnicity
Gail MH et al: J Natl Cancer Inst 81:1879, 1989
Breast Cancer Risk Continuum
5%
10%
20%
30%
40%
50%
Lifetime Breast Cancer Risk
60%
70%
80%
Risk Analysis: Modified Gail Model
Age: 39
Age at menarche: 12
Previous breast biopsies: 2
Atypical hyperplasia: No
Age at birth of 1st child: none
Sister with breast cancer: 1
Ethnicity: Caucasian
Modified Gail Model
5 year risk: 2.6%
Lifetime risk: 29.3%
Estimating Breast Cancer Risk
Age: 39
Age at menarche: 12
Previous breast biopsies: 0
Atypical hyperplasia: No
Age at birth of 1st child: none
Mother/sisters with breast cancer: 1
Beth
Ovarian, 57
Gail
model
Diana
Breast, 32
5 yr: 1%
Life: 18.9%
Cindy
39, unaffected
BRCA1
carrier
80%
Pedigree Assessment Tool
Diagnosis


Cindy 39 yo
Caucasian female
unaffected
Family history:

Mother with ovarian
cancer

Sister age 32 with
breast cancer
Points Assigned
Breast Cancer ≥ 50 yo
3
Breast Cancer < 50 yo
4
Ovarian cancer any age
5
Male breast cancer any age
8
Bilateral breast cancer
x2 points to 1st cancer
Ashkenazi Jewish heritage
+4 points to final score
Maternal
4
5
9
Paternal
4
0
4
Hoskins, et al. Cancer 2006;107:1769-76
New Standards of Care for
Women at Increased Breast
Cancer Risk
 Intensified Surveillance (screening breast MRI)
American Cancer Society (2007)
CA Cancer Journal for Clinicians, March/April 2007
 Chemoprevention: SERM’s
USPSTF (2002)
Annals of Internal Medicine, July 2002
 Genetic counseling and predictive testing of BRCA genes
USPSTF (2005)
Annals of Internal Medicine, September 2005
Spectrum of Care Options
(Encourage referral for genetic counseling/testing)
Gabram SGA et al: Breast Cancer and Res Treatment 2004;88: S95.
Breast Magnetic Resonance Imaging
ACS Guidelines for Breast Screening with MRI as
an Adjunct to Mammography

Recommend (Based on Evidence)
 BRCA1
or BRCA2 mutation
 1st degree relative BRCA carrier, untested
 Lifetime risk 20-25%

Recommend (Based on Expert Consensus)
 Radiation
to chest between ages 10 and 30
 Li-Fraumeni and 1st degree
 Cowden’s and 1st degree
Saslow D, et al: CA Cancer J Clin 57:75-89, 2007
ACS Guidelines for Breast Screening with MRI as
an Adjunct to Mammography

Insufficient Evidence for or against
 Lifetime
risk 15-20%
 LCIS, ADH, ALH
 Hetero or extremely dense breasts
 Personal history of breast cancer

Recommend Against (Expert Consensus)
 Women
at <15% lifetime risk
Saslow D, et al: CA Cancer J Clin 57:75-89, 2007
BREAST CANCER
CHEMOPREVENTION
Stop Progression
Terminal
Simple
Lobule
HyperDuct
plasia
Unit
Reverse
Normal
Low
Grade
Atypical
Hyperplasia
High
Grade
Atypical
Hyperplasia
Low
Grade
In
Situ
High
Grade
In
Situ
Invasive
Cancer
Reverse
Breast Intraepithelial Neoplasia
Invasive
Cancer
Tamoxifen Reduced Invasive Breast
Cancer in All Ages
# Invasive Breast Cancers
200
Placebo
Tamoxifen
154
150
100
85
59
50
38
46
49
24
23
0
Total
35-49
50-59
Age Group
60 +
Cumulative Incidence of Invasive and
Non-invasive Breast Cancer
Vogel V et al: JAMA 295(23): 2727-2741, 2006
Efficacy of bilateral prophylactic mastectomy in
women with a family history of breast cancer

Mayo clinic retrospective review 1960-1993
 639

women (425 mod risk, 214 high risk)
Risk reduction (Moderate/High)
 37.4
expected, 4 cancers(89.5% decrease)
 38.7% vs 1.4% (90% decrease)

PM decreases incidence of breast cancer in
mod/high risk pts
Hartmann LC et al: NEJM 340: 77, 1999
Risk-reducing salpingo-oophorectomy in
women with a BRCA1 or BRCA2 mutation



Prospective study for BRCA1/2 pts, 24.2 months
Chose: surveillance or risk-reducing surgery
Results (n=72 and n=98 respectively)
Surveillance: 8 Br CA, 4 ovar CA, 1 peritoneal CA
 Surgery: 3 Br CA, 1 peritoneal CA


BRCA1/2 pts, risk reducing salpingo-oophorectomy
decreases Breast (by 50%) and GYN cancers
Kauff ND et al: NEJM 346: 1609-1615, 2002
Prophylactic
Surgery
Should not be performed on healthy women before
offering genetic counseling/testing
Women tend to overestimate their risk
Never an emergent or urgent procedure
Body image and effect on sexuality
Wood WC: Oncology 18: 28-32, 2004.
Implants/Expanders
Latissimus Dorsi Flap
TRAM Flap
Breast presentations
Presenting SX
Palpable mass
Likelihood CA
Risk missed dx
High
Low
Low
High
Abnormal mammo
Vague nodularity
Nipple discharge
Areolar eczema
Breast pain
Breast infection
Identifying a Mass



Distinct from surrounding tissues
Generally asymmetrical
Remember normal structures:
 Rib,
costochondral junction
 firm margin at edge of breast
 edge of defect due to excisional biopsy
Donegan WL: NEJM 327: 937-942, 1992
Diagnostic vs Screening

Screening:
Consists of four views—two views of each breast.
 For women without any specific breast complaints


Diagnostic:
The four standard views are supplemented with
additional views, and ultrasound or MRI as needed.
 For women who are having symptoms such as a lump or
unusual nipple discharge or pain.
 Generally read by the radiologist right after it has been
performed
 For all male patients with symptoms and for those with
implants

Abnormal Mammogram




BIRADS 0 ------> more films
BIRADS 1,2 ----> routine
screening
BIRADS 3 ------> 6 mo f/u w/
imaging
BIRADS 4,5,6 -> referral
When to screen < 40 years
Mammography

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BRCA 1/2 mutation
Strong FH of pre-menopausal breast cancer
Personal history of breast cancer
Diagnosis of ADH or LCIS on biopsy
Hodgkin’s Disease (8 years after XRT)
Preoperative for reduction mammoplasty
Cancer phobia
Vague nodularity



May be more common than discrete mass
Understand normal breast tissue densities on
physical exam
Role of further imaging studies/biopsy
Nipple discharge

Benign features

Suspicious features
 induced
 spontaneous
 bilateral
 unilateral
 color:
 color:
green, gray,
brown
serosanguinous,
bloody, watery
Areolar eczema



Rule out Paget’s disease
Punch biopsy
Features of Paget’s
60% have palpable masses
 66% intraductal, 33% invasive carcinoma
 Paget’s cells: large, rounded ovoid intraepidermoid cells
with abundant pale cytoplasm

Breast Pain
(Mastodynia)

Determine characteristics
 non-cyclical,


point tenderness, increasing symptoms
Role of imaging modalities
Treatment
 reassurance,
NSAIDS, withhold caffeine, vitamin E,
primrose oil, rarely Danazol
Breast Infection




Determine underlying etiology
Understand usual age group distribution
Treat short course of antibiotics
Early vs. late referral for biopsy
Appropriate referral guidelines
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Breast mass: not a simple cyst
Abnormal mammogram: BI-RADS 3/4/5
Vague nodularity: patient concerned
Nipple discharge: unilateral, spontaneous
Areolar eczema: needs punch biopsy
Focal constant breast pain and MD concerned
Breast infection: persists after Antibiotics
Trends: Treatment of Breast Cancer

Surgical Oncology


Medical Oncology


Less is more
Targeted therapy
Radiation Oncology

Options for treatment
Surgical Trend: Less is More
That was then…

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Diagnosis at Surgery
Mastectomy
14 day hospital stay
Hormonal therapy
+/- Chemo therapy
+/- Radiation therapy
Delayed Reconstruction
This is Now…

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
Core or FNA biopsy
Multi-disciplinary
Ambulatory/observation
Breast Conservation
Sentinel node surgery
Chemo/Hormonal (preop)
Radiation options
Reconstruction: Immediate
vs. delayed
Biopsy

Percutaneous
 U/S
guided
 Stereotactic
 FNA

Open Incisional
 Not

excising entire lesion
Open excisional
 Excising
entire lesion, but not wide margins
Surgical Oncology Options

Breast conserving surgery
 Lumpectomy/Partial

Mastectomy
 Modified
Radical
 Simple/Total
 Skin sparing

Reconstruction
 Immediate
 Delayed
mastectomy
Lymph Nodes

Sentinel Lymph node biopsy
 Blue
dye
 Technetium sulfur colloid

Axillary dissection
 Risks:
nerve injury and lymphedema
Breast Surgical Procedures
Medical Oncology
“Targeted Therapy”


Neoadjuvant approaches
Determination for Chemotherapy
 Adjuvant!
online
 OncotypeDx

Hormonal therapies
 Tamoxifen
 Arimidex/Femara

Biologic therapy

Herceptin
Neoadjuvant


Chemotherapy or hormone therapy given PRIOR to
surgical excision
Benefits:
 Can
determine effectiveness of therapy
 Can shrink tumor for breast conservation
Trial Assigning Individualized Options
for Treatment: TAILORx
40%
Intermediate
Risk Group
Distant Recurrence at 10 Years
Low Risk Group
35%
High Risk Group
My RS is 30, What is the
chance of recurrence within
10 yrs?
30%
25%
20%
15%
10%
5%
95% CI
0%
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
Paik et al, NEJM 2004
Radiation Oncology
“Options for Treatment”

Indications
Breast conservation
 Post mastectomy


Approaches
Standard: CT planning
 Intensity modulated radiotherapy (IMRT)
 Partial breast irradiation (Mammosite)
 3D conformal radiation therapy
 Intra-operative radiation therapy (IORT)

Kuerer HM: Ann Surg 239: 338, 2004
Whole Breast Radiation



Goal is to kill microscopic
disease that may remain
in the breast
Entire breast is targeted
with BOOST to tumor bed
5-6 weeks of daily
therapy
NSABP B-06


Randomized trial to compare segmental
mastectomy and with and without radiation and
total mastectomy
5 year results:
Overall survival was no worse with breast conservation
therapy
 In lumpectomy group, local recurrence rates were lower
when radiation was given (8% vs 28%)
- Fisher et al NEJM 1985
20 year results:
 No difference in overall survival
 In lumpectomy group, local recurrence rates were lower
when radiation was given (39% vs 14%)


- Fisher et al NEJM 2003
Definition of Brachytherapy:
“therapy given at arms length”
Implantation of radioactive material
directly into various malignancies
“Radiation from the inside out”
Accelerated Partial Breast
Irradiation



Delivered directly to the cavity
from which the breast cancer
was removed
Higher daily dose compared to
that used during the standard
whole breast radiation therapy
course
Amount of radiation given
during one week of high dose
APBI is approximately equal to
that delivered during 6-7
weeks of standard
Partial Breast Irradiation


Placement of catheter
within tumor cavity
Radioactive seed
placed within catheter
and radiation is
delivered twice daily
for 5 days
Survivorship
“…If you want to go
quickly, go alone
If you want to go far, go
together…”
African Proverb
Questions