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EARLY DETECTION AND TREATMENT OF
BREAST CANCER
S Y LV I A S . E S T R A D A , D N P, W H N P - B C , M S H C M , C B C N
NURSE PRACTITIONER
SAUL AND JOYCE BRANDMAN BREAST CENTER
CEDARS-SINAI MEDICAL CENTER
OBJECTIVES
• Identify risk factors for breast cancer
• Know the recommended screening guidelines
for breast cancer from the American Cancer
Society
• Recognize surgical options for breast cancer
DETECTION AND TREATMENT OF BREAST CANCER
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Risk factors
Screening
Treatment
Surgical
Recent advancements
RISK FACTORS
Risk factors that you cannot change
 Female gender
 Aging
 Genetic risk factors
 Family history
 Personal history of breast cancer
 Race
 Dense breast tissue
 “Proliferative” breast conditions
 Prior chest radiation
 DES exposure
RISK FACTORS
Risk factors related to life-style
Not having children, or 1st child at later age
HRT
Alcohol
Obesity
Poorly managed DM
WHAT IS A MUTATION?
A change within the gene that causes it to stop working
properly
Sugar
phosphate
backbone
Bases
ASCO
GERMLINE VS. SOMATIC MUTATIONS
Mutations can occur in any cell. They only
affect future generations if they occur in
the cells that produce the gametes: these
are “germinal” or “germ line” mutations.
Mutations in other cells are rarely noticed,
except in the case of cancer, where the
mutated cell proliferates uncontrollably.
Mutations in cells other than germ line
cells are “somatic” mutations.
SOMATIC (TUMOR) MUTATIONS
Mutations happen in all of our cells all the
time
Chance during replication
Environmental Exposures
Chemicals
Radiation
Pesticides
Hiroshima
Chernobyl
INHERITANCE
INHERITANCE
How many working copies of a gene do you need?
 Varies by condition and gene
 Sometimes one non-functional copy enough to cause
disease
Autosomal dominant
 Sometimes need two non-functional copies cause
disease
Autosomal recessive
 Non-functioning copy on X-chromosome
X-linked
INHERITANCE: AUTOSOMAL DOMINANT
Why Does Family History Matter?
BRCA1 AND BRCA2 ACCOUNT FOR ONLY ABOUT 50%
OF HEREDITARY BREAST CANCER
What have we been
missing?
Castera, et al 2014 European Journal of Human
Genetics
“RED FLAGS” OF HEREDITARY CANCER
• Same type of cancer in multiple individuals
• Early age of diagnosis
Typically defined as under 50
• Multiple cancers in one person
• Rare cancers, or cancer in paired organs
WHY SHOULD WE CARE?
If we can understand cancer genetics, we can:
 High-risk breast screening for BRCA1, BRCA2, CDH1, PTEN,
STK11, and TP53 mutation carriers:
 Clinical breast exams more frequently
 Breast imaging with mammogram & breast MRI
 Initiate screening at a younger age
 Discuss the option of risk-reducing bilateral mastectomy with
patients with a mutation
 Avoid radiation treatment, if possible, for TP53 mutation carriers
WHY SHOULD WE CARE?
 Targeted surveillance and prevention options specific to the
gene mutation and syndrome identified
 Identify at-risk family members with targeted genetic testing
for identified family mutation and develop an individualized
cancer screening and prevention program
 Assist couples in reproductive decision making (e.g. advise
mutation carriers about assisted reproduction options
including pre-implantation genetic diagnosis)
GENE MUTATION CARRIERS AND PRE-IMPLANTATION
GENETIC DIAGNOSIS
• Early embryo from IVF is “biopsied” and DNA
is analyzed before embryo transfer
• 90% carriers concerned about transmitting
gene mutation to offspring
• 33% would consider PGD themselves and
majority feel HCPs should discuss option with
them
Quinn Fertil Steril 2009, 2010
POSSIBLE RESULTS OF GENETIC TESTING
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Positive result: deleterious mutation identified
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Negative result: no mutation identified
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Variant of uncertain significance: a genetic change was
identified, it is unclear at this point in time if this
change leads to an increased cancer risk.
GREY vs. GRAY
RECENT EVENTS INCREASE GENE TESTING
• Supreme Court Ruling
• Affordable Care Act
• The Angelina Effect
SELF BREAST EXAM OR SELF AWARENESS
Option for women starting age 20-30
Perform regularly (once a month)
Goal is to learn your own breasts so that you can
detect any changes
Lumps, skin changes, nipple changes
Most changes in the breast are not cancer
SELF BREAST EXAM
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SIGNS AND SYMPTOMS OF BREAST CANCER
Swelling of the breast
Skin dimpling
Nipple retraction
Nipple discharge (usually bloody and spontaneous)
Scaliness of the nipple
Breast or nipple pain (rarely a sign of breast
cancer)
SCREENING
ACS guidelines recommend:
Age 40
Clinical breast exam every year
Annual mammogram every year
High risk
Clinical breast exam every 6-12 months
Annual mammogram every year
If strong family history, start 5-10 yr prior to age of
youngest relative diagnosed w/ breast cancer
Consider MRI, ULSD
CLINICAL BREAST EXAM
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Performed by a clinician with patient sitting up and lying supine
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Detects 5 cancers per 1,000 women*
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Sensitivity: 58.8%* (likelihood exam will detect)
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Specificity: 93.4%*(what is the chance there is a tumor)
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Use of CBE shown to detect additional 4% cancers to screening mammography
MAMMOGRAPHY
Age group
Reduction in mortality
40-49
15-20%
50-59
30%
60-69
33%
>70
Insufficient data
Lancet 2002; 359:909-19
MAMMOGRAPHY
Breast Density
Extremely
dense
Fatty breasts
Sensitivity
Specificity
63%
89%
87%
97%
Ann Intern Med 2003;138(3):168-75
MAMMOGRAPHY
• Digital mammography
• Computer-Aided Detection
(CAD)
• Breast Tomosynthesis
• Conventional Film
MAMMOGRAPHY
What do doctors look for in a mammogram?
Mass (spiculated)
Architectural distortion
Microcalcifications
Faint, pleomorphic, clustered
BREAST ULTRASOUND
• Used to evaluate breast problems found on exam
or mammogram
• Not a screening tool
• Useful in patients with dense breasts
• Non-invasive, less expensive
• Lower sensitivity and operator-dependent
COMPARISON OF SCREENING METHODS IN DENSE
BREASTS
Modality
Sensitivity
Specificity
Mammography
78%
99%
Clinical Breast Exam
28%
99%
Ultrasound
75%
97%
Radiology 2002 225(1):165-75
BREAST MRI
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Sensitivity: 91-100%*
Specificity: 88%*
Misses microcalcifications
Technology varies
Expensive ($1200-1800)more?
MRI-guided biopsy
No data available demonstrating reduction in
breast cancer mortality
*New Eng J Med 2007;356:1295-303
BREAST MRI
Who should get a breast MRI?*
Someone with a diagnosis of breast cancer
Lifetime risk of breast cancer > or = 20%
BRCA1/2 mutation carrier
Strong family history of breast or ovarian cancer
History of radiation therapy to chest (lymphoma)
*ASCO 2007 Guidelines for Breast MRI
OTHER SCREENING METHODS
• Ductal lavage
• Tomosynthesis
• Whole Breast Ultrasound
TREATMENT OF BREAST CANCER
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Surgery
Radiation
Chemotherapy
Hormonal therapy
SURGICAL TREATMENT OF BREAST
CANCER
Halsted radical mastectomy, 1882
Removal of entire breast, chest muscle and axillary
lymph nodes
High morbidity
Deforming cosmetic
outcome
Performed from late
1800’s to mid-70’s
SURGICAL TREATMENT OF BREAST
CANCER
• Modified radical mastectomy
• Removal of breast and axillary lymph nodes,
sparing the chest muscles
- Significant improvement in cosmesis
- Performed in l970’s
RADICAL MASTECTOMY VS. MODIFIED
RADICAL MASTECTOMY
Procedure
Disease-free
Survival
Overall Survival
Radical
mastectomy
19%
25%
Modified radical
mastectomy
19%
26%
25-year follow-up
New Engl J Med 2002;347(8):567-75
BREAST CONSERVATION THERAPY
Breast conservation therapy introduced in early 80’s:
Lumpectomy
Axillary lymph node dissection
Radiation therapy
Better cosmetic outcome than MRM
BREAST CONSERVATION THERAPY
BREAST CONSERVATION THERAPY
Is there a difference in survival between
mastectomy and breast conservation
therapy?
BREAST CONSERVATION THERAPY
• Radiation following lumpectomy and axillary
surgery is the standard of care
• Large randomized, controlled trials demonstrate a
50% reduction in recurrence rate with radiation
compared to no radiation
AXILLARY LYMPH NODE DISSECTION
• Axillary lymph nodes: first place cancer cells go
before going to the rest of the body
• Staging: tells how many lymph nodes are involved
• Local control: removes any source of cancer if
lymph nodes are involved
• Complications: lymphedema, pain, numbness
AXILLARY LYMPH NODE DISSECTION
Does everyone with breast cancer need an axillary
lymph node dissection?
Only 10-25% of early breast cancer will have positive
lymph nodes
SENTINEL LYMPH NODE BIOPSY
WHAT IS THE SENTINEL LYMPH NODE?
SENTINEL LYMPH NODE BIOPSY
SENTINEL LYMPH NODE BIOPSY
If SLN is positive
If SLN is negative
axillary LN dissection
no ALND
Lower rate of lymphedema, less pain, less
numbness for patients who are spared from
axillary lymph node dissection
SENTINEL LYMPH NODE BIOPSY
• Standard means to evaluate the axilla in
patients with early stage cancer
• Patients with clinically palpable or positive
axillary lymph nodes must have axillary
lymph node dissection
SKIN-SPARING MASTECTOMY
• Developed early ’90s to preserve skin envelope
• Variation to mastectomy optimized for reconstruction
• Recurrence rate equivalent to conventional
mastectomy
• Nipple reconstruction can be performed with a skin
graft/tattoo
BREAST RECONSTRUCTION
Tissue expander/implant reconstruction
Advantages: shorter operation, faster recovery
Disadvantages: foreign body, less natural, requires
frequent office visits, may require revisional surgery
in future, asymmetry with other side
Not recommended if insufficient skin to cover
implant following mastectomy
BREAST RECONSTRUCTION
Autologous tissue transfer (flaps)
 Advantages: natural tissue, better symmetry with other side,
“tummy tuck”
 Disadvantages: long operation, long recovery
 Not recommended for:
Smokers
Obesity
Age > 70
History of prior abdominal surgery
History of cardiac, pulmonary or collagen vascular disorders
FREE “TRAM” FLAP
LATISSIMUS FLAP RECONSTRUCTION
GLUTEAL FLAP RECONSTRUCTION
NIPPLE-SPARING MASTECTOMY
• Preservation of the skin envelope and nipple
areola complex
• Performed with immediate reconstruction
• Series of small studies reporting good cosmesis
and minimal complications
• Select patient population only
• Data on recurrence rate not available
NIPPLE-SPARING MASTECTOMY
WHO IS CONSIDERED A BREAST CANCER
SURVIVOR?
• National Coalition of Cancer Survivorship
Care
Starting “from the time of its (cancer) discovery
and extending for the balance of life”
SURVIVORSHIP CARE
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Generally targets the time near end of treatment to the balance of life.
IOM, 2006 From Cancer Patient to Cancer Survivors, Lost in Transition
COMPONENTS OF SURVIVORSHIP CARE
Coordination
- Communication management among patients,
oncologists, primary care providers, and other healthcare
professionals.
- Treatment summaries
- Survivorship care plans
Prevention
- Promote healthy behaviors
- Physical activity
- Diet
- Tobacco cessation
- Sun Protection
- Screening procedures
Surveillance
- Assessment of
recurrence
- Late effects
Interventions for
Consequences of
Cancer and Treatment
- Physical
- Psychological
- Social
- Spiritual
HOT TOPICS FOR FUTURE OF BREAST CANCER CARE
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Adjuvant endocrine therapy-how to optimize duration and address adherence?
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New targeted precision drug therapies for HER2+, triple negative breast
cancers and metastatic breast cancer
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Novel agents and subtype-specific treatment paradigms for breast cancers
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How does obesity impact early-stage breast cancer treatment strategies?
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Emerging immunotherapies for breast cancer
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Use of novel genomic and proteomic diagnostic assays to determine utility in
the clinical arena
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Strategies for reducing breast cancer development and recurrence
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Implications of health care reform for oncology practice
Questions?