Transcript Update on Breast Cancer presentation for HCP 9.13.12

Update in Breast Cancer
Ana Maria Lopez, MD, MPH, FACP
Associate Dean, Outreach and Multicultural Affairs
Professor of Medicine and Pathology
Medical Director, Arizona Telemedicine Program
Breast Cancer Updates in…
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Epidemiology
Screening
Treatment
Survivorship
Prevention
Educational Objectives
1. View current screening controversies
and recommendations
2. Discuss new therapeutic approaches
3. Outline the impact of personalized
medicine on breast cancer treatment
Breast cancer
• Most common cancer in women: 240,000
new patients in US annually
• New patient diagnosed every 3 minutes
• 2nd leading cause of cancer death in
women
• Every 12 minutes-breast cancer claims a life
• Lifetime risk: 12 %
Breast Cancer Incidence
Breast Cancer Detection
Early Detection
and
Long-Term Survival
• Local disease 90%
• Regional disease 84%
• Distant disease 23%
The Effect of Tumor Size
on Survival
Tumor
Size
Survival
As tumor size
increases, the
chance of
survival
decreases
Clinical Staging
Table taken from How to Prevent Breast Cancer, page 37.
T
N
M
5-Year Survival
Stage 0
Tis
N0
M0
> 95%
Stage I
T1
N0
M0
Overall = 85%
Stage II
(Stage IIA)
(Stage IIB)
Overall = 66%
T0
N1
M0
T1
N1
M0
T2
N0
M0
T2
N1
M0
T3
N0
M0
Stage III
(Stage IIIA)
(Stage IIIB)
Stage IV
Overall = 41%
T0
N2
M0
T1
N2
M0
T2
N2
M0
T3
N1, N2
M0
T4
Any N
M0
Any T
N3
M0
Any T
Any N
M1
Overall 10%
Breast Cancer Screening
• 2010 CDC
• 81% women (50-74 yo) screening in 2008
• 1/3 of breast cancer diagnoses are late
stage
Who is least likely to be
screened?
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60-79 yo
African American
Asian/Pacific Islander
American Indian/Alaska Native
Recent immigrants
Mammography
• Film or digital
• Both effective
• More FP in younger women
• Digital:
• Can’t lose films
• May be better in women with dense breasts,
<50 yo
Mammography Screening
Controversy
• 2009 USPSTF: biennial film
mammography for women, 50-74 yo at
average risk for BC (B)
• One month later: “the decision to start
regular, biennial screening mammography
before the age of 50 years should be an
individual one and take patient context into
account, including the patient's values
regarding specific benefits and harms” .
Mammography Screening
Controversy
2009 USPSTF evidence base:
• meta-analyses of screening effectiveness trials (8 trials in
women between the ages of 39 and 49 years and 6 in women
between the ages of 50 and 59 years)
• similar relative risk reductions for breast cancer mortality for
each group (0.85 and 0.86, respectively).
• 39–49 age group
• absolute number of deaths prevented was lower and the harms of
overscreening were greater
• to prevent one cancer-related death
• 1904 mammograms would be required in the 39–49 age group,
compared with 1339 mammograms in the 50–59 age group.
• benefit of screening in each of these groups appeared to be
equivalent; in the 39-49 age group the net benefit was “small.”
• grade C recommendation for routine screening of averagerisk women younger than 50 years .
American College of
Obstetricians and Gynecologists
• annual mammography: women 40 yo+
• change from their previous
recommendation of screening every 1 to 2
years for women in their 40s and annual
screening beginning at age 50
American Cancer Society (2010)
• 20 and 39 yo: CBE every 3 years is recommended.
• 40 yo+: annual mammography, in the absence of
serious chronic health problems, and annual CBE are
recommended.
• BSE: no recommendation for or against but advises
that women be told about the risks and benefits of
BSE. Women who choose to do BSE are advised to
have their technique reviewed by a clinician
• High risk for BC: an annual screening MRI in addition
to mammography, beginning at age 30 years, is
recommended. Women at moderate risk should
discuss the potential benefits and limitations of
screening MRI with their clinician.
American College of Obstetricians
and Gynecologists (2009)
• For women age 40 years and older,
annual mammography is recommended.
• For women age 19 years and older,
annual CBE is recommended. BSE can be
recommended, because it has the
potential to detect palpable breast cancer.
Breast Self Exam (BSE)
• USPSTF: no evidence to
support its use to
decrease mortality
• American Cancer Society:
does not take sides
• American College of
Obstetricians and
Gynecologists: supports
monthly/regular BSE
Breast Cancer Screening
Summary
• Mammography: every 1-2 yrs, 50-75 yo
• If < 50 yo or >75 yo, discuss with clinician
• High risk: breast MRI (increased FP),
genetic testing
• BSE value questionable
Mammography with Computer-aided
detection and diagnosis (CAD)
kodak.com
Risk Assessment
Risk Factors
• Age:
• 95% in women 40yo +
• highest in 70-74 yo
• FH
• Personal history
• Genetic risk:
• BRCA 1/2, TP 53,
ATM
• Nulliparous
• 1st full term pregnancy
after 35 yo
• No lactation
• HRT
• Alcohol
• Overweight/obesity
• Physical inactivity
Risk Factors
70% of breast cancers are in patients w/out
identifiable risk factors
Risk Calculators
• www.cancer.gov/bcrisktool
NCI/NSABP
Hereditary
Breast Cancer Risks
5-10% of all breast cancers
• Ashkenazi Jewish descent
• 3 or more 1st or 2nd degree relatives
• 1st degree relative with bilateral breast
cancer
• 2 or more 1st or 2nd degree relatives with
ovarian cancer
• Male breast cancer
BRCA 1 and BRCA 2
• Code for DNA repair
• Presence of gene, increases the risk of getting breast
cancer up to 80% in her lifetime
• BRCA1 or BRCA2 mutations make up about half of all
cases of inherited breast cancer
• associated with ovarian cancer and prostate cancer
• can be inherited either from the mother or the father.
Other Inherited Genes
• TP53 gene
• codes for the tumor suppressor protein p53
• Mutations cause Li-Fraumeni syndrome: associated
with early onset breast cancer
• Ataxia Telangiectasia (ATM) gene
Females with one defective copy of the ATM gene and
one normal copy of the gene are at increased risk for
breast cancer.
Treatment
Therapy
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Surgical
Chemotherapy
Radiation
Hormonal
Targeted
Surgery
• Local
• Mastectomy
• Reconstruction
Surgical Treatment
• Sentinel LN assessment
Isolated Tumor Cells on SLN
• Significance unknown
• No known difference in outcome in
patients with isolated tumor cells and
negative SLN
Breast Reconstruction
Chemotherapy
• Neoadjuvant
• Adjuvant
Predicting Outcome
• Prognostic Factors:
• Worse: lymph node involvement, tumor size,
histologic grade
• Better: ER positivity , 10% lower risk of relapse at
5 years compared with ER-negative tumors.
• Prognosis is estimated for each patient over a
period of time. For example, a woman with a 5cm ER-negative high-grade breast cancer and 4
involved lymph nodes has a 10-year mortality of
about 70%. In contrast, a woman with an ERpositive well-differentiated node-negative tumor
smaller than 1 cm has a mortality of only 10%
over 10 years.
Predicting Outcome
• Predictive factors:
• Hormone-receptor status, identify patients
who will respond to certain therapies such as
endocrine therapy. Patient characteristics,
including overall health, comorbidities, and
personal preferences, must also be
considered.
• Goals of treatment: improve overall
survival, lengthen disease-free survival
Molecular Classification
Reddy KB, Current Oncology, 2011
Adjuvant Chemotherapy
• Chemotherapy
• < 50 yo: 10-year proportional reduction in recurrence
of 35% and a 10-year reduction in mortality of 27%
• 50 and 69 yo: 10-year proportional reduction in
recurrence of 20% and in mortality of 11%.
• Anthracycline-based chemotherapy (eg,
doxorubicin) has been shown to have a small but
significant advantage over nonanthracyclinebased therapy
• Generally, for BC greater than 1 cm, node-positive
disease, or ER-negative cancers.
Adjuvant Chemotherapy
• Proportional risk reduction for adjuvant
chemotherapy is equivalent regardless of
risk
• Patient with a 70% risk of mortality would
have same % risk reduction as a patient
with a 10% risk
• the absolute benefit would vary
Triple Negative Disease
• ER/PR/Her-2 negative
• PARP inhibitor: Iniparib
• Enhanced effectiveness of chemotherapy
• Prolonged survival
• Definitive study: results pending
Targeted Therapy
• At diagnosis: Her-2 neu evaluation
• By immunohistochemistry
• Confirmed by FISH
• Trastuzumab=Herceptin
• Treat for 1 year
• Study comparing 1-2 years pending
Chemotherapy Side Effects
• Acute: neutropenia, alopecia, and nausea.
• Anthracycline-related cardiotoxicity is rare
and dose-related.
• Long-term: premature ovarian failure and
its associated postmenopausal symptoms;
rare risk of myelodysplastic syndrome or
acute leukemia
Breast Cancer:
Assessing Risk of Recurrence
• Oncotype DX
• MammaPrint
Oncotype DX
• Analyzes 21 genes
• LN neg/ER pos
• Defines benefit of chemotherapy on top of
hormonal therapy:
• High risk, intermediate risk, low risk
MammaPrint
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70 genes are analyzed
LN negative, < 5 cm
Not dependent on hormone status
High risk or low risk for distant metastases
risk
ER positive disease
• Premenopausal
• Tamoxifen x 5 years
• Postmenopausal
• Tamoxifen x 5 years followed by letrozole x 5
years
• Aromatase inhibitor (letrozole, anastrozole,
exemestane x 5 years)
• No evidence to take longer than 5 years (studies
pending)
Radiation
• Traditional
• MammoSite
Radiation
• Adjuvant postmastectomy radiotherapy is
recommended in patients with a high risk
of local or regional relapse.
• This includes patients with large primary
tumors (>5 cm) and with 4 or more
involved lymph nodes.
• Improves local control, decreases the risk
of systemic recurrence, unclear gain in
overall survival
Metastatic Breast Cancer
What are tumor markers?
• Most commonly used tumor markers for
breast cancer are CA 27-29, CEA, CA 153
• Can be used to monitor response to
treatment and post treatment relapse
• Not always elevated
• Do not focus on minor fluctuations
Circulating Tumor Cells
• Prognostic indicator
• Unclear benefit to follow response to
treatment
Metastatic Breast Cancer
• ER positive
• Hormonal therapy choice depends on
history
• Use hormonal therapy as long as possible
d/t good efficacy less side effects
Targeted Therapy
• In metastatic setting: may need to recheck
Her-2/neu status
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Trastuzumab
Lapatinib=Tykerb
Pertuzumab just released, use with docetaxel
Others under study
Bone Metastases Only
• Decrease complications of bone
metastases
• Decrease pain
• Increase risk for osteonecrosis of the jaw
• Zoledronic Acid=Zometa
• Denosumab=Xgeva
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Osteonecrosis of the Jaw
• Risk of bisphosphonates
• Prevent:
• Meticulous oral care
• Always let dentist/oral surgeon know of use of
bisphosphonates
Brain Metastases
• Radiation mainstay of therapy
• Temador may be used in conjunction with
radiation
• May be seen in setting of good systemic
control outside the CNS
Survivorship
Psychosocial Impact
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Depression
Anxiety
Fear
Anger
Sense of loss
• Panic
• Guilt
• Difficulty adapting to
illness
• Overwhelmed
• Marital/sexual
problems
Long term effects of
chemotherapy
• Adriamycin/doxorubicin
• Paclitaxel/oxaliplatin
• Cytoxan
Cancer Screening
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Continue:
Breast cancer screening
Cervical cancer screening
Colorectal cancer screening
Skin cancer screening
Lymphedema
• Identify early
• Intervene early with massage therapy
• Exercise with monitoring
Maintaining bone density in
breast cancer patients
• Usual therapies including zoledronic acid
annually
• Role of bisphosphonates in preventing
breast cancer recurrence, preventing bone
metastases remains undefined: conflicting
data
Prevention
Prevention Studies
• Tamoxifen
• Raloxifen: STAR (Study of Tamoxifen and
Raloxifene)
• Raloxifene is as effective as tamoxifen in
reducing invasive but not nonivasive (DCIS) BC
risk
• Both drugs reduce invasive BC risk by about 50%
• Raloxifene: 36% fewer uterine cancers, 29%
fewer blood clots
• Both increase blood clots.
Aspirin
• In an epidemiologic study, aspirin
appeared to lower breast cancer risk
• Need prospective trial
Vitamin D
• Helps with calcium absorption to maintain
bone density
• In clinical trials
Fat
• WINS
• Low fat diet (< 30%)
• 5Y FU: new breast cancers--9.8% low-fat
diet; 12.4% standard diet (24% reduction)
• largest risk reduction – 42%--in ER
negative tumors
What about soy? Flax?
Phytoestrogens?
• Eat what you like!
• Eat healthy!
• Do not change your diet drastically to
include phytoestrogens.
• There may be safety concerns re:
pharmaceutically concentrated soy
products
Lifestyle
• Maintain a healthy weight
• Decrease intake overall. Increase vegetables
in specific (2/3 of plate)
• Increase activity: 3-4 hours of exercise per
week
• Decrease alcohol intake