Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
2/9/2015
1
What is the Gynecologist’s Role in What is the Gynecologist’s Role in Detection, Management, and Detection, Management, and
Surveillance?Surveillance?
Breast Cancer: Breast Cancer:
James W. Orr, Jr. M.D. FACOG, FACSJames W. Orr, Jr. M.D. FACOG, FACSChair, Florida Board of Medicine Chair, Florida Board of Medicine
Medical Director: Regional Cancer Center &Medical Director: Regional Cancer Center &
Florida Gynecologic OncologyFlorida Gynecologic Oncology
Fort Myers, FloridaFort Myers, Florida
Surveillance? Surveillance?
Fort Fort MyersMyers
• Women comprise ~100%100% of our practice.
• The high prevalence of breast disease and breast cancer (i.e. the problem is in every OB/GYN office, every day)
2nd t f d th i US
It is Important that we It is Important that we Understand Breast Disease?Understand Breast Disease?
• 2nd most common cause of death in US women leading leading cause of premature mortality from cancer cause of premature mortality from cancer in women as measured by total in women as measured by total years of years of life lostlife lost
• It’s important to be an advocate and provide the best level of care for your patients.
•• MedicalMedical--legal aspects abound! legal aspects abound! FFailure to diagnoseailure to diagnose
History of Gynecologists and CancerHistory of Gynecologists and Cancer
• In 19131913, a group of gynecologic surgeons formed the American American Society for the Control of Society for the Control of Cancer.Cancer.
Lee Cancer Care
• Aims– Educate Physicians– Educate the public
• Ladies Home Journal - with Samuel Hopkins Adams - May 1913 “What Can We Do About Cancer ?
2/9/2015
2
• Forerunner of the American Cancer Society
History of Gynecologists and CancerHistory of Gynecologists and Cancer
• 2 OB/GYNs are recent Past Presidents of the American Cancer Society.
• The concept of a new American society dedicated to a multidisciplinary approach to breast health management was first discussed at an informal gathering of members of the
f COGCOGAnnual Meeting of ACOGACOG in 19761976.• The 1st formal meeting was 1977.• The first issue of Breast DiseaseBreast Disease was published
in 1987 and continued publication until 1996. Currently the official journal is The Breast The Breast JournalJournal.
2/9/2015
3
mat
ed N
ew
Cas
esm
ated
Ne
w C
ases
stim
ated
Dea
ths
>60,000 DCIS
Est
imE
stim Es
20152015ACSACS
635/day635/dayAlabama: 3,680/year
118/100,000
AlabamaUterine 660 Ovary 315Cervix 230
1205
2/9/2015
4
“Incidence”“Incidence”Increased use ofIncreased use ofmammographymammography
2007-2011Incidence + 0.03%/yearMortality – 1.9%/yearDeclined 34% between 1990 –2011
(33 to 22 per 100,000 women) ( p , )
Probability (%) of Developing Probability (%) of Developing Invasive Cancer Age Invasive Cancer Age Intervals Intervals
• Birth to 49
• Age 50-59
• Age 60-69
• 1 in 53 1.9%
• 1 in 44 2.3%
• 1 in 29 3 5%
13.1%13.1%
Lee Cancer CareACS 2015
• Age 60-69
• Age >70
• Ever
• 1 in 29 3.5%
• 1 in15 6.7%
• 1 in 8 12.3%
Number 122, August 2011 (Reaffirmed 2014)
If Current Age Is…
The Probability of Developing Breast Cancer in the Next
10 Years†
Or 1 in:
20 0.06% 1,760
30 0 44% 22930 0.44% 229
40 1.44% 69
50 2.39% 42
60 3.40% 29
70 3.73% 27
Lifetime risk 12.08% 8
2/9/2015
5
Role of the ObstetricianRole of the Obstetrician––Gynecologist Gynecologist in the Screening and Diagnosis of in the Screening and Diagnosis of
Breast MassesBreast MassesNumber 122, April 2011;
Reaffirmed 2014
Breast Cancer ScreeningBreast Cancer Screening
Number 103, April 2009
Hereditary Breast and Hereditary Breast and Ovarian Cancer Syndrome Ovarian Cancer Syndrome
Management of Gynecologic Management of Gynecologic Issues in Women with Issues in Women with
Breast Cancer.Breast Cancer.
Number 126, March 2012
gg
Role of the Obstetrician–Gynecologist in the Screening and Diagnosis of Breast Masses
1. Should elicit “risk factors” risk factors” during the medical and family history
2. Clinical breast examinationexamination
3.3. InstructionsInstructions for periodic breast self-examination
4. Encourage screening mammographyscreening mammography
5. Perform diagnostic procedures or referral to those who “specialize” in breast disease
6.6. EvaluateEvaluate all palpable masses
7. Referral
Who is at Risk?Who is at Risk?
2/9/2015
6
All women are
Obesity
Not having hild
ObesityNot having
h ld
Breast Cancer Risk FactorsThat Can Be CControlledontrolled
E iAll All
women arewomen arewomen are at risk
Breastfeeding
children
Birth ControlPills
AlcoholHormone
ReplacementTherapy
Exercise
Breastfeeding
children
Birth ControlPills
AlcoholHormoneReplacement
Therapy
Exercise women are women are at riskat risk
GENDER GENDER
All All
Age ReproductiveHistory
Breast Cancer Risk FactorsBreast Cancer Risk FactorsThat That CannotCannot Be ChangedBe Changed
women are women are at riskat risk
FH/Personal HxMenstrualHistoryRace
Genetic Factors
RadiationTreatment with
DES
• Why are breast cancer risk assessment models important?– To offer patients accurateaccurate cancer risk
assessment
– To identify appropriate referrals for genetic genetic counselingcounseling
Risk Assessment ModelsRisk Assessment Models
counselingcounseling
– To determine eligibility for chemopreventionchemoprevention
– To determine screeningscreening initiation and frequency
– Fewer than 1 in 10 high risk1 in 10 high risk women have discussed risks with their physician
2/9/2015
7
http://www.cancer.gov/bcrisktool/about-tool.aspx
NCI/NSABP1. Personal history of breast
cancer/DCIS/LCIS/Chest RT7. Ever breast biopsya. # biopsy
2. BRCA or other genetic risk factor
3. Current age4. Age at menarche5. Age at 1st birth6. # 1st degree relatives with
breast cancer
a. # biopsyb. + atypical
hyperplasia 8. Race/ethnictya. Sub ethnicity
5 year risk and lifetime risk
Probability of an inherited a deleterious change in BRCA1/BRCA2
Any size pedigree includes• family history of breast and ovarian cancer, • history of male breast cancer, • oophorectomies and
BRCAPRO http://astor.som.jhmi.edu/BayesMendel/brcapro.html
oophorectomies, and • bilateral synchronous and asynchronous diagnoses
Provides updated age-dependent penetrance and prevalence estimates for both breast and ovarian
cancer.
• There are limitations to all these models:– The Gail Model is not validnot valid for families with
BRCA1-2 mutations.
Can We Rely on These Risk Models Can We Rely on These Risk Models Alone?Alone?
– The Gail Model does not predict the increased risk of hereditary ovarian cancerovarian cancer..
– The Clause model does not take personal riskpersonal riskfactors into consideration.
2/9/2015
8
Guideline for High Risk Guideline for High Risk ((>>20%)20%)
Screening*Screening*Based on nonrandomized screening trials and observational studies
• Known BRCA1 or BRCA2 gene mutation• Have a first-degree relative (mother, father, brother, sister,
or child) with a BRCA1 or BRCA2 gene mutation, and have not had genetic testing themselves
• Have a lifetime risk of breast cancer of 20%-25% or greater
Yearly MRI and MammogramYearly MRI and Mammogram
• Have a lifetime risk of breast cancer of 20%-25% or greater, according to risk assessment tools that are based mainly on family history
Based on Expert Opinion
• Had radiation therapy to the chest when they were between the ages of 10 and 30 years
• Have a genetic disease such as Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcabasyndrome, or have one of these syndromes in first-degree relatives
* Begin at age 30Facility to do MRI guided biopsy
Guideline for Moderate Risk Guideline for Moderate Risk (< 20%)(< 20%) ScreeningScreening
• Have a lifetime risk of breast cancer of 15%-20%, according to risk assessment tools that are based mainly on family history
Insufficient Evidence forInsufficient Evidence for Yearly MRI Yearly MRI
based mainly on family history • Have a personal history of breast cancer, ductal
carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH)
• Have extremely dense breasts or unevenly dense breasts when viewed by mammograms
Family history: Still Relevant in the Genomics Era
ARE PATIENTS’ REPORTS RELIABLE?• Reported negative FH in 1st or 2nd degree relative was
accurate: Over-reporting = 2.4%2.4%• Reported + FH (Breast) in 1st degree relative > 90% > 90%
accurate
CCJM 2012
• Reported + FH (Breast) in 2nd degree relative > 80% > 80% accurate
DOES TAKING A FH REDUCE COSTS?• Testing and preventive treatment for “high risk” could
save up to $800 million of the more than $8 billion spent each year on breast cancer diagnosis, prevention, and treatment.
2/9/2015
9
Minimum adequate family history for patients with cancer:Family history of cancer in 11stst degree relatives (parents, children,
and full siblings) and 22ndnd degree relatives (grandparents, aunts/uncles, nieces/nephews, grandchildren, and half siblings).
Th f ll i h ld b d d f h l i i hThe following should be recorded for each relative with cancer,● Type of primary cancer(s)● Age at diagnosis of each primary cancer● Lineage (maternal and/or paternal)
Patients should be asked;- A known hereditary cancer predisposition syndrome, - Prior genetic testing, - Any relevant information regarding ethnicity- Periodic updating
Cancers for Which Genetic Counseling and Testing Should Be Considered, Even in Absence of Family History
•• Triple negative Breast CancerTriple negative Breast Cancer• Epithelial Ovarian Fallopian Tube or• Epithelial Ovarian, Fallopian Tube or
Peritoneal Cancer• Colon Cancer demonstrating
mismatch repair deficiency• Endometrial Cancer demonstrating
mismatch repair deficiency
Importance of Importance of Breast SelfBreast Self--AwarenessAwareness
Women themselves detect
• ~ 50% of allall breast cancers• ~ 50% of allall breast cancers
• 70% of those cancers diagnosed < 50 years old
Cancer 2002
2/9/2015
10
Periodic Breast SelfPeriodic Breast Self--ExaminationExamination
• Two large populationpopulation--based studiesbased studies
(388,535 women).
•• No statistically significantNo statistically significant difference in breast cancer mortality, relative risk 1.05cancer mortality, relative risk 1.05– 95% confidence interval (CI) 0.90 to 1.24)
• Almost twice as many biopsiestwice as many biopsies (3406) with benign results were performed in the screening group compared to the control group (1856), relative risk 1.881.88– 95% CI 1.77 to 1.99
Regular self-examination or clinical examination for early detection of breast cancer.
Cochrane Database of Systematic Reviews. 2006.
Canadian National Breast Screening Canadian National Breast Screening Study (NBSS) Study (NBSS)
• CBE: (5 to 10 minutes per breast) • CBE alone vs CBE + Mammography• Breast cancer mortality (mean 13 years) not
different 4040 4949 5050 5959• CBE alone
J Natl Cancer Inst. 2000
4040--4949 5050--5959
# Patients 25,620 19,965
Sensitivity ~70% ~77%
Specificity 84% 90%
PPV 1.5% <5%
Clinical Breast Examination: Clinical Breast Examination: Preliminary Results Preliminary Results from a Cluster from a Cluster
Randomized Controlled Randomized Controlled Trial in India Trial in India
CBE ControlNo. No. P value
Breast cancers 80 63
Lee Cancer Care J Natl Cancer Inst 2011
Breast cancers 80 63Tumor, ≤2 cm 15 4 .030.030
No pathological node 40 22 .071.071
Early-stage 35 16 .023.023
Advanced disease 36 43 .005005
2/9/2015
11
Patient Detected Breast Cancer Not Patient Detected Breast Cancer Not Seen on MammographySeen on Mammography
Seen Not Seen
Tumor Size N (column%) N (column%) Chi Square p Value
< 1 5 cm 176 (20 7%) 101 (35 8%) 35 56 < 001
Tumor Size in cm Categories by Mammography (n=1,131)
< 1.5 cm 176 (20.7%) 101 (35.8%) 35.56 <.001
1.5-1.9 cm 165 (19.4%) 42 (14.9%)
2.0-2.9 cm 238 (28.0%) 62 (22.0%)
3.0-4.9 cm 160 (18.8%) 30 (10.6%)
> 5.0 cm 110 (13.0%) 47 (16.7%)
Total 849 (75.1%) 282 (24.9%)
San Antonio Breast Symposium 2005.
37%37%
30%30%
San Antonio Breast Symposium 2005.
•• 19131913: Salomon "Roentgen photographs of excised breast specimens give a demonstrable overview of the form and spread of cancerous tumors."
•• 19761976: ACS recommends annual screening•• 19791979: NIH recommends annual screening
Mammography….brief historyMammography….brief history
19791979: NIH recommends annual screening •• 19921992: Mammography Quality Standards Act (MQSA)
required FDA certification of mammography facilities (ensure standardized personnel training and technique utilizing a low radiation dose)
•• 19981998: MQSA Reauthorization Act require patients to receive a written lay-language summary of results
Mammographic Views (Screening)
MLO Correctness Criteria• Nipple well aligned• Pectoral muscle displayed until the
level of the posterior nipple line • Presence of submammary angle free • Folds and the absence of artifacts
CC Cranio-caudal viewCorrectness Criteria
• External lateral portion of the breast
• Retromammary fat tissue (Chassaignac's bag)
• Pectoral muscle on the posterior edge
• Nipple in profile
2/9/2015
12
Mammographic Views (Diagnostic)
• True lateral view - 90º view ◦ mediolateral view - ML view ◦ lateromedial view - LM view
• Lateromedial oblique view - LMO view • Late mediolateral view - late ML view• Step oblique views• Spot view - spot compression view p p p• Double spot compression view• Magnification view(s)• Exaggerated craniocaudal views - exaggerated CC
views ◦XCCL view◦XCCM view
• Axillary view - axillary tail view • Cleavage view - valley view • Others
MammographyMammography
Average-size lump found by woman practicing occasionalbreast self-exam (BSE)
Average-size lump found byAverage-size lump found by woman practicing regularbreast self-exam (BSE)
Average-size lump found by first mammogram
Average-size lump found by getting regular mammograms
BIBI--RADSRADSBreast Imaging Reporting and Data SystemBreast Imaging Reporting and Data System
• Category 0: Need additional imaging evaluation!!!!! • Category 1: Negative• Category 2: Benign • Category 3: Probably benign finding: short interval
follow-up suggested (2% risk)(2% risk)(2% risk)(2% risk)
• Category 4: Suspicious abnormality: biopsy should be considered:
(34% risk)(34% risk)• Category 5: Highly suggestive of malignancy
(>81% risk)(>81% risk)• Category 6: Known biopsy proven malignancy,
appropriate action is being taken
2/9/2015
13
Breast Composition CategoriesAs of the BI-RADS 5th edition
a. The breasts are almost entirely fatty (10% of women)
b. There are scattered areas of fibro-glandular density (40% of women)
c. The breasts are heterogeneously dense, which may obscure small masses (40% of women)
d. The breasts are extremely dense, which lowers the sensitivity of mammography (10% of women)
Increased Breast Density: Increased Breast Density: • 50% incidence 39-80 y/o• 40% incidence > 50 y/o• Mammogram sensitivity: 88% to 62%• Independent risk factor for cancer: 1.5X-4.6X
Society of Breast Imaging 2011
Mammograms CBE BSESelf-
Awareness
ACOG > 40: annually20-39 (1-3 yrs)>40: annually
Consider for high risk
Recommended
ACS> 40: annually
20-39 (1-3 yrs)>40: annually Optional > 20
Recommended
NCCN> 40: annually
20-39 (1-3 yrs)Recommended Recommended
NCCN> 40: annually
>40: annuallyRecommended Recommended
NCI > 40: 1-2 years
Recommended Not Recommended -------
USPTF (2009)
50-74 biennially
Insufficient evidence
Not Recommended -------
ACOG Practice Bulletin 2011
Survival of 2294 Invasive Survival of 2294 Invasive BBreast reast CCancer ancer PPatients atients by size by size of tumorof tumor, Swedish Two, Swedish Two--County Trial of Breast County Trial of Breast CCancer ancer
SScreeningcreening
0.60.70.80.9
1
ob
abil
ity
1-9 mm10-14 mm15-19 mm
00.10.20.30.40.5
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16Time in years since diagnosis
Su
rviv
al p
ro 15 19 mm20-29 mm30-49 mm50+ mm
Nystrom L et al. Lancet. 2002;359:909-19.
Duffy SW, Tabar L, Vitak B, Warwick J. Breast J. 2006;12 (1):S91-S95.
2/9/2015
14
Breast Cancer ScreeningBreast Cancer ScreeningMammographyMammography
• Meta-analysis of 8 randomized trials:
– Reduction of rate of death for women > 40 years old
– Reduction of mortality by 16 to 35% for ages 50 to 69 years old
– Reduction of mortality by 15 to 20% for ages 40 to 49 years old
Humphrey LL, Ann Inter Med. 2002;137:347-360.
Fletcher SW, N Eng J Med. 2003;348:1672-1680.
Mean diameter of breast cancer has been decreasing by 10% Mean diameter of breast cancer has been decreasing by 10% every 5 years since the advent of mammographic screeningevery 5 years since the advent of mammographic screening
Pooled Relative Risk of Breast Cancer Pooled Relative Risk of Breast Cancer Mortality Related to MammographyMortality Related to Mammography
(age 39(age 39--49)49)
Ann Internal Medicine, 2009
Pan-Canadian Study of Mammography Screening and Mortality from Breast
Cancer
• 2,796,472 screened participants. • 1990-2009: 85% of the Canadian population• Breast cancer mortality: 40% lower than
expected ( i f 27% t 59%)
J Natl Cancer Inst. 2014
expected (range across provinces of 27% to 59%).
• No effect of age at entry • No evidence that self-selection biased the
reported mortality results
2/9/2015
15
Twenty Five year Follow-up for Breast Cancer Incidence and Mortality of the Canadian
National Breast Screening Study
VariablesControl arm
(n=524)
Cancers in mammography arm
Detected (n=666)
Palpable (n=454)
Non-palpable
(n=212)
DOBD: No 353 (67.4) 486 (73.0) 316 (69.6) 170 (80.2)(80.2)
BMJ 2014
DOBD: Yes 171 (32.6) 180 (27.0) 138 (30.4) 42 (19.8)
Tumor size (cm) 2.1 (0.2-7.0) 1.9 (0.2-9.0) 2.1 (0.2-9.0) 1.4 1.4 (0.2-9.0)
Lymph node status:
Negative 303 (57.8) 394 (59.2) 252 (55.5) 142 (67.0)(67.0)
Positive 170 (32.4) 204 (30.6) 169 (37.2) 35 (16.5)
Twenty Five year Follow-up for Breast Cancer Incidence and Mortality of the Canadian
National Breast Screening Study
• Fifteen years after enrolment, an excess of 106 cancers occurred in the “screened” group. R t 22%22% f ll d t t d
Estimated that 31% 31% of all breast cancers breast cancer were over diagnosed (i.e., tumors were detected
BMJ 2014
• Represents 22% 22% of all screen detected invasive cancers
• One over-diagnosed breast cancer for every 424424 women who received mammography screening in the trial.
g ( ,on screening that would never have led
to clinical symptoms)
Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence
Screening • Advance the time of diagnosis of cancers that are
destined to cause death.• Allow early treatment to confer some advantage over
treatment at clinical presentation• Screening mammography: doubling the # early-stage
Breast cancer was over diagnosed in 31% 31% ( ) f ll b t
N Engl J Med 2012
Screening mammography: doubling the # early stage breast cancers (112 to 234 cases per 100,000 women) — absolute increase of 122 cases per 100,000 women.
• Concomitantly, late-stage cancer has decreased by 8%, (102 to 94 cases per 100,000 women) — absolute decrease of 8 cases per 100,000 women.
(70,000) of all breast cancers diagnosed in
2008
2/9/2015
16
Personalizing Mammography by Breast Density and Other Risk Factors for Breast Cancer: Analysis of Health
Benefits and Cost-Effectiveness
Ann Intern Med. 2011.
• 80 to 100: recalled for additional evaluation (additional views and/or ultrasound)
• 45 to 65 recalled have a “false positive”• 20 restudied in 6 months (<2% cancers)
For every 1000 women For every 1000 women screened…..screened…..
20 restudied in 6 months (<2% cancers)
• 15 biopsy recommended • 2 to 5 have breast cancer (10 to 13 negative biopsy
“false positives”)
• 1 in 4 to 1 in 5 women biopsied for calcifications will have cancer.
• 1 in 3 biopsied for suspicious masses will have cancer.
ng
ton
, D
C:
s, 2
006
Age at Exposure
(yrs)
Lifetime Incidence of Excess Breast
Cancers per 100,000100,000
Excess Breast Cancer Mortality per
100,000 100,000
20 17 430 10 2
40 5.6 1 4
BE
IR V
II, P
has
e 2.
Was
hin
Nat
ion
al A
cad
emie
s P
ress40 5.6
(>200 naturally)1.4
50 2.8 .0860 1.2 0.470 0.5 0.280 0.2 0.1
The radiation exposure to the breasts from annual natural background radiation is about ¾ that of the exposure to the breasts from 2-view bilateral mammography (4 milligray).
2/9/2015
17
Film vs DigitalFilm vs Digital
Analog Digital
Digital vs. Analog MammographyDigital vs. Analog Mammography
• 49,528 asymptomatic women
• Both digital and film screening mammogram
•• Increased accuracy in women <50Increased accuracy in women <50
• Heterogeneously dense breast
• Premenopausal and perimenopausal
• Increased detection breast cancer by 15 to 20%15 to 20%
Pisano ED,. N Engl J Med. 2005;353(17):1773-1783.
Diagnostic Accuracy of Digital Mammography: Diagnostic Accuracy of Digital Mammography: DMISTDMIST
Radiology, 2008: 246; 376
33 institutions(n = 49,528)
2/9/2015
18
ComputerComputer--aided Detection Mammography for aided Detection Mammography for Breast Cancer Screening: Systematic Review Breast Cancer Screening: Systematic Review
and Metaand Meta--analysis.analysis.• Pooled sensitivity was 86.0%sensitivity was 86.0% (95% CI 84.2-87.6%) and
specificity was 88.2%specificity was 88.2% (95% CI 88.1-88.3%).
• Of the 100,000 women screened, CAD yielded an additional 5050 (95% CI 30-80) correct breast cancercorrect breast cancerdiagnoses, 1,190 1,190 (95% CI 1,090-1,290) recalls recalls of healthy
(n = 347,324)(n = 347,324)
g , ,, ( , , ) ywomen, and 8080 (95% CI 60-100) biopsies of healthy biopsies of healthy women.women.
• A total of 96% (95% CI 93.9-97.3%) of women recalled based upon CAD and 65.1% (95% CI 52.3-76.0%) of women biopsied based upon CAD were healthy. No studies reported patient-oriented clinical outcomes
Noble, Arch Gynecol Obstet. 2009;279:881-90
Breast Cancer ScreeningBreast Cancer Screening
• US acknowledged to be a highly operator dependent with inter-observer and intra-observer
Role of Ultrasound
variability, unknown sensitivity, and low specificity.
Detection of Breast Cancer With Addition of Annual Screening Ultrasound or a Single Screening MRI to Mammography in Women With Elevated Breast Cancer Risk
Conclusion The addition of screening ultrasound or MRI to mammography in women at
JAMA 2012
increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings
2012: FDA approved the first ultrasound system, the somo-v Automated Breast Ultrasound System (ABUS), for breast cancer screening in
combination with standard mammography specifically for women with dense breast tissue
2/9/2015
19
Breast Cancer ScreeningBreast Cancer Screening
• Typically used to distinguish a cyst from a solid lesion or to guide biopsy!
• 3 features of a lesion are evaluated:
Role of Ultrasound
– Boundaries and shape
– Internal architecture (echoes)
– Its posterior shadowing
• No RCT showing survival benefit of screening women with dense breasts with supplemental whole breast ultrasound screening + mammography
• DMIST: DM (digital mammography) was significantly more sensitive than film (.59 vs .27 p < .0013) in women < 50 or with dense breasts . DM should be used for women with dense breasts regardless of any decision regarding
Supplemental Screening with Ultrasound in Women with Dense Mammograms?
g y g gultrasound.
• WB-US requires long scanning time (median 19 mins in
ACRIN666), expertise, training, and incremental breast imaging radiologist time.
• Mammography and MR have consistently outperformed mammography and WB-US for very high-risk women independent of breast density
Society of Breast Imaging 2011
Breast Cancer ScreeningBreast Cancer Screening
SSolid masses typically olid masses typically require pathologicrequire pathologicq p gq p g
evaluation!evaluation!
Lee Cancer Care
2/9/2015
20
Breast Cancer Screening MRIBreast Cancer Screening MRIPro’s
• Nearly 100% negative predictive value for invasive carcinoma
• 3-4% of cancers only
Con’s• EXPENSIVE• Time consuming• Inconsistent between
centersdetected by MRI
• Noninvasive
• No radiation
• Reserved for high-risk women
Lee Cancer Care
Comparative SensitivityComparative Sensitivity
Histology Mammo US MRI
DCIS 55% 47% 89%
IDC 81% 94% 95%
ILC 34% 86% 96%
Lee Cancer Care
Clinical Indications for Breast MRIClinical Indications for Breast MRI• Implant evaluation• Axillary carcinoma of unknown primary• Screening women at high risk• Breast cancer patients??
- Extent of disease- Contralateral screening for occult disease- Positive or close margins- Prior to surgery response to
neoadjuvant chemotherapy
Lee Cancer Care
2/9/2015
21
Breast Breast TomosynthesisTomosynthesis: : 3D Digital Mammography3D Digital Mammography
• Clinical Trials
– Increased lesion visibility
– Facilitation of margin analysis
– Reduction in call-back rate from screening
– Lesion location
Jong RAl. Radiology. 2003;228(3):842-850.
FDA approval 2011
Emerging TechnologyEmerging TechnologyBreast Breast TomosynthesisTomosynthesis
• Tomosynthesis is a 3-dimensional digital mammographic technique
• Detector remains stationary while the tube movesmoves
• Acquires data through a series of 11 positions through a 50 degree arch
• Detector “reads out” the captured information to create an image
Screening Digital Breast Tomosynthesis: Effect Recall Type and Patient Treatment
Screening digital mammography (DM) + tomosynthesis• Recall rate: DM= 9.3% DBT= 6.4% Overall reduction of
31% (P < .00001). • Recall rate:
Masses: DM = 8.9% DBT = 26.8% Distortions DM = 0 6% DBT = 5 3%
Limitations of DBT:• Longer interpretation times,• Higher costs
Radiology 2015
Distortions DM 0.6% DBT 5.3% Calcifications DM = 13.4% DBT 20.3%Asymmetries DM = 32.2% DBT = 13.3% Focal asymmetries DM = 32.2% DBT= 18.2%
• Ultrasonography: DM= 2.6% DBT =28.3% • No significant difference in biopsy PPV (30% vs 23%) • No significant difference in cancer detection rate per 1000
patients (prior studies suggest a benefit)
• Higher costs, • Increased radiation dose.
2/9/2015
22
Breast PEM/PETBreast PEM/PET
Tissue Diagnosis: Tissue Diagnosis: Ductal Carcinoma In Situ and Invasive Ductal CarcinomaDuctal Carcinoma In Situ and Invasive Ductal Carcinoma
Lee Cancer Care
Ductal Carcinoma In Situ and Invasive Ductal CarcinomaDuctal Carcinoma In Situ and Invasive Ductal Carcinoma
X-Ray PEM Flex™Whole
Body PETX-Ray CT
Preoperative Preoperative identification of non-invasive breast cancer (DCIS) which accounts for 30% of newly diagnosed patients and. PEM has a 91% sensitivity for DCIS which far exceeds all other imaging modalities.
ScintimammographyScintimammographyBreastBreast--specific specific Gamma Imaging Gamma Imaging (BSGI), (BSGI),
or or Molecular Breast Imaging Molecular Breast Imaging (MBI(MBI) )
2010 practice guideline Society of Nuclear Medicine
1. Recently detected breast malignancy2. Patients at high risk for malignancy 3 Patients with indeterminate breast abnormalities
Lee Cancer Care
3. Patients with indeterminate breast abnormalities 4. Patients with technically difficult breast imaging 5. Patients for whom MRI is indicated but
contraindicated 6. Patients undergoing preoperative chemotherapy
Tc-99m sestamibi
Chemoprevention of Breast Cancer
Women at increased BC risk: 5-year projected absolute risk of BC 1.66% based on BCRAT or with lobular carcinoma in situ.
• Age >35 years, t ift if h ld b
J Clin Oncol 2013
tamoxifentamoxifen (20 mg per day for 5 years) should be discussed as a risk reducing option.
• Postmenopausal women:raloxifeneraloxifene (60 mg per day for 5 years) orexemestaneexemestane (25 mg per day for 5 years) should be discussed as a risk reducing option.
2/9/2015
23
Chemoprevention: All CancersChemoprevention: All Cancers
Chemoprevention: ER + CancersChemoprevention: ER + Cancers
nst
200
9;10
1: 3
84 –
398
RR 0.67Pre-Postmenopausal
Cu
mm
ing
s J
Nat
l Can
cer
In
RR 0.41Post menopausal
Atypical Hyperplasia of the Breast:Risk Assessment and Management Options
• Atypical hyperplasia: found in approximately 10% of the 1,000,000 benign breast biopsies
Atypical ductal and atypical lobular
Hartman NEJM 2015
• Atypical ductal and atypical lobular hyperplasia: equal frequency.
• RR of Breast cancer 44• Cumulative risk 30% @ 25 years• No effect of a + Family History
2/9/2015
24
Atypical Hyperplasia of the Breast:Risk Assessment and Management Options
MANAGEMENT• Chemoprevention:
- 38% 38% relative reduction in therisk of breast cancer (invasive and noninvasive) among all the study
Hartman NEJM 2015
noninvasive) among all the study participants who were enrolled in the SERM randomized trials
- Relative-risk reductions in women with atypical hyperplasia subgroup: 41 to 79%41 to 79%
Atypical Hyperplasia of the Breast:Risk Assessment and Management Options
• Risk of subsequent cancer
Hartman NEJM 2015
Atypical Hyperplasia of the Breast:Risk Assessment and Management Options
MANAGEMENT• Core Biopsy:
Atypical ductal hyperplasia “Upgrading” 15 to 30% with surgical excision , despite the use of large-gauge (9- or 11-gauge) core needle biopsy with vacuum assisted
Hartman NEJM 2015
core-needle biopsy with vacuum assisted devices
Atypical lobular hyperplasia“Upgrading < 6%
• NCCN: ExcisionExcision remains the current standard of atypical ductal hyperplasia on core biopsy
2/9/2015
25
How Do We Know How Do We Know Where or Which Way to Go?Where or Which Way to Go?
Gonadotropin-Releasing Hormone Analogues for the Prevention of Chemotherapy-induced Premature Ovarian Failure in Cancer Women: Systematic review and Meta-Analysis of Randomized trials.
• Nine studies 225 events of POF occurring in 765 analyzed patients.
Cancer Treat Rev. 2014
y p• Significant reduction in the risk of POF (OR=0.43;
95% CI: 0.22-0.84; p=0.013) in patients receiving GnRHa.
• Similar in subgroups of patients defined by age and timing of POF assessment,
• Present in breast cancer but unclear in ovarian cancer and lymphoma.
Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a meta-analysis of randomized controlled trials
• 5 RCTs: 528 patients • GnRH agonist protected against post-
chemotherapy POF, RR of 0.40 RR of 0.40 • Both treatment groups experienced
similar rates of - resumed menses - spontaneous pregnancy
•Breast. 2013
2/9/2015
26
Clinical Utility of Gene-expression Profiling in Women with Early Breast Cancer: an Overview of Systematic Reviews• Oncotype DX and MammaPrint: ability to
predict treatment outcomes, change in treatment decisions, and cost-effectiveness,
• Five systematic reviews:
Genet Med. 2014
Five systematic reviews: • No direct evidence of clinical utility for either
test. • Indirect evidence that Oncotype DX predicted
treatment effects of adjuvant chemotherapy • No indirect evidence of predictive value was
found for MammaPrint.
Oncotype DX® Breast Cancer Assay: intended to predict potential benefit of chemotherapy and likelihood of distant breast cancer recurrence
• Node negative or node positive, ER-positive, HER2-negative invasive breast cancer. O t DX® B t C A f DCIS• Oncotype DX® Breast Cancer Assay for DCIS patients quantifies the 10-year risk of local recurrence (DCIS or invasive carcinoma) in women with ductal carcinoma in situ treated by local excision, with or without tamoxifen.