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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 ?

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• 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.

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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

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“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

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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?

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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

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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.

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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.

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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

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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

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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

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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

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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.

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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

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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

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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

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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

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Was

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(>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).

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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)

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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

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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

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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

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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.

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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.

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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.