Pamela J DiPiro, MDClinical Director of CT and Breast Imager

Dana-Farber Cancer Institute

Imaging after Breast Cancer

Conflict of Interest Disclosure

I have no financial relationships with a commercial entity producing healthcare-related products and/or services.

Pamela J. DiPiro, MD

Breast Imaging

• Mammography• Tomosynthesis (3-D mammo)• Ultrasound• Magnetic Resonance Imaging (MRI)• Molecular Breast Imaging (MBI)

Mammography

• 2005 (DMIST) Digital Mammography Imaging Screening Trial– digital vs film

• women < 50 yrs• heterogeneous or extremely dense• pre- or perimenopausal

• 2D imaging – 2 MLO, 2 CC– +/- magnification, spot, exaggerated views

45 yo female 7 yrs after lumpectomy and radiation. Asymptomatic.

51 yo female 3 yrs post lumpectomy and radiation. Asymptomatic.

2014 2015 2016

Mammography• Breast screening workhorse• Overall sensitivity =78%*• Varies with breast density• As high as 87% in fatty breasts**• As low as 30% in dense breasts***

*National Cancer Institute website**Carney PA. Ann Intern Med 2003*** Mandelson MT et al. J Natl Cancer Inst 2000

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Digital Breast Tomosynthesis (DBT)

• (3-D) imaging technology that acquires images of a stationary compressed breast at multiple angles during a short scan.

• Individual images are reconstructed into series of thin high-resolution slices.

• Can reduce or eliminate tissue overlap effect

From Radiol Clin North Am, Sept 2010

European Prospective Trials

• Oslo - Norway• STORM - Italy• Malmö – Sweden

• Equal or better accuracy in cancer detection with breast tomosynthesis (DBT) compared to digital mammography (2D)

Tomosynthesis Breast Screening Study * (Oslo, Norway)

• 25,547 women (50-69 yo), biennial• 2D vs 2D+DBT• Improved cancer detection rate:

– 6.4/1000 (63%) – 2D– 8.3/1000 (82%) – 2D + DBT– 1.9 additional cancers/1000

*Skaane et al RSNA 2014

STORM trial Screening with Tomo OR standard Mammo

• 7292 women (> 48 yo), biennial• 2D vs 2D+DBT• Improved cancer detection rate:

– 5.3/1000 – 2D– 8.1/1000 – 2D + DBT– 2.8 additional cancers/1000– 34% increased detection

*Ciatto et al 2013, Lancet Oncol 2013

Tomosynthesis in US

• No large prospective studies• Not systematically evaluated (DMIST)• Driven by lay press• Multiple observational studies• Various roles of DBT

– Screening– Diagnostic – Callbacks (+/- spot compression)

Friedewald et al. JAMA 2014

• Retrospective analysis of 13 acad and nonacad breast ctrs

• Total >450,000 mammos• 2D vs 2D+DBT• Cancer detection increased by 1.2/1000 • Decreased callbacks by 16/1000 (15%)

Indications for DBT

• Screening (esp Baseline*)–Decreased recall rate– Increased sensitivity

• Diagnostic workup (if BL or request)• Callbacks (not calcifications-mags)**

*McDonald ES et al AJR 2015**Zuley et al. Radiology 2013, Peppard HR. Radiographics 2015

2012 2011 2008

62 yo woman w skin dimpling and palpable mass in right lower mid-inner breast

US(-), MRI bx – radial scar

Tomosynthesis Limitations

• Longer acquisition time• Longer interpretation time (at least 2x)• Greater need for computer power and storage• Slightly more costly• Higher radiation dose (synthesized image*)• May obscure margins of circumscribed masses• Detecting more radial scars

Tomosynthesis Benefits

• Decreased recall rate• Improved cancer detection 1/1000-2/1000

– spiculated masses– architectural distortion– small, node(-) invasive cancers

Ultrasound• Important adjunct to mammography

• Indications:– Evaluate palpable lesion– Characterize mammographic finding– Follow response to neoadjuvant

chemotherapy– Attempt to isolate MRI findings– Biopsy/aspiration guidance

– ? Role for dense breast screening

32 yo female with palpable lump in left breast

Simple cyst

32 yo female noted discomfort and “fullness” at lumpectomy site.

Seroma = post-operative fluid collection

42 yo female, 1 yr post lumpectomy and radiation with new palpable lump near scar. Mammogram 2 months earlier was (-).

Courtesy of Dr. Sughra Raza

2011 2013 2015

2 years after treatment, new palpable area of concern

Courtesy of Dr. Sona Chikamarne

Ultrasound Screening

• Controversial• Non-specific• Operator-dependent• Time-consuming• Poor visualization of calcifications • Utilized in Europe, was less popular in

US, until recently

Dense Breast Tissue

• Approx 40% of women 40-74 yrs• Category C, D• Confers slightly increased cancer risk• Makes cancers harder to detect via

mammography (masks lesions)*

A B C D

Dense Breast Legislation• 1st CT in 2009• 28 states* (discussion of federal legislation)• MA - passed legislation 1/1/2015• Mandates informing patient of their breast

density• Variable approaches by state re: disclosure

and recommendation for supplemental imaging

*7 additional states in process

Discussions in MA

• No immediate test recommended• MD and patient should discuss risk and

further evaluation• Use some type of model to calculate risk• Awareness of U/S thru popular press

ACRIN 6666 (ACR Imaging Network)

• Prospective trial, April 2004 – Feb 2006 • 2809 women• at least heterogeneous dense + high risk• 21 sites, mammo + U/S (MD-performed)• MD masked to results of other studies

Conclusions*:• U/S yielded additional 4.2 cancers/1000 • Substantial increase # of false (+)

*JAMA 2008. Berg et al.

Multiple additional studies

• Different populations, including dense screening

• Increased cancer detection (3-4/1000)• Small, invasive cancers, most node (-)• Low PPV for biopsies

Screening Whole Breast Ultrasound technical limitations

• Long scanning time (19 min – ACRIN 6666)

• Training• Expertise• MD vs tech scan

Automated Breast Ultrasound

• 1st FDA approved automated breast u/s (9/18/2012)

• 60-70 sec acquisition; 10-15 min total• 3D U/S images (3 planes)• Intended use:

• dense breasts• neg/benign mammogram• no prior invasive procedures

Ultrasound Overview• Important adjunct to mammo

– Characterizing lesions (palpable, imaged)– Guidance for biopsies/aspirations– Following response to chemotherapy

• Screening– 3-4/1000 additional cancers– High false (+)– High risk women where MRI is unavailable*– Controversial for women with dense breasts as

only risk factor**Sickles EA. Rad Clin North Am

2010

Magnetic Resonance Imaging (MRI)

• Evolving role in screening and evaluation of breast cancer

• Variably used• ACR Practice Guidelines based on multiple

studies from different institutions

ACR Practice Parameters for Performance of Contrast Enhanced Breast MRI

• Screening– High risk– Contralateral breast in newly dx’d malignancy (3.1-5%)*– Breast augmentation

• Extent of disease– IDC/DCIS (multifocality/multicentricity)– Invasion deep to fascia– Post-lumpectomy with (+) margins– Neoadjuvant chemotherapy

• Additional evaluation of clinical/imaging findings– Recurrence of breast cancer– Met cancer of unknown primary (suspect breast)– Lesion characterization– Post-op tissue reconstruction with suspected recurrence

*Liberman AJR 2003, Lehman NEJM 2007

ACS Guidelines for breast screening with MRI as an adjunct to mammography*

• Based on nonrandomized trials/observational studies, annual screening recommended:

» BRCA mutations (and untested 1st degree relatives)» Patients with lifetime risk > 20-25%

• Based on expert consensus and evidence of lifetime risk, annual screening recommended:

» Li-Fraumeni Sx (and 1st degree relatives)» Cowden and Bannayan-Riley-Ruvalcaba Sx (PTEN gene

mutations)

• Insufficient evidence to recommend for or against annual screening (decide on case by case basis):

» Patients with lifetime risk < 15-20%» h/o LCIS, ALH, ADH» Heterogeneously or extremely dense breasts» Personal h/o breast cancer (including DCIS)

*Saslow D et al. CA Cancer Clin 2007

MRI screening in high risk patients

• BRCA1 and BRCA2 mutations• Li-Fraumeni and PTEN gene

mutations• Strong family history• Prior mantle irradiation for HD

High Risk Breast Screening

• Annual mammogram• Annual MRI• Typically, stagger 6 mos apart• Can get same time, annually

54 yo BRCA1 mutation carrier s/p left lumpectomy and radiation for breast cancer and benign right breast biopsy –

screening MRI

Right Breast

Ultrasound (-) Pathology: DCIS

Breast MRI sensitivity for cancer detection

• Range: 71-100% in screening MRI studies*• As supplement to mammography: 80-

100% sensitivity**• Sensitivity is lower for in situ than invasive

cancer

• *Mahoney MC. Magn Reson Imaging Clin N Am 2013• ** Warner E. Ann Intern Med 2008

MRI

• Increased sensitivity• Variable specificity• However- IS used to screen in high

risk populations

Molecular Breast Imaging (MBI)

• 99mTc-sestamibi mammoscintigraphy • MBI, though less widespread, has been

used for years at sev’l centers• New, dual-head gamma imaging camera

with reported increased sensitivity/specificity and lower dose when compared with earlier systems (sens/spec 96.4% 59.5%)*

• Potential adjunct breast screening modality

*Radiology 2008. Brem et al

Combined MBI and FFDM1585 women, dense breasts

2D vs 2D + MBI• Yield/1000: 2D 3.2, 2D + MBI 12.0• Sensitivity: 2D 24%, 2D + MBI 91%• Specificity: 2D 89%, 2D + MBI 83%• PPV3: 2D 25%, 2D + MBI 28%

Conclusion:Addition of MBI to screening mammo yielded supplemental

cancer detection rate of 8.8/1000 AJR 2015, Rhodes et al

Courtesy of Robin Shermis,MD, ProMedica Toledo Hospital, Toledo, OH

63 year old woman with prior history of breast cancer

Mam

mog

ram

MBI

Advantages: Inexpensive Accessible: Tc99m-sestamibi

Improved sens/equiv spec

Disadvantages: No biopsy device yet Effective dose equivalent of 2.7 mSv to whole body

Screening• Mammography- imperfect, but remains

screening tool for gen’l population• Tomosynthesis- slight increase in detection,

though increased time +/- radiation• Ultrasound- excellent adjunct, but false (+)

quite high for screening• MRI- screening high risk patients (where cost

and false + acceptable) • MBI- potential adjunct screening in dense

breasts (decrease radiation)