Breast MRI: Friend or Foe? Comments: 0 ASSOCIATED PRESS 8/19/2008 - - PowerPoint PPT Presentation

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Breast MRI: Friend or Foe?

UCSF Postgraduate Course May 18, 2013 Cheryl Ewing, MD Clinical Professor of Surgery UCSF Department of Surgery APPLEGATE HAS DOUBLE MASTECTOMY IN CANCER SCARE

DIAGNOSED WITH CANCER IN ONE BREAST

• Comments: 0

ASSOCIATED PRESS 8/19/2008

Applegate's cancer was detected early through a doctor-

• rdered MRI. She

said she's starting a program to help women at high risk for breast cancer to meet the costs of an MRI, which is not always covered by insurance.

Breast MRI: background

• First performed nearly 30 years ago

as one of the first applications for body MRI

• Provides both spatial and temporal

resolution – Morphology – Kinetic characteristics

• Advantages:

– High sensitivity – Ability to detect occult cancers

• Disadvantages

– Lower, more variable specificity – Overlap in the imaging of benign and malignant lesions

Breast MRI

The breast is scanned in an MRI device before and after the intravascular injection of a contrast agent (Gadolinium DTPA). The pre-contrast images are "subtracted" from the post-contrast images, and any areas that have increased blood flow are seen as bright spots (enhancements) on a dark background. Since breast cancers generally have an increased blood supply, the contrast agent causes these lesions to "light up” (enhance) on the images.

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Breast MRI

Normal nipple enhancement

MRI, normal study Sagittal MIP (maximum intensity projection)

Sensitivity and Specificity

• Sensitivity: the probability that the

test will be positive in someone with the disease a / (a + c) = (“PID: positive in disease”) SnOUT=Sensitive tests, when Negative, rule OUT disease

• Specificity: the probability that the

test will be negative in someone who does not have the disease d / (b + d) = (“NIH: negative in health”) SpPIN=Specific tests, when Positive, rule IN a disease

• Accuracy: (a + d) / (a + b + c + d)

a true positives b false positives c false negatives d true negatives

+

• +
• disease

test

ACS Guidelines for Breast MRI

• MRI screening recommended for:

– Patients with known genetic mutation – First-degree relative with known mutation – 20-25% lifetime risk of breast cancer – History of chest wall radiation between ages 10 and 30 – Two first degree relatives with breast cancer

• NOT recommended for:

– Personal history of breast cancer (unless mammographically occult) – Mammographically dense breast tissue – ADH or LCIS – Average-risk women

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Bilateral screening MRI high risk patient (BRCA-1) Axial MIP

MRI Screening Studies in High Risk Women

Sensitivity (%) Study Year % Cancers detected/#screened MMG U/S MRI % Biopsies recommended based on MRI Tilanus- Linthorst, Netherlands 2000 2.8

• 100

4.6 Podo, Italy 2002 7.6 13 13 100 8.6 Morris, USA 2003 3.8

• 100

16.1 Kriege, Netherlands 2004 2.4 40

• 71

2.9 Warner, Canada 2004 9.3 36 33 77 15.7 Kuhl, Germany 2005 8.1 33 40 91 14.7 Lehman, USA 2005 1.1 25

• 100

6.3 Leach, UK 2005 5.1 40

• 77
• Lehman, USA

2007 3.5 33 17 100 8.2 Sardanelli, Italy 2007 6.5 59 65 94 9.0

Invasive lobular carcinoma (occult on PE, mammo) Early post Late post

Right breast screening MRI

R breast MRI post Gd subtracted images

Occult Ipsilateral Cancer

4 BIRAD 4 Dense Breast

Breast MRI

Dense Breast ACR recommendations:

• Breast MRI for women with a breast cancer diagnosis

for extent of disease and to rule occult disease in both breast

• Not recommended for women with no risk factors.

Impact of MRI on Ipsilateral Surgical Management Dense Breast

Study Year n % with additional ipsilateral disease Orel 1995 64 11 Fischer 1999 336 15 Tan 1999 83 6 Tillman 2002 207 9 Bedrosian 2003 267 18 Shelfout 2004 170 25 Berg 2004 111 26 TOTAL 1238 16

*BCT to wider excision or mastectomy

Right ILC Left DCIS

Occult Contralateral Cancer

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MRI-detected Contralateral Cancer in Patients with Diagnosis of Breast Cancer

Study Year n % with additional contralateral disease Rieber 1997 34 9 Fischer 1999 463 3 Slanetz 2002 17 24 Liberman 2003 223 5 Lee 2003 182 4 Viehweg 2004 119 3 Berg 204 111 3 Lehman 2005 103 4 Pediconi 2007 118 19 Lehman 2007 969 3 TOTAL 2339 4.4

Breast MRI for Unknown Primary

• Rare; <1% of reported breast cancers
• Outcome may be better than in those with known

primary and axillary metastasis

• Breast MRI identified the primary cancer in the breast

in 60% of cases

• Has allowed breast conservation in patients

presenting with unknown primary or

• Radiation therapy alone if negative.

Pre-chemotherapy Post-chemotherapy

MRI allows more accurate measure of response to neoadjuvant therapy

LD=47 mm LD=16 mm (AC, 4 cycles)

Investigation of Serial studies to Predict Your Therapeutic Response with

Imaging and

And

moLecular analysis CALGB INTERSPORE ACRIN NCICB

I SPY WITH MY LITTLE EYE . . . . . . . A BIO- MARKER BEGIN- ING WITH X . . . .

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I SPY 1 TRIAL Design

Neoadjuvant Chemotherapy Surgery Serial Core Biopsies Serial MR Imaging Outcomes

• Residual Disease
• Recurrence

MRI Reveals Several Phenotypes

1: Single predominant mass with identifiable rim, displacing 2: Nodular pattern, irregular borders 3: Diffuse infiltrative pattern 4: Patchy enhancement 5: Septal spread 1 2 3 4 5

Breast MRI for DCIS

• ACRIN study 6667 (Lehman, NEJM 2007)

– Mammo occult contralateral breast cancer study- 969 women, 135 recommended for bx, 121 underwent sampling (needle bx or mastectomy) – 30 (3.1%) occult cancers diagnosed; 12 were DCIS

• Prospective observational study (Kuhl, Lancet 2007)

– 167 women diagnosed with DCIS (MMG and MRI) – Sensitivity of MMG compared to that of MRI:

All DCIS 56% 92% High grade DCIS 52% 98% MMG MRI

MRI assessment of letrozole response in DCIS

Responder: ER-positive, postmenopausal pathological CR baseline treated

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MRI assessment of letrozole response

Responder: ER-positive postmenopausal baseline treated

MRI assessment of letrozole response

baseline treated Mixed Responder: ER-positive postmenopausal

CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS

6-months

MMG MRI core bx MMG MRI Surgery (only if progression) MMG MRI Surgery

Inclusion criteria:

• Postmenopausal
• Pure ER and/or PR (+)

DCIS on core biopsy

• DCIS visible on MRI
• Non high-grade

disease Exclusion criteria:

• Suspicion of invasive

cancer on core biopsy

• r MRI
• Palpable DCIS
• Extent >5 cm
• Current exogenous

hormone use

CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS

• primary study endpoints: 3-month and 6-month radiographic

response of MRI-measured tumor volume

• V3: defined as the difference in tumor volume between

baseline (pre-treatment) and 3-month MRI

• V6: defined as the difference in tumor volume between

baseline and 6-month MRI

• primary measurements:
• Mean of V3 for all patients
• Mean of V6 for all patients

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CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS

• Secondary study endpoints:
• MMG change with treatment
• Lumpectomy rate
• Margin status (pos/neg, margin

size)

• Prevalence of invasive cancer
• Prevalence of pathologic CR
• Treatment-related adverse

events

Summary

• Recommended for:

– Screening patients at high risk – Evaluation of extent of disease in newly diagnosed breast cancer – Monitoring treatment response in neoadjuvant setting – Work up of patients with unknown primary – Planning size of lumpectomy to improve margin status

• Consideration of potential benefits and harms important to

appropriate use of this technology. Stress and unnecessary biopsies/mastectomies.

BRCA1-Associated Cancers: Lifetime Risk

Breast Cancer 85% Second Primary Breast Cancer 3% per year Ovarian Cancer 30-54% Male Breast Cancer ?% Prostate Cancer 30 to 50%

BRCA2-Associated Cancers: Lifetime Risk

breast cancer (56%−85%)

• varian cancer

(20%−30%) male breast cancer (6-8%)

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Breast Cancer Risk

Terminology BRCA Reports (Myriad) Loss of Heterozygosity (LOH) the functional allele become non functional (environmental hit). Loss of tumor suppression. Deleterious Mutation- germline frame shift mutation in both allele. Impact on protein production for DNA

• repair. Varying penetrance.

Variant of Unknown Significance (VUS) mutation identified but unknown if harmful. Variant favor polymorphism is variation believed to be harmless. Benign polymorphism-no mutations

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Breast Cancer Risk

Special Risk for being a mutation carrier for the BRCA 1 and 2 gene. 1.Any women diagnosed with breast cancer under the age

• f 40 years or multifocal, bilateral breast cancer under the

age of 60 years. 2.Any women under the age of 60 and triple Negative ER(-), PR(-), HER-2 (-). 3.Any women of Jewish Ancestry (Ashkenazi), Hispanic, Mediterranean, Norwegian diagnosed with breast cancer under the age of 60 years. 4.Breast cancer diagnosis and family history of breast and

• varian cancer including 2nd degree relatives.

5.Recurrent breast cancer in women under the age of 60 years.

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Breast Cancer Risk

• 1. Women with a strong family history for breast

cancer ( 2 or more first degree relatives with breast). 1 first degree relative with bilateral breast cancer.

• 2. Women with a family history of pre-

menopausal breast cancer and/or Ovarian cancer.

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Breast Cancer Risk

• 6. All men with a breast cancer diagnosis

should be tested for the BRCA 1 and 2 gene. Special attention for TP53 mutation in melanoma families and colon carcinoma. Others to screen are Cowden’s and Li Fraumeni

• families. Li-Fraumeni strong family history of

Leukemia, brain cancer, sarcoma, skin cancers. Cowden’s Disease (multiple hamatomas) multiple hamatomas on nose by age 20 and in nasal and oral mucosa. Lifetime risk for breast cancer is 81%. Other associated cancers are thyroid, renal, uterine. Benign disorders multi- nodular goiters and fibroadenomatosis.

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Thank you