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Breast MR Imaging in Women with High Genetic Risk Liliane Ollivier Institut Curie- Paris France ICIS International Cancer Imaging Society Marie Curie

Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

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Page 1: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Breast MR Imaging in Women with High Genetic Risk

Liliane Ollivier

Institut Curie- Paris France

ICIS International Cancer Imaging Society

Marie Curie

Page 2: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

High-genetic risk of breast cancer

•  Patients with mutations : – BRCA1/ BRCA2 (BReast CAncer) – Rare :

–  TP53 : Li-Fraumeni –  PTEN : Cowden disease –  STK11 : Polypose de Peutz-Jeghers

•  Patient without mutations :

– Familial history of breast and/or ovarian cancer – Mediastinal irradiation in childhood for Hodgkin disease

Page 3: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

•  High risk of developing breast and ovarian cancer –  Lifetime risk in BRCA1

•  Breast cancer : 65% •  Ovarian cancer : 10% •  Breast cancer in young women : 40% at age 40 years

–  Lifetime risk in BRCA2 : •  Breast cancer : 45% •  Ovarian cancer : 7% •  Breast cancer in men

Intra-ductal carcinoma in a man BRCA2 40 years old

Page 4: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

0

5

10

15

20

25

30

35

40

Ris

k of

bre

ast c

ance

r (%

)

20-29 30-39 40-49 50-59 60-69

Absolute Risk per decade

General population BRCA1

BRCA2

Page 5: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

•  Prophylactic surgery : at age 40 in BRCA1/ 50 in BRCA2 –  Bilateral prophylactic mastectomy :

•  Reduce the risk ok breast cancer by 90% –  Bilateral prophylactic oophorectomy :

•  Reduce the risk of ovarian cancer by 96 % •  Reduce the risk of breast cancer by 50%

•  Close surveillance : beginning at age 30 or even younger –  Physical examinations every 6-12 months –  Annual screening : MRI, mammography +/- ultrasound MRI should be integrated into surveillance programs

Page 6: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

•  Particular features of BRCA1/BRCA2 : Histopathology :

Invasive carcinoma •  Poorly differenciated, High nuclear grade

•  Medullar carcinoma •  Triple negative (Hormonal receptor, Her2 negative)

•  Basal like phenotype (CK5, 6+, p53+, EGFR +)

Ductal carcinoma in situ : •  Rare •  High grade +++

P53 + CK 5, 6 +

Page 7: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

Particular features of BRCA1/2 :

Mammography and ultrasound

•  Benign morphologic features •  Round or oval shape

•  Circumscribed or smooth margins •  Mimicking cysts or fibro-adenomas

•  Location : •  Posterior part of the breast

•  Particularly the immediate pre pectoral region

Page 8: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

Particular features of BRCA1/2 :

Breast-MRI 1.  Mass : •  Benign morphologic features

•  Round shape •  Smooth margins

•  Location : •  Posterior part of the breast •  Particularly the immediate pre pectoral region

•  Malignant kinetic features •  Rim enhancement •  Early intense contrast uptake •  Washout phenomenon

Page 9: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BRCA1 and BRCA2 gene mutation

Particular features of BRCA1/2 :

Breast-MRI 2. Focus:

•  Particularly in forbidden areas : •  Pre-pectoral area •  Inner quadrants

3. Non-mass-like enhancements : •  With features suggestive for malignancy :

•  Asymmetric, heterogeneous, clumped •  Ductal or segmental distribution

Invasive carcinoma

Ductal carcinoma

c

Page 10: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

T1

1st subtracted image

1st subtracted image Second look US

Invasive ductal carcinoma

MR finds a spiculated mass Second look US with biopsy = invasive ductal carcinoma

Page 11: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

3 MIN 6 MIN

Page 12: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Lymphocytes Tumoral cells

BRCA 2 carrier

Medullar carcinoma

Page 13: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

2. Others Mutations

•  Li-Fraumeni Syndrome (TP53) : •  Autosomal dominant pattern •  Increase the risk of developing several types of cancer •  Particularly in children and young adults

•  Breast cancer •  0steosarcomas and cancers of soft tissues •  Leukemias •  Brain tumors •  Adrenocortical carcinoma •  Lung carcinoma

Breast Invasive carcinoma associated with lung adenocarcinoma

Others Mutations

Li-Fraumeni Syndrome (TP53) :

Page 14: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Follow-up In France

•  Organized system –  Money from the National Health System –  Optimal geographic network

•  72 towns, 107 consultation sites –  Quality control => Accreditation of centers

•  Annual activity report (laboratories, consultations) –  Free genetic tests for women

–  Patients enrolled in trials or specific programs

Page 15: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

When ?

•  At 30 year- old? •  Before 30 year-old

–  p53 mutation –  Family history (cancers at very young ages) –  Thoracic Irradiation

•  Surveillance starts 8 years after the end of RXT

Page 16: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

How?

•  Every year

•  MRI (same sequences), Mx ± US (3 examinations at the same period) •  Additional value of a specific program

•  In women without mutation, –  annual MRI is added based on –  a probability value > 40% –  or lifetime risk > 30%

•  (ACS recommendation: lifetime risk > 20-25%)

Page 17: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

•  Gene carrier BCRA 1 ou 2, p53, PTEN, STK11 •  Non tested women with a gene mutation in the family at a first degree •  Non tested or negative women

family history of breast or ovary cancer with a risk calculated > 20-25% onco- genetic consultation +++

•  High breast density ?(ACS)

•  Previous history of thoracic radiotherapy before 30

Who?

Page 18: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Stop ?

•  No limitation concerning age…? •  Economical considerations

•  UK: 45 years, •  The Netherlands: 55 years

•  Annual screening is highly anxiogenic

Page 19: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Is Mammography Useful ?

•  Additional value of Mx to MRI in most of published prospective trials

•  Benefit of Mx in BRCA mutation carriers ? –  YES at age 35 or older –  0 or SMALL at age 30-34 years (4 views/year at 25- 29 years)

•  European recommendation : starting Mx at 36 years

Page 20: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

DCIS Warner Kuhl Netherl MARIBS

% 27% 22% 12% 17% MRI 67% 89% 17% 33%

Mammo 50% 33% 83% 83%

BRCA1 DCIS, High Grade

Page 21: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Interpretation of MRI

•  Clinical background +++ •  Phase of cycle may modify images

•  Physiological parenchymal enhancement

•  Enhancing benign structures Intramammary lymph node

•  Already known benign enhancement enhancement after conservative treatment

Pitfalls and benign anomalies

Page 22: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Parenchymal enhancement

•  New ITEM in BI-RADS-MRI

4 Categories

Minimal < 25% Mild 25-50% Moderate* 50-75% Marked* >75%

Page 23: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Symetric

–  Diffuse homogeneous

–  Diffuse heterogeneous •  punctiform (foci) •  around the gland •  regional •  multiple micronodules

Asymetric Causes of false positive or false negative (mask)

Parenchymal enhancement

Page 24: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk
Page 25: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Changes after therapy

personal history of left breast carcinoma

Right Breast : ACR2 benign fat necrosis Left breast : ACR1

Cytosteatonecrosis :

•  Fat center (high signal in T1 and low signal in T1 fat suppressed)

•  +/- Rim enhancement •  Patient previously treated

Page 26: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Normal MRI

Mammograms

Normal Cluster of Ca + = Complete Workup Comparison /previous Mx, US?

Recommendation based on Mx findings

* If US performed, only pick up very suspicious findings

STOP

Page 27: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Abnormal MRI

Targeted MX, US

Non mass- like Enhancement

Search Ca+ on Mx

(Magnification views)

Mass enhancement

Search lesion especially at US

Clinical BGround Menstrual Cycle Treated breast Prophyl. oorophorectomy

Compare with previous Exam

Page 28: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

•  Mass •  Prepectoral location •  Round shape •  Smooth margins •  High signal on STIR •  Rim enhancement ACR 4 ? because of the location, and the context

T1 STIR 54 years old BRCA1 mutation carrier Annual checking

Page 29: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Second look ultrasound : Mass US-guided biopsy : invasive ductal carcinoma

Page 30: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

BCRA1, Treated right cancer, Prophyl. oorophorectomy

2013 2012

Progressive heterogeneous enhancement on successive examinations Negative Mammograms, US

Mixed IDC and ILC, Grade II Triple negative

MR- Guided Biopsies

Page 31: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Key point

•  Patients with mutation : –  Particular features of BRCA1 cancers :

•  Benign morphologic features (round or oval shape, circumscribed, or non significative, glandular like enhancement, but very suspect in this case )

•  Location : posterior part of the breast, particularly the immediate prepectoral

region

•  Second look ultrasound : –  In more than 60% : a lesion is found with second look ultrasound –  If not, MR guided biopsy may be necessary

Page 32: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

T1

1st injected sequence 1° Subtracted image

STIR 42years BRCA1 no personal history, first MRI Mass •  Shape Oval •  Margin irregular •  Homogeneous enhancement •  Curve type 1

Second look US, guided biopsy? US normal, MR biopsy ? Before, Have a look back at the mammogram

Page 33: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

•  mammography-magnified shows cluster of microcalcifications

Stereotactic biopsy

High grade in situ

Page 34: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Key point

ACR4 enhancement with a negative targeted US Always do a mammography with magnification to search for microcalcifications In patients with mutation, in situ carcinomas are frequently of a high grade

Page 35: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Woman 41 years old BRCA1 carrier Personal history of breast cancer at age 38: Invasive ductal carcinoma of right and left breast : Annual checking

T1 STIR

1st injected sequence 1st subtracted sequence

•  Isolated Focus

1. Second look ultrasound +/- biopsy 2.  If no lesion in US, MR surveillance at 4 months

Page 36: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

May

Increasing size of isolated focus ACR4

January

MRI in 4 months

Second look US with biopsy

Invasive ductal carcinoma

No lesion at second look US

This time a nodule is found

Page 37: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Key point

•  Isolated focus in MRI : –  Second look ultrasound :

•  Lesion visible : US-biopsy •  Lesion non visible : MR follow up 4 months later

•  Importance of context : –  Personal history of breast carcinoma in a patient BRCA1 : suspect +++

Page 38: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Mass •  Ovale shape •  Smooth margins •  High signal in STIR •  Homogeneous enhancement •  but Wash out curve

History of left breast invasive ductal carcinoma at age 31(mastectomy)

Ultrasound : ACR4 a : -  Oval shape -  Circumscribed margins US guided biopsy : Fibroadenoma

Page 39: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Mass •  Irregular shape •  Spiculated margins •  Rim enhancement

ACR5

One year later

Invasive ductal carcinoma, grade III, triple negative, high mitotic index proliferation

US guided biopsy

Page 40: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Key point

•  Possibility of interval cancer ( specially in BRCA1/BRCA2)

•  Importance of annual checking : –  Clinical examination++ –  Imaging : MRI, mammography +/- ultrasound

Page 41: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Conclusions

•  Use the BIRADS lexicon •  Give a global ACR assessment for all imaging, avoid ACR 0… •  Always give recommendations for further patient management (targeted second look

US, US-biopsy, MR-biopsy, surveillance…) •  Always use the conventional modalities first and second look •  Use subtracted images but also pre contrast images T1,T2 and first images after

injection •  Beware of the technique: coil position and compression of the breast, try to have

comparative examinations, date in the menstrual cycle…

Page 42: Liliane ollivier : Breast MR Imaging in Women with High Genetic Risk

Conclusions

•  Particular histological types

•  Particular features of conventional and MR imaging mimmicking benign lesions •  Location in forbidden areas

•  Interval cancers

•  Special tight follow-up, women enrolled in a specific program

•  Importance of clinical background, onco-genetic consultation