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

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

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

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

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

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 +

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

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

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

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

3 MIN 6 MIN

Lymphocytes Tumoral cells

BRCA 2 carrier

Medullar carcinoma

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) :

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

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

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%)

•  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?

Stop ?

•  No limitation concerning age…? •  Economical considerations

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

•  Annual screening is highly anxiogenic

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

DCIS Warner Kuhl Netherl MARIBS

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

Mammo 50% 33% 83% 83%

BRCA1 DCIS, High Grade

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

Parenchymal enhancement

•  New ITEM in BI-RADS-MRI

4 Categories

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

Symetric

–  Diffuse homogeneous

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

Asymetric Causes of false positive or false negative (mask)

Parenchymal enhancement

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

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

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

•  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

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

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

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

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

•  mammography-magnified shows cluster of microcalcifications

Stereotactic biopsy

High grade in situ

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

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

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

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 +++

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

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

Key point

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

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

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…

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