liliane ollivier : breast mr imaging in women with high genetic risk
DESCRIPTION
TRANSCRIPT
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