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

2. 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

3. 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

4. 0
5
10
15
20
25
30
35
40
Riskofbreastcancer(%)
20-29 30-39 40-49 50-59 60-69
Absolute Risk per decade
General population
BRCA1
BRCA2

5. 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

6. 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 +

7. 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

8. 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

9. 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

10. 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

11. 3 MIN 6 MIN

12. Lymphocytes Tumoral cells
BRCA 2 carrier
Medullar carcinoma

13. 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) :

14. 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

15. 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

16. 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%)

17. • 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?

18. Stop ?
• No limitation concerning age…?
• Economical considerations
• UK: 45 years,
• The Netherlands: 55 years
• Annual screening is highly anxiogenic

19. 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

20. DCIS Warner Kuhl Netherl MARIBS
% 27% 22% 12% 17%
MRI 67% 89% 17% 33%
Mammo 50% 33% 83% 83%
BRCA1 DCIS, High Grade

21. 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

22. Parenchymal enhancement
• New ITEM in BI-RADS-MRI
4 Categories
Minimal < 25%
Mild 25-50%
Moderate* 50-75%
Marked* >75%

23. Symetric
– Diffuse homogeneous
– Diffuse heterogeneous
• punctiform (foci)
• around the gland
• regional
• multiple micronodules
Asymetric
Causes of false positive or false negative (mask)
Parenchymal enhancement

25. 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

26. 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

27. 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

28. • 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

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

30. 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

31. 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

32. 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

33. • mammography-magnified
shows cluster of microcalcifications
Stereotactic biopsy
High grade in situ

34. 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

35. 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

36. 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

37. 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 +++

38. 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

39. 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

40. Key point
• Possibility of interval cancer ( specially in BRCA1/BRCA2)
• Importance of annual checking :
– Clinical examination++
– Imaging : MRI, mammography +/- ultrasound

41. 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…

42. 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