- Breast cancer screening provides an opportunity to assess cardiovascular risk by reporting breast arterial calcifications (BAC) seen on mammograms. BAC has been associated with increased risk of coronary artery disease. - Radiologists are encouraged to universally report any seen BAC and include language on the association with cardiovascular risk and the need for further discussion on lifestyle and medical prevention. Some patients are interested to know if BAC is present. - Accurate assessment of individual breast cancer risk beyond age could help identify women who may benefit from supplemental screening like MRI. Risk models may be enhanced through integration with artificial intelligence applied to mammographic features.

1. Breast Imaging
Overcoming the risky business
Dr. Giacomo Bertacchi
Department of Medical Imaging
9th

2. • Leading cause of mortality in women: CVD
• Both breast cancer and CVD are significant causes of morbidity and mortality
(47.8 versus 3.32 million women in the US)
• Deaths attributable to CVD 1/3.3; to CHD 1/8.3; to breast cancer 1/31.5
• Annual mortality is decreasing for both CVD (6.7%) and breast cancer (1.8%)
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Putting risks in perspective
Mehta L et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from
the american heart association. Circulation. 2018; 137(8):30-66

3. 9th
Shared risk factors

4. • Lifetime risk of developing breast cancer 12.4%
• Nearly 90% of breast cancer patients survive at least 5 years after the initial
diagnosis
• Risk of mortality for CVD is higher in breast cancer survivors than in women
without the history of breast ca
• Cancer treatment can result in early or delayed cardiotoxicity.
• Early recognition and treatment of CVD risk factors is important to breast
radiologists
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Breast cancer patients are at risk for CVD
Mehta L et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from
the american heart association. Circulation. 2018; 137(8):30-66

5. 9th
• Screening mammography is a potential source of information on cardiac risk
in patients presenting with chest pain
• In symptomatic patients BAC should be considered an important risk factor for
coronary disease and an important predictor of CAD-RADS > 3
(> 50-69% coronary stenosis - ACS possible)*
• 95% of patients are interested in knowing if their breast arteries are calcified
(Margolies et al)**
• EUSOBI launched two weeks ago a survey among breast radiologists about routine
BAC reporting
Breast arterial calcifications
*Kelly B et al.Breast arterial calcification on screening mammography can predict significant coronary artery disease in women. Clinical Imaging. 2018; 49:48-53
**Margolies L. Breast arterial calcification in the mammography report: the patient perspective. Am J Roentgenology. 2019; 209-214

6. Margolies L et al. Digital mammography and screening for coronary artery disease. JACC.
2016; 9 (4): 350-360
1: less than 1/3 of the vessel
2: between 1/3 and 2/3 of the vessel
3: more than 2/3 of the vessel
1: 1 vessel only
2…6: from 2 to 6 vessels
6: more than 6 vessels
0 (None): no burden
1 (mild): clear visualization of the lumen
2 (moderate): clouding of the lumen and
calcification of both tangential walls
3 (severe): no visible lumen

7. • A) Grade 1 = no calcifications
• B) Grade 2 = few punctate vascular
calcifications. No tram-track or ring
calcifications
• C) Grade 3 = Coarse or tram-track
calcifications affecting < 3 vessels
• D) Grade 4 = Coarse or tram-track
calcifications affecting > 3 vessels
Mostafavi L et al. Prevalence of coronary disease evaluated by coronary CT angiography in
women with mammographically detected breast arterial calcifications. 2015

8. • “Given the strength of the association between BAC and CVD, we propose that
radiologists should begin universally reporting the presence of BAC on all
mammograms as an important step forward. This will be important in facilitating
needed studies”.
• “Furthermore we suggest that the reports include a statement…noting the
association of BAC with CAC and that significance depends on the overall
cardiovascular risk profile and clinical correlation.”
• “We strongly believe that the presence of BAC should initiate a personalized
patient-provider discussion surrounding lifestyle changes and targeted medical
therapies for prevention of cardiovascular disease or consideration for referral for
cardiovascular risk assessment…”
A call for breast radiologists
Bui Q. Daniels L. A review of the role of breast arterial calcification for cardiovascular risk stratification in women.
Circulation. 2019; 139:1094-1101

9. Adding risk to age screening
• “Mammography screening has been used in more or less the same way over the
past 40 years and very little has been done to increase efficiency. Age of entry
into the programme and screening intervals are discussed, but most programmes
assume that the risk of breast cancer is solely dependent on age, that is, a
woman will benefit equally from screening as long as she is within a certain age range”
• “All women should be evaluated for breast cancer risk no later than age 30,
so that those at highest risk can be identified and benefit for supplemental screening”
Hall P. Easton D. Breast cancer screening: time to target women at risk. Br J Cancer. 2013; 108(11): 2202-04
Monticciolo D et al. Breast cancer screening in women at higher than average risk: recommendations from the ACR.
J Am Coll Radiol. 2018; 15: 408-414

10. Groups at higher than average risk
• Lifetime risk ≥ 20% of developing BC
• BRCA1 (40-87% risk) or BRCA 2 (27-84% risk) gene mutation carrier
• Untested 1st degree relative of BRCA mutation carrier
• H/o chest/mantle radiation from age 10 to age 30 y (20-25% risk at 45 if treated at 25)
• H/o breast cancer < 50 y and dense breasts (at least 20% risk)
• Dense breast at mammography (D=4xA; C or D=1.5xB)
• African american ancestry (higher rate of TN and BRCA1)
• SBLA/Li Fraumeni (49-54%), Peutz-Jeghers (up to 54%)/Cowden (25-50%)/Ruvalcaba,
NF1, Hereditary gastric ca, Ataxia telangiectasia (33-38%),…

11. Rationale of risk stratification
• 300,000 new breast cancers diagnosed annually
• 40,000 breast cancer deaths annually
• 2,000,000 women in need of genetic testing
• 95% of BRCA mutation carriers are unaware of their status*
• Most women are unaware of being at high risk and only <6% of eligible women are
screened with supplemental MRI*
• 75% of “screening breast MRI” do not meet high risk guidelines*
*Miles et al. Underutilization of supplemental MRI screening among patients at high breast cancer risk.
Journal of Women’s Health. 2018; 27:748-754

12. • Personalized and systematic breast cancer risk assessment is not yet a diffuse and
established practice
• Final recommendations are a necessary part of the report and should reflect the
individual patient’s risk
• Reports must always include breast density evaluation (w/o affecting the BIRADS final
category).
• “Supplemental screening should be a thoughtful choice after a complete risk
assessment, not an automatic reaction to breast density itself.”*
• Counseling should be based on the patient’s personal risk
A call for clinical breast imagers
*ACR statement on reporting breast density in mammography reports and patient summaries - Nov 26, 2017

13. • Modified Gail. Claus
• BRCAPRO. BOADICEA. Tyrer-Cuzick
• BRCAPRO excludes other nonhereditary risk factors except BRCA and underpredicts
mutation carriers in some subgroups
• “Prospective comparative data of model performance in clinical practice suggest that the
Tyrer-Cuzick model is the most consistently accurate for predicting breast cancer
risk”
Risk stratification: models
Monticciolo D et al. Breast cancer screening in women at higher than average risk: recommendations from the ACR.
J Am Coll Radiol. 2018; 15: 408-414

14. 9th

15. • Bayesian analysis based on breast cancer incidence, prevalence of BRCA mutations
and patient’s input
• Latest version (V 8/2018) incorporates also mammography breast density
• Output: 10-year and lifetime risk for breast cancer (DCIS + invasive) & risk for BRCA
mutations
• Calculator available and downloadable from the web at: http://www.ems-trials.org/
riskevaluator/
Tyrer-Cuzick

17. 9th

18. Bertacchi G et al. How to identify women above average risk for developing breast cancer. Preliminary results after implementation of a
breast cancer risk assessment program. Poster presentation. 8th SEHA Int. Radiol. Conference. 2019
• 435 women prospectively assessed
• 102 women did not meet the inclusion criteria (under oncology surveillance or treatment
for breast cancer and at age >50y)
• 333 women assessed for breast ca. risk (age range 16-78) in two consecutive months
• 14/333 women identified at higher than average risk (4.2%)
• 3/14 not eligible for early start of screening: counseling
• 11/14 women underwent MRI screening (all w/final BIRADS 1 or 2)
Preliminary data

19. • A hybrid deep learning model incorporating Tyrer-Cuzick v.8 into image based A.I.
analyses was more accurate than the statistical models alone (AUC: 0.71 vs 0.62)
• Mammography seems to contain informative indicators of risk not captured by traditional
risk factors, including breast density
• “Hybrid A.I. models based on both mammography and statistical risk factors models have
the potential to replace conventional risk prediction models”*
*Yala A et al. A deep learning mammography-based model for improved breast cancer risk prediction. Radiology.
2019; 291 (1): 60-66
Integration of statistical models with A.I.

20. • 1/400-800 women has BRCA gene mutation
• 5-10% of breast cancer are associated to BRCA mutation
(particularly in pre-menopause)
• Median age of breast cancer at age 40 (versus age 61)
• Approximately 3% risk of breast cancer before age 30 (versus 0.07%)
• Mutation carriers bear a lifetime risk up to 87%
• Multiple variations of BRCA gene mutations (>3500)
• Up to 25% present as interval cancers (mostly BRCA 1)
• 80% IDC and 2-8% ILC
• Medullary is less than 1% (but 15-19% of medullary ca are BRCA associated)
BRCA subtype cancers

21. BRCA 1
• Up to 63% risk of developing a second contralateral primary
• Younger age at diagnosis in comparison with general and BRCA 2 population
• BRCA1 DCIS are rarely identifiable
• Most frequently high grade, invasive, “triple negative” (up to 70%), with accelerated
clinical course and high rate of recurrence
• More often and early metastasis to the brain, less to bone

22. • Often present morphologic features characteristic of benign lesions
• Can mimic fibroadenomas or even complicated cysts
• Mammography: Lack of calcifications and dense breasts
• Ultrasound: Markedly hypoechoic, mimicking cysts. May be associated with posterior
acoustic enhancement
• MRI: Frequently rim enhancement. However, they can be T2 hyper intense centrally,
mimicking a benign lesion. Enhancement kinetics can be helpful.
• BIRADS 3 is NOT recommended in patients known to belong to this group
BRCA 1 imaging features

23. • Oval mass w/
circumscribed
margins
• Oval markedly
hypo echoic
lesion
• LN w/ slightly
thickened cortex

24. BRCA 2
• As many DCIS (often calcified) as in sporadic cancers
• Luminal B associated (75% are ER+ and only 16% are triple negative)
• At higher grade than their sporadic cancers counterparts
• Brain metastasis are rare
• Present in up to 40% of male breast cancers
• Irregular or spiculated masses +/- calcifications

25. • Spiculated mass w/skin thickening and
architectural distortion
• Predominantly hypo echoic solid lesion w/
angular margins

26. • Breast awareness starting at age 18
• CBE every 6-12 months starting at age 25
• Annual MRI starting at age 25-29
• From 30 to 75 years: Annual MRI + mammography
• When pregnant, continue screening!
Recommendations for BRCA

27. Pregnant patient - specific risk
• Mammography during
pregnancy is not
contraindicated
• Most radiation to the
fetus is from the
scatter component,
significantly
reducible by
shielding the patient
(dose to uterus <50%)
• DBT decreases the
masking effect in
dense breast tissue

28. Pregnant patient
• Pregnancy associated breast cancer (PABC) is the most common invasive cancer
diagnosed during pregnancy
• PABC represents up to 3% of breast cancers
• Most PABC are ER/PR negative and often triple negative
• Tendency to delayed child bearing into the 4th decade correlates with the increased
incidence of PABC
• Controversies exist regarding the delayed diagnosis and the patients’ young age as the
main factors of the poor prognosis of PABC

29. Risk associated with delayed diagnosis
• Increased estimated risk of axillary metastasis from PABC
(w/tumor doubling time of 130 days):
• 0.9% after 1-month delay
• 2.6% after 3-month delay
• 5.1% after 6-month delay

30. Pregnant patient - palpable lump
• Ultrasound is the workhorse in pregnancy, in particular for assessment of palpable
masses and nodules
• It may diagnose DCIS (up to 20% of DCIS are not calcified)
• It may not be the best way of assessing the disease extension
• Beware the characteristic differentials

31. • Benign, hormone sensitive
• Rapid growth and it may infarct
• Often presenting as a painful lump
• Heterogeneously hypoechoic, with cystic spaces due to secretory changes
Hypertrophic Fibroadenoma

32. • Rapidly growing painless lump
• Presentation in late pregnancy/peripartum
• Reducing/resolving after cessation of breast feeding
• Hypo to isoechoic with sharp margins and cystic areas
Lactating adenoma

33. PI-granulomatous mastitis
• Associated w/ high prolactin
• Painful palpable, sparing the subareolar
region
• It mimics inflammatory breast carcinoma
• Affects young women within 6 years of
pregnancy
• Unknown origin

34. • Higher risk of bleeding and infection (due to increased vascularity and
ductal dilatation)
• Higher risk of milk-duct fistula (rare, usually associated with open surgery rather than
needle biopsy, more common with larger core/vacuum needles)
Pregnant patient - IR procedures

35. • Disease extension of newly diagnosed breast cancer
• Response assessment to NACT
• Screening of high risk patients
• GBCA crosses the placenta and deposits in the fetal brain. However no
evidence on how the fetus is affected. Controversies exist between EMA and
FDA about the safety of GBCA
Pregnant patient - MRI

36. Uematsu et al. Non-contrast-enhanced breast MR screening for women with dense breasts. Poster presentation. RSNA 2019
Nissan N et al. Noncontrast breast MRI during pregnancy using diffusion tensor imaging: a feasibility study. J Magn Reson Imaging. 2018; 49 (2):508-517
A role for Breast DWIBS and/or Breast DTI?

37. • BAC should not be overlooked, but seen as a possible indicator of risk for CVD
• Breast risk assessment should be proposed to our patients and recognized
as valuable by our institutions
• High risk patients should receive appropriate counseling and management by the
breast radiologist
• Care should be taken when studying a known or suspected BRCA1 case
• Breast imaging in pregnancy is still a challenging and controversial arena. However
pregnancy per se should not delay the necessary investigations
Take home points

38. Thank you !