HealthManagement, Volume 12 - Issue 2-3, 2012

Breast Imaging in High Risk Populations

share Share

Recent evidence suggests that contrast-enhanced breast MRI is becoming an established technique that offers good quality in safety, performance and patient outcomes. In this article, Prof. Francesco Sardanelli, a frequently invited speaker and educator on this topic at international meetings, writes about the growing effectiveness of breast MRI, the special attention that must be paid to high-risk patient groups, and the need for radiologists to interact with other relevant medical professionals in an interdisciplinary paradigm.


Breast Cancer: The Case for High-Risk Patients

Breast cancer affects from 1:7 up to 1:11 women in western countries. Although this disease is mainly a sporadic one, about 15 percent of cases are clustered in families with highly or moderately elevated incidence. Pathogenic mutations in high-risk genes at autosomic dominant inheritance are held responsible for about 5 percent of cases, in which the disease may have early onset, with an estimated cumulative lifetime risk as high as 50 – 85 percent. About 50 percent of hereditary breast cancers can be explained by mutations in BRCA1 and BRCA2 genes. 

In women at high risk of developing breast cancer, screening mammography has shown a lower sensitivity (29–50 percent) compared with that of screening of the general female population (70–80 percent), with higher percentages of interval cancers (35–50 percent versus 20-25 percent) and a higher rate of nodal involvement (20 - 56 percent versus 22 percent). In the last decade, a number of prospective, non-randomised studies have been conducted in Europe and North America to assess the value of dynamic contrast- enhanced MRI as a screening tool to be used as an adjunct to mammography, or to mammography plus ultrasonography, for the surveillance of women at high genetic- familiar risk of breast cancer. The general result of these studies is that MRI largely outperforms mammography and/or ultrasound in detecting breast cancers in asymptomatic high-risk women, as confirmed by reviews and meta-analyses.


Evidence Points to MRI as a Screening Tool in High-Risk Women

In 2007, on the basis of the early evidence available in the literature, the American Cancer Society issued a recommendation in favour of screening with MRI as an adjunct to mammography for high-risk women, a group defined as follows: women with an approximately 20 - 25 percent or greater lifetime breast cancer risk, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin’s disease between eight and 30 years of age with mantle radiation therapy. 

Despite the general agreement on the use of MRI as a screening tool in high-risk women, breast cancer specialists face three problems:

  1. How to model the risk of breast cancer for an individual woman? Software is freely available, also from certain websites, such as that derived from the Tyrer-Cuzick model ( However, all the models show relevant limitations. Better performance is expected with the inclusion of breast density (from mammography, or better, from MRI) as a parameter in risk modeling.
  2. Which level of risk justifies an annual MRI? A cost-effectiveness analysis agrees on MRI screening for highrisk women, but further research is needed to clarify what to do for lower risk levels.
  3. Do we still need mammography and ultrasound if screening MRI is negative? Evidence in favour of screening high-risk women with MRI alone comes from two recent studies from Germany and Italy, which demonstrate no significant added value from mammography and/or ultrasound when MRI is used as a screening tool.

The choice to reduce the use of mammography in BRCA mutation carriers is corroborated by the higher risk of breast cancer induction from x-ray radiation. Moreover, a word of caution is needed for triple negative cancers, defined by lack of oestrogen and progesterone receptor expression and absence of HER2 amplification, as there is a potential for false negatives also in MRI screening, especially in BRCA1 mutation carriers.


Development of Contrast-Enhanced Breast MRI

Contrast enhancement on breast MRI offers another avenue of diagnosis in the case of breast cancer imaging. The first analysis of breast tissues was closely connected to the origins of medical use of nuclear magnetic resonance (NMR), since Damadian’s experiments during the 1970’s. However, the first clinical studies using standard T1-, proton density-, and T2- weighted sequences were disappointing. A dramatic change came about in 1986, when S.H. Heywang firstly obtained contrast-enhanced (CE) MR images after intravenous administration of gadopentetate dimeglumine (Gd-DTPA). The availability of faster T1- weighted gradient-echo sequences allowed for dynamic imaging, permitting the combination of morphologic and dynamic parameters, the latter studied by W.A. Kaiser and finally classified by C.K. Kuhl in 1999.

Two methods for breast MRI followed, on either side of the Atlantic ocean: dynamic CE imaging with temporal resolution in Europe and fat-saturated high-resolution CE imaging in the US, now partially unified by protocols which permit high spatial resolution and sufficient temporal resolution with or without fat-saturation. on the other hand, clinical research studies on 1-H (proton) MR spectroscopy using single-voxel technique were performed looking for the choline peak as a marker of malignancy, while during the nineties, MR-guided breast needle biopsy became available, finally filling a fundamental gap in clinical practice. Afterwards, especially in the last decade, technical developments such as strong and rapid field gradients, multichannel dedicated coils and parallel imaging, high-field magnets (3T), new dedicated sequences, including those for diffusion-weighted imaging or 2D/3D multi-voxel proton MRS, made breast MRI technology more and more robust and attractive in terms of multiple options offered to clinicians and researchers.


Diagnostic Performance of Breast MRI

Notwithstanding the growing evidence for the increasing diagnostic performance of breast MRI, including high sensitivity not only for invasive but also in situ cancers, there propounds a long-standing false idea, frequently repeated also by breast radiologists, that has unfortunately acted against its clinical adoption: that breast MRI as a diagnostic tool has high sensitivity but low specificity, a “mantra” to be abandoned, as recently remarked by W. A Kaiser.

In 2008, the large meta-analysis by Peters et al. finally offered a reference point for this discussion, demonstrating 90 percent sensitivity and 72 percent specificity, even though the diagnostic performance of each test depends on many factors, including the clinical setting and patient selection. Last but not least, new contrast materials with a higher diagnostic performance are now entering breast MRI with promising results in terms of higher diagnostic performance.

A large debate among breast cancer specialists is open on the indications for breast MRI. Some indications are largely accepted: high-risk screening, carcinoma unknown primary, breast implant integrity evaluation, and evaluation of the effect of neoadjuvant chemotherapy. other indications, especially preoperative MRI, are under discussion. As radiologists, we should be more and more able to interact for clinical use of breast MRI with surgeons, oncologists, radiation therapy specialists, and other colleagues, in the European perspective of the breast unit. While future directions are already proposed in terms of technical developments, such as diffusion tensor imaging or MRI-PET fusion, a new change of paradigm is around the corner: breast MRI, from diagnosis to prognosis.

Prof. Francesco Sardanelli is Professor of Radiology, Department of Medical and Surgical Sciences, Faculty of Medicine, University of Milan.
Director of Radiology Unit Scientific Institute (IRCCS), Policlinico San Donato, Milan, Italy

«« CIRSE 2012: A Widespread Success

Carestream Strike PACS Gold With Cheshire and Merseyside NHS Consortium »»


1. Goldsmith M, Koutcher JA, Damadian R. NMR in cancer, xIII: application of the NMR malignancy index to human mammary tumours. Br J Cancer. 1978 Oct;38(4):547-54.

2. Heywang SH, Hahn D, Schmidt H, et al. MR imaging of the breast using gadolinium-DTPA. J Comput Assist Tomogr. 1986 Mar-Apr; 10(2):199-204.

3. Kuhl CK, Mielcareck P, Klaschik S, et al. Dynamic breast MR imaging:are signal intensity time course data useful for differential diagnosisof enhancing lesions? Radiology. 1999 Apr;211(1):101-10.

4. Katz-Brull R, Lavin PT, Lenkinski RE. Clinical utility of proton magnetic resonance spectroscopy in characterizing breast lesions. J Natl Cancer Inst. 2002 Aug 21;94(16):1197-203.

5. Heywang-Köbrunner SH, Sinnatamby R, Lebeau A, Lebrecht A, Britton PD, Schreer I; Consensus Group. Interdisciplinary consensus on the uses and technique of MR-guided vacuum-assisted breast biopsy (VAB): results of a European consensus meeting. Eur J Radiol. 2009 Nov;72(2):289-94.

6. Peters NH, Borel Rinkes IH, Zuithoff NP, Mali WP, Moons KG Peeters PH. Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology. 2008 Jan;246(1):116-24.

7. Sardanelli F, Boetes C, Borisch B, Decker T, et al. Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer. 2010 May;46(8):1296-316.

8. Sardanelli F. Overview of the role of pre-operative breast MRI in the absence of evidence on patient outcomes. Breast. 2010 Feb;19(1):3-6.

9. Sardanelli F. Additional findings at preoperative MRI: a simple golden rule for a complex problem? Breast Cancer Res Treat. 2010 Dec;124(3):717-21.

10. Dent R, Warner E. Screening for hereditary breast cancer. Semin Oncol. 2007;34:392-400.

11. Humphrey LL, Helfand M, Chan BK, et al. Breast cancer screening: a summary of the evidence for the US.. Preventive Services Task Force. Ann Intern Med 2002;137:347-360.

12. Robson M, Offit K. Management of an inherited predisposition to breast cancer. New Engl J Med 2007;357:154-162.

13. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427-437.

14. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 2004;292:1317-1325.

15. Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005;365:1769-1778.

16. Kuhl CK, Schrading S, Leutner CC, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol. 2005;23:8469-8476.

17. Lehman CD, Blume JD, Weatherall P, et al. Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 2005;103:1898-1905.

18. Hagen AI, Kvistad KA, Marhle L, et al. Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series. Breast 2007;16:367-374.

19. Riedl CC, Ponhold L, Flöry D, et al. Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer. Clin Cancer Res. 2007;13:6144-6152.

20. Kuhl C, Weigel S, Schrading S, et al. Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol 2010; 28:1450-1457.

21. Sardanelli F, Podo F, Santoro F, et al. Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results. Investigative Radiology 2010; 46:94-105.

22. Sardanelli F, Podo F. Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection? Eur Radiol 2007;17:873-887.

23. Lord SJ, Lei W, Craft P, et al. A systematic review of the effectiveness of magnetic resonance imaging (MRI) as an addition to mammography and ultrasound in screening young women at high risk of breast cancer. Eur J Cancer. 2007 Sep;43(13):1905-17.

24. Warner E, Messersmith H, Causer P, et al. Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 2008;148(9):671-9.

25. Granader EJ, Dwamena B, Carlos RC. MRI and mammography surveillance of women at increased risk for breast cancer: recommendations using an evidence-based approach. Acad Radiol 2008;15(12):1590-5.

26. Sardanelli F, Boetes C, Borisch B, Decker T, et al. Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer. 2010 May;46(8):1296-316.

27. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007 Mar-Apr;57(2):75-89.

28. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004;23(7):1111-30.

29. Moore SG, Shenoy PJ, Fanucchi L, Tumeh JW, Flowers CR. Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population. BMC Health Serv Res 2009;9:9.

30. Taneja C, Edelsberg J, Weycker D, Guo A, Oster G, Weinreb J. Cost effectiveness of breast cancer screening with contrast-enhanced MRI in high-risk women. J Am Coll Radiol 2009;6(3):171-9.

31. Feig S. Cost-effectiveness of mammography, MRI, and ultrasonography for breast cancer screening. Radiol Clin North Am 2010;48(5):879-91.

32. Sardanelli F, Podo F. Management of an inherited predisposition to breast cancer. N Engl J Med 2007;357:1663.

33. Berrington de Gonzalez A, Berg CD, Visvanathan K, et al. Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. J Natl Cancer Inst 2009;101:205–209.

34. Short SC, Bourne S, Martindale C, et al. DNA damage responses at low radiation doses. Radiat Res 2005;164:292–302.

35. Heyes GJ, Mill AJ, Charles MW. Mammography-oncogenecity at low doses. J Radiol Prot 2009;29:A123–A132.

36. Colin C, Foray N. DNA damage induced by mammography in high family risk patients: Only one single view in screening. Breast. 2011 Dec 31. [Epub ahead of print]

37. Bosch A, Eroles P, Zaragoza R, et al. Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research. Cancer Treat Rev 2010;36:206-215.

38. Podo F, Buydens LM, Degani H, et al. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol 2010;4:1-21.


Related Articles

No consensus on surveillance imaging after treatment. Geography affects what post-treatment imaging women with low-risk... Read more

Breast Imaging in High Risk Populations Breast Imaging in High Risk Populations

No comment

Please login to leave a comment...

Highlighted Products