Correspondence

Management of an Inherited Predisposition to Breast Cancer

N Engl J Med 2007; 357:1663October 18, 2007

Article

To the Editor:

Robson and Offit (July 12 issue)1 report that among breast cancers detected by screening, 12% were seen on mammography but not on magnetic resonance imaging (MRI). The authors recommend that MRI be considered as a complement to mammography among women who are at increased risk for hereditary breast cancer. Among the “areas of uncertainty,” they note the possibility that mammography may induce breast cancer in mutation carriers. The probability that mutation carriers have a high sensitivity to ionizing radiation may not be negligible,2,3 as was shown regarding the BRCA2 mutation in an animal model.4 This risk is probably more important for young women than for the general female population.5

In three prospective studies in which mammography, MRI, and ultrasonography were used,6 a total of 80 tumors were detected; only 3 of the tumors (all of which were ductal carcinoma in situ [DCIS]) were detected solely on mammography, and 3 invasive cancers were detected solely on ultrasonography. Thus, the rate of undetected cancers that could have been seen only on mammography was 4%, and the cancers were limited to DCIS. A good choice might be to avoid mammography and to use MRI and ultrasonography in high-risk women, at least up to the age of 35 years.

Francesco Sardanelli, M.D.
University of Milan School of Medicine, 20097 Milan, Italy
f.sardanelli@grupposandonato.it

Franca Podo, Dr.Sci.
Istituto Superiore di Sanità, 00161 Rome, Italy

6 References

1. 1

   Robson M, Offit K. Management of an inherited predisposition to breast cancer. N Engl J Med 2007;357:154-162
   Full Text | Web of Science | Medline

2. 2

   Den Otter W, Merchant TE, Beijerinck D, Koten JW. Breast cancer induction due to mammography screening in hereditarily affected women. Anticancer Res 1996;16:3173-3175
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   Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 1997;386:804-810
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   Beemsterboer PM, Warmerdam PG, Boer R, de Koning HJ. Radiation risk of mammography related to benefit in screening programmes: a favourable balance? J Med Screen 1998;5:81-87
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   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
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Drs. Sardanelli and Podo that there is uncertainty regarding the relative contribution of mammography for women who are at increased hereditary risk and are undergoing breast MRI surveillance. Mammography may add more to screening in situations in which centers have less experience with MRI. In two large multicenter trials, 14 of 86 breast cancers (16%), of which 6 were invasive, were detected on mammography but not on MRI.1,2 It is not known how many of the cancers detected on mammography in these series would have been identified on ultrasonography. Mammography may also identify invasive cancers if the quality of the MRI is compromised (e.g., by motion artifact or background enhancement).3 Outside the research setting, the availability of mammoghapic images may be helpful in interpreting MRI studies.

Mammography is the only method of breast-cancer screening with a proven mortality-reduction benefit in any population. A more developed evidence base is needed before it is recommended that mammography not be used routinely in mutation carriers. That said, although we and others have as yet found no increased risk associated with mammography among mutation carriers, the issue of radiation risk remains important.4 Additional data and analysis are particularly needed to define the role of mammography in BRCA mutation carriers under the age of 35 years.

Mark Robson, M.D.
Kenneth Offit, M.D., M.P.H.
Memorial Sloan-Kettering Cancer Center, New York, NY 10021
robsonm@mskcc.org

4 References

1. 1

   Kriege M, Brekelmans CTM, 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
   Full Text | Web of Science | Medline

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   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[Erratum, Lancet 2005;365:1848.]
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   Sardanelli F, Podo F, D'Agnolo G, et al. Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT study): interim results. Radiology 2007;242:698-715
   CrossRef | Web of Science | Medline

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   Goldfrank D, Chuai S, Bernstein JL, et al. Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2. Cancer Epidemiol Biomarkers Prev 2006;15:2311-2313
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Francesco Sardanelli, Franca Podo, Filippo Santoro, Siranoush Manoukian, Silvana Bergonzi, Giovanna Trecate, Daniele Vergnaghi, Massimo Federico, Laura Cortesi, Stefano Corcione, Sandro Morassut, Cosimo Di Maggio, Anna Cilotti, Laura Martincich, Massimo Calabrese, Chiara Zuiani, Lorenzo Preda, Bernardo Bonanni, Luca A. Carbonaro, Alma Contegiacomo, Pietro Panizza, Ernesto Di Cesare, Antonella Savarese, Marcello Crecco, Daniela Turchetti, Maura Tonutti, Paolo Belli, Alessandro Del Maschio. (2011) 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). Investigative Radiology 46:2, 94-105
   CrossRef

2. 2

   F. Sardanelli, G.M. Giuseppetti, G. Canavese, L. Cataliotti, S. Corcione, E. Cossu, M. Federico, L. Marotti, L. Martincich, P. Panizza, F. Podo, M. Rosselli Del Turco, C. Zuiani, C. Alfano, M. Bazzocchi, P. Belli, S. Bianchi, A. Cilotti, M. Calabrese, L. Carbonaro, L. Cortesi, C. Maggio, A. Maschio, A. Esseridou, A. Fausto, M. Gennaro, R. Girometti, R. Ienzi, A. Luini, S. Manoukian, S. Morassutt, D. Morrone, J. Nori, A. Orlacchio, F. Pane, P. Panzarola, R. Ponzone, G. Simonetti, P. Torricelli, G. Valeri. (2008) Indications for breast magnetic resonance imaging. Consensus document “Attualità in senologia”, Florence 2007. La radiologia medica 113:8, 1085-1095
   CrossRef

3. 3

   &NA;. (2008) BRCA Screening. Obstetrics & Gynecology 111:5, 1205-1206
   CrossRef