CORRESPONDENCE

Re: Magnetic Resonance Imaging and Mammography in Women With a Hereditary Risk of Breast Cancer

John Goffin, Pierre O. Chappuis, Nora Wong, William D. Foulkes

Affiliations of authors: J. Goffin (Department of Oncology), P. O. Chappuis (Research Institute, McGill University Health Centre), N. Wong (Cancer Prevention Research Unit, Sir M. B. Davis-Jewish General Hospital), W. D. Foulkes (Program in Cancer Genetics, Departments of Oncology and Human Genetics), McGill University, Montreal, PQ, Canada.

Correspondence to: William D. Foulkes, Ph.D., Division of Medical Genetics, Montreal General Hospital, Rm. L10–120, 1650 Cedar Ave., Montreal, PQ, Canada H3G 1A4 (e-mail: william. foulkes{at}mcgill.ca).

In a recent report, Stoutjesdijk et al. (1) determined that the operating characteristics of magnetic resonance imaging (MRI) were superior to mammography in a cohort of women, predominantly less than 50 years of age, who were at high risk for breast cancer. Similarly, other studies have found that mammography is a suboptimal screening method in BRCA1/2 mutation carriers (2,3) and that MRI may be superior (4,5).

We examined the sensitivity of mammography in a retrospective cohort of Ashkenazi Jewish women who were diagnosed with primary invasive breast cancer at age less than 65 years at one institution in Montreal, Canada, between 1980 and 1995 and who were tested for the three Ashkenazi Jewish founder mutations in BRCA1/2. Details of the mammogram performed before surgery were obtained by chart review by two physicians who were blinded to the BRCA1/2 status of the patients. We used Fisher's exact test and the Mann–Whitney rank-sum test to assess the statistical significance of our results.

Mammography reports were available for 161 patients. Nineteen and four patients had mutations in BRCA1 or BRCA2, respectively. BRCA1/2 mutation carriers (hereafter "BRCA1/2 carriers") were younger (median age, 45.8 years versus 54.3 years; P = .02) and had larger tumors at diagnosis (median tumor size, 1.9 cm versus 1.4 cm; P = .05) than noncarriers, but there was no difference in the median interval between mammography and the surgical diagnosis of breast cancer between the two groups (13 versus 11 days for BRCA1/2 carriers and noncarriers, respectively; P = .99). Suspicious lesions were found in 15 (65.2%) of 23 of the BRCA1/2 carriers and in 119 (86.2%) of 138 of the noncarriers (P = .03). We stratified the data by tumor size (<=2 cm versus >2 cm) or age at diagnosis (<=50 years versus >50 years). When BRCA1/2 carriers were compared with noncarriers, there was no statistically significant difference in the number of detectable cancers if the cancers were greater than 2 cm (P = .65) or the patients were greater than 50 years of age (P = .53). However, breast cancers less than or equal to 2 cm in size occurring in BRCA1/2 carriers (median cancer size, 1.3 cm) were statistically significantly less likely to be detectable than similar-sized cancers in noncarriers (median cancer size, 1.2 cm) (six [46%] of 13 versus 96 [89%] of 108; P<.001). In women diagnosed at age 50 years or less with breast cancers less than or equal to 2 cm in size, only two (25%) of eight breast cancers were detected in BRCA1 mutation carriers compared with 27 (77%) of 35 in noncarriers (P = .009). Although it is uncertain why breast cancers occurring in BRCA1/2 carriers were less detectable by mammography than those occurring in noncarriers, one likely explanation is that the smooth, noninfiltrative edge of many BRCA1/2-related breast cancers (6) reduces their mammographic detectability. Of interest, in one study of symptomatic women who underwent mammography, medullary breast cancers were overrepresented in the false-negative group (5.5%) when compared with the true-positive group (0.8%) (7). Other possible explanations include a deficit of ductal carcinoma in situ (6) (which could be associated with less microcalcification surrounding BRCA1-related cancers) or increased mammographic density (2).

Recommendations regarding the use of mammography in BRCA1/2 carriers have not been based on clinical studies. Our data support the emerging evidence (15) that mammography is insensitive in detecting invasive breast cancer in BRCA1/2 carriers. Furthermore, such data suggest that, for BRCA1/2 carriers, alternative forms of early detection and an increased focus on prevention are likely to be more beneficial than a reliance on mammography as an early diagnostic tool.

NOTES

Supported in part by grants from the Department of Defense (DAMD17–98–1-8112) and by the Fonds de la recherche en Santé du Québec.

We thank Drs. L. R. Bégin and J. Deschênes for assistance with pathology and A.-J. Paradis and N. Hamel for technical assistance.

REFERENCES

1 Stoutjesdijk MJ, Boetes C, Jager GJ, Beex L, Bult P, Hendriks JH, et al. Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer. J Natl Cancer Inst 2001;93:1095–102.[Abstract/Free Full Text]

2 Chang J, Yang WT, Choo HF. Mammography in Asian patients with BRCA1 mutations. Lancet 1999;353:2070–1.[Medline]

3 Brekelmans CT, Seynaeve C, Bartels CC, Tilanus-Linthorst MM, Meijers-Heijboer EJ, Crepin CM, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol 2001;19:924–30.[Abstract/Free Full Text]

4 Kuhl CK, Schmutzler RK, Leutner CC, Kempe A, Wardelmann E, Hocke A, et al. Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 2000;215:267–79.[Abstract/Free Full Text]

5 Warner E, Plewes DB, Shumak RS, Catzavelos GC, Di Prospero LS, Yaffe MJ, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 2001;19:3524–31.[Abstract/Free Full Text]

6 Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver M, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 1998;90:1138–45.[Abstract/Free Full Text]

7 Wallis MG, Walsh MT, Lee JR. A review of false negative mammography in a symptomatic population. Clin Radiol 1991;44:13–5.[Medline]


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