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Abstract , Full Text , Text+Graphics
Efficacy of MRI and Mammography for Breast-Cancer Screening in
W omen w ith a Familial or Genetic Predisposition
Mieke Kriege, Cecile T M Brekelmans, Carla Boetes, Peter E Besnard, et al. The New England Journal of
Medicine. Boston: Jul 29, 2004.Vol.351, Iss. 5; pg. 427, 12 pgs
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Nuclear magnetic resonance--NMR, Mammography, Breast cancer, Medical screening, Women
Mieke Kriege, Cecile T M Brekelmans, Carla Boetes, Peter E Besnard, et al
Document features:Tables, Graphs, References
The New England Journal of Medicine. Boston: Jul 29, 2004. Vol. 351, Iss. 5; pg. 427, 12 pgs
ProQuest document ID: 673735791
Text Word Count5876
Abstract (Document Summary)
Surveillance consisted of a clinical breast examination performed by an experienced physician every six months and
imaging studies performed annually by experienced radiologists.
Full Text (5876 words)
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Copyright Massachusetts Medical Society, Publishing Division Jul 29, 2004
The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is
currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for
screening in this group of high-risk women.
Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a
clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of
the cancers that were detected were compared with the characteristics of those in two different age-matched control groups.
We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9
years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were
detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was
17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8
percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05).
The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group
(43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined
incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared
with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups.
MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast
THE CUMULATIVE LIFETIME RISK OF breast cancer among Dutch women is approximately 11 percent.1 A family
history of breast cancer or the presence of a germ-line mutation of the BRCA1 or BRCA2 gene increases this risk
considerably and is often associated with a diagnosis at a young age.2,3 Among high-risk women, the risk of breast
cancer can be reduced by prophylactic mastectomy,4,5 prophylactic oophorectomy,6,7 or chemoprevention.8 Early
diagnosis as a result of intensive surveillance may also decrease the rate of death from breast cancer.
Randomized trials have shown that mammographic screening of all women who are between 50 and 70 years of age
can reduce mortality from breast cancer by about 25 percent.9 Although these findings were recently disputed,10
there is a consensus among clinicians that breast-cancer screening of women in this age group is effective.
Screening is one of the main factors contributing to the decrease in mortality associated with breast cancer in the
Netherlands.11 However, there is no consensus about the value of breast-cancer screening among women who are
40 to 49 years old.12-14 One of the reasons for the lack of agreement is the difficulty in detecting tumors by
mammographic screening in younger women, who have denser breasts than postmenopausal women.15,16
Although screening is frequently offered to women with a genetic predisposition to breast cancer who are under the
age of 50 years, the efficacy of this approach is unproven. Preliminary results of surveillance by mammography and
clinical breast examination in such women showed that mammographic screening has a low sensitivity for detecting
tumors, especially in carriers of a BRCA mutation.17-21 Possible reasons, apart from the high rate of growth of
tumors in women with such mutations, include the atypical changes seen on screening mammograms and specific
histopathological characteristics in carriers of BRCA mutations, as compared with noncarriers of the same age.22-24
In a diagnostic setting, magnetic resonance imaging (MRI) is a sensitive method of breast imaging, and it is virtually
uninfluenced by breast density, but the specificity is variable and the costs are high.25-27 Because MRI may improve
the sensitivity of screening in women with a familial or genetic predisposition to breast cancer, we prospectively
compared MRI with mammography for screening women with such a predisposition in order to determine whether
screening with MRI facilitated the early diagnosis of hereditary breast cancer.
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The design of our MRI screening study, in which six subcommittees in different disciplines were involved, has been
described previously.28 Between November 1, 1999, and October 1, 2003, 1952 women with a genetic risk of breast
cancer were recruited for the study by six familial-cancer clinics in the Netherlands. The six centers were Erasmus
Medical Center-Daniel den Hoed Cancer Center, Rotterdam; the Netherlands Cancer Institute, Amsterdam;
University Medical Center Nijmegen, Nijmegen; Leiden University Medical Center, Leiden; University Hospital
Groningen, Groningen; and Free University Medical Center, Amsterdam. The study was approved by the ethics
committees of all the centers. All the women who participated gave written informed consent.
The inclusion criteria for participation were a cumulative lifetime risk of breast cancer of 15 percent or more owing to
a familial or genetic predisposition, according to the modified tables of Claus et al.,29 and an age of 25 to 70 years.
Women could be tested at an age younger than 25 if they had a family history of breast cancer diagnosed before the
age of 30 years, since testing began at an age 5 years younger than that at which the youngest family member was
found to have breast cancer. Women with symptoms that were suggestive of breast cancer or women who had a
personal history of breast cancer were excluded.
Surveillance consisted of a clinical breast examination performed by an experienced physician every six months and
imaging studies performed annually by experienced radiologists. The imaging included a mammographic study
(oblique and craniocaudal views and, if necessary, compression views or magnifications) and a dynamic breast MRI
with gadolinium-containing contrast medium according to a standard protocol.25 Whenever possible, both imaging
investigations were performed on the same day or in the same time period, between day 5 and day 15 of the
menstrual cycle. The results of mammography and MRI were scored in a standardized way, according to the Breast
Imaging Reporting and Data System (BI-RADS) classification,30,31 and the results were blinded so that the two
examinations were not linked. When one of the examinations was scored as either BI-RADS category 3 ("probably
benign [i.e., uncertain] finding") or category 0 ("need additional imaging evaluation"), rurther investigation by
ultrasonography with or without fine-needle aspiration was advised, or mammography or MRI was repeated. When
one of the two examinations was scored as BI-RADS category 4 ("suspicious abnormality") or category 5 ("highly
suggestive of malignancy"), a cytologic or histologic evaluation of a biopsy specimen was performed. When the
results of mammography and MRI were negative but the findings on clinical breast examination were rated as
uncertain or suspicious, additional investigation was also performed. The diagnosis of malignant tumors was based
on the results of a histologic examination. One of the investigators, an expert pathologist, reviewed all the biopsy
specimens that formed the basis for the diagnosis of breast cancer.
The women were divided into three categories according to the cumulative lifetime risk of breast cancer, as follows:
carriers of the BRCA1 or BRCA2 or other mutations (cumulative lifetime risk, 50 to 85 percent), a high-risk group
(risk, 30 to 49 percent), and a moderate-risk group (risk, 15 to 29 percent).28,29 The characteristics of the women in
each risk group were compared by analysis of variance or Pearson's chi-square test.
The rates of detection of breast cancer for the group as a whole and for each of the three risk groups were
calculated, and a Poisson distribution was assumed in order to calculate the 95 percent confidence intervals. Person-
years at risk were calculated from the date of the first examination, irrespective of the type of examination, to the date
of detection of breast cancer, bilateral prophylactic mastectomy, or death; the date that a patient stopped
surveillance; or the cutoff date for this analysis (October 1, 2003). An "interval cancer" was defined as a carcinoma
detected between two rounds of screening after initially negative findings on screening. In our analysis, we defined as
positive a mammographie or MRI study with a BI-RADS score of 0, 3, 4, or 5 and a clinical breast examination that
was classified as "uncertain" or "suspicious," because those were the results that triggered an additional examination.
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To compare the three different screening methods, we calculated the sensitivity, specificity, and positive predictive
value of each. The sensitivity used is that of one screening method relative to the others, meaning that a test result is
a false negative when a proven cancer (diagnosed on the basis of a histologic examination) is detected in the interval
or by one of the other methods. Receiver-operating-characteristic (ROC) curves for the two imaging methods were
generated. The area under the curve was used as an index in evaluating the inherent capacity of a screening method
to discriminate between "positive" and "negative" cases. We used a z-test to compare the area under the curve for
the results of mammography and MRI. For the analysis of the screening variables, we used only the screening data
that included the results of both mammography and MRI.
To determine whether breast cancer was diagnosed by screening at a stage more favorable to treatment, the
characteristics of breast tumors detected in the study group were compared with those in two control groups. The first
control group was derived from all women who had breast cancers diagnosed in 1998 in the Netherlands. These data
were obtained from the National Cancer Registry. The second control group consisted of unselected patients who
had received a diagnosis of primary breast cancer in Leiden or Rotterdam between 1996 and 2002 and who were
participating in a prospective study of the prevalence of gene mutations.32 Subjects in both control groups were
matched for age with the patients in the study group (in five-year categories). From this series of consecutive patients
in the second control group, we chose all the unscreened patients who were between 25 and 60 years old and whose
cumulative lifetime risk of breast cancer was more than 15 percent because of a family history of the disease -
information that was routinely recorded in this database. The differences in tumor characteristics between the study
group and the control groups were tested with the use of Pearson's chi-square test or the chi-square test for trend. A
two-sided P value of less than 0.05 was considered to indicate statistical significance. All statistical analyses were
performed with the use of SPSS software (version 9.0).
Of the women who were invited to participate in the study, 90 percent agreed. Initially, 1952 women were included; 8
withdrew from the study before their first screening visit and another 35 were excluded because they ultimately
proved not to be carriers in a family with a proven mutation and therefore had less than a 15 percent cumulative
lifetime risk of breast cancer. Of the 1909 remaining women, 88 (4.6 percent) left the study or were lost to
surveillance before October 1, 2003; 65 of these 88 women underwent prophylactic mastectomy. Another 89 women
(4.7 percent) remained under surveillance but later refused screening by MRI, because of claustrophobia or for other
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Table 1. Characteristics of Participating Women at Study Entry, According to Risk Group.*
Table 1 lists the characteristics of the 1909 women according to risk category. The mean age at entry was 40 years
(range, 19 to 72). Within the group of 358 carriers of pathogenic mutations, 276 had a BRCA1 mutation, 77 had a
BRCA2 mutation, 1 had both a BRCA1 and a BRCA2 mutation, 2 had a PTEN mutation, and 2 had a TP53 mutation.
From November 1, 1999, to October 1, 2003, 51 malignant tumors (44 invasive breast cancers, 6 ductal carcinomas
in situ, and 1 non-Hodgkin's lymphoma) were detected (Fig. 1), during a median follow-up period of 2.9 years (mean
2.7, range, 0.1 to 3.9 years); 1 lobular carcinoma in situ was also found. Table 2 shows the detection rate for the
whole group and separately for the different risk groups. The overall rate of detection for all breast cancers (invasive
plus in situ) was 9.5 per 1000 woman-years at risk (95 percent confidence interval, 7.1 to 12.3), with the highest rate
(26.5 per 1000) in the group of women who were carriers of the BRCA1, BRCA2, PTEN, and TP53 mutations.
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Figure 1. Women at Increased Risk for Breast Cancer Enrolled and Tumors Detected.
Table 2. Detection of Cases of Breast Cancer (Including Ductal Carcinoma in Situ) According to Risk Group.
PERFORMANCE OF THE SCREENING METHODS
Table 3 shows the results with the three screening methods. Of the 50 breast cancers that were detected, 5 were
excluded from the analysis (Table 3). The 45 cancers that were evaluated in the comparison of the methods included
4 interval cancers (i.e., cancers detected between two episodes of screening). The first was symptomatic (30 mm in
diameter, node-negative), detected seven months after screening by imaging and clinical breast examination and one
month after screening by clinical breast examination only. The second (4 mm, node-negative) was detected in a
specimen from a prophylactic mastectomy. The third was symptomatic (45 mm, node-negative) and was detected
seven months after screening by imaging; the fourth, also symptomatic (13 mm, with isolated tumor cells in a lymph
node), was detected three months after screening by imaging.
Table 3. Sensitivity, Specificity, and Positive Predictive Value (PPV) of the Three Screening Methods.*
Overall, 32 breast cancers were found by MRI (22 of these were not visible on mammography), whereas 13 were
missed by MRI (8 of the 13 were visible on mammography, including 5 ductal carcinomas in situ; 4 were interval
cancers; and 1 tumor was detected only by clinical breast examination). In this group of 45 breast cancers,
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mammographic screening detected 18 tumors (10 of these were visible by MRI) and missed 27 tumors (including the
22 that were visible on MRI, the 4 interval cancers, and the 1 that was detected only by clinical breast examination).
With respect to all breast cancers (invasive and ductal carcinoma in situ), the sensitivity of clinical breast
examination, mammography, and MRI was 17.8 percent, 40.0 percent, and 71.1 percent, respectively, when the BI-
RADS score was 3 or higher (Table 3). For invasive cancers only, the respective percentages were 17.9 percent,
33.3 percent, and 79.5 percent. The specificity was 98.1 percent for clinical breast examination, 95.0 percent for
mammography, and 89.8 percent for MRI.
Of the 41 cancers found by screening, 22 were detected at the first imaging screening in the study; of the women in
whom cancer was detected, 16 had undergone mammographic screening before the start of the study. Two of the
interval cancers were detected after the first imaging screening, and two others after a subsequent imaging
screening. The sensitivity of mammography was 37.5 percent for the first screening and 42.9 percent for subsequent
screening (P=0.71). The sensitivity of MRI was 79.2 percent for the first screening and 61.9 percent for subsequent
Among the 83 clinical breast examinations with findings that were judged as probably benign or suspicious, or highly
suggestive of cancer, 8 cases of malignant disease were confirmed, for a positive predictive value of 9.6 percent
(Table 3). Among the 225 mammograms with findings categorized as BI-RADS 3 or higher, 18 cases of malignant
disease were confirmed, for a positive predictive value of 8.0 percent. A total of 32 cancers were confirmed among
452 MRI screenings with such findings, for a positive predictive value of 7.1 percent (Table 3). With a cutoff level of
BI-RADS 4, the sensitivity for both imaging methods decreased, whereas the specificity increased.
To evaluate the discriminating capacity of the imaging methods, we generated ROC curves (Fig. 2). The area under
the curve was 0.686 for mammography and 0.827 for MRI; the difference between the areas was 0.141 (95 percent
confidence interval, 0.020 to 0.262; P<0.05).
Ultrasonography was performed 889 times in 627 different women according to the protocol. Fine-needle aspiration
was carried out 312 times: 267 times in combination with ultrasonography and 45 times with palpation. Biopsy was
performed 85 times in 82 women and showed malignant disease in 50 cases and 1 lobular carcinoma in situ, making
the rate of positive histologic findings 60.0 percent. Sixty-seven of these 85 biopsies were performed after a
screening visit at which both MRI and mammography were performed. Of the 25 biopsies in women who had
mammographic findings with a score of 3 or higher, 7 (28.0 percent) showed no cancer. Of the 56 biopsies in women
who had MRI findings with a score of 3 or higher, 24 (42.9 percent) showed no cancer (Table 3). One of the 51
tumors was found in a specimen from a prophylactic mastectomy.
Table 4 compares the characteristics of tumors found in the study group with those of tumors in the two age-matched
control groups. In the study group, 19 of the 44 women with an invasive breast cancer (43.2 percent) had a small
tumor (< or =10 mm in diameter) - a proportion that was significantly higher than that in the first control group (14.0
percent, P<0.001) or the second control group (12.5 percent, P=0.04). Six of 42 invasive tumors (14.3 percent) with
known axillary status in the study group were node-positive and 3 (7.1 percent) had micrometastases (combined
total, 21.4 percent). This rate was significantly lower than those in both control groups, in which the rates of node-
positive cancer were 52.4 percent (P<0.001) and 56.4 percent (P=0.001), respectively. There were no major
differences between the study and control groups with respect to histologic features, with the exception of a relatively
high incidence of the medullary type in the study group (11.3 percent, vs. 1.8 percent in the first control group). In the
study group, a high proportion of grade 1 tumors were in women at high risk (68.8 percent) or moderate risk (75.0
percent); however, the group of women with BRCA1, BRCA2, or other mutations had a high percentage of grade 3
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tumors (63.2 percent), in addition to a high percentage of tumors that were negative for steroid receptors (Table 4).
DISEASE-FREE AND OVERALL SURVIVAL
In the study group, none of the 50 patients with breast cancer (44 with invasive cancer and 6 with ductal carcinoma in
situ) died before the end of the study period; the total follow-up after diagnosis was 87.6 woman-years for these 50
patients (median, 1.5 years). Contralateral breast cancer occurred in one patient. The patient with non-Hodgkin's
In this prospective study, we compared the efficacy of mammographic and MRI screening for breast cancer in
women with a family history of the disease or a genetic predisposition to breast cancer. Among the women examined
by both methods at the same screening visit, we detected 45 breast cancers (including 6 ductal carcinomas in situ):
32 by MRI (sensitivity, 71.1 percent) and 18 by mammography (40.0 percent); five other patients were excluded from
this comparison for various reasons (Table 3). Thus, the sensitivity of MRI was higher than that of mammography,
but both the specificity and positive predictive value of MRI were lower.
In our sensitivity and specificity calculations, we defined lesions that were in BI-RADS category 3 and higher as
positive, but most other authors have included in their calculations only lesions in BI-RADS categories 4 and 5 as
positive.21,33,34 If we had followed that policy, the sensitivity would have been 24.4 percent for mammography and
46.6 percent for MRI, in accord with the higher sensitivity previously reported for MRI.21,33,35,36 However, the
previous studies enrolled small groups of women, included some retrospective data,35 evaluated heterogeneous
groups that included women with previous breast cancers,21,33,36 or had a plan for follow-up after a suspicious
finding on MRI that differed from the follow-up plan for a suspicious mammographie finding.33 All these factors might
have artificially increased the sensitivity of MRI. We also investigated sensitivity in relation to specificity as
determined by ROC curves, showing that the area under the curve was significantly higher for MRI than for
mammography; this means that MRI screening could better discriminate between malignant and benign cases.
Figure 2. Receiver-Operating-Characteristic Curves for Mammography and MRI.
When we included only invasive breast cancers, the difference between the sensitivity of the MRI and mammography
(79.5 percent vs. 33.3 percent) was even greater than the difference overall (71.1 percent vs. 40.0 percent). MRI
detected 20 cancers (including 1 ductal carcinoma in situ) that were not found by mammography or clinical breast
examination. The stage of these 20 cancers was favorable; 11 of the 19 invasive tumors were smaller than 10 mm,
and only 1 was associated with a positive node.
Another important matter that we addressed was the best method for detecting carcinoma in situ. Our study showed
that mammography had a higher sensitivity than MRI for detecting ductal carcinoma in situ: 83 percent (five out of six
cancers detected), as compared with 17 percent (one out of six) for MRI (P=0.22).
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To investigate whether screening improves the chance of diagnosing breast cancer at an early stage, we compared
the distribution of tumor stages in our study with the distribution in two external control groups. The first group
consisted of age-matched women in a database of all breast cancers diagnosed in 1998 in the Netherlands. A
drawback of this group is that we had no information about whether or not they had been screened or the family
history. Therefore, we added a second control group from a prospective population-based study of the prevalence of
mutations in patients with breast cancer. From this group, we selected all patients with an age and a family history of
breast cancer that were similar to the women in our surveillance study. The tumors in our study group were
significantly smaller and were less likely to be node-positive than those in the two control groups. Most screening
studies (without MRI) in high-risk women have shown a higher incidence of positive nodes (30 to 45 percent) than we
found (21 percent).17,18,37 Moreover, Kollias et al.38 found no significant differences in the size or grade of invasive
tumors or in lymph-node status between women who had symptoms of cancer and women whose cancers had been
found on screening by mammography. So we may conclude that MRI screening did indeed contribute to the early
detection of hereditary breast cancer.
Table 4. Characteristics of Women with Breast Cancer and Breast Cancers Detected in the Three Risk Groups and in the
Two Control Groups.*
However, larger tumors (>2 cm in diameter) were found more often in the women with BRCA1, BRCA2, PTEN, and
TP53 mutations than in the other two risk groups in our study, suggesting that more frequent screening is needed for
women with these mutations. A drawback of MRI screening is that it has a lower specificity than mammography, and
as a result, MRI will generate more findings judged as uncertain, which require short-term follow-up or additional
investigations.39In our study, screening by MRI led to twice as many unneeded additional examinations as did
mammography (420 vs. 207) and three times as many unneeded biopsies (24 vs. 7).
In conclusion, our study shows that the screening program we used, especially MRI screening, can detect breast
cancer at an early stage in women at risk for breast cancer.
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Supported by a grant (OG 98-03) from the Dutch Health Insurance Council.
We are indebted to Petra Bos, Titia van Echten, Irene Groot, Marijke Hogenkamp, Arjan Nieborg, Angelique Schlief,
and Manita Verhoeven for data collection; to Leon Aronson for computer assistance; and to Truuske de Bock and
Ronald Damhuis for help in selecting the control groups.
Choose the single best answer to each of the questions below.
Efficacy of MRI and Mammography for Breast-Cancer Screening in Women with a Familial or Genetic Predisposition
Kriege M, Brekelmans CTM, Boetes C, et al. N Engl J Med 2004;351:427-37.
What is the cumulative lifetime risk of breast cancer in women who are carriers of the BRCA1 or BRCA2 mutations?
A. 15 to 20 percent.
B. 20 to 30 percent.
C. 35 to 45 percent.
D. 50 to 85 percent.
Which one of the following statements is true with regard to the comparison of magnetic resonance imaging (MRI)
and mammography in screening for breast cancer?
A. In this study, MRI was significantly more sensitive than mammography in detecting ductal carcinoma in situ.
B. MRI is more influenced by breast density than is mammography.
C. In this study, screening by MRI led to twice as many unneeded additional examinations and three times as many
unneeded biopsies as compared with mammography.
D. In this study, mammography was more sensitive than MRI when only invasive breast cancers were considered.
This study compared the efficacy of MRI with that of mammography for screening women with a genetic
predisposition to cancer. Which one of the following statements is true regarding their findings in this group of
A. The sensitivity of MRI was essentially the same as that of mammography.
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B. MRI screening appears to be more sensitive than mammography in detecting tumors in women with an increased
inherited susceptibility to breast cancer.
C. The specificity of MRI was higher than that of mammography.
D. MRI screening can detect breast cancer only at later stages.
Which one of the following statements accurately reflects a finding of this study or a conclusion that the authors draw
from this study?
A. The tumors found in the women in the study group were of a similar size as those found in the women in either
B. Smaller tumors were found more often in the subgroup of women with BRCA mutations than among women in the
other risk categories.
C. All women should be screened with MRI instead of mammography.
D. In this study, MRI detected 20 cancers that were not found by mammography or clinical breast exam.
After evaluating a specific article published in the New England Journal of Medicine, participants in the NEJM Weekly
CME Program should be able to demonstrate an increase in, or affirmation of, their knowledge of clinical medicine.
Participants should be able to evaluate the appropriateness of the clinical information as it applies to the provision of
This program is designed for physicians who are involved in providing patient care and who wish to advance their
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The Massachusetts Medical Society designates each NEJM Weekly CME program for a maximum of 1 category 1
credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he or she
actually spent in the activity.
The Massachusetts Medical Society is accredited by the Accreditation Council for Continuing Medical Education
(ACCME) to sponsor continuing medical education for physicians.
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2. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in
breast cancer families. Am J Hum Genet 1998;62: 676-89.
3. Klijn JGM, Meijers-Heijboer H. Gene screening and prevention of hereditary breast cancer: a clinical view. Eur J Cancer
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mutation carriers. J Nad Cancer Inst 2001;93:1633-7.
5. Meijers-Heijboer H, van Geel B, van Putten WLJ, et al. Breast cancer after prophylactic bilateral mastectomy in women
with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:159-64.
6. Rebbeck TR, Lynch HT, Neuhausen SL, etal. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N
Engl J Med 2002-346:1616-22.
7. Kauff ND, Satagopan JM, Robson ME, et al. Risk-reduction salpingo-oophorectomy in women with a BRCA1 or BRCA2
mutation. N Engl J Med 2002;346:1609-15.
8. Cuzick J, Powels T, Veronesi U, et al. Overview of the main outcomes in breastcancer prevention trials. Lancet 2003;361:
9. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjold B, Rutqvist LE. Long-term effects of mammography
screening: updated overview of the Swedish randomised trials. Lancet 2002;359:909-19. [Erratum, Lancet 2002;360:724.]
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Copyright © 2004 Massachusetts Medical Society.
Mieke Kriege, M.Sc., Cecile T.M. Brekelmans, M.D., Ph.D., Carla Boetes, M.D., Ph.D., Peter E. Besnard, M.D., Ph.D.,
Harmine M. Zonderland, M.D., Ph.D., Inge Marie Obdeijn, M.D., Radu A. Manoliu, M.D., Ph.D., Theo Kok, M.D., Ph.D., Hans
Peterse, M.D., Madeleine M.A. Tilanus-Linthorst, M.D., Sara H. Muller, M.D., Ph.D., Sybren Meijer, M.D., Ph.D., Jan C.
Oosterwijk, M.D., Ph.D., Louk V.A.M. Beex, M.D., Ph.D., Rob A.E.M. Tollenaar, M.D., Ph.D., Harry J. de Koning, M.D., Ph.
D., Emiel J.T. Rutgers, M.D., Ph.D., and Jan G.M. Klijn, M.D., Ph.D., for the Magnetic Resonance Imaging Screening Study
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From the Rotterdam Family Cancer Clinic, Department of Medical Oncology (M.K., C.T.M.B., J.G.M.K.), and the
Departments of Radiology (I.M.O.) and Surgery (M.M.A.T.-L), Erasmus Medical CenterDaniel den Hoed Cancer Center,
Rotterdam; the Department of Radiology (C.B.) and the Department of Medical Oncology and Family Cancer Clinic (L.V.A.M.
B.), University Medical Center Nijmegen, Nijmegen; the Departments of Radiology (P.E.B., S.H.M.), Pathology (H.P.), and
Surgery (E.J.T.R.), Netherlands Cancer Institute, Amsterdam; the Departments of Radiology (H.M.Z.) and Surgery (R.A.E.M.
T.), Leiden University Medical Center, Leiden; the Departments of Radiology (R.A.M.) and Surgery (S.M.), Free University
Medical Center, Amsterdam; the Departments of Radiology (T.K.) and Clinical Genetics (J.C.O.), University Hospital
Groningen, Groningen; and the Department of Public Health, Erasmus Medical Center, Rotterdam (H.J.K.) - all in the
Netherlands. Address reprint requests to Dr. Klijn at Erasmus Medical Center-Daniel den Hoed Cancer Center, Groene
Hilledijk 301 3075 EA, Rotterdam, the Netherlands, or at firstname.lastname@example.org.
*Other investigators in the Magnetic Resonance Imaging Screening (MRISC) study are listed in the Appendix.
N Engl J Med 2004;351:427-37.
Copyright © 2004 Massachusetts Medical Society.
In addition to the authors, the following investigators participated in the MRJSC Study: Erasmus Medical Center, Rotterdam -
C.C.M. Bartels, A. Ciurea, A.N. van Geel, E.J. Meijers-Heijboer, M. Menke, A.J. Rijnsburger, C. Seynaeve, D. Urich; Leiden
University Medical Center, Leiden - C. van Asperen, M.N.J.M. Wasser; Netherlands Cancer Institute, Amsterdam - R. Kaas,
W. Koops, M. Piek-den Hartog, M. van de Vijver; University Hospital Groningen, Groningen - C. Dorbritz, S. van Hoof, A.M.
van der Vliet, J. de Vries; University Medical Center Nijmegen, Nijmegen-J.O. Barentsz, H. Brunner, J.H.C.L. Hendriks, R.
Holland, N. Hoogerbrugge, M. Stoutjesdijk, A.L.M. Verbeek, T. Wobbes; Free University Medical Center, Amsterdam - F.
Menko, A. Taets van Amerongen.
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