ASCOThree studies of MRI screening for women at
high risk of breast cancer, presented at the 39th Annual meeting of the
American Society of Clinical Oncology, show high sensitivity and the ability to
detect cancers missed on mammography or ultrasound, but in two of the studies,
the technique had lower specificity than mammography, resulting in unnecessary
biopsies. The better specificity seen in the study from Germany may stem from
the greater experience of the physicians involved in that study.
The researchers agreed that MRI is not recommended for
breast cancer screening in the general population, but should be considered in
high-risk women as a complement to mammography, in an attempt to find breast
cancers early in these women and reduce the need for prophylactic mastectomies.
The German researchers, however, suggested that MRI could replace mammography
screening in women at high risk of developing the disease.
When MRI was compared with mammography and ultrasound in a
German study of 462 women with proven or suspected hereditary breast cancer
(abstract 4), it "was the most powerful tool to detect cancer, classify
lesions, and prevent unnecessary biopsies," said Christiane Kuhl, MD,
associate professor of radiology and neuroradiology, University of Bonn. The
study included women who had or were likely to have BRCA mutations based on
genetic testing or pedigree analysis. Women in the study underwent annual
two-view mammography, high-resolution ultrasound, and MRI. Dr. Kuhl reported on
imaging findings after the first 5 years (1996 to 2001) of the ongoing study.
The first midterm results of this prospective clinical trial
showed that MRI was more sensitive in detecting breast cancer than either of
the other imaging modalities. MRI had a sensitivity of 95% vs 34% for
mammography and 42% for ultrasound. MRI depicted all but 2 of a total of 51
cancers detected in the study population, while mammography and ultrasound
found less than half of the cancers, Dr. Kuhl said.
"High sensitivity was not achieved at the expense of
specificity," she said. Specificity was 95%, 94%, and 88% for MRI,
mammography, and ultrasound, respectively. Moreover, MRI was associated with
the lowest rate of unnecessary biopsies.
MRI also had a higher positive predictive value (PPV) (54%)
than mammography (26%) or ultrasound (16%), and it found 20 of 51 cases of
multicentric disease. Dr. Kuhl said that the higher specificity and higher PPV
in this study are due to the team’s 12 years of experience in reading MRIs.
In one woman who had ultrasound and MRI scanning on the same
day, ultrasound identified a lesion in the left breast and no abnormalities in
the right breast. MRI clearly demonstrated that the suspicious area in the left
breast was scar tissue, and it revealed an enhancing area in the right breast
that turned out to be a 4 mm invasive carcinoma.
In addition to its diagnostic ability, MRI may be safer than
mammography for women with a BRCA mutation, Dr. Kuhl said. Because the BRCA
gene deficit is thought to affect tumor suppression, in theory, women who
harbor the genetic defect may not be able to fight off the mutagenic effects of
ionizing radiation. "MRI is not done with ionizing radiation, so there is
no harm to the patient with a BRCA mutation," Dr. Kuhl said.
Because the breast parenchyma in carriers of BRCA gene
mutations may be sensitive to radiation and mammography has a lower diagnostic
yield than MRI, Dr. Kuhl suggested that MRI should replace mammography when
screening women with familial breast cancer.
Although Jan Klijn, MD, PhD, chair of the Rotterdam Family
Cancer Center, The Netherlands, agreed that MRI is needed to detect small
tumors in high-risk women, he stressed that "it is too early to leave out
Dr. Klijn reported on the Dutch MRI Screening Study (MRISC),
the largest prospective, nonrandomized, multicenter trial of MRI and
mammography in women with a mutation in the BRCA1 or BRCA2 gene or with a
family history of breast cancer (abstract 5).
In the study, women underwent mammography and
contrast-enhanced MRI once a year as well as clinical breast examination twice
a year. A total of 1,874 women were eligible for study analysis.
After a median follow-up of 2.1 years, a total of 41 tumors
have been detected: 34 invasive breast carcinomas, one lobular carcinoma in
situ, five ductal carcinoma in situ (DCIS), and one lymphoma. Sensitivity for
MRI was 71% vs 36% for mammography. Specificity was 88% for MRI vs 95% for
Dr. Klijn noted that 42% of tumors found by MRI were less
than 1 cm in size, compared with 13% detected by mam-mography. Further, 76% of
cases found by MRI were node negative and 52% were grade 1. These findings
suggest that by detecting early-stage cancers, MRI screening may be able to
reduce the number of deaths due to breast cancer, he said.
The overall event rate was 1% a year, which is seven times
more than expected in a normal patient population of the same age (average 40
The overall breast cancer detection rate was 10.5/1,000
woman-years. The rate of cancer detection per 1,000 woman-years varied by risk
category: 25.9 in women with a 50% to 55% risk of developing breast cancer in
their lifetime, 7.0 in those with a 30% to 50% lifetime risk of breast cancer,
and 9.1 in women with a 15% to 30% breast cancer risk.
For detecting invasive carcinoma, MRI was more sensitive
than mammography: 83% vs 37%. Dr. Klijn explained that, for every 10 patients
with invasive cancer, MRI will detect at least 8 tumors and mammography will
detect fewer than 4. For finding DCIS, however, the opposite is true. Of five
cases of DCIS, four were detected by mammography. In this case, mammography is
more sensitive than MRI, he concluded.
The US study, from Memorial Sloan-Kettering Cancer Center
(abstract 362), looked only at women with known BRCA1 or BRCA2 mutations. The
54 BRCA-positive women were part of a larger breast cancer surveillance program
at the center. Mark E. Robson, MD, assistant attending physician, reported the
The women underwent 97 screening breast MRIs in addition to
their routine mammograms between July 1998 and April 2003, Dr. Robson said.
Another 28 MRIs were performed as short-term follow-up approximately 6 months
after the previous MRI had detected a minor abnormality. Four more MRI
examinations were performed either at the time of a contralateral breast cancer
diagnosis or before a prophylactic mastectomy.
During the study period, 2 of the 54 women developed DCIS,
and 1 developed invasive breast cancer, all detected by MRI. All three of these
women had reportedly normal mammograms within 6 months of their MRI. No woman
on the study has yet developed cancer with 12 months of a normal MRI.
MRI was 100% sensitive for breast cancer detection, with 83%
specificity. A significant number of women had false-positive exams. Only 3
(14.3%) of 21 biopsies recommended after the 129 MRI studies resulted in a
"MRI should not be recommended to the general
population at the present time because its specificity is not yet adequate, and
the majority of abnormalities detected in average-risk women would turn out to
be false positives," Dr. Robson said. High-risk women considering breast
MRI screening, he said, must be counseled about the pros and cons of the test.
The discussant for the two plenary session studies
(abstracts 4 and 5), Elizabeth Morris, MD, assistant attending physician,
Memorial Sloan-Kettering Cancer Center, said that while MRI was superior in
finding early breast cancers in high-risk populations, "at this time, it
cannot replace mammography as a primary breast cancer screening tool."
Dr. Morris, a coauthor of the Memorial Sloan-Kettering
study, said that for high-risk women, "by adding another layer of
screening with breast MRI, we may be able to show which patients have cancer so
that more aggressive therapies, such as prophylactic mastectomy or
chemo-prevention, are not needed."