Role of MRI in breast cancer detection unclear for majority of women
Available data confine the use of MRI to women at high risk for the disease.
There is no dispute that magnetic resonance imaging can detect microscopic breast cancers that cannot be detected with mammography. However, whether using magnetic resonance imaging is necessary during the course of the disease, from diagnosis to treatment to follow-up, is still unknown.
Photo by Karen M. Cheung
According to the ACS, mammography can detect early-stage breast cancer and reduce mortality related to the disease. However, the society stated in its 2003 breast cancer screening guidelines that women at higher risk for the disease may benefit from additional screening using other modalities, such as breast ultrasound and MRI.
The 2007 ACS guidelines echo the 2003 guidelines and include more evidence. Screening with MRI is still recommended for women with about a 20% to 25% greater lifetime risk for breast cancer, which includes women with a family history of the disease and women who have been treated for Hodgkin’s disease, according to data from a study conducted by Saslow et al published in CA: A Cancer Journal for Clinicians.
For other groups of women, however, the role of MRI is still unclear.
“This is an area of evolution,” Eric Winer, MD, director of the Breast Oncology Center at Dana-Farber Cancer Institute, told HemOnc Today. “The only clear role for MRI thus far is for screening in high-risk women and further characterizing indeterminate findings on mammography.”
On mammography, benign and malignant lesions often have a similar appearance, a limitation that also applies to a clinical breast exam.
An imaging method that accurately detects more cancers, but distinguishes between lesion types, would be a helpful tool for both radiologists and oncologists.
“For some women, it is fairly easy to justify the use of breast MRI for screening,” Doug Yee, MD, director of the University of Minnesota Cancer Center and a member of HemOnc Today’s Editorial Board, said in an interview. “At the same time, it can promote a fair amount of unnecessary anxiety.”
Use of MRI as a screening tool does come with challenges. It is sensitive at detecting smaller cancers but also yields false positives, which result in the use of additional and often unnecessary procedures, as well as increased anxiety for women, Winer said.
MRI findings may lead to changes in treatment course, particularly the type of surgery, according to Yee. Women may choose to have a mastectomy instead of breast conserving surgery due to microscopic findings on MRI. This change in surgery has not shown any benefit thus far. The survival benefit related to detecting these microscopic cancers earlier is also unknown.
There is no uniformity among various radiology centers pertaining to MRI as with mammography. There are technical standards and certification requirements for mammography, but to date, there is no such standard for MRI, Yee said.
The variability in the quality of MRI vs. mammography is due in part to the immaturity of MRI technology, according to Steven Harms, MD, a radiologist at the Breast Center of Northwest Arkansas and a clinical professor of radiology at the University of Arkansas for Medical Sciences.
“The results of the tests can vary greatly depending upon what kind of technology you have and what kind of doctor you have interpreting the images,” Harms said in an interview. “It’s the same with all medicine. If you have a well-performed breast MRI with an experienced reader, then you are talking about an exceptional procedure with sensitivity close to 100%.”
MRI is, however, an expensive procedure that is not yet cost effective for routine screening in all women, Harms said.
“If it were inexpensive, there would be no question, and MRI would be done in all women,” he said. “We’re getting closer to that point, but it is only cost effective for high-risk women. We defined these high-risk groups of women to spend health care dollars wisely.”
Conversely, mammography has missed cancers in some women, especially in women at a particularly high risk. According to Constance Lehman, MD, PhD, a professor of radiology and section head of breast imaging at the University of Washington Medical Center and the Seattle Cancer Care Alliance, high-risk women are more likely to have a cancer at any given time, compared with average-risk women. For the high-risk women, mammography is just not enough.
In studies of high-risk women, as many as 45 cancers for every 1,000 women screened are detected, compared with four to five cancers for every 1,000 women at average risk, Lehman said.
The high-risk group comprises women with a family history of the disease and women with BRCA1 or BRCA2 mutations. Women with these mutations have an increased risk for both breast and ovarian cancers in their lifetimes, when compared with the general population of women, according to the NCI.
“High-risk women are a unique group of women,” Lehman told HemOnc Today. “They tend to develop their breast cancers at a younger age. This is important because when women are younger, their breast tissue is denser, and therefore a mammogram is more likely to miss their cancers.”
About one-half of the women at high risk will have their cancers missed by mammography. One-half of those women will then have their cancers diagnosed at a later stage when they are more difficult to treat, Lehman said.
According to the NCI, the average woman has about a 13% lifetime risk for developing breast cancer. Women with BRCA1 mutations have about a 65% lifetime risk, and women with BRCA2 mutations have about a 45% risk for developing breast cancer, according to data from a study conducted by Antoniou et al published in the American Journal of Human Genetics. Many experts recommend that women aged 25 to 31 years with these mutations start receiving yearly mammograms, according to data from a study conducted by Lehman et al published in Cancer in 2005.
Data from several studies have indicated the utility of MRI for women with BRCA mutations. In a study of 1,909 women, Kriege et al found that MRI was more sensitive at detecting invasive breast cancer in women with BRCA mutations, compared with mammography and clinical breast exam.
Kuhl et al conducted a surveillance cohort study of 529 women with suspected BRCA1 or BRCA2 mutations. They also found that MRI is more sensitive at detecting breast cancers. They said that mammography with or without ultrasound is not sufficient for early breast cancer diagnoses in high-risk women.
MRI and surgical choice
The standard of care for most patients is breast conservation therapy, which entails a lumpectomy and radiation therapy. According to Monica Morrow, MD, chief of breast surgery at Memorial Sloan-Kettering Cancer Center, MRI detects microscopic areas of cancer around the breast in 10% to 25% of women.
The detection of these microscopic cancers has led some women to choose a mastectomy in place of a lumpectomy, Morrow said. However, the presence of these microscopic cancers is not new information.
“We know these microscopic cancers are scattered around the breast because pathologists told us 25 years ago,” Morrow told HemOnc Today. “The question is whether identifying these cancers by MRI does the women any good. Are these women having unnecessary mastectomies for microscopic areas of cancer that could be successfully treated with radiation?”
Harms also said that MRI does not just detect microscopic disease. According to the results of a study conducted by Harms et al published in Radiology, the average occult cancer picked up on MRI was 2.5 cm. In many instances, the MRI–detected lesion had a higher histologic grade than the lesion that was evident by conventional methods, Harms said.
The effect of MRI on surgical decisions also goes both ways, according to Harms.
“We have converted patients to lumpectomy when, if they had not had an MRI, they would have had a mastectomy,” he said. “Treatment is not one size fits all. We want the right treatment for each patient, and MRI helps determine what that is.”
When women have breast conservation therapy after cancer detection from a physical exam, mammography or ultrasound, the likelihood of cancer recurring in the breast in the next 10 years is 5% or less, Morrow said. There is no evidence that altering treatment due to results on MRI improves that risk.
In a study of 759 women with breast cancer, Solin et al found that there was no difference in the eight-year rates of local recurrence, contralateral breast cancer, distant metastasis or overall survival between women who had MRI at diagnosis and women who did not. All women had had breast conservation treatment.
“We are debating whether MRI plays a role before surgery,” Yee said. “MRI may help the surgeon with planning the resection. On the other hand, women are making decisions that might not have been made without the information from an MRI. We have to be cautious about that, since such a choice may not affect their overall care.”
Women with average risk
MRI is beneficial for detecting recurrence in the high-risk woman. In the average-risk woman, the role of MRI is not quite so clear. There are no trials that show a survival benefit to MRI in general-risk women at the time of diagnosis, Lehman said.
Survival and recurrence are not the only evidence of a benefit, though, Harms said.
“On one side, you’ll hear people that say there is only a 5% recurrence rate, and we are doing just fine without MRI,” Harms said. “It is short-sighted to think the only measurement we have for the benefit of MRI is recurrence.”
According to Morrow, there are no ongoing studies to determine whether MRI has a benefit in reducing the rate of local recurrence. Part of the reason for that is that the risk for local recurrence is low. To conduct such a study in the breast cancer population at large would require thousands of women, she said.
“Studies in this population need to focus on a different question entirely,” Morrow said. “For example, can you use MRI to identify women who do not need radiation after a lumpectomy, because the rest of the breast is normal?”
To study survival benefits of MRI, the same restrictions apply, Lehman said. It would require a trial that takes thousands of women and many years before data were available.
Lehman said that looking at surrogate markers would be a good way to study survival in these women. Possible surrogate markers include the tumor size at diagnosis and whether the cancers have already spread to the lymph nodes.
Contralateral breast cancer
In women with breast cancer, the most common second primary cancer is found in the contralateral breast, with an incidence as high as 12%. Contralateral cancers are found in up to 10% of women who had normal mammograms on the contralateral breast at the time of diagnosis, according to data from a study conducted by Heron et al that was published in Cancer.
In women with newly diagnosed breast cancer, MRI often identifies abnormalities in the contralateral breast, Winer said. Although, many of these abnormalities turn out to be benign, some women choose to have a bilateral mastectomy regardless because of fear or a desire to be done with evaluation, he said.
According to study data published in The New England Journal of Medicine, among 969 women with breast cancer who had no clinical or mammographic abnormalities on the contralateral breast, MRI detected possible cancers in 135 women. Thirty of these were confirmed with biopsy, according to data from a study conducted by Lehman et al published in The New England Journal of Medicine in 2007.
Where MRI fits in
For high-risk women, many oncologists and radiologists believe that MRI is beneficial at detecting cancers missed by mammography and clinical exam.
To date, the established role of MRI is in the following women: women with BRCA1 or BRCA2 mutations who want to consider not having mastectomies; women with cancer in the lymph nodes but no detectable cancer in the breast; and women who have equivocal findings on mammogram and dense breasts, Morrow said. These comprise less than 20% of breast cancers, she said.
More data are needed before MRI can play a role in the screening and treatment of women with a general risk, Winer said. – by Emily Shafer
For more information:
- Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117-1130.
- Harms SE, Flamig DP, Hesley KL, et al. MR Imaging of the breast with rotating delivery of excitation off-resonance: clinical experience with pathologic correlations. Radiology. 1993;187:493-501.
- Heron DE, Komarnicky LT, Hyslop T, et al. Bilateral breast carcinoma: risk factors and outcome for patients with synchronous and metachronous disease. Cancer. 2000;88:2739-2750.
- Kriege M, Brekelmans C, 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.
- Kuhl CK, Schrading CK, 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.
- 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.
- Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;356:1295-1303.
- 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;57:75-89.
- Solin LJ, Orel SG, Hwang WT, et al. Relationship of breast magnetic resonance imaging to outcome after breast conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol. 2008;26:386-391.