Breast MR shows promise for population at high risk

Breast carcinomas are the leading cause of cancer death for women worldwide. World Health Organization figures show that more than 1.2 million women are diagnosed with breast cancer each year. About 385,000 of these cases occur in Asia.1

The incidence of breast cancer among Asian women is lower than that of other ethnic groups, but many Asian women face a greater risk because they do not routinely self-examine their breasts or undergo regular mammography screening. This means that their cancers are not detected in the early stages, when treatment is most likely to be successful.

Simply increasing access to mammography screening may not be the answer, however. Asian women tend to have dense or more glandular breasts, which greatly lowers the sensitivity of mammography. Mammography is known to miss 10% to 15% of cancers in women aged 50 and older and up to 25% of cancers in women in their forties.2 The higher percentage of missed cancers among younger women is alarming because these women tend to develop more aggressive and invasive tumors.

HIGH-RISK SCREENING STRATEGY

Alternative screening techniques such as MRI are showing considerable promise for some groups of women, especially those who have a high risk of developing breast cancer because they have a personal or first-degree family history of breast or ovarian cancer (mother, daughter, and/or sister), carry BRCA1 or BRCA2 gene mutations, or have had a suspicious physical examination or mammogram. Women who have undergone breast surgery and those who have used hormone replacement therapy may also be at higher risk of getting breast cancer during their lifetime. MRI may be of particular importance to Asian women, because of the overwhelming prevalence of dense breasts in this population (Figure 1).

A consensus is growing among medical societies worldwide that the ideal screening regimen for high-risk women is alternate mammography and MRI examinations at six-month intervals. The American Cancer Society, for instance, has updated its screening recommendations to include annual MRI for women with a 25% or higher risk of developing breast cancer. MRI does not involve ionizing radiation, so its addition to routine screening regimes will not increase patients' radiation burden as would a follow-up mammography examination.

Having recognized the growing role of MRI in diagnosing and treating breast cancer, our facility purchased a 1.5T system dedicated to breast imaging early in 2007 (Aurora Breast MRI System, Aurora Imaging Technology). The system delivers ultrathin 1-mm slices for superior resolution and clarity (Figure 2). The acquisition of this dedicated unit means that we do not need to compete for slots on our department's two whole-body MR scanners, which are already in considerable demand.

Performing diagnostic breast MRI on some conventional scanners may require two separate time slots on consecutive days. This is because only one breast can be centered over the coil at a time on some machines, but safety dictates that patients cannot be injected with gadolinium contrast more than once within a 24-hour period. The Aurora System's elliptical MR imaging capability allows both breasts to be imaged at once, which is also important for comparison studies. Radiologists can view the chest wall and bilateral axillary lymph nodes as well. Scans typically take less than 30 minutes, though the examination may be lengthened if the presence of breast implants means that additional sequences are required.

We are now performing breast MRI on two or three patients per day, thanks to our dedicated system. The quick one-day procedure allows us to see more patients in a shorter period of time. We can also reduce patients' anxiety by providing diagnostic answers almost immediately. Some women find our system to be more comfortable than a conventional MR unit. Examinations are performed with the patient lying on her stomach and entering the bore feet first, a position that may reduce claustrophobia.

TREATMENT PLANNING

MRI is also proving beneficial in women who are newly diagnosed with breast cancer and in those undergoing treatment for breast cancer. A number of studies suggest that women who have cancer diagnosed in one breast should have an MRI in the contralateral breast. A recent multicenter study focused on 969 women who had been newly diagnosed with cancer in one breast but had no detected cancer in the second breast.3 MRI of the apparently cancer-free breast subsequently revealed possible tumors in 121 cases. Biopsies confirmed that 18 of the women had invasive carcinomas in their second breast, and 12 had very early stage cancer or ductal carcinoma in situ.

MRI is ideal for guiding biopsy and interventional procedures for staging purposes. Our system accommodates core biopsy and vacuum-assisted biopsy devices easily. Its large aperture allows for increased access to the breasts for both medial and lateral approaches. The scanner's software allows us to mark, target, and guide interventional procedures accurately. Taken together, these features enable us to reach multiple targets in the same breast in a single procedure, quickly and precisely.

Breast MRI is becoming increasingly important in women who are diagnosed with breast cancer and need treatment. MRI can provide an accurate assessment of tumor size by finding residual disease beyond excisional margins. We recommend that women attending our practice have an MRI of both breasts before undergoing any definitive treatment. The results can be used to stage the cancer; evaluate the extent of disease; determine the feasibility of breast conservation versus mastectomy; and assess the potential need for radiation, chemotherapy, or chest wall resection.

MRI has been shown to change surgical management of breast cancer patients in 7% to 51% of cases.4 Some observers have criticized MRI when scan results have led to lumpectomy candidates becoming mastectomy patients.5 The diagnostic test should instead be applauded. If the extent of disease is greater than physicians have anticipated, then it is fortunate to know this before surgery. MRI is able to provide this information.6

The opposite situation can happen as well. We have had cases of women who were scheduled for mastectomy, or even bilateral mastectomy, but were able to undergo a less radical lumpectomy. The clarity of tumor margins seen on MRI gave the surgeon confidence that the tumors could be removed completely. Postsurgical MRI could, in some cases, be used to determine the presence of significant residual disease in patients with positive surgical margins. This information would then help determine the necessity of additional surgery, either re-excision of margins or mastectomy.

The ability of MRI to determine the extent of disease could be critical in Asian women. Studies have shown that Asian women are more likely to have undergone mastectomy for early-stage tumors than women from other ethnic groups.7 MRI also is useful for distinguishing postoperative and/or postradiation therapy scarring from recurrent cancer. This is something that mammography and ultrasound cannot always do, even in comparison with previous post-treatment studies. As many as 30% of women with stage I and II disease may have local recurrence.8 MRI can show enhancement at the lumpectomy site 12 to 18 months after treatment. Enhancement occurring during this period suggests strongly that malignancy has recurred.

Breast MRI can be used to help evaluate the effectiveness of treatment and extent of residual disease in patients undergoing neoadjuvant or induction chemotherapy. It may also be used to monitor the effectiveness of chemopreventive therapy such as tamoxifen.

EARLY DIAGNOSIS

Certain early-stage cancers, such as invasive lobular carcinomas, that are difficult to detect on mammography can be seen more clearly on MRI. DCIS can be difficult to see on MRI because it does not exhibit wash-out enhancement curves. Even computer-aided detection programs will not detect it. There is evidence that the high spatial resolution provided by a dedicated breast MR system, however, makes it possible to detect the linear branching that can indicate DCIS better than the lower resolution in whole-body systems (Figure 3).

Our MR system has enabled us to detect cancers in women, particularly younger women, whose mammograms were normal. One memorable case involved a patient with discharge but a normal ductogram. MRI of the area in question revealed a previously undetected abnormality that needed further investigation.

Ultrasound can be used to detect breast cancers in dense tissue that may be missed on mammography, but ultrasound is only as good as the operator holding the transducer. MRI is the best option for patients with a palpable mass that is not seen on mammography or ultrasound. Breast MRI requires interpretation by a radiologist who is well trained in breast imaging and becomes better with experience at determining which findings require further investigation.

PRACTICAL POINTS

The sensitivity of contrast-enhanced breast MRI ranges from 94% to 100%, almost guaranteeing that any area that is suspicious or of possible concern will not be missed. Studies show that breast MRI of high-risk women indicates that 15% to 25% of the patients require a follow-up investigative procedure, whether ultrasound or needle biopsy.9 The high sensitivity of MRI is not, however, matched by its specificity, which is only moderate. Just 40% of women referred for biopsy following breast MRI will actually have a malignancy.10

Given the likelihood of false positives and the needless worry that these may cause, are we justified in using breast MRI? I certainly believe so. Our physicians would rather do further tests than dismiss areas that could be of concern. I am sure that our patients would concur. MRI does, after all, have the highest sensitivity of all available imaging modalities for detecting invasive cancers, and we certainly do not want to miss these.

Some technologies on the horizon promise to help increase the positive predictive value of breast MRI. One idea is to combine MRI with PET. This may not be too far in the future given that PET/CT scanners are already in clinical practice.

Studies have shown that spectroscopy can increase the ability of MRI to distinguish benign breast lesions from malignant ones.11-13 Radiologists use the spectral data to seek out biological markers of cancer, such as choline, which concentrates in rapidly reproducing cancer cells. The downside of MR spectroscopy is that it is technically challenging. Spectroscopy should, however, improve radiologists' detection of cancers on breast MRI. It also has the potential to reduce the number of false positives and unnecessary biopsies.

The major drawback of MRI is its relatively high cost. The cost of mammography is already limiting women's access to routine breast screening in many Asian countries, but an MR scanner can cost 10 times that of a mammography system. It is consequently impractical to consider using MRI as a first-line screening tool for the general population. Breast MRI can, however, be cost-effective in high-risk populations given that early detection of breast cancer increases a patient's treatment options. The cost of MR systems and the time required for individual examinations both need to decrease significantly if MRI is ever to replace mammography.

The future for breast MRI looks promising. As the technology continues to advance, access to breast MRI will become more widespread. MRI will then play an increasingly important role in diagnosing and managing women at high risk of developing breast cancer.

REFERENCES

International Agency for Research on Cancer, World Health Organization. Biennial Report 2004-2005.

Kerlikowske K, Grady D, Barclay J, et al. Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA 1996;276:33-38.

Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. NEJM 2007;356(13):1295-1303.

Tillman GF, Orel SG, Schnall MD, et al. Effect of magnetic resonance imaging on the clinical management of women with early-stage breast carcinoma. J Clin Oncol 2002; 20(16):3413-3423.

Morrow M. Magnetic resonance imaging in breast cancer: one step forward, two steps back? [Editorial]. JAMA 2004;292:2779-2780.

Bedrosian I, Mick R, Orel SG, et al. Changes in the surgical management of patients with breast carcinoma based on preoperative magnetic resonance imaging. Cancer 2003; 98:468-473.

Lee MM, Lin SS, Wrensch MR, et al. Alternative therapies used by women with breast cancer in four ethnic populations. J Natl Cancer Inst 2000;92(1):42-47.

Mollick JA, Carlson RW. Rational surveillance programs for early stage breast cancer patients after primary treatment. Breast Dis 2004;21:47-54.

Port ER, Park A, Borgen PI, et al. Results of MRI screening for breast cancer in high-risk patients with LCIS and atypical hyperplasia. Ann Surg Oncol 2007;14(3):1051-1057.

Morris EA, Schwartz LH, Drotman MB, et al. Evaluation of pectoralis major muscle in patients with posterior breast tumors on breast MR images: early experience. Radiology 2000;214(1):67-72.

Tsa GM, Cheung HS, Pang LM, et al. Characterization of lesions of the breast with proton MR spectroscopy: comparison of carcinomas, benign lesions, and phyllodes tumors. AJR 2003;181:1267-1272.

Huang W, Fischer PR, Dulaimy K, et al. Detection of breast malignancy: diagnostic MR protocol for improved specificity. Radiology 2004;232:585-591.

Bartella L, Morris EA, Dershaw DD, et al. Proton MR spectroscopy with choline peak as malignancy marker improves positive predictive value for breast cancer diagnosis: preliminary study. Radiology 2006;239:686-692.

Prof. Tsai is Hasso Brothers-endowed chair of the department of radiological sciences at the University of California, Irvine. He received his medical education from Taipei Medical University and began his medical career in Taipei, Taiwan.