Magnetic resonance imaging (MRI) has been used to manage breast cancer for more than two decades. Despite this familiarity, or perhaps because of it, the controversy over the utility of breast MRI has continued to grow.
Early reports showed that breast MRI had the ability to detect disease that mammography otherwise missed. These early reports were confirmed repeatedly and many centers reported that these additional findings on breast MRI resulted in change in the surgical treatment approach, most often converting patients from planned lumpectomy to mastectomy.1 In addition, MRI has been shown to spot cancers in the opposite breast in 3 percent of newly diagnosed breast cancer patients with a negative contralateral mammogram.2
Surely it is important to find these otherwise occult areas of cancer. If “missed,” would they not result in recurrence or a new primary in the opposite breast? Given the ability of breast MRI to stage the extent of disease most accurately, why has preoperative staging MRI not become the standard of care? Why has it instead generated more controversy over the years?
Hypotheticals versus evidence
At the heart of the MRI debate is the disconnect between the hypothetical gains in patient care brought about by breast MRI and the actual evidence that has emerged in recent years. In theory, the improved cancer detecting and staging capability of breast MRI should translate into the following: better surgical planning, thereby minimizing the number of patients who have to undergo re-excision to achieve margin-negative surgery; reduced local recurrence rates in the affected breast; and fewer new cases of breast cancer in the opposite breast.
In practice, however, these gains have not materialized. We have learned from the recently concluded comparative effectiveness of MRI in breast cancer (COMICE) trial in the UK that women who undergo preoperative breast MRI have the same probability of re-excision surgery (20 percent) as women who did not receive additional MRI before surgery.3 It has also been discovered by studying a large series of women treated at the University of Pennsylvania in Philadelphia—an early pioneer in the field of breast MRI—that the local recurrence rate among women who had undergone breast MRI was the same as the rate of local relapse among women who were surgically treated without the benefit of preoperative breast MRI.4 Furthermore, the University of Pennsylvania data indicated that there is also no difference in the rate of new cancers in the opposite breast between these two groups of patients.
Although these emerging data on the lack of benefit of breast MRI on patient outcomes are important and worthy of further consideration, they also have many limitations. First, the COMICE trial remains the only randomized prospective trial to address the effectiveness of breast MRI in improving patient outcomes, and it has several shortcomings; most importantly, that the quality of the MRI in the trial was not standardized. In other words, the information from preoperative breast MRI was not used in the best possible way, which, in turn, might have negatively affected the results. Secondly, although the data from the University of Pennsylvania represented a large cohort of women, follow-up is retrospective and, therefore, very likely subject to selection biases that may have distorted the findings. Lastly, the overall body of data on clinical benefits of breast MRI is very limited, with the COMICE data and the retrospective series from University of Pennsylvania functioning as the only two notable studies on this subject. So, although the emerging information about the lack of benefit of breast MRI staging in breast cancer patients is compelling, it also must be viewed as preliminary.
Another reason why it is too early to close the chapter on the potential role of breast MRI in the management of breast cancer patients is that, over the last decade, health care professionals have learned that breast cancer is not one disease but several. Each subtype carries with it different risks for distant and local relapse. The estrogen receptor (ER)-negative subtypes were shown early on to have a poorer prognosis with a higher risk of metastasis. Similarly, we are now learning that the ER-negative subtype also confers a higher risk of local recurrence following either breast conserving therapy or mastectomy.5,6 Why this association exists is rather unclear, but intriguing data suggest that the ER-negative tumors are relatively resistant to radiation therapy.7 If this theory is true, then one may suggest that it is important to detect—and surgically treat—mammographically occult disease in this ER-negative population of patients. Whereas it may be possible to effectively use adjuvant radiation following lumpectomy to treat mammographically occult cancer in women with ER-positive tumors, the same concept may not apply to women with ER-negative tumors.
New clinical trial
This question is at the heart of a new clinical trial testing the potential oncologic benefit of breast MRI in the management of breast cancer patients. American College of Surgeons Oncology Group trial Z11101, which will be conducted in collaboration with the American College of Radiology Imaging Network and conducted through the Alliance, will randomize women with ER-negative, Stage I and II breast tumors to additional preoperative staging with breast MRI or no further work-up prior to surgery (see figure). To qualify for this trial, women must be deemed eligible for breast conserving surgery by the treating surgeon and based only on clinical examination and standard imaging (mammogram +/-ultrasound).
In addition to the primary goal of determining whether preoperative breast MRI in breast cancer patients reduces recurrences rates, this trial will examine two other important outcomes: rates of re-excision surgery and cost-effectiveness. Similar to the COMICE trial, women will be tracked to determine whether breast MRI reduces the number of second procedures needed to achieve negative surgical margins.
However, learning from the limitations of the COMICE trial, we have outlined very clear guidelines as to how findings on breast MRI are to be interpreted and acted upon. Furthermore, this trial will attempt to measure the costs and cost-effectiveness of preoperative breast MRI. Because clinical trials must be designed with sample size and accrual feasibility in mind, it may be that small differences between trial arms fall below the preset threshold for significance. However, it’s possible that such small, statistically insignificant differences, either in the local recurrence or re-excision rates, may still be sufficient to make preoperative MRI a cost-effective strategy and thus warranted for routine use in the clinic. Therefore, by including a cost-effectiveness analysis, this trial will provide a comprehensive assessment of both the oncologic and economic effects of breast MRI.
- Houssami N, Ciatto S, Macaskill P, Lord SJ, Warren RM, Dixon JM, Irwig L. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: Systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol. 2008;26(19):3248-3258.
- Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, Peacock S, Smazal SF, Maki DD, Julian TB, DePeri ER, Bluemke DA, Schnall MD. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;356(13):1295-1303.
- Turnbull L, Brown S, Harvey I, Olivier C, Drew P, Napp V, Hanby A, Brown J. Comparative effectiveness of MRI in breast cancer (COMICE) trial: A randomised controlled trial. Lancet. 2010;375(9714):563-571.
- Solin LJ, Orel SG, Hwang WT, Harris EE, Schnall MD. 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(3):386-391.
- Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373-2378.
- Dominici LS, Mittendorf EA, Wang X, Liu J, Kuerer HM, Hunt KK, Brewster A, Babiera GV, Buchholz TA, Meric-Bernstam F, Bedrosian I. Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy. Breast Cancer Res. 2012;14(3):R82.
- Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: The Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26(9):1419-1426.