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In Reply

Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA

Susan G. Orel, Mitchell D. Schnall

Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA

Wei-Ting Hwang

Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA

Eleanor E. Harris

Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL

We appreciate the thoughtful letter by Peters et al regarding our recent publication in Journal of Clinical Oncology.¹ We offer some comments in response.

To our knowledge, no randomized clinical trial, published or ongoing, evaluates the value of a pretreatment breast magnetic resonance imaging (MRI) study relative to outcomes after breast conservation treatment (BCT), with or without radiation, for patients with early-stage breast cancer. By outcomes, we here refer to those end points typically reported in clinical trials, for example, local failure, survival, and contralateral breast cancer. With the exception of a small number of patients reported by Fischer et al,² ours is the only clinical study to report such outcomes after BCT.

Peters et al make an apples-to-oranges comparison of what constitutes outcomes in reported studies. In our study, we analyzed 8-year outcomes after BCT.¹ The randomized study described by Peters et al evaluates the number of biopsies and surgical procedures performed as the primary study end point.³ However, analysis in that study is planned neither for outcome after treatment nor for cost effectiveness. Preliminary results from the first patients enrolled in that study showed that 38% of patients (66 of 174) were not able to participate in the protocol study for various reasons, and that only 35% of the biopsies (40 of 113) obtained showed invasive or noninvasive carcinoma. Thus, relatively few patients in that study will have a pathologically confirmed breast malignancy. A British randomized trial of 1,850 patients will evaluate the impact of MRI on the selection of patients for BCT and the adequacy of breast conservation surgery.^4-5 That breast MRI can have an impact on surgical management and treatment decision making at the time of initial diagnosis of breast carcinoma has already been reported, albeit in retrospective studies.^6-8

In the original report, we openly acknowledged that our study was retrospective and from a single institution. Patient, tumor, and treatment characteristics were detailed in the original study, including some imbalances between the two groups. For example, compared to the patients without a breast MRI, the patients with a breast MRI were slightly younger (median age, 53 v 56 years, respectively), suggesting higher risk and more dense breast tissue on mammography. However, the patients with a breast MRI study were more commonly pathologically node negative (88% v 79%, respectively), although this difference did not achieve statistical significance (P = .071). No differences were seen between the two groups for the 8-year rates of any local failure, local only first failure, contralateral breast cancer, freedom from distant metastases, overall survival, and cause-specific survival (all P .16). A multivariate analysis was performed to control for imbalances between the two groups, and there continued to be no differences (all P .19). No differences in local failure were seen for the patients with invasive carcinoma (P = .62) or ductal carcinoma in situ (P = .58). If only the 54% of patients (117 of 215) with a preoperative MRI study had been analyzed, the power to detect any potential difference between the groups would have been substantially reduced.

The importance of randomized clinical trials is not in dispute. The value of local modalities, including local imaging studies and local treatments, can be and has been measured relative to clinical outcomes in randomized clinical trials. For example, the value of mammography in reducing breast cancer mortality has been demonstrated and measured in such randomized trials. Similarly, the direct relationship of local control to breast cancer mortality has also been demonstrated and measured.

In our view, a truly definitive study to test the value of breast MRI would randomly assign patients with early-stage breast cancer to standard mammography versus the same plus breast MRI, and then measure long-term outcomes. The primary end point of such a hypothetical randomized study would be local failure, and secondary end points would include such outcomes as contralateral breast cancer and survival, as well as surgical management at the time of initial treatment. Obstacles to performing such a study potentially would include the enormous numbers of patients required to test for any small difference between the two groups, standardization of obtaining and reading the breast MRI studies, and management of any MRI findings in the ipsilateral and contralateral breasts. However, a truly definitive randomized study of the value of breast MRI appears to be difficult, if not impossible, to perform, especially given the findings in our study.

We believe that our study contains valuable information for treating patients with newly diagnosed early-stage invasive breast carcinoma or ductal carcinoma in situ, especially given that there are currently no reported randomized trial data, and given that no such randomized data will be reported in the near future. Hopefully, our study will encourage other investigators with large clinical experiences in using breast MRI to review and report their outcome data.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: Mitchell D. Schnall, Berlex (C) Stock Ownership: None Honoraria: Mitchell D. Schnall, Berlex, Siemens Research Funding: Mitchell D. Schnall, Siemens Expert Testimony: None Other Remuneration: None

REFERENCES

1. Solin LJ, Orel SG, Hwang W-T, 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 26:386-391, 2008[Abstract/Free Full Text]

2. Fischer U, Zachariae O, Baum F, et al: The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol 14:1725-1731, 2004[Medline]

3. Peters NHGM, Borel Rinkes IHM, Mali WPTM, et al: Breast MRI in nonpalpable breast lesions: A randomized trial with diagnostic and therapeutic outcome –MONET –study. Trials 8:40, 2007[CrossRef][Medline]

4. Turnbull LW, Barker S, Liney GP: Comparative effectiveness of magnetic resonance imaging in breast cancer (COMICE trial). Breast Cancer Res 4:39, 2002 (suppl 1; abstr)[CrossRef]

5. Dodwell D, Horgan K: Locoregional treatment for breast cancer. BMJ 327:1062-1063, 2003[Free Full Text]

6. Tillman GF, Orel SG, Schnall MD, et al: Effect of breast magnetic resonance imaging on the clinical management of women with early-stage breast carcinoma. J Clin Oncol 20:3413-3423, 2002[Abstract/Free Full Text]

7. Tan JE, Orel SG, Schnall MD, et al: Role of magnetic resonance imaging and magnetic resonance imaging-guided surgery in the evaluation of patients with early-stage breast cancer for breast conservation treatment. Am J Clin Oncol 22:414-418, 1999[CrossRef][Medline]

8. 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 98:468-473, 2003[CrossRef][Medline]

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