Review Article
Magnetic Resonance Imaging in Patients With Newly Diagnosed Breast Cancer A Review of the Literature Melissa Pilewskie, MD; and Tari A. King, MD
The use of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer remains controversial. Here we review the current use of breast MRI and the impact of MRI on short-term surgical outcomes and rates of local recurrence. In addition, we address the use of MRI in specific patient populations, such as those with ductal carcinoma in situ, invasive lobular carcinoma, and occult primary breast cancer, and discuss the potential role of MRI for assessing response to neoadjuvant chemotherapy. Although MRI has improved sensitivity compared with conventional imaging, this has not translated into improved short-term surgical outcomes or long-term patient benefit, such as improved local control or survival, in any patient population. MRI is an important diagnostic test in the evaluation of patients presenting with occult primary breast cancer and has shown promise in monitoring response to neoadjuvant chemotherapy; however, the data do not support the routine use of perioperative MRI in patients with newly diagnosed C 2014 American Cancer Society. breast cancer. Cancer 2014;120:2080–9. V KEYWORDS: magnetic resonance imaging (MRI), breast cancer, breast-conserving surgery, local recurrence.
INTRODUCTION The use of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer requires balancing the positive and negative aspects of additional imaging and, as evidenced by the growing number of editorials and reviews arguing for or against the routine use of MRI,1-8 remains an area of significant controversy. This debate has been fueled by inconsistent data largely comprised of small, single-institution retrospective studies, although 2 randomized controlled trials (RCTs) and several meta-analyses have provided more robust data evaluating MRI in the perioperative setting. The “pros” of perioperative MRI include improved sensitivity compared with conventional imaging and therefore increased identification of multifocal, multicentric, or contralateral disease. With improved sensitivity comes a theoretical improvement in short-term surgical management and/or long-term outcomes. The “cons” of perioperative MRI include the high falsepositive rate, potential treatment delays, increased mastectomy rates and cost, and, some argue, overdiagnosis and overtreatment of MRI-only detected disease. Here we review the relevant data regarding MRI use in patients with newly diagnosed breast cancer, examining both the short-term and long-term outcomes, MRI use in populations of women with ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), MRI’s role in patients presenting with occult primary breast cancer, and MRI’s ability to evaluate neoadjuvant chemotherapy (NAC) response. Current MRI Use
In contrast to the well-established guidelines for MRI screening in patients with an inherited predisposition to breast cancer,9 to our knowledge, there are no guidelines for MRI use in patients with newly diagnosed breast cancer; nevertheless, a report from Western Washington State’s Surveillance, Epidemiology, and End Results (SEER) registry demonstrated that 27% of 9196 women with breast cancer underwent MRI for staging or treatment planning between 2002 and 2009,10 and by 2009, 46% of women underwent perioperative breast MRI. MRI use varied significantly based on age, with 45% of women aged 18 years to 40 years undergoing an MRI compared with 10% of those aged 81 years (P < .001). Patients were also more likely to undergo MRI if they had commercial health care plans, lived in an urban area, lacked medical
Corresponding author: Tari A. King, MD, Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY 10065; Fax: (646) 888-4921; [email protected] Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York DOI: 10.1002/cncr.28700, Received: December 6, 2013; Revised: February 21, 2014; Accepted: March 14, 2014, Published online April 18, 2014 in Wiley Online Library (wileyonlinelibrary.com)
2080
Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
comorbidities, or had stage I to III breast cancer, lobular histology, or hormone receptor-negative tumors. The association between MRI use, young patient age, and hormone receptor-negative cancer may be attributable to the presence of known or suspected BRCA mutation carriers in the population; however, this information is not available in the SEER registry. Breslin et al reported an even higher rate of use of advanced imaging, with 53% of patients with non-stage IV breast cancer aged < 65 years undergoing breast MRI in 2008. In this cohort of 52,202 women, MRI use increased annually from 2005 to 2008 for women with both invasive and in situ carcinoma.11 Studies examining MRI use in older patients have reported an overall MRI receipt rate of 7% to 10% among women aged 65 years,12-14 with significant variation based on geographic location and chronologic year (P < .01). Wang et al found that by 2007, 27% of women in the SEER-Medicare database with stage 0 to II breast cancer had undergone a perioperative MRI13 and, as in younger patients, preoperative MRI was found to increase mastectomy rates among older patients,14 many of whom likely would have been good candidates for breastconserving surgery (BCS) and anti-estrogen therapy alone.15 A survey sent to the membership of the American Society of Breast Surgeons in 2010 sought to evaluate indications and practice patterns for MRI use among treating physicians. Of 1034 respondents, 41% reported routinely (> 75% of the time) recommending breast MRI to patients with newly diagnosed breast cancer.16 Variation in the recommendation for MRI was noted with respect to both physician and patient factors, with academic surgeons less likely to obtain an MRI compared with private practice surgeons (P 5 .01). Routine recommendation for MRI was more frequent for women with a strong family history of breast cancer (73%), those with ILC (69%), in women undergoing BCS (47%), and in those with increased mammographic breast density (88%). Although physician perception is that MRI is particularly beneficial in the setting of dense breast tissue, studies have demonstrated no significant difference in the diagnostic yield, sensitivity, or negative predictive value of MRI according to breast density.17 Similarly, studies examining the value of MRI in women with lobular cancers have generated conflicting results. MRI for Treatment Selection
The increased sensitivity of MRI for the detection of multifocal or multicentric disease has been widely reported and summarized in a meta-analysis by Houssami et al,18 Cancer
July 15, 2014
which included 2610 patients with breast cancer who underwent perioperative MRI in addition to conventional imaging. MRI identified additional disease in 16% of patients (range, 6%-34% in individual studies), resulting in a change from wide local excision to mastectomy in 8.1% of women (95% confidence interval [CI], 5.9%11.3%) and a larger local excision in 11.3% of women (95% CI, 6.8%-18.3%). A more recent meta-analysis by Plana et al included 10,811 women from 50 studies and found very similar results, with additional lesions identified by MRI in 20% of cases (range, 6%-71%).19 Although data consistently demonstrate an increased detection rate of multifocal and multicentric disease, to our knowledge, there are few data demonstrating improved outcomes based on the treatment of MRI-only detected disease. Therefore, the value of MRI in selecting local therapy remains elusive. MRI and Short-Term Surgical Outcomes
Proponents of breast MRI argue that MRI better characterizes tumor extent and, as such, should improve surgical planning and decrease the rate of positive surgical resection margins and, therefore, the need for re-excision. However, studies have demonstrated significant variability in tumor size estimation by MRI, with underestimation reported in 8% to 59% of cases and overestimation in 11% to 70% of cases.20-24 Two prospective RCTs evaluated the effect of MRI on re-operation rates (both re-excision and conversion to mastectomy) in patients deemed appropriate for BCS.25,26 The COMICE (Comparative Effectiveness of MRI in Breast Cancer) trial multicenter collaboration included 1625 women randomized to either perioperative MRI or no additional imaging between 2002 and 2007. There was no difference noted with regard to the primary endpoint of re-operation rate, which was 19% in both the MRI and the no-MRI groups (odds ratio [OR], 0.96; 95% CI, 0.75-1.24 [P 5 .77]), despite the finding that 5 times as many patients in the MRI group (n 5 58) converted to mastectomy before an initial attempt at BCS compared with the no-MRI group (n 5 10). Among those who underwent an initial mastectomy in the MRI group, in 28% of patients (16 of 58 patients) it was considered pathologically unnecessary.26 Similarly, the MONET (MR mammography of non-palpable breast tumours) trial randomized 418 women with nonpalpable lesions, classified as Breast Imaging Reporting and Data System (BI-RADS) 3 to BIRADS 5 and detected on mammogram or ultrasound, to biopsy or the addition of MRI before biopsy. In total, 163 2081
Review Article TABLE 1. Summary of the Literature Evaluating the Impact of MRI on IBTR Rates
Reference
Patients With MRI/Total No. of Patients
Variables Controlled For on MV Analysis
Follow-Up, Years
IBTR Rates: MRI
IBTR Rates: No MRI
P
3.4 8.0 8.0
1.2% 3.0% 1.8%
6.5% 4.0% 2.5%
90% of cases,31 serial sectioning of mastectomy specimens demonstrates that 21% to 63% of clinically and mammographically detected unicentric tumors are actually multifocal or multicentric.32-38 As such, a large percentage of patients treated with BCS will have microscopic residual disease in the breast, yet multiple prospective RCTs and the updated Early Breast Cancer Trialists’ Collaborative Group overview continue to demonstrate equivalent survival between patients undergoing BCS and mastectomy,39-41 and IBTR rates have substantially decreased over time.42,43 To the best of our knowledge, the only randomized controlled data evaluating the impact of MRI on recurrence rates come from short-term follow-up in the COMICE trial, in which rates of local recurrence (LR) were assessed as a secondary endpoint. At 3 years, local recurrence-free interval rates of 94% and 96% were reported for the MRI and no-MRI groups, respectively.44 Several retrospective single-institution series have compared LR outcomes in women imaged with and without MRI (Table 1).45-50 Only the study by Fischer et al45 reported a lower IBTR rate in women undergoing MRI. This study compared 121 patients with breast cancer who underwent a perioperative MRI with 225 patients who did not. At a mean follow-up of 40 months, the MRI group had an IBTR rate of 1.2% compared with 6.5% in Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
TABLE 2. Summary of the Literature Evaluating the Impact of MRI on the Development of CBC Reference
Patients With MRI/ Total No. of Patients
Follow-Up, Years
CBC Rates: MRI
CBC Rates: No MRI
P
121/346 (35%) 215/756 (28%) 1771/3094 (57%)a 229/615 (37%)
3.4 8.0 3.8 5.7
1.7% 6.0% 0.5% 2.2%
4.0% 6.0% 1.4% 1.3%
3 years) and because statistical adjustments were not performed to control for differences between both groups. The MRI group had a higher percentage of small (T1) lymph node-negative tumors and fewer high-grade lesions, and, paradoxically, a higher percentage of patients in the MRI group received chemotherapy, all of which may have impacted IBTR rates. The 5 subsequent studies shown in Table 1 failed to find a significant improvement in IBTR rates with the addition of MRI when controlling for patient and tumor factors, and all reported low (0.4%5.0%) rates of IBTR at 2 to 8 years of follow-up.46-50 A recent individual-person data meta-analysis including 3169 women from 4 of the above-mentioned trials reported no difference in 8-year LR-free survival (97% for the MRI group vs 95% in the no-MRI group; P 5 .87) or 8-year distant recurrence-free survival (89% in the MRI group and 93% in the no-MRI group; P 5 .37). On multivariable analysis, there was no association noted between perioperative MRI and LR-free survival (hazard ratio for MRI vs no-MRI, 0.88; 95% CI, 0.52-1.51 [P 5 .65]).51 The recognition that IBTR rates differ by breast cancer subtype and, notably, the significantly higher LR rates reported among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-amplified breast cancers in the pre-trastuzumab era,52,53 combined with ongoing controversy regarding the theoretic advantages of perioperative MRI, have led to an RCT supported by the American College of Radiology Imaging Network and the Alliance for Clinical Trials in Oncology. The objective of the trial is to assess the impact of MRI on reoperation rates, LR, quality of life, and cost-effectiveness in women with triple-negative and HER2-amplified breast cancer. Although this study may provide useful information in the cohort of patients with triple-negative breast cancer, the RCTs of adjuvant trastuzumab demonstrated significantly lower IBTR rates with the addition of trastuzumab,54 and the low IBTR and CBC rates noted Cancer
July 15, 2014
among patients with HER2-amplified cancers in more modern series will likely limit the impact of MRI among patients with HER2-amplified cancer.55,56 MRI and Long-Term Outcomes: CBC
MRI has the potential to decrease metachronous CBC rates through the identification of otherwise occult contralateral disease. Table 2 summarizes 4 retrospective studies that have compared rates of metachronous CBC in women imaged with and without MRI at the time of their index breast cancer diagnosis.45,46,49,57 Criticisms of the study by Fischer et al45 have been mentioned previously. Overall, CBC development rates were low (0.5%-6.0%) in both groups. It is important to note that the 2 studies reporting a significant difference in CBC rates both found an absolute difference of 1% to 2% in the MRI and no-MRI groups.45,57 A meta-analysis by Brennan et al58 evaluating the rate of CBC detection by MRI among 3253 women presenting with unilateral cancer reported that 4.1% of patients were diagnosed with a synchronous CBC based on MRI. In comparison, a SEER population-based study from 1973 to 1996 reported the actuarial 10-year risk of metachronous CBC in women treated for unilateral stage 0 to stage II breast cancer to be 6.1%,59 and more recent studies have demonstrated that CBC incidence has been decreasing by approximately 3% per year since 1985.60 Together, these data suggest that either a single MRI at the time of breast cancer diagnosis will identify the majority of breast cancers that will develop over time or, conversely, that many MRI-detected contralateral cancers will be adequately treated as a by-product of appropriate systemic therapy for the index cancer and would remain clinically irrelevant.39 MRI and Long-Term Outcomes: Survival
The Early Breast Cancer Trialists’ Collaborative Group overview established that there is an important relationship between local control and survival in patients with breast cancer; however, as systemic therapies continue to improve, substantially larger differences in local control 2083
Review Article TABLE 3. Summary of the Literature Evaluating the Impact of MRI on Surgical Outcomes in Patients With DCIS
Reference Allen 201061 Itakura 201162 Kropcho 201263 Davis 201265 Pilewskie 201364
Patients With MRI/Total No. of Patients
Re-excision Rate: MRI
Re-excision rate: No MRI
P
Mastectomy Rate: MRI
Mastectomy Rate: No MRI
P
63/98 (64%) 38/149 (26%) 60/158 (38%) 154/218 (71%) 217/352 (62%)
21.2% 16.0% 30.7% 34.1% 14.3%
30.8% 11.0% 24.7% 39.2% 20.0%
.41 .42 .40 .52 .19
20.3%a 45.0%b 17.7%c 27.9%a 34.6%b
25.7%a 14.0%b 4.1%c 23.4%a 27.4%b
.62 67% of cases.72 A negative MRI also provides reassurance that a large tumor burden is unlikely and that the patient may be safely treated with axillary lymph node dissection, whole-breast radiotherapy, and appropriate systemic therapy. In a meta-analysis of 8 retrospective studies,72 which included 220 women with occult primary breast cancer, MRI identified a suspicious breast lesion in 72% of cases, with a sensitivity of 90% and a specificity of 31%. The mean pathologic tumor size ranged from 5 mm to 16 mm, and > 90% were invasive carcinomas. When MRI identified an occult breast lesion in patients without metastatic disease, 21% to 60% of patients were able to undergo successful BCS. MRI for Problem Solving
Similar to patients with an occult primary breast cancer, women with Paget disease or abnormal physical examination findings and negative conventional imaging may benefit from the addition of MRI for disease localization. Paget disease, which is characterized by nipple erythema, erosion, or ulceration caused by epidermal infiltration of malignant cells, is associated with an underlying breast malignancy in > 90% of cases, yet mammographic imaging may be normal in up to 50% of patients.73 Morrogh et al74 reviewed imaging and pathology data on 34 women with Paget disease who were treated at a single institution and 94% were found to have an underlying carcinoma. Mammography detected the underlying malignancy in 22% of cases, and supplemental MRI performed among 8 women with a negative mammogram demonstrated the underlying malignancy in 4 cases (50%). MRI Imaging in the NAC Setting
NAC is being used with increasing enthusiasm to convert patients requiring an upfront mastectomy to BCS as well as to assess the impact of treatment on rates of Cancer
July 15, 2014
pathologic complete response (pCR).75 Multiple studies have evaluated the ability of MRI to predict response to NAC. In the American College of Radiology Imaging Network 6657 study, part of the I-SPY 1 trial, MRI was obtained at 4 time points: before the initiation of chemotherapy, after the first cycle, between the anthracycline-based regimen and taxane therapies, and at the conclusion of NAC before surgery. Compared with clinical examination, MRI was found to be a stronger predictor of both pCR and residual cancer burden, with tumor volume change measured at the time of the second MRI being the strongest predictor.76 However, from a clinical standpoint, the comparison of MRI with physical examination is not particularly relevant, and a more practical comparison is that between MRI and conventional breast imaging. A meta-analysis of 2050 women from 44 NAC studies conducted between 1980 and 2008 reported that MRI correctly identified residual disease with a median sensitivity of 0.92. However, the ability of MRI to correctly identify patients who achieved a pCR in the current analysis was limited, with a median specificity of 0.60, and, expectedly, the accuracy of MRI for predicting pCR varied based on the pCR definition used. MRI was found to have a higher accuracy than mammography (P 5 .02), but no difference was noted between MRI and ultrasound accuracy for the identification of a pCR (P 5 .15).77 Similarly, a multicenter retrospective collaboration from the Translational Breast Cancer Research Consortium (TBCRC 017), which included 746 patients treated from 2002 through 2011, reported an overall accuracy rate of 74% of MRI for predicting a pCR. Given this study’s more recent timeframe, information regarding hormone receptor and HER2 status was available, and the authors demonstrated that MRI had the highest negative predictive value in patients with triple-negative and HER2-amplified tumors (60% and 62%, respectively).78 2085
Review Article
Figure 1. MRI assessment of neoadjuvant chemotherapy response. Images courtesy of Dr. Elizabeth Morris, Memorial Sloan Kettering Cancer Center.
Although prediction of pCR is an important endpoint for therapeutic monitoring, it is not an absolute endpoint for the ability to perform lesser surgery as women with a partial response may still be good candidates for conversion to BCS after NAC. Data from the ISPY 1 trial were analyzed to assess a “clinically meaningful tumor reduction,” defined as a change in tumor size from > 4 cm to 4 cm after NAC, as a surrogate for patients who may become candidates for BCS. Of 174 women with an initial tumor size of > 4 cm, 81% had a pathologic tumor size of 4 cm after NAC, 37% of 2086
whom were successfully treated with BCS. In 38% of the total study population, there was a discrepancy of 2 cm between post-NAC MRI measurements and final pathologic tumor size. In this study, MRI accuracy also was found to differ by tumor pattern and receptor subtype, with improved performance noted among patients with breast cancer subtypes that are known to have higher pCR rates.79 A meta-analysis by Marinovich et al compared the agreement in tumor size between different imaging modalities and final pathology after NAC in 958 patients from 19 studies.80 MRI and ultrasound were found to Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
have similar overestimations of tumor size (mean differences of 0.1 cm), whereas MRI had a lower overestimation of tumor size than mammography (mean difference of 0.4 cm). Although the pooled mean difference between MRI and final pathology was 0.1 cm, the 95% limits of agreement ranged from 24.2 cm to 4.4 cm, which is a clinically significant margin of error when planning surgical therapy.80 The wide margin of error in MRI estimations of post-NAC tumor response and size is likely related to both tumor subtype and treatment regimen, and requires further investigation. Important unanswered questions relate to the ability to predict successful BCS after NAC, which likely relates to the pattern of tumor response (concentric vs multicentric) (Figure 1). Given the increased cost of MRI, a direct comparison of MRI with conventional imaging in this setting may be prudent. Although the use of MRI for planning BCS after NAC is an area of future research, if a patient is known upfront to require mastectomy after NAC, such as individuals with extensive multicentric or inflammatory disease, post-treatment MRI is not indicated. Conclusions
The available literature does not appear to support the routine use of MRI for the evaluation of patients with newly diagnosed breast cancer. Data from RCTs and several retrospective series have failed to demonstrate an improvement in short-term surgical outcomes, and studies have consistently demonstrated increasing mastectomy rates with the addition of MRI. Data supporting improved long-term outcomes with the addition of perioperative breast MRI, including IBTR, CBC development, and survival, are also lacking. Multiple series demonstrating increasing trends in MRI use without a benefit in surgical or long-term outcomes require a reevaluation of practice patterns. Although there are clinical situations in which MRI can provide valuable information, such as in patients with occult primary breast cancer and, potentially, in monitoring response to NAC, the increasing costs of advanced imaging in patients with cancer81 highlight the need for clinicians to critically evaluate the literature and focus on spending health care dollars in an evidence-based manner. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
Cancer
July 15, 2014
REFERENCES 1. Hede K. Preoperative MRI in breast cancer grows contentious. J Natl Cancer Inst. 2009;101:1667-1669. 2. Solin LJ. Counterview: Pre-operative breast MRI (magnetic resonance imaging) is not recommended for all patients with newly diagnosed breast cancer. Breast. 2010;19:7-9. 3. Morrow M. Magnetic resonance imaging for screening, diagnosis, and eligibility for breast-conserving surgery: promises and pitfalls. Surg Oncol Clin N Am. 2010;19:475-492. 4. Sardanelli F. Overview of the role of pre-operative breast MRI in the absence of evidence on patient outcomes. Breast. 2010;19:3-6. 5. Brasic N, Wisner DJ, Joe BN. Breast MR imaging for extent of disease assessment in patients with newly diagnosed breast cancer. Magn Reson Imaging Clin N Am. 2013;21:519-532. 6. McLaughlin S, Mittendorf EA, Bleicher RJ, McCready DR, King TA. The 2013 Society of Surgical Oncology Susan G. Komen for the Cure Symposium: MRI in breast cancer: where are we now? Ann Surg Oncol. 2014;21:28-36. 7. Jatoi I, Benson JR. The case against routine preoperative breast MRI. Future Oncol. 2013;9:347-353. 8. Houssami N, Morrow M. Pre-operative breast MRI in women with recently diagnosed breast cancer–where to next? Breast. 2010; 19:1-2. 9. Mainiero MB, Lourenco A, Mahoney MC, et al. ACR Appropriateness Criteria Breast Cancer Screening. J Am Coll Radiol. 2013;10: 11-14. 10. Gold LS, Buist DS, Loggers ET, et al. Advanced diagnostic breast cancer imaging: variation and patterns of care in Washington state. J Oncol Pract. 2013;9:e194-e202. 11. Breslin TM, Banerjee M, Gust C, Birkmeyer NJ. Trends in advanced imaging use for women undergoing breast cancer surgery. Cancer. 2013;119:1251-1256. 12. Sommer CA, Stitzenberg KB, Tolleson-Rinehart S, Carpenter WR, Carey TS. Breast MRI utilization in older patients with newly diagnosed breast cancer. J Surg Res. 2011;170:77-83. 13. Wang SY, Virnig BA, Tuttle TM, Jacobs DR Jr, Kuntz KM, Kane RL. Variability of preoperative breast MRI utilization among older women with newly diagnosed early-stage breast cancer. Breast J. 2013;19:627-636. 14. Killelea BK, Long JB, Chagpar AB, et al. Trends and clinical implications of preoperative breast MRI in Medicare beneficiaries with breast cancer. Breast Cancer Res Treat. 2013;141:155-163. 15. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382-2387. 16. Parker A, Schroen AT, Brenin DR. MRI utilization in newly diagnosed breast cancer: a survey of practicing surgeons. Ann Surg Oncol. 2013;20:2600-2606. 17. 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. 18. Houssami N, Ciatto S, Macaskill P, et al. 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;26:3248-3258. 19. Plana MN, Carreira C, Muriel A, et al. Magnetic resonance imaging in the preoperative assessment of patients with primary breast cancer: systematic review of diagnostic accuracy and meta-analysis. Eur Radiol. 2012;22:26-38. 20. Boetes C, Veltman J, van Die L, Bult P, Wobbes T, Barentsz JO. The role of MRI in invasive lobular carcinoma. Breast Cancer Res Treat. 2004;86:31-37. 21. Onesti JK, Mangus BE, Helmer SD, Osland JS. Breast cancer tumor size: correlation between magnetic resonance imaging and pathology measurements. Am J Surg. 2008;196:844-848; discussion 849-850. 22. Behjatnia B, Sim J, Bassett LW, Moatamed NA, Apple SK. Does size matter? Comparison study between MRI, gross, and microscopic tumor sizes in breast cancer in lumpectomy specimens. Int J Clin Exp Pathol. 2010;3:303-309.
2087
Review Article 23. Kim Do Y, Moon WK, Cho N, et al. MRI of the breast for the detection and assessment of the size of ductal carcinoma in situ. Korean J Radiol. 2007;8:32-39. 24. Muttalib M, Ibrahem R, Khashan AS, Hajaj M. Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management. Clin Radiol. 2014;69:23-28. 25. Peters NH, van Esser S, van den Bosch MA, et al. Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET-randomised controlled trial. Eur J Cancer. 2011;47:879-886. 26. Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet. 2010;375:563-571. 27. Houssami N, Turner R, Morrow M. Preoperative magnetic resonance imaging in breast cancer: meta-analysis of surgical outcomes. Ann Surg. 2013;257:249-255. 28. King TA, Sakr R, Patil S, et al. Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol. 2011;29:2158-2164. 29. Sorbero ME, Dick AW, Beckjord EB, Ahrendt G. Diagnostic breast magnetic resonance imaging and contralateral prophylactic mastectomy. Ann Surg Oncol. 2009;16:1597-1605. 30. Chung A, Huynh K, Lawrence C, Sim MS, Giuliano A. Comparison of patient characteristics and outcomes of contralateral prophylactic mastectomy and unilateral total mastectomy in breast cancer patients. Ann Surg Oncol. 2012;19:2600-2606. 31. Morrow M, Bucci C, Rademaker A. Medical contraindications are not a major factor in the underutilization of breast conserving therapy. J Am Coll Surg. 1998;186:269-274. 32. Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985;56:979-990. 33. Anastassiades O, Iakovou E, Stavridou N, Gogas J, Karameris A. Multicentricity in breast cancer. A study of 366 cases. Am J Clin Pathol. 1993;99:238-243. 34. Egan RL. Multicentric breast carcinomas: clinical-radiographicpathologic whole organ studies and 10-year survival. Cancer. 1982; 49:1123-1130. 35. Lagios MD. Multicentricity of breast carcinoma demonstrated by routine correlated serial subgross and radiographic examination. Cancer. 1977;40:1726-1734. 36. Qualheim RE, Gall EA. Breast carcinoma with multiple sites of origin. Cancer. 1957;10:460-468. 37. Rosen PP, Fracchia AA, Urban JA, Schottenfeld D, Robbins GF. “Residual” mammary carcinoma following simulated partial mastectomy. Cancer. 1975;35:739-747. 38. Schwartz GF, Patchesfsky AS, Feig SA, Shaber GS, Schwartz AB. Multicentricity of non-palpable breast cancer. Cancer. 1980;45:29132916. 39. Clarke M, Collins R, Darby S, et al; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087-2106. 40. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241. 41. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347: 1227-1232. 42. Pass H, Vicini FA, Kestin LL, et al. Changes in management techniques and patterns of disease recurrence over time in patients with breast carcinoma treated with breast-conserving therapy at a single institution. Cancer. 2004;101:713-720. 43. Ernst MF, Voogd AC, Coebergh JW, Poortmans PM, Roukema JA. Using loco-regional recurrence as an indicator of the quality of breast cancer treatment. Eur J Cancer. 2004;40:487-493. 44. Turnbull LW, Brown SR, Olivier C, et al; COMICE Trial Group. Multicentre randomised controlled trial examining the cost-
2088
45.
46.
47.
48. 49.
50. 51. 52.
53.
54.
55. 56.
57. 58.
59.
60.
61. 62.
effectiveness of contrast-enhanced high field magnetic resonance imaging in women with primary breast cancer scheduled for wide local excision (COMICE). Health Technol Assess. 2010;14:1-182. Fischer U, Zachariae O, Baum F, von Heyden D, Funke M, Liersch T. The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol. 2004;14: 1725-1731. Solin LJ, Orel SG, Hwang WT, Harris EE, Schnall MD. Relationship of breast magnetic resonance imaging to outcome after breastconservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol. 2008;26:386-391. Hwang N, Schiller DE, Crystal P, Maki E, McCready DR. Magnetic resonance imaging in the planning of initial lumpectomy for invasive breast carcinoma: its effect on ipsilateral breast tumor recurrence after breast-conservation therapy. Ann Surg Oncol. 2009;16: 3000-3009. Shin HC, Han W, Moon HG, et al. Limited value and utility of breast MRI in patients undergoing breast-conserving cancer surgery. Ann Surg Oncol. 2012;19:2572-2579. Ko ES, Han BK, Kim RB, et al. Analysis of the effect of breast magnetic resonance imaging on the outcome in women undergoing breast conservation surgery with radiation therapy. J Surg Oncol. 2013;107:815-821. Miller BT, Abbott AM, Tuttle TM. The influence of preoperative MRI on breast cancer treatment. Ann Surg Oncol. 2012;19: 536-540. Houssami N, Turner R, Macaskill P, et al. An individual person data meta-analysis of preoperative magnetic resonance imaging and breast cancer recurrence. J Clin Oncol. 2014;32:392-401. Metzger-Filho O, Sun Z, Viale G, et al. Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from International Breast Cancer Study Group trials VIII and IX. J Clin Oncol. 2013;31:3083-3090. Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133: 831-841. Dahabreh IJ, Linardou H, Siannis F, Fountzilas G, Murray S. Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist. 2008;13:620-630. McArthur HL, Mahoney KM, Morris PG, et al. Adjuvant trastuzumab with chemotherapy is effective in women with small, nodenegative, HER2-positive breast cancer. Cancer. 2011;117:5461-5468. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236-244. Kim JY, Cho N, Koo HR, et al. Unilateral breast cancer: screening of contralateral breast by using preoperative MR imaging reduces incidence of metachronous cancer. Radiology. 2013;267:57-66. Brennan ME, Houssami N, Lord S, et al. Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: systematic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol. 2009;27:5640-5649. Gao X, Fisher SG, Emami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2003;56:10381045. Nichols HB, Berrington de Gonzalez A, Lacey JV Jr, Rosenberg PS, Anderson WF. Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol. 2011;29:15641569. Allen LR, Lago-Toro CE, Hughes JH, et al. Is there a role for MRI in the preoperative assessment of patients with DCIS? Ann Surg Oncol. 2010;17:2395-2400. Itakura K, Lessing J, Sakata T, et al. The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ. Clin Breast Cancer. 2011;11:33-38.
Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
63. Kropcho LC, Steen ST, Chung AP, Sim MS, Kirsch DL, Giuliano AE. Preoperative breast MRI in the surgical treatment of ductal carcinoma in situ. Breast J. 2012;18:151-156. 64. Pilewskie M, Kennedy C, Shappell C, et al. Effect of MRI on the management of ductal carcinoma in situ of the breast. Ann Surg Oncol. 2013;20:1522-1529. 65. Davis KL, Barth RJ Jr, Gui J, Dann E, Eisenberg B, Rosenkranz K. Use of MRI in preoperative planning for women with newly diagnosed DCIS: risk or benefit? Ann Surg Oncol. 2012;19:32703274. 66. Pilewskie M, Olcese C, Eaton A, et al. Perioperative breast MRI is not associated with lower locoregional recurrence rates in DCIS patients treated with or without radiation [published online ahead of print January 3, 2014]. Ann Surg Oncol. 67. Mann RM, Hoogeveen YL, Blickman JG, Boetes C. MRI compared to conventional diagnostic work-up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature. Breast Cancer Res Treat. 2008;107:1-14. 68. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat. 2010;119:415-422. 69. Heil J, Buhler A, Golatta M, et al. Does a supplementary preoperative breast MRI in patients with invasive lobular breast cancer change primary and secondary surgical interventions? Ann Surg Oncol. 2011;18:2143-2149. 70. McGhan LJ, Wasif N, Gray RJ, et al. Use of preoperative magnetic resonance imaging for invasive lobular cancer: good, better, but maybe not the best? Ann Surg Oncol. 2010;17(suppl 3):255-262. 71. Walker GV, Smith GL, Perkins GH, et al. Population-based analysis of occult primary breast cancer with axillary lymph node metastasis. Cancer. 2010;116:4000-4006. 72. de Bresser J, de Vos B, van der Ent F, Hulsewe K. Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg Oncol. 2010;36:114-119.
Cancer
July 15, 2014
73. Lim HS, Jeong SJ, Lee JS, et al. Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation. Radiographics. 2011;31:1973-1987. 74. Morrogh M, Morris EA, Liberman L, Van Zee K, Cody HS 3rd, King TA. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple. J Am Coll Surg. 2008;206:316-321. 75. Kaufmann M, von Minckwitz G, Smith R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol. 2003;21:2600-2608. 76. Hylton NM, Blume JD, Bernreuter WK, et al; ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy–results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663-672. 77. Marinovich ML, Houssami N, Macaskill P, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst. 2013;105:321-333. 78. De Los Santos JF, Cantor A, Amos KD, et al. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 2013;119:1776-1783. 79. Mukhtar RA, Yau C, Rosen M, Tandon VJ; I-SPY 1 TRIAL and ACRIN 6657 Investigators, Hylton N, Esserman LJ. Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol. 2013;20:38233830. 80. Marinovich ML, Macaskill P, Irwig L, et al. Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy. Br J Cancer. 2013;109:1528-1536. 81. Dinan MA, Curtis LH, Hammill BG, et al. Changes in the use and costs of diagnostic imaging among Medicare beneficiaries with cancer, 1999-2006. JAMA. 2010;303:1625-1631.
2089
Magnetic Resonance Imaging in Patients With Newly Diagnosed Breast Cancer A Review of the Literature Melissa Pilewskie, MD; and Tari A. King, MD
The use of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer remains controversial. Here we review the current use of breast MRI and the impact of MRI on short-term surgical outcomes and rates of local recurrence. In addition, we address the use of MRI in specific patient populations, such as those with ductal carcinoma in situ, invasive lobular carcinoma, and occult primary breast cancer, and discuss the potential role of MRI for assessing response to neoadjuvant chemotherapy. Although MRI has improved sensitivity compared with conventional imaging, this has not translated into improved short-term surgical outcomes or long-term patient benefit, such as improved local control or survival, in any patient population. MRI is an important diagnostic test in the evaluation of patients presenting with occult primary breast cancer and has shown promise in monitoring response to neoadjuvant chemotherapy; however, the data do not support the routine use of perioperative MRI in patients with newly diagnosed C 2014 American Cancer Society. breast cancer. Cancer 2014;120:2080–9. V KEYWORDS: magnetic resonance imaging (MRI), breast cancer, breast-conserving surgery, local recurrence.
INTRODUCTION The use of magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer requires balancing the positive and negative aspects of additional imaging and, as evidenced by the growing number of editorials and reviews arguing for or against the routine use of MRI,1-8 remains an area of significant controversy. This debate has been fueled by inconsistent data largely comprised of small, single-institution retrospective studies, although 2 randomized controlled trials (RCTs) and several meta-analyses have provided more robust data evaluating MRI in the perioperative setting. The “pros” of perioperative MRI include improved sensitivity compared with conventional imaging and therefore increased identification of multifocal, multicentric, or contralateral disease. With improved sensitivity comes a theoretical improvement in short-term surgical management and/or long-term outcomes. The “cons” of perioperative MRI include the high falsepositive rate, potential treatment delays, increased mastectomy rates and cost, and, some argue, overdiagnosis and overtreatment of MRI-only detected disease. Here we review the relevant data regarding MRI use in patients with newly diagnosed breast cancer, examining both the short-term and long-term outcomes, MRI use in populations of women with ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), MRI’s role in patients presenting with occult primary breast cancer, and MRI’s ability to evaluate neoadjuvant chemotherapy (NAC) response. Current MRI Use
In contrast to the well-established guidelines for MRI screening in patients with an inherited predisposition to breast cancer,9 to our knowledge, there are no guidelines for MRI use in patients with newly diagnosed breast cancer; nevertheless, a report from Western Washington State’s Surveillance, Epidemiology, and End Results (SEER) registry demonstrated that 27% of 9196 women with breast cancer underwent MRI for staging or treatment planning between 2002 and 2009,10 and by 2009, 46% of women underwent perioperative breast MRI. MRI use varied significantly based on age, with 45% of women aged 18 years to 40 years undergoing an MRI compared with 10% of those aged 81 years (P < .001). Patients were also more likely to undergo MRI if they had commercial health care plans, lived in an urban area, lacked medical
Corresponding author: Tari A. King, MD, Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY 10065; Fax: (646) 888-4921; [email protected] Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York DOI: 10.1002/cncr.28700, Received: December 6, 2013; Revised: February 21, 2014; Accepted: March 14, 2014, Published online April 18, 2014 in Wiley Online Library (wileyonlinelibrary.com)
2080
Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
comorbidities, or had stage I to III breast cancer, lobular histology, or hormone receptor-negative tumors. The association between MRI use, young patient age, and hormone receptor-negative cancer may be attributable to the presence of known or suspected BRCA mutation carriers in the population; however, this information is not available in the SEER registry. Breslin et al reported an even higher rate of use of advanced imaging, with 53% of patients with non-stage IV breast cancer aged < 65 years undergoing breast MRI in 2008. In this cohort of 52,202 women, MRI use increased annually from 2005 to 2008 for women with both invasive and in situ carcinoma.11 Studies examining MRI use in older patients have reported an overall MRI receipt rate of 7% to 10% among women aged 65 years,12-14 with significant variation based on geographic location and chronologic year (P < .01). Wang et al found that by 2007, 27% of women in the SEER-Medicare database with stage 0 to II breast cancer had undergone a perioperative MRI13 and, as in younger patients, preoperative MRI was found to increase mastectomy rates among older patients,14 many of whom likely would have been good candidates for breastconserving surgery (BCS) and anti-estrogen therapy alone.15 A survey sent to the membership of the American Society of Breast Surgeons in 2010 sought to evaluate indications and practice patterns for MRI use among treating physicians. Of 1034 respondents, 41% reported routinely (> 75% of the time) recommending breast MRI to patients with newly diagnosed breast cancer.16 Variation in the recommendation for MRI was noted with respect to both physician and patient factors, with academic surgeons less likely to obtain an MRI compared with private practice surgeons (P 5 .01). Routine recommendation for MRI was more frequent for women with a strong family history of breast cancer (73%), those with ILC (69%), in women undergoing BCS (47%), and in those with increased mammographic breast density (88%). Although physician perception is that MRI is particularly beneficial in the setting of dense breast tissue, studies have demonstrated no significant difference in the diagnostic yield, sensitivity, or negative predictive value of MRI according to breast density.17 Similarly, studies examining the value of MRI in women with lobular cancers have generated conflicting results. MRI for Treatment Selection
The increased sensitivity of MRI for the detection of multifocal or multicentric disease has been widely reported and summarized in a meta-analysis by Houssami et al,18 Cancer
July 15, 2014
which included 2610 patients with breast cancer who underwent perioperative MRI in addition to conventional imaging. MRI identified additional disease in 16% of patients (range, 6%-34% in individual studies), resulting in a change from wide local excision to mastectomy in 8.1% of women (95% confidence interval [CI], 5.9%11.3%) and a larger local excision in 11.3% of women (95% CI, 6.8%-18.3%). A more recent meta-analysis by Plana et al included 10,811 women from 50 studies and found very similar results, with additional lesions identified by MRI in 20% of cases (range, 6%-71%).19 Although data consistently demonstrate an increased detection rate of multifocal and multicentric disease, to our knowledge, there are few data demonstrating improved outcomes based on the treatment of MRI-only detected disease. Therefore, the value of MRI in selecting local therapy remains elusive. MRI and Short-Term Surgical Outcomes
Proponents of breast MRI argue that MRI better characterizes tumor extent and, as such, should improve surgical planning and decrease the rate of positive surgical resection margins and, therefore, the need for re-excision. However, studies have demonstrated significant variability in tumor size estimation by MRI, with underestimation reported in 8% to 59% of cases and overestimation in 11% to 70% of cases.20-24 Two prospective RCTs evaluated the effect of MRI on re-operation rates (both re-excision and conversion to mastectomy) in patients deemed appropriate for BCS.25,26 The COMICE (Comparative Effectiveness of MRI in Breast Cancer) trial multicenter collaboration included 1625 women randomized to either perioperative MRI or no additional imaging between 2002 and 2007. There was no difference noted with regard to the primary endpoint of re-operation rate, which was 19% in both the MRI and the no-MRI groups (odds ratio [OR], 0.96; 95% CI, 0.75-1.24 [P 5 .77]), despite the finding that 5 times as many patients in the MRI group (n 5 58) converted to mastectomy before an initial attempt at BCS compared with the no-MRI group (n 5 10). Among those who underwent an initial mastectomy in the MRI group, in 28% of patients (16 of 58 patients) it was considered pathologically unnecessary.26 Similarly, the MONET (MR mammography of non-palpable breast tumours) trial randomized 418 women with nonpalpable lesions, classified as Breast Imaging Reporting and Data System (BI-RADS) 3 to BIRADS 5 and detected on mammogram or ultrasound, to biopsy or the addition of MRI before biopsy. In total, 163 2081
Review Article TABLE 1. Summary of the Literature Evaluating the Impact of MRI on IBTR Rates
Reference
Patients With MRI/Total No. of Patients
Variables Controlled For on MV Analysis
Follow-Up, Years
IBTR Rates: MRI
IBTR Rates: No MRI
P
3.4 8.0 8.0
1.2% 3.0% 1.8%
6.5% 4.0% 2.5%
90% of cases,31 serial sectioning of mastectomy specimens demonstrates that 21% to 63% of clinically and mammographically detected unicentric tumors are actually multifocal or multicentric.32-38 As such, a large percentage of patients treated with BCS will have microscopic residual disease in the breast, yet multiple prospective RCTs and the updated Early Breast Cancer Trialists’ Collaborative Group overview continue to demonstrate equivalent survival between patients undergoing BCS and mastectomy,39-41 and IBTR rates have substantially decreased over time.42,43 To the best of our knowledge, the only randomized controlled data evaluating the impact of MRI on recurrence rates come from short-term follow-up in the COMICE trial, in which rates of local recurrence (LR) were assessed as a secondary endpoint. At 3 years, local recurrence-free interval rates of 94% and 96% were reported for the MRI and no-MRI groups, respectively.44 Several retrospective single-institution series have compared LR outcomes in women imaged with and without MRI (Table 1).45-50 Only the study by Fischer et al45 reported a lower IBTR rate in women undergoing MRI. This study compared 121 patients with breast cancer who underwent a perioperative MRI with 225 patients who did not. At a mean follow-up of 40 months, the MRI group had an IBTR rate of 1.2% compared with 6.5% in Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
TABLE 2. Summary of the Literature Evaluating the Impact of MRI on the Development of CBC Reference
Patients With MRI/ Total No. of Patients
Follow-Up, Years
CBC Rates: MRI
CBC Rates: No MRI
P
121/346 (35%) 215/756 (28%) 1771/3094 (57%)a 229/615 (37%)
3.4 8.0 3.8 5.7
1.7% 6.0% 0.5% 2.2%
4.0% 6.0% 1.4% 1.3%
3 years) and because statistical adjustments were not performed to control for differences between both groups. The MRI group had a higher percentage of small (T1) lymph node-negative tumors and fewer high-grade lesions, and, paradoxically, a higher percentage of patients in the MRI group received chemotherapy, all of which may have impacted IBTR rates. The 5 subsequent studies shown in Table 1 failed to find a significant improvement in IBTR rates with the addition of MRI when controlling for patient and tumor factors, and all reported low (0.4%5.0%) rates of IBTR at 2 to 8 years of follow-up.46-50 A recent individual-person data meta-analysis including 3169 women from 4 of the above-mentioned trials reported no difference in 8-year LR-free survival (97% for the MRI group vs 95% in the no-MRI group; P 5 .87) or 8-year distant recurrence-free survival (89% in the MRI group and 93% in the no-MRI group; P 5 .37). On multivariable analysis, there was no association noted between perioperative MRI and LR-free survival (hazard ratio for MRI vs no-MRI, 0.88; 95% CI, 0.52-1.51 [P 5 .65]).51 The recognition that IBTR rates differ by breast cancer subtype and, notably, the significantly higher LR rates reported among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-amplified breast cancers in the pre-trastuzumab era,52,53 combined with ongoing controversy regarding the theoretic advantages of perioperative MRI, have led to an RCT supported by the American College of Radiology Imaging Network and the Alliance for Clinical Trials in Oncology. The objective of the trial is to assess the impact of MRI on reoperation rates, LR, quality of life, and cost-effectiveness in women with triple-negative and HER2-amplified breast cancer. Although this study may provide useful information in the cohort of patients with triple-negative breast cancer, the RCTs of adjuvant trastuzumab demonstrated significantly lower IBTR rates with the addition of trastuzumab,54 and the low IBTR and CBC rates noted Cancer
July 15, 2014
among patients with HER2-amplified cancers in more modern series will likely limit the impact of MRI among patients with HER2-amplified cancer.55,56 MRI and Long-Term Outcomes: CBC
MRI has the potential to decrease metachronous CBC rates through the identification of otherwise occult contralateral disease. Table 2 summarizes 4 retrospective studies that have compared rates of metachronous CBC in women imaged with and without MRI at the time of their index breast cancer diagnosis.45,46,49,57 Criticisms of the study by Fischer et al45 have been mentioned previously. Overall, CBC development rates were low (0.5%-6.0%) in both groups. It is important to note that the 2 studies reporting a significant difference in CBC rates both found an absolute difference of 1% to 2% in the MRI and no-MRI groups.45,57 A meta-analysis by Brennan et al58 evaluating the rate of CBC detection by MRI among 3253 women presenting with unilateral cancer reported that 4.1% of patients were diagnosed with a synchronous CBC based on MRI. In comparison, a SEER population-based study from 1973 to 1996 reported the actuarial 10-year risk of metachronous CBC in women treated for unilateral stage 0 to stage II breast cancer to be 6.1%,59 and more recent studies have demonstrated that CBC incidence has been decreasing by approximately 3% per year since 1985.60 Together, these data suggest that either a single MRI at the time of breast cancer diagnosis will identify the majority of breast cancers that will develop over time or, conversely, that many MRI-detected contralateral cancers will be adequately treated as a by-product of appropriate systemic therapy for the index cancer and would remain clinically irrelevant.39 MRI and Long-Term Outcomes: Survival
The Early Breast Cancer Trialists’ Collaborative Group overview established that there is an important relationship between local control and survival in patients with breast cancer; however, as systemic therapies continue to improve, substantially larger differences in local control 2083
Review Article TABLE 3. Summary of the Literature Evaluating the Impact of MRI on Surgical Outcomes in Patients With DCIS
Reference Allen 201061 Itakura 201162 Kropcho 201263 Davis 201265 Pilewskie 201364
Patients With MRI/Total No. of Patients
Re-excision Rate: MRI
Re-excision rate: No MRI
P
Mastectomy Rate: MRI
Mastectomy Rate: No MRI
P
63/98 (64%) 38/149 (26%) 60/158 (38%) 154/218 (71%) 217/352 (62%)
21.2% 16.0% 30.7% 34.1% 14.3%
30.8% 11.0% 24.7% 39.2% 20.0%
.41 .42 .40 .52 .19
20.3%a 45.0%b 17.7%c 27.9%a 34.6%b
25.7%a 14.0%b 4.1%c 23.4%a 27.4%b
.62 67% of cases.72 A negative MRI also provides reassurance that a large tumor burden is unlikely and that the patient may be safely treated with axillary lymph node dissection, whole-breast radiotherapy, and appropriate systemic therapy. In a meta-analysis of 8 retrospective studies,72 which included 220 women with occult primary breast cancer, MRI identified a suspicious breast lesion in 72% of cases, with a sensitivity of 90% and a specificity of 31%. The mean pathologic tumor size ranged from 5 mm to 16 mm, and > 90% were invasive carcinomas. When MRI identified an occult breast lesion in patients without metastatic disease, 21% to 60% of patients were able to undergo successful BCS. MRI for Problem Solving
Similar to patients with an occult primary breast cancer, women with Paget disease or abnormal physical examination findings and negative conventional imaging may benefit from the addition of MRI for disease localization. Paget disease, which is characterized by nipple erythema, erosion, or ulceration caused by epidermal infiltration of malignant cells, is associated with an underlying breast malignancy in > 90% of cases, yet mammographic imaging may be normal in up to 50% of patients.73 Morrogh et al74 reviewed imaging and pathology data on 34 women with Paget disease who were treated at a single institution and 94% were found to have an underlying carcinoma. Mammography detected the underlying malignancy in 22% of cases, and supplemental MRI performed among 8 women with a negative mammogram demonstrated the underlying malignancy in 4 cases (50%). MRI Imaging in the NAC Setting
NAC is being used with increasing enthusiasm to convert patients requiring an upfront mastectomy to BCS as well as to assess the impact of treatment on rates of Cancer
July 15, 2014
pathologic complete response (pCR).75 Multiple studies have evaluated the ability of MRI to predict response to NAC. In the American College of Radiology Imaging Network 6657 study, part of the I-SPY 1 trial, MRI was obtained at 4 time points: before the initiation of chemotherapy, after the first cycle, between the anthracycline-based regimen and taxane therapies, and at the conclusion of NAC before surgery. Compared with clinical examination, MRI was found to be a stronger predictor of both pCR and residual cancer burden, with tumor volume change measured at the time of the second MRI being the strongest predictor.76 However, from a clinical standpoint, the comparison of MRI with physical examination is not particularly relevant, and a more practical comparison is that between MRI and conventional breast imaging. A meta-analysis of 2050 women from 44 NAC studies conducted between 1980 and 2008 reported that MRI correctly identified residual disease with a median sensitivity of 0.92. However, the ability of MRI to correctly identify patients who achieved a pCR in the current analysis was limited, with a median specificity of 0.60, and, expectedly, the accuracy of MRI for predicting pCR varied based on the pCR definition used. MRI was found to have a higher accuracy than mammography (P 5 .02), but no difference was noted between MRI and ultrasound accuracy for the identification of a pCR (P 5 .15).77 Similarly, a multicenter retrospective collaboration from the Translational Breast Cancer Research Consortium (TBCRC 017), which included 746 patients treated from 2002 through 2011, reported an overall accuracy rate of 74% of MRI for predicting a pCR. Given this study’s more recent timeframe, information regarding hormone receptor and HER2 status was available, and the authors demonstrated that MRI had the highest negative predictive value in patients with triple-negative and HER2-amplified tumors (60% and 62%, respectively).78 2085
Review Article
Figure 1. MRI assessment of neoadjuvant chemotherapy response. Images courtesy of Dr. Elizabeth Morris, Memorial Sloan Kettering Cancer Center.
Although prediction of pCR is an important endpoint for therapeutic monitoring, it is not an absolute endpoint for the ability to perform lesser surgery as women with a partial response may still be good candidates for conversion to BCS after NAC. Data from the ISPY 1 trial were analyzed to assess a “clinically meaningful tumor reduction,” defined as a change in tumor size from > 4 cm to 4 cm after NAC, as a surrogate for patients who may become candidates for BCS. Of 174 women with an initial tumor size of > 4 cm, 81% had a pathologic tumor size of 4 cm after NAC, 37% of 2086
whom were successfully treated with BCS. In 38% of the total study population, there was a discrepancy of 2 cm between post-NAC MRI measurements and final pathologic tumor size. In this study, MRI accuracy also was found to differ by tumor pattern and receptor subtype, with improved performance noted among patients with breast cancer subtypes that are known to have higher pCR rates.79 A meta-analysis by Marinovich et al compared the agreement in tumor size between different imaging modalities and final pathology after NAC in 958 patients from 19 studies.80 MRI and ultrasound were found to Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
have similar overestimations of tumor size (mean differences of 0.1 cm), whereas MRI had a lower overestimation of tumor size than mammography (mean difference of 0.4 cm). Although the pooled mean difference between MRI and final pathology was 0.1 cm, the 95% limits of agreement ranged from 24.2 cm to 4.4 cm, which is a clinically significant margin of error when planning surgical therapy.80 The wide margin of error in MRI estimations of post-NAC tumor response and size is likely related to both tumor subtype and treatment regimen, and requires further investigation. Important unanswered questions relate to the ability to predict successful BCS after NAC, which likely relates to the pattern of tumor response (concentric vs multicentric) (Figure 1). Given the increased cost of MRI, a direct comparison of MRI with conventional imaging in this setting may be prudent. Although the use of MRI for planning BCS after NAC is an area of future research, if a patient is known upfront to require mastectomy after NAC, such as individuals with extensive multicentric or inflammatory disease, post-treatment MRI is not indicated. Conclusions
The available literature does not appear to support the routine use of MRI for the evaluation of patients with newly diagnosed breast cancer. Data from RCTs and several retrospective series have failed to demonstrate an improvement in short-term surgical outcomes, and studies have consistently demonstrated increasing mastectomy rates with the addition of MRI. Data supporting improved long-term outcomes with the addition of perioperative breast MRI, including IBTR, CBC development, and survival, are also lacking. Multiple series demonstrating increasing trends in MRI use without a benefit in surgical or long-term outcomes require a reevaluation of practice patterns. Although there are clinical situations in which MRI can provide valuable information, such as in patients with occult primary breast cancer and, potentially, in monitoring response to NAC, the increasing costs of advanced imaging in patients with cancer81 highlight the need for clinicians to critically evaluate the literature and focus on spending health care dollars in an evidence-based manner. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
Cancer
July 15, 2014
REFERENCES 1. Hede K. Preoperative MRI in breast cancer grows contentious. J Natl Cancer Inst. 2009;101:1667-1669. 2. Solin LJ. Counterview: Pre-operative breast MRI (magnetic resonance imaging) is not recommended for all patients with newly diagnosed breast cancer. Breast. 2010;19:7-9. 3. Morrow M. Magnetic resonance imaging for screening, diagnosis, and eligibility for breast-conserving surgery: promises and pitfalls. Surg Oncol Clin N Am. 2010;19:475-492. 4. Sardanelli F. Overview of the role of pre-operative breast MRI in the absence of evidence on patient outcomes. Breast. 2010;19:3-6. 5. Brasic N, Wisner DJ, Joe BN. Breast MR imaging for extent of disease assessment in patients with newly diagnosed breast cancer. Magn Reson Imaging Clin N Am. 2013;21:519-532. 6. McLaughlin S, Mittendorf EA, Bleicher RJ, McCready DR, King TA. The 2013 Society of Surgical Oncology Susan G. Komen for the Cure Symposium: MRI in breast cancer: where are we now? Ann Surg Oncol. 2014;21:28-36. 7. Jatoi I, Benson JR. The case against routine preoperative breast MRI. Future Oncol. 2013;9:347-353. 8. Houssami N, Morrow M. Pre-operative breast MRI in women with recently diagnosed breast cancer–where to next? Breast. 2010; 19:1-2. 9. Mainiero MB, Lourenco A, Mahoney MC, et al. ACR Appropriateness Criteria Breast Cancer Screening. J Am Coll Radiol. 2013;10: 11-14. 10. Gold LS, Buist DS, Loggers ET, et al. Advanced diagnostic breast cancer imaging: variation and patterns of care in Washington state. J Oncol Pract. 2013;9:e194-e202. 11. Breslin TM, Banerjee M, Gust C, Birkmeyer NJ. Trends in advanced imaging use for women undergoing breast cancer surgery. Cancer. 2013;119:1251-1256. 12. Sommer CA, Stitzenberg KB, Tolleson-Rinehart S, Carpenter WR, Carey TS. Breast MRI utilization in older patients with newly diagnosed breast cancer. J Surg Res. 2011;170:77-83. 13. Wang SY, Virnig BA, Tuttle TM, Jacobs DR Jr, Kuntz KM, Kane RL. Variability of preoperative breast MRI utilization among older women with newly diagnosed early-stage breast cancer. Breast J. 2013;19:627-636. 14. Killelea BK, Long JB, Chagpar AB, et al. Trends and clinical implications of preoperative breast MRI in Medicare beneficiaries with breast cancer. Breast Cancer Res Treat. 2013;141:155-163. 15. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382-2387. 16. Parker A, Schroen AT, Brenin DR. MRI utilization in newly diagnosed breast cancer: a survey of practicing surgeons. Ann Surg Oncol. 2013;20:2600-2606. 17. 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. 18. Houssami N, Ciatto S, Macaskill P, et al. 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;26:3248-3258. 19. Plana MN, Carreira C, Muriel A, et al. Magnetic resonance imaging in the preoperative assessment of patients with primary breast cancer: systematic review of diagnostic accuracy and meta-analysis. Eur Radiol. 2012;22:26-38. 20. Boetes C, Veltman J, van Die L, Bult P, Wobbes T, Barentsz JO. The role of MRI in invasive lobular carcinoma. Breast Cancer Res Treat. 2004;86:31-37. 21. Onesti JK, Mangus BE, Helmer SD, Osland JS. Breast cancer tumor size: correlation between magnetic resonance imaging and pathology measurements. Am J Surg. 2008;196:844-848; discussion 849-850. 22. Behjatnia B, Sim J, Bassett LW, Moatamed NA, Apple SK. Does size matter? Comparison study between MRI, gross, and microscopic tumor sizes in breast cancer in lumpectomy specimens. Int J Clin Exp Pathol. 2010;3:303-309.
2087
Review Article 23. Kim Do Y, Moon WK, Cho N, et al. MRI of the breast for the detection and assessment of the size of ductal carcinoma in situ. Korean J Radiol. 2007;8:32-39. 24. Muttalib M, Ibrahem R, Khashan AS, Hajaj M. Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management. Clin Radiol. 2014;69:23-28. 25. Peters NH, van Esser S, van den Bosch MA, et al. Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET-randomised controlled trial. Eur J Cancer. 2011;47:879-886. 26. Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet. 2010;375:563-571. 27. Houssami N, Turner R, Morrow M. Preoperative magnetic resonance imaging in breast cancer: meta-analysis of surgical outcomes. Ann Surg. 2013;257:249-255. 28. King TA, Sakr R, Patil S, et al. Clinical management factors contribute to the decision for contralateral prophylactic mastectomy. J Clin Oncol. 2011;29:2158-2164. 29. Sorbero ME, Dick AW, Beckjord EB, Ahrendt G. Diagnostic breast magnetic resonance imaging and contralateral prophylactic mastectomy. Ann Surg Oncol. 2009;16:1597-1605. 30. Chung A, Huynh K, Lawrence C, Sim MS, Giuliano A. Comparison of patient characteristics and outcomes of contralateral prophylactic mastectomy and unilateral total mastectomy in breast cancer patients. Ann Surg Oncol. 2012;19:2600-2606. 31. Morrow M, Bucci C, Rademaker A. Medical contraindications are not a major factor in the underutilization of breast conserving therapy. J Am Coll Surg. 1998;186:269-274. 32. Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985;56:979-990. 33. Anastassiades O, Iakovou E, Stavridou N, Gogas J, Karameris A. Multicentricity in breast cancer. A study of 366 cases. Am J Clin Pathol. 1993;99:238-243. 34. Egan RL. Multicentric breast carcinomas: clinical-radiographicpathologic whole organ studies and 10-year survival. Cancer. 1982; 49:1123-1130. 35. Lagios MD. Multicentricity of breast carcinoma demonstrated by routine correlated serial subgross and radiographic examination. Cancer. 1977;40:1726-1734. 36. Qualheim RE, Gall EA. Breast carcinoma with multiple sites of origin. Cancer. 1957;10:460-468. 37. Rosen PP, Fracchia AA, Urban JA, Schottenfeld D, Robbins GF. “Residual” mammary carcinoma following simulated partial mastectomy. Cancer. 1975;35:739-747. 38. Schwartz GF, Patchesfsky AS, Feig SA, Shaber GS, Schwartz AB. Multicentricity of non-palpable breast cancer. Cancer. 1980;45:29132916. 39. Clarke M, Collins R, Darby S, et al; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087-2106. 40. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241. 41. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347: 1227-1232. 42. Pass H, Vicini FA, Kestin LL, et al. Changes in management techniques and patterns of disease recurrence over time in patients with breast carcinoma treated with breast-conserving therapy at a single institution. Cancer. 2004;101:713-720. 43. Ernst MF, Voogd AC, Coebergh JW, Poortmans PM, Roukema JA. Using loco-regional recurrence as an indicator of the quality of breast cancer treatment. Eur J Cancer. 2004;40:487-493. 44. Turnbull LW, Brown SR, Olivier C, et al; COMICE Trial Group. Multicentre randomised controlled trial examining the cost-
2088
45.
46.
47.
48. 49.
50. 51. 52.
53.
54.
55. 56.
57. 58.
59.
60.
61. 62.
effectiveness of contrast-enhanced high field magnetic resonance imaging in women with primary breast cancer scheduled for wide local excision (COMICE). Health Technol Assess. 2010;14:1-182. Fischer U, Zachariae O, Baum F, von Heyden D, Funke M, Liersch T. The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol. 2004;14: 1725-1731. Solin LJ, Orel SG, Hwang WT, Harris EE, Schnall MD. Relationship of breast magnetic resonance imaging to outcome after breastconservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol. 2008;26:386-391. Hwang N, Schiller DE, Crystal P, Maki E, McCready DR. Magnetic resonance imaging in the planning of initial lumpectomy for invasive breast carcinoma: its effect on ipsilateral breast tumor recurrence after breast-conservation therapy. Ann Surg Oncol. 2009;16: 3000-3009. Shin HC, Han W, Moon HG, et al. Limited value and utility of breast MRI in patients undergoing breast-conserving cancer surgery. Ann Surg Oncol. 2012;19:2572-2579. Ko ES, Han BK, Kim RB, et al. Analysis of the effect of breast magnetic resonance imaging on the outcome in women undergoing breast conservation surgery with radiation therapy. J Surg Oncol. 2013;107:815-821. Miller BT, Abbott AM, Tuttle TM. The influence of preoperative MRI on breast cancer treatment. Ann Surg Oncol. 2012;19: 536-540. Houssami N, Turner R, Macaskill P, et al. An individual person data meta-analysis of preoperative magnetic resonance imaging and breast cancer recurrence. J Clin Oncol. 2014;32:392-401. Metzger-Filho O, Sun Z, Viale G, et al. Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from International Breast Cancer Study Group trials VIII and IX. J Clin Oncol. 2013;31:3083-3090. Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133: 831-841. Dahabreh IJ, Linardou H, Siannis F, Fountzilas G, Murray S. Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist. 2008;13:620-630. McArthur HL, Mahoney KM, Morris PG, et al. Adjuvant trastuzumab with chemotherapy is effective in women with small, nodenegative, HER2-positive breast cancer. Cancer. 2011;117:5461-5468. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236-244. Kim JY, Cho N, Koo HR, et al. Unilateral breast cancer: screening of contralateral breast by using preoperative MR imaging reduces incidence of metachronous cancer. Radiology. 2013;267:57-66. Brennan ME, Houssami N, Lord S, et al. Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: systematic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol. 2009;27:5640-5649. Gao X, Fisher SG, Emami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2003;56:10381045. Nichols HB, Berrington de Gonzalez A, Lacey JV Jr, Rosenberg PS, Anderson WF. Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol. 2011;29:15641569. Allen LR, Lago-Toro CE, Hughes JH, et al. Is there a role for MRI in the preoperative assessment of patients with DCIS? Ann Surg Oncol. 2010;17:2395-2400. Itakura K, Lessing J, Sakata T, et al. The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ. Clin Breast Cancer. 2011;11:33-38.
Cancer
July 15, 2014
MRI and Newly Diagnosed Breast Cancer/Pilewskie and King
63. Kropcho LC, Steen ST, Chung AP, Sim MS, Kirsch DL, Giuliano AE. Preoperative breast MRI in the surgical treatment of ductal carcinoma in situ. Breast J. 2012;18:151-156. 64. Pilewskie M, Kennedy C, Shappell C, et al. Effect of MRI on the management of ductal carcinoma in situ of the breast. Ann Surg Oncol. 2013;20:1522-1529. 65. Davis KL, Barth RJ Jr, Gui J, Dann E, Eisenberg B, Rosenkranz K. Use of MRI in preoperative planning for women with newly diagnosed DCIS: risk or benefit? Ann Surg Oncol. 2012;19:32703274. 66. Pilewskie M, Olcese C, Eaton A, et al. Perioperative breast MRI is not associated with lower locoregional recurrence rates in DCIS patients treated with or without radiation [published online ahead of print January 3, 2014]. Ann Surg Oncol. 67. Mann RM, Hoogeveen YL, Blickman JG, Boetes C. MRI compared to conventional diagnostic work-up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature. Breast Cancer Res Treat. 2008;107:1-14. 68. Mann RM, Loo CE, Wobbes T, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat. 2010;119:415-422. 69. Heil J, Buhler A, Golatta M, et al. Does a supplementary preoperative breast MRI in patients with invasive lobular breast cancer change primary and secondary surgical interventions? Ann Surg Oncol. 2011;18:2143-2149. 70. McGhan LJ, Wasif N, Gray RJ, et al. Use of preoperative magnetic resonance imaging for invasive lobular cancer: good, better, but maybe not the best? Ann Surg Oncol. 2010;17(suppl 3):255-262. 71. Walker GV, Smith GL, Perkins GH, et al. Population-based analysis of occult primary breast cancer with axillary lymph node metastasis. Cancer. 2010;116:4000-4006. 72. de Bresser J, de Vos B, van der Ent F, Hulsewe K. Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg Oncol. 2010;36:114-119.
Cancer
July 15, 2014
73. Lim HS, Jeong SJ, Lee JS, et al. Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation. Radiographics. 2011;31:1973-1987. 74. Morrogh M, Morris EA, Liberman L, Van Zee K, Cody HS 3rd, King TA. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple. J Am Coll Surg. 2008;206:316-321. 75. Kaufmann M, von Minckwitz G, Smith R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol. 2003;21:2600-2608. 76. Hylton NM, Blume JD, Bernreuter WK, et al; ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy–results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663-672. 77. Marinovich ML, Houssami N, Macaskill P, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst. 2013;105:321-333. 78. De Los Santos JF, Cantor A, Amos KD, et al. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 2013;119:1776-1783. 79. Mukhtar RA, Yau C, Rosen M, Tandon VJ; I-SPY 1 TRIAL and ACRIN 6657 Investigators, Hylton N, Esserman LJ. Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol. 2013;20:38233830. 80. Marinovich ML, Macaskill P, Irwig L, et al. Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy. Br J Cancer. 2013;109:1528-1536. 81. Dinan MA, Curtis LH, Hammill BG, et al. Changes in the use and costs of diagnostic imaging among Medicare beneficiaries with cancer, 1999-2006. JAMA. 2010;303:1625-1631.
2089
