A, Overall. B, By breast cancer stage. Stage data were not available for 2003, and stage was missing for 4547 patients. C, Across Ontario Local Health Network (LHIN) regions. COMICE indicates Comparative Effectiveness of MRI in Breast Cancer (COMICE) trial.17
Investigations between diagnosis and surgery. CPM indicates contralateral prophylactic mastectomy.
eFigure. Cohort Creation (TOH = Ottawa Hospital).
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Arnaout A, Catley C, Booth CM, et al. Use of Preoperative Magnetic Resonance Imaging for Breast CancerA Canadian Population-Based Study. JAMA Oncol. 2015;1(9):1238–1250. doi:10.1001/jamaoncol.2015.3018
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Contrary to practice guidelines, breast magnetic resonance imaging (MRI) is commonly used in the preoperative evaluation of women with breast cancer. While existing literature has found little benefit to MRI in most patients, potential downstream consequences associated with breast MRI are not well described.
To describe patterns of preoperative breast MRI utilization in a health care system with universal insurance and its association with downstream investigations and clinical outcomes.
Design, Setting, and Participants
This was a population-based retrospective cohort study using administrative heath care databases in Ontario, Canada (2012 population, 13.5 million) over 14 geographic regions were evaluated within the data set. Participants comprised 53 015 patients with primary operable breast cancer treated from 2003 to 2012.
Main Outcomes and Measures
Use of preoperative breast MRI by year, geographic region, and breast cancer stage. Postdiagnosis imaging, biopsy, and short-term surgical outcomes were also evaluated between those who did and did not receive MRI.
Overall, 14.8% of patients (7824 of 53 015) had a preoperative MRI. During the 10-year study period, MRI use increased across all stages by 8-fold (from 3% to 24%; P < .001 for trend). Factors associated with MRI use were younger age, higher socioeconomic status, higher Charlson comorbidity score, surgery performed in a teaching hospital, and fewer years of surgeon experience. Multivariate analyses showed that preoperative breast MRI was associated with higher likelihood of the following: postdiagnosis breast imaging (odds ratio [OR], 2.09; 95% CI, 1.92-2.28), postdiagnosis breast biopsies (OR, 1.74; 95% CI, 1.57-1.93), postdiagnosis imaging to assess for distant metastatic disease (OR, 1.51; 95% CI, 1.42-1.61), mastectomy (OR, 1.73; 95% CI, 1.62-1.85), contralateral prophylactic mastectomy (OR, 1.48; 95% CI, 1.23-1.77), and a greater than 30-day wait to surgery (OR, 2.52; 95% CI, 2.36-2.70) (all ORs are adjusted).
Conclusions and Relevance
Preoperative breast MRI use has increased substantially in routine clinical practice and is associated with a significant increase in ancillary investigations, wait time to surgery, mastectomies, and contralateral prophylactic mastectomies.
Preoperative imaging of patients with breast cancer is used to determine the extent of disease, assist in surgical planning, and assess the need for neoadjuvant systemic therapy.1-8 Current guidelines recommend bilateral mammography as the primary imaging modality and, if necessary, preoperative ultrasonography.1-3 In recent years, there has been growing use of preoperative breast magnetic resonance imaging (pMRI), based on its potential to detect occult disease that might not have been seen with traditional breast imaging.4-6 However, compared with mammography, breast MRI has a modest specificity that leads to higher false-positive rates, is more expensive, and requires the use of intravenous contrast medium.4-10 In addition, randomized clinical trials, systematic reviews, and meta-analyses consistently show that pMRI fails to improve surgical outcomes, breast cancer recurrence rates, or survival.9-17 Moreover, pMRI has been associated with higher mastectomy rates.11-15
Population-based studies can provide insight into patterns of care and outcomes among patients treated in routine clinical practice.18 Recently, several reports have described rapid expansion of breast pMRI use in the United States,4,5,19-21 ranging from a 3-4 to 20-fold5 increase in the past 10 years. To our knowledge, there are no large-scale studies demonstrating the potential associated downstream negative consequences associated with pMRI in routine clinical practice. Our study objectives were to (1) evaluate patterns of pMRI use in newly diagnosed breast cancer in the general population, (2) examine factors associated with pMRI, and (3) identify potential secondary outcomes associated with pMRI.
From 2003 to 2012, preoperative magnetic resonance imaging (pMRI) use for breast cancer increased by 8-fold (all stages) in Ontario, Canada.
Receipt of pMRI was associated with higher likelihood of postdiagnosis breast imaging and biopsies, staging imaging, mastectomy, contralateral prophylactic mastectomy, and a greater than 30-day wait to surgery.
Even within a single-payer universal health insurance system, there exists significant provincial variability in pMRI use.
This study has potential implications to assist policy makers in their efforts in enforcing the Choosing Wisely Canada campaign.
This was a population-based retrospective cohort study to describe use of pMRI in women with a new diagnosis of primary operable breast cancer between 2003 and 2012 in the Canadian province of Ontario. Ontario has a population of approximately 13.5 million people and a single-payer universal health insurance program.22 All female patients with breast cancer older than 19 years and diagnosed between January 1, 2003, and December 31, 2012, were eligible. The study population was restricted to female patients with a primary diagnosis of breast cancer who had breast-related surgery within 3 months of their tissue diagnosis date. This window was selected in an effort to exclude patients who may have received preoperative therapy for locally advanced disease. Patients with stage 0 or IV disease were excluded because the purpose of this study was to assess pMRI use on primary operable invasive breast cancer. Identification of the study population is shown in the eFigure in the Supplement. This study was approved by the University of Ottawa research ethics board.
All incident cases of breast cancer in Ontario were identified using the Ontario Cancer Registry (OCR), a passive, population-based cancer registry that captures diagnostic and demographic information on at least 98% of all incident cases of cancer in the province of Ontario.23 A variety of electronic administrative health databases were linked to the OCR to create the study cohort, identify relevant pMRI, and obtain information regarding secondary imaging procedures and short-term surgical outcomes. Records of hospitalization from the Canadian Institute for Health Information’s Discharge Abstract Database (DAD) provided information about diagnostic, procedural, and treatment information for all acute care hospitalizations in Canada.24,25 From the DAD, we identified all patients who received any of the following surgical interventions: breast-conserving surgery, mastectomy, axillary lymph node dissection, or sentinel lymph node biopsy.
Ontario physicians submit billing codes for imaging procedures to the Ontario Health Insurance Plan (OHIP) for remuneration. Physician billing codes for imaging procedures were linked to the study database, allowing identification of which patients received imaging prior to their surgery and the date the imaging test was performed. To quantify all breast MRI, the cohort of patients with primary operable breast cancer was linked with the OHIP database to identify MRI-related fee codes during the study period.
We performed an external validation of this approach by comparing the pMRI rates from a medical chart review (performed by A.A., primary author and surgical oncologist) at The Ottawa Hospital with those obtained using the OHIP fee code case definition. Using the same cohort creation logic described herein (see the eFigure in the Supplement) we created a validation cohort that included only those patients with primary operable cancer having their breast cancer–related intervention at our local hospital between January 2010 and December 2012. We identified that a 3-month interval between diagnosis and surgery captured more than 93% of the patients identified in our validation medical chart review at our local hospital. This preoperative time period was therefore chosen to describe pMRI usage in patients newly diagnosed as having primary operable breast cancer within the administrative data sets used in this study.
We considered the following patient-, disease-, and system and clinician–related covariates in the multivariable models. Patient-related factors included age at diagnosis and socioeconomic status (SES); the SES of each patient was based on community median household income reported in the Canadian census.22,26 Quintiles of the median household income were based on the household income distribution for the full province of Ontario. Level 1 represents the communities where the poorest 20% of the Ontario population resided. Comorbidity was determined using the Deyo modification27 of the Charlson comorbidity index.28 Patients’ status at diagnosis was classified as urban if they were living in an area with a population concentration of 1000 or more and a population density of 400 or more per square kilometer based on previous Canadian census data.
Disease-related factors included histologic type, diagnosis year, and breast cancer stage. Staging information was based on the OCR “best stage” variable, which is determined algorithmically based on resolution between the clinical and pathological stages29 in that the OCR determines patient stage by pulling from the electronic medical records after all the patient’s evaluations have been received. As such, this stage is considered the “best” available stage. Staging was categorized as I, II, III, or null, where null indicates that the patient was seen at a Regional Cancer Centre, but staging information was not sent to OCR.
System-related data included institution type (teaching vs small community hospitals)30 and the Local Health Integration Network (LHIN)31,32 of the hospital performing the breast cancer–related surgery. Ontario is divided geographically into 14 LHINs that administer and coordinate local health systems, and each patient belongs to an LHIN. For each patient, we extracted the clinician billing number associated with the breast-related surgery and calculated the total number of breast-related surgical procedures performed over the study period divided into quintiles; this was used as an estimate of surgeon volume. Surgeon experience was measured as years since graduation from medical school and divided into quintiles.
To examine the association between receiving pMRI and secondary outcomes that have been previously associated with pMRI use, we used OHIP fee codes to identify all patients having ancillary investigations in the period between diagnosis and surgery, including breast needle biopsy, breast imaging (mammogram and breast ultrasonography), and staging imaging (chest or skeletal radiography; computed tomography of the chest, abdomen, and brain; bone scan; pMRI of the abdomen, pelvis, and bone).
Associated short-term surgical outcomes of interest included whether (1) the patient received a mastectomy (compared with less invasive breast-conserving surgery); (2) the patient received a concurrent contralateral prophylactic mastectomy (CPM), defined as receiving a bilateral mastectomy as the initial surgery in patients without a diagnosis of bilateral breast cancer and without bilateral axillary procedures; and (3) wait time from diagnosis to surgery.
The proportion of patients having pMRI from 2003 to 2012 was calculated for the entire time period, by stage, individual year, and by LHIN. Trends were evaluated with the Cochran-Armitage test. The associations between patient, disease, and system and clinician–related factors with pMRI were evaluated by multivariate logistic regression. Multivariate logistic regression was also performed to examine the relationship between pMRI use and short-term surgical outcomes (mastectomy, CPM, and surgery wait time) and postdiagnosis ancillary investigations (breast biopsies, breast imaging, and staging imaging). All multivariate models were fully adjusted for all patient-, disease-, system-, and clinician-related covariates. Predictors were included as categorical variables and results were reported as odds ratios (ORs). Results were considered statistically significant at P < .05. All P values are 2-sided. All analyses were performed using SAS statistical software (version 9.3; SAS Institute).
From 2003 to 2012, 53 015 patients in Ontario underwent surgery for early-stage breast cancer. Characteristics of the study population are shown in Table 1. Among the total study population, pMRI was performed in 7824 patients (15%); most patients (65%) underwent breast-conserving surgery. Over the 10-year period, pMRI use increased across all stages by 8-fold (P < .001 for trend), from 3% of patients newly diagnosed as having breast cancer in 2003 to 24% in 2012; with the most rapid increase from 2005 to 2008 (Figure 1). An increase in pMRI use was evident across all geographic LHINS over the 10-year study period (P < .001 for trend), although there were marked regional variations between overall pMRI rate by LHIN. The range in pMRI use varies from 5% in one LHIN to approaching 70% in another.
Table 1 includes factors associated with the use of pMRI; the multivariate model was adjusted for all characteristics shown in Table 1. Patient-related factors associated with higher pMRI use on adjusted analyses included younger age, higher socioeconomic status, and higher Charlson comorbidity score. Disease-related factors associated with higher pMRI use included higher stage, lobular histologic type, and later year of diagnosis. System and clinician–related factors associated with increased pMRI use included having surgery in a teaching hospital, getting treatment in certain LHINs, and being patients of surgeons who had higher patient volumes and who were more recent medical school graduates.
Figure 2 shows that patients who had pMRI were more likely to experience all of the secondary outcomes of interest; this was also shown with multivariate analysis after adjusting for all patient-, disease-, system-, clinician-related characteristics (Table 2 and Table 3). For short-term surgical outcomes, Table 2 shows that patients undergoing pMRI had more than a 2-fold increase in the odds of waiting more than 30 days between diagnosis and surgery (OR, 2.52; 95% CI, 2.36-2.70). The mean number of days to surgery was higher in the pMRI group by 12 days (P < .001). In addition, patients undergoing pMRI had significantly higher odds of having a mastectomy (OR, 1.73; 95% CI, 1.62-1.85) and CPM (OR, 1.48; 95% CI, 1.23-1.77). For additional ancillary investigations, Table 3 shows that compared with those patients who did not receive a pMRI, those undergoing pMRI had significantly higher odds of receiving postdiagnosis confirmatory breast imaging (OR, 2.09; 95% CI, 1.92-2.28), postdiagnosis breast needle biopsies (OR, 1.74; 95% CI, 1.57-1.93), and staging imaging for the purposes of identifying distant metastatic disease (OR, 1.51; 95% CI, 1.42-1.61).
Breast cancer, the most commonly diagnosed malignant neoplasm among women in North America, is associated with high initial and ongoing costs compared with other tumor types, and the use of advanced medical imaging is a major contributing component to these costs.33,34 In parallel to the United States, the Choosing Wisely Canada35 and Imaging Wisely36 campaigns were launched in 2014 in an effort to encourage physicians and patients to engage in conversations about unnecessary tests, treatments, and procedures while helping both groups make informed and effective choices to ensure that patients receive the highest quality care. Currently, there are no recommendations supporting the routine use of pMRI in the preoperative assessment of breast cancer.3,16,17,37-40 The National Comprehensive Cancer Network describes pMRI testing as an optional procedure for perioperative planning.1 Other guidelines worldwide recommend extreme caution when using pMRI for perioperative treatment planning16,17,37-40 or support its use only in specific clinical situations,2,7,12,33,40,41 such as in the neoadjuvant setting or situations in which there is an unidentified breast primary tumor. Our data demonstrate substantial utilization of pMRI among patients with early-stage breast cancer treated in routine clinical practice. Previously published studies4,5 demonstrate similar trends in the United States. This increase in use has occurred without strong evidence of benefit for initial or long-term surgical or oncologic outcomes.7,8,11-15,32
There are several potential explanations for the increased use of pMRI. As with most medical technologies, “indication creep,” in which indications for a test are expanded into areas beyond what has been evidence proven, is likely inevitable.4,26,42 Other influences that may have contributed to this growth in pMRI use include the increased availability of MRI scanners, rising patient demand, institutional pressure to use expensive capital equipment, and potential radiologists’ self-referral for diagnostic imaging services.33,42-44 Consistent with findings of other studies,3-5,33 our data demonstrate that pMRI use is greater among younger patients and those with higher socioeconomic status. This finding may relate to higher patient demand, increased access to breast pMRI in more affluent communities, and/or decreased sensitivity of traditional imaging, such as mammography and ultrasonography, in younger patients. In addition, our study demonstrates that surgeon attributes, such as less experience (in years), working in a teaching hospital, and performing more breast-related surgical procedures were associated with greater use of pMRI. Younger surgeons with less experience may desire or be more reliant on additional preoperative tests such as pMRI. Two of the LHINS stand out as having the highest pMRI use, and, interestingly, they are the 2 LHINS with the highest volume of patients with breast cancer, are urban areas, and contain the highest proportion of academic hospitals. Perhaps issues of timing and ease of access to pMRI and patient profile may explain some of the differences between community and academic hospitals. Finally, as shown in Figure 1, it is interesting to note that there seems to be a reduction in the rate of increase in pMRI in the later years, across all LHINS and stages of breast cancer, a finding that has also been reported in some other studies.4,5 This suggests that perhaps there has been an improvement in clinical alignment with clinical evidence and greater efforts at limiting resource use in an increasingly cost-conscious health care system. Indeed, the Comparative Effectiveness of MRI in Breast Cancer (COMICE) trial,17 the first and largest randomized clinical trial ever published (1623 patients) demonstrating the lack of correlation between pMRI use and improved oncologic outcomes, was first published in abstract form in 200913 and then as a report in 2010.10 This and other smaller trials15 may have contributed to the reduction in the increase in pMRI use in patients with breast cancer during the later years evaluated in our study.
Irrespective of the reasons for increased pMRI use, in an era of ever-increasing focus on cost containment in health care, consideration must also be given to the unintended consequences of those who undergo pMRI. The increased sensitivity of breast MRI is achieved at the cost of lower specificity; in practice, this translates into more confirmatory imaging and biopsies needed to rule out a diagnosis of cancer.6-10 Implications of this include increased associated resource use and cost, as well as potential harm to women through the cascade of additional imaging and invasive procedures for diagnostic resolution that are associated with increased anxiety and medical visits for the patient.4,6,10,44 This was clearly demonstrated in our study, with the results showing a higher proportion of patients who underwent pMRI having additional, postdiagnosis, breast-related imaging tests and needle biopsies. It should be noted that despite the increased sensitivity of breast pMRI at detecting the extent of the disease compared with traditional breast imaging, such as mammography and ultrasonography, this has not been shown to translate to lower positive margin rates and reexcisions for margins in the literature.15,17
To our knowledge, the relationship between the additional associated staging tests and pMRI has not been previously reported and could be explained by the fact that breast pMRI can also include findings in the lung, bone, upper abdomen, and the neck that may need additional, higher-resolution confirmatory imaging to rule out distant metastatic disease. In addition, breast pMRI could upstage the tumors of patients by virtue of demonstrating a greater extent of disease, and a higher clinical breast cancer stage can lead to the physician requesting additional imaging to rule out distant metastasis.
In this study, use of pMRI was associated with longer wait times for surgery, a quality metric that is currently used by the Cancer Care Ontario in allocating cancer-related funds to hospitals.30 While the observed difference may not be clinically significant, the increase in wait time may result in increased patient anxiety and treatment dissatisfaction.45,46
The association between increased mastectomy rates and breast pMRI is well known and is also demonstrated in our cohort (OR, 1.73; 95% CI, 1.62-1.85). Although mastectomy is a valid option for certain patients (eg, those who would like to avoid radiation or high-risk patients), the increased overall mastectomy rates associated with pMRI are consistent with those of a recently published meta-analysis15 containing 2 randomized clinical trials and 7 comparative cohort studies (OR, 1.51; 95% CI, 1.21-1.89). Recent data also show a significant increasing worldwide trend in removal of the contralateral healthy breast, even though this provides minimal or no survival benefits.46-49 Few studies have looked at the association between breast pMRI and contralateral prophylactic mastectomy, and the results are conflicting because not all studies are adjusted for confounding factors such as socioeconomic and demographic variables.3,50-53 The current study demonstrated that after adjusting for other factors associated with pMRI use, we found a 1.48 increased odds in the incidence of contralateral prophylactic mastectomy. It is possible that these patients proactively ask for breast pMRI and/or the treating surgeon or oncologist prefers to do more extensive workups in these patients.
This study has some potential limitations. Our study used claims-based registry data, which do not include documented clinical indications for the pMRI or any of the outcomes associated with pMRI use in this study. As such, we could not address patients’ lifetime or baseline risk of cancer, such as that associated with a gene mutation, which would have led to higher rates of mastectomies and contralateral prophylactic mastectomies and the use of pMRI for screening purposes. In addition, it is conceivable that the associated increase in ancillary investigations may be a result of general overtreatment rather than in response to pMRI results. Second, administrative billing data do not provide details regarding whether actual treatment decisions were changed based on test results. For example, we were unable to evaluate whether the decision to undergo contralateral prophylactic mastectomy was based on findings of pMRI. Some patients who initially considered breast-conserving surgery may have opted for mastectomy after pMRI, and vice versa, depending on test results, personal preference, or physician input. Third, if patients had preoperative imaging or surgery performed outside of Ontario, or outside of the 3-month preoperative window, it was not included in the analysis. As described in our validation study, the 3-month preoperative window between diagnosis and surgery was chosen to ensure that our patient population was representative of those with operable breast cancer who were undergoing primary surgical treatment. However, this could potentially exclude patients whose disease was upstaged based on the pMRI results and received neoadjuvant systemic therapy. In addition, although we were unable to provide long-term outcomes in this data set for recurrence and survival, it is our hope to be able to do so in a future study. Finally, the optimal utilization rate for pMRI is not known, and our data are not able to address this important issue.
A strength of our study is that it provides, to our knowledge, the only multifacility evaluation of pMRI use patterns across Canadian practice. The data set is a large cohort representing all of the province of Ontario; Ontario is unique in that it has a comprehensive collection of linked health administrative databases allowing linkage of patient data from diagnosis to postsurgery. Our cohort is representative of the Ontario population because all costs of imaging are covered by the provincial health care plan. It is interesting to note that even within a single-payer universal health insurance program, there exists geographic variability in pMRI use. Similarly illustrated by studies by Makarov et al53 and Swisher-McClure and Bekelman,54 regional culture and infrastructure within the geographic regions may account for varying health care utilization patterns. We also expect variability among other provinces across Canada; and further research should be conducted to determine causes of regional and provincial variability to assist policy makers in their efforts in enforcing the Choosing Wisely campaign.
Preoperative breast MRI use has increased substantially in routine clinical practice and is associated with a significant increase in ancillary investigations, wait time to surgery, mastectomies and contralateral prophylactic mastectomies.
Corresponding Author: Angel Arnaout, MD, MSc, CW 1606, Ottawa Hospital General Campus, 501 Smyth Rd, Ottawa, ON K2C4H2, Canada (Anarnaout@toh.on.ca).
Accepted for Publication: July 8, 2015.
Published Online: September 24, 2015. doi:10.1001/jamaoncol.2015.3018.
Author Contributions: Drs Arnaout and Catley had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.
Study concept and design: Arnaout, Catley, Booth, McInnes, Graham, Simos, Clemons.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Arnaout, Catley, Booth, Simos, Clemons.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Catley, Graham, Van Walraven.
Obtained funding: Arnaout, Simos.
Administrative, technical, or material support: Arnaout, Simos, Clemons.
Study supervision: McInnes, Simos.
Conflict of Interest Disclosures: None reported.
Funding/Support: Financial support for this project has been obtained from the 2013 University of Ottawa, Department of Medicine, Patient Safety Grant.
Role of the Funder/Sponsor: The funding institution (University of Ottawa) had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Additional Contributions: We acknowledge the Ontario ICES program and its office staff for creation of database and their immense assistance for our use of the program.