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No Effect of Pretreatment Breast MRI on the Timing of Surgical Treatment of Newly Diagnosed Breast Cancer
ORIGINAL ARTICLE
No Effect of Pretreatment Breast MRI on the Timing of Surgical Treatment of Newly Diagnosed Breast Cancer Brian Pogatchnik, MD, Jessica Kuehn-Hajder, MD, Michael Nelson, MD, Tim Emory, MD Abstract Background: Although breast MRI has been shown to be more sensitive in the diagnosis of breast cancer than conventional mammography, one criticism breast MRI has faced in the preoperative treatment planning is that it can delay treatment. Methods: A retrospective analysis was performed of all women diagnosed and treated for breast cancer over three consecutive years at an American university hospital. The subjects were divided into two groups: those who received preoperative breast MRI and those who did not. There were 189 patients included in this study, of whom 109 (57.67%) received pretreatment breast MRI. Results: Median time to treatment was not significantly different between pretreatment MRI and no pretreatment MRI groups (32 days versus 34.5 days, P ¼ .950). Adjusting for age, detection method, stage, and histology type did not change this conclusion. Conclusions: At this institution, preoperative breast MRI for patients with newly diagnosed breast cancer seemed to have no significant effect on the timing of surgical treatment in cases of newly diagnosed breast cancer. Key Words: Breast, breast MRI, time to treatment, breast cancer, mastectomy rate J Am Coll Radiol 2017;-:---. Copyright 2017 American College of Radiology
INTRODUCTION Breast MRI has repeatedly been shown to be the most sensitive imaging method for the detection and determination of the extent of involvement of newly diagnosed breast cancer. Studies have also shown MRIs increased sensitivity has proven useful in detecting additional foci of ipsilateral or contralateral in situ or invasive malignancy not identified with traditional mammography or ultrasound [1-4]. As such, MRI has become widely accepted as an optional tool for staging evaluation of newly diagnosed breast cancer to define the extent of known cancer and the presence of additional sites of ipsilateral cancer, as well as to screen for the presence of contralateral cancer. However, the use of pretreatment breast MRI in cases of newly detected breast cancer is a controversial topic. Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota. Corresponding author and reprints: Tim Emory, MD, Department of Radiology, University of Minnesota Medical School, MMC 292, 420 Delaware St SE, Minneapolis, MN 55455; e-mail: [email protected]. The authors have no conflicts of interest related to the material discussed in this article.
ª 2017 American College of Radiology 1546-1440/17/$36.00 n http://dx.doi.org/10.1016/j.jacr.2017.06.032
Criticism of its use includes the claim that pretreatment breast MRI does not improve surgical margins and is associated with an increased rate of mastectomies without proof that it impacts survival [5,6]. However, MRI has not been alone in association with increased mastectomy rates; additional commonly cited associations with increased mastectomy rate include higher stage, cancer histology, and age [7,8]. Studies have reported that preoperative breast MRI may delay surgical therapy in patients with breast cancer [9-11]. Delays in therapy have been cited by multiple articles in the surgical and radiological literature as arguments against the use of preoperative breast MRI [12-15]. The time to treatment after the breast cancer diagnosis is made relies on a number of factors in addition to pretreatment breast MRI. Depending on the case, this time includes scheduling and completing consultations with not only the surgeon but often a team of professionals including the medical oncologist, plastic surgeon, radiation oncologist, and genetic counselor, in addition to working around the patient’s own personal schedule [11,15]. Notably, if patients divide their care up between multiple institutions, other time-consuming variables
1
including repetitions of the process may be introduced [16]. The delay in treatment due to repetitions of the process when patients seek care from multiple sites has not been accounted for in prior studies that link preoperative MRI with treatment delays [9-11]. We hypothesized that pretreatment MRI did not delay surgery in patients who were biopsied and treated at our single academic institution. We reviewed the records of patients who fit these criteria in this regard, and we evaluated our patients with respect to our detection rates of additional foci of cancer, mastectomy rates, histologic subtypes, and age.
Because the primary outcome variable was time to treatment, methods of survival analysis were applied: Kaplan-Meier curves and proportional hazards [Cox] regression using SAS version 9.3 (SAS Institute Inc; Cary, NC, USA). For dichotomous data, the Fisher test was used on data where at least one cell had a value of less than 5 (because a c2 test assumes an expected frequency of 5 or greater) and c2 tests were performed on everything else. Online calculators from the Physics Department at The College of St Benedict/St John’s University were used to calculate the c2 test [18]. An alpha value of 0.05 was used to signify statistical significance.
MATERIALS AND METHODS After obtaining approval by the Institutional Review Board, a retrospective study was carried out using the breast center biopsy log, the institutional breast MRI list, and patients’ charts. The medical records of consenting women with newly diagnosed breast cancer over three consecutive years were studied. For this study, patients were included who had their diagnostic imaging workup, breast biopsy diagnosis of primary breast cancer, possible pretreatment MRI and any subsequent MRI-related workup, and eventual breast cancer surgery all performed at our institution. The patient’s age, type of surgery, pathologic findings from biopsies and surgery, and imaging findings from the diagnostic workup were all recorded. Time to treatment, cancer histopathology, cancer stage, additional lesions detected by pretreatment MRI with workup including biopsies, and mastectomy rates were tabulated for pretreatment MRI and no pretreatment MRI groups. Excluded from our cohort were patients who had their diagnostic workup or surgery elsewhere. Patients who were treated initially with neoadjuvant therapy were excluded. Patients who had metastatic disease at presentation were excluded. And patients who had their initial breast cancer diagnosed at screening MRI were excluded. The study cohort consisted of 189 patients who met these criteria. Time to treatment was calculated as the number of days between the day of initial diagnosis and the day of surgery. Patient age was the age at the time of initial biopsy. Cancer histopathology was from the surgery pathology report. Method of cancer detection was taken from the medical record including diagnostic imaging workup. Staging was performed by synthesizing the pathology reports from each patient and calculating a stage based on the 2010 American Joint Committee on Cancer staging manual [17].
RESULTS
2
Age Characteristics Of the 189 patients who met inclusion criteria, 109 (57.67%) received a pretreatment breast MRI study. The mean age of the patients in this study was 57.92 years with a range of 28 to 86 years. Those who had a pretreatment MRI were on average 10 years younger (53.65 years, SD ¼ 10.06 years) compared with those without pretreatment MRI (63.74 years, SD ¼ 11.59 years, P < .001). Women who underwent mastectomy were on average 4 years younger than those who underwent breast-conserving surgery (BCS) (P ¼ .028). Detection Characteristics Overall, screening mammography and patients’ selfdetection were the most common ways to first detect their breast cancer. Patients with self-detected breast cancer were far more likely to undergo preoperative breast MRI (37.61% versus 20%, P ¼ .028, Table 1). Additional methods of detection included physical examination by a physician, CT scan, and PET/CT scans. Cancer Characteristics Regarding histologic subtypes, invasive ductal carcinoma not otherwise specified made up a significantly greater percentage of the MRI cohort (68.81%) versus the non-MRI group (57.50%), whereas ductal carcinoma in situ (DCIS) made up a significantly smaller share of the MRI cohort than the non-MRI cohort (12.88% versus 23.75%, P ¼ .023, Table 2). Other histopathologic types of breast cancer found included mucinous, papillary, metaplastic, and neuroendocrine tumors. They comprised a smaller percentage of those in the MRI cohort than the non-MRI cohort (4.59% versus 12.50%). Overall, there was no significant difference in the distribution of cancer stage in the MRI versus non-MRI groups (P ¼ .311). Journal of the American College of Radiology Volume - n Number - n Month 2017
Table 1. Methods of cancer detection based on whether the patient underwent pretreatment MRI Pretreatment MRI %
Method of Detection
n
Screening mammography Patient detected Mass found by physician PET/CT CT
62 41 4 2 0
56.88 37.61 3.67 1.84 0
No Pretreatment MRI n % 60 16 1 1 2
P Value
75.00 20.00 1.25 1.25 2.50
.028
MRI Findings Of the patients who underwent MRI, 45 (41.3%) had a new lesion detected by MRI (Fig. 1). Seven of these were not biopsied because they had benign imaging characteristics such as simple cysts. One of these lesions was felt to be indeterminate, but the decision was made to not proceed with a biopsy because the patient planned on undergoing bilateral mastectomies. On final pathology, the additional lesion was found to be malignant. Five indeterminate lesions were not followed up. Of the 32 patients who were biopsied, 14 (43.8%) were found to have additional foci of cancer.
Cox regressions (with time to treatment as the outcome) had no effect on this conclusion. Furthermore, there was no indication of interactions of pretreatment MRI with age, histopathology, or cancer detection method as determinants of time to therapy. Additionally, the occurrence of a second lesion requiring an additional biopsy found on their pretreatment MRI also did not indicate any significant delayed surgical treatment (Table 3). Furthermore, there was no indication of an interaction of pretreatment MRI with age, histopathology, or cancer detection method as determinants of time to surgery.
Time to Treatment There was no significant delay in therapy for patients undergoing pretreatment MRI with median time in the pretreatment group 32 days versus 34.5 days in the no pretreatment MRI group (P ¼ .950, Table 3). Controlling for age, histopathology, and cancer detection method in
Surgical Treatment Overall, there was no difference in the mastectomy rate in patients receiving pretreatment breast MRI with those who did not (P ¼ .391, Table 4). In total, 77 (70.64%) of those who underwent pretreatment breast MRI had a BCS in contrast to 61 (76.25%) of those who did not
Table 2. Cancer characteristics based on whether or not the patient underwent pretreatment MRI Cancer Characteristics Histology Ductal carcinoma in situ Invasive ductal carcinoma, not otherwise specified Invasive lobular carcinoma Papillary Mucinous Metaplastic Neuroendocrine IDC and ILC Overall stage In situ I II III
Pretreatment MRI n %
No Pretreatment MRI n %
18 75
16.51 68.81
19 46
23.75 57.50
12 0 1 2 0 1
11.01 0.00 0.92 1.84 0 0.92
6 1 7 0 1 0
7.5 1.25 8.75 0.00 1.25 0.00
18 60 27 4
16.51 55.05 24.77 3.67
19 45 12 4
23.75 56.25 15.00 5.00
P Value .023
.311
One patient in the pretreatment group had both invasive ductal carcinoma and invasive lobular carcinoma and so was counted twice. Furthermore, if the patient had focus of ductal carcinoma in situ in addition to an invasive cancer, only the invasive cancer was recorded. IDC ¼ invasive ductal carcinoma, ILC ¼ invasive lobular carcinoma.
Journal of the American College of Radiology Pogatchnik et al n Pretreatment Breast MRI
3
Total PaƟents N=189
No MRI N=80 (42.3%)
MRI N=109 (57.7%)
No New Lesion Found N=64 (58.7%)
New Lesion Found N= 45 (41.3%)
Biopsy N= 32 (71.1%)
Benign N=18 (56.2%)
No Follow Up N=5 (11.1%)
No Biopsy N= 8 (17.8%)
Malignant N= 14 (43.8%)
Benign N= 7 (87.5%)
Malignant N= 1 (12.5%)
Fig 1. Flowchart showing the results of the additional findings on MRI.
undergo MRI. However, if a patient had a second lesion found on breast MRI shown to be another focus of cancer, she was significantly less likely to undergo BCS (P ¼ .0080). In fact, only 6 of 15 (40.00%) of those with a second malignant lesion found underwent BCS, and 21 (80.77%) of those who had a benign lesion underwent BCS. Of note, one patient elected to undergo mastectomy of her left breast and BCS on her right breast for a newly discovered lesion.
DISCUSSION There was no effect of pretreatment breast MRI on the timing of surgical treatment of newly diagnosed breast
cancer in our group of patients, with the mean time to treatment in the MRI group in our study being 32 days. This is contrary to prior publications. Hulvat et al concluded that multimodality imaging including MRI is likely associated with the increase in time to treatment at their institution, which was 21.8 days in 1998 and 41.1 days in 2008 [11]. Bleicher et al reported a mean time to treatment interval of 56.9 days in the pretreatment MRI group versus 38.1 for patients who did not have MRI [9]. The difference in results of our study compared with prior results may be at least partially explained by including patients who seek surgery at a site different from where they received a diagnosis, especially if those patients had been more likely to receive pretreatment MRI. Controlling for other factors that differ between the pretreatment MRI and no pretreatment MRI groups, which also can affect the time to surgery, did not alter our conclusion regarding the effect of pretreatment MRI. Richards et al in 1999 reported that delays of 3 to 6 months from the onset of symptoms to the initiation of therapy are associated with lower survival [19]. Mansfield et al recently reported that time to treatment of less than 60 days did not influence breast cancer outcomes [15]. Time to treatment in our study was well under that figure, even in the group that had new lesions on their MRI. Thus, with prompt scheduling of MRIs and follow-up if new lesions are discovered, pretreatment breast MRIs do not necessarily delay treatment, which was well within the 60-day time frame. Many aspects of this study were in line with previous investigations. The difference in mean age of those receiving pretreatment MRI has been seen in many studies [20]. Of the 109 women who underwent preoperative breast MRI, an additional 14 biopsyproven synchronous cancers were discovered. The rate of detecting additional lesions was within what had been seen in other studies, as was the diagnostic positive predictive value for biopsied new lesions [21]. Furthermore, de Rijke et al showed that older patients tend to have more contraindications to MRI and prefer less extensive workups [22]. This could also explain some of the discrepancy between histological subtypes and MRI
Table 3. Time to treatment based on whether or not the patient underwent pretreatment MRI Dependent Variable
Pretreatment MRI, Median (95% CI)
No Pretreatment MRI, Median (95% CI)
Time to treatment (days)
32 (29, 34)
34.5 (30, 37)
Time to treatment (days)
New Lesion, Median (95% CI)
No New Lesion, Median (95% CI)
34 (29, 39)
31 (27, 34)
P value .950
.288
CI ¼ confidence interval.
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Journal of the American College of Radiology Volume - n Number - n Month 2017
Table 4. Mastectomy rates with respect to preoperative breast MRI and an additional lesion detected Pretreatment MRI %
Treatment Type
n
Breast-conserving surgery Mastectomy
77 32
No Pretreatment MRI n %
70.64 29.36
61 19
Benign Second Lesion (n ¼ 19) n % Breast-conserving surgery Mastectomy
21 5
Journal of the American College of Radiology Pogatchnik et al n Pretreatment Breast MRI
.391
Malignant Second Lesion (n ¼ 14) n %
80.77 19.23
cohorts. Mucinous cancers are more common with increased age according to a study by Cardenosa et al, and of the eight in this study, seven were in the cohort without pretreatment MRI [23]. The discrepancy could also be that invasive ductal carcinoma not otherwise specified is felt to warrant a greater workup versus the ductal carcinoma in situ that was seen in higher numbers among those who did not receive pretreatment MRI. Furthermore, the MRI cohort tended to have breast cancer discovered through self-reported symptoms, which could indicate a higher degree of selfadvocacy leading to a more intensive workup. Thus, the difference in age and histological subtypes are interesting findings that could point to differences in management outside of MRI alone. MRI has been reported to result in increased mastectomy rates without improvement in outcomes [6,9]. Additional commonly cited associations with increased mastectomy rate include higher stage, cancer histology, and age [7,8]. This study found no significant overall difference in the mastectomy rate for patients with respect to whether they received preoperative MRI, which has also been reported in the surgical literature [11]. The absence of a significant increase in mastectomies was still true even accounting for other variables that were significantly associated with preoperative breast MRI, namely patient age, histopathology, and initial cancer detection method. However, the finding of additional cancer by pretreatment MRI was associated with an increased mastectomy rate in our group. This study did have notable limitations, however. First, it was a retrospective analysis of data. Consequentially, there was no way to limit selection biases for who received pretreatment MRI. Furthermore, the data only represent one site’s experience and may not apply to all populations. In conclusion, this study demonstrated that breast MRI did not necessarily delay treatment in patients with newly diagnosed breast cancer, even when new lesions
72.07 23.75
P Value
6 8
40 60
.008
were detected on MRI. Women who underwent pretreatment breast MRI were on average 10 years younger. This study also demonstrated no significant overall increase in mastectomy rates among those who received pretreatment MRI, although patients with additional cancer detected had a much increased mastectomy rate, which may very well be appropriate. Finally, we hope that this study will remove the assumption that pretreatment MRI in newly diagnosed breast cancer will necessarily delay definitive treatment.
TAKE-HOME POINTS -
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Preoperative breast MRI does not necessarily delay treatment in patients with newly diagnosed breast cancer. There was no significant effect of observing a new lesion on the MRI as a determinant of time to surgery. Of the women who underwent preoperative breast MRI, 12.8% had a synchronous breast cancer detected by MRI. Despite having a significantly younger population, those who underwent preoperative breast MRI did not have a significantly increased mastectomy rate at this facility. The effects of age, histopathology, and cancer detection method did not alter the conclusion that pretreatment MRI had no significant effect on the time to surgery.
REFERENCES 1. Sardanelli F, Giuseppetti GM, Panizza P, et al. Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer in fatty and dense breasts using the whole-breast pathologic examination as a gold standard. AJR Am J Roentgenol 2004;183:1149-57. 2. Hagen AI, Kvistad KA, Maehle L, et al. Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series. Breast 2007;16:367-74.
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3. Orel SG, Schnall MD. MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 2001;220:13-30. 4. Morrogh M, Morris EA, Liberman L, et al. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple. J Am Coll Surg 2008;206:316-21. 5. Turnbull L, Brown S, Harvey I, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial. Lancet 2010;375:563-71. 6. Hwang N, Schiller DE, Crystal P, et al. 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;16:3000-9. 7. Chen K, Li S, Li Q, et al. Breast-conserving surgery rates in breast cancer patients with different molecular subtypes: an observational study based on Surveillance, Epidemiology, and End Results (SEER) database. Liu. B, ed. Medicine 2016;95:e2593. 8. Dragun AE, Pan J, Riley EC, et al. Increasing use of elective mastectomy and contralateral prophylactic surgery among breast conservation candidates: a 14-year report from a comprehensive cancer center. Am J Clin Oncol 2013;36:375-80. 9. Bleicher RJ, Ciocca RM, Egleston BL, et al. Association of routine pretreatment magnetic resonance imaging with time to surgery, mastectomy rate, and margin status. J Am Coll Surg 2009;209:180-7. 10. Krishnan M, Thorsteinsson D, Horowitz N, et al. The influence of preoperative MRI in the timing and type of therapy in women newly diagnosed with breast cancer. AJR Am J Roentgenol 2008;190:A31-4. 11. Hulvat M, Sandalow N, Rademaker A, et al. Time from diagnosis to definitive operative treatment of operable breast cancer in the era of multimodal imaging. Surgery 2010;4:746-50. 12. Pengel KE, Loo CE, Wesseling J, et al. Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy. Eur J Radiol 2014;83:273-8.
13. Parsyan A, Alqahtani A, Mesurolle B, et al. Impact of preoperative breast MRI on surgical decision making and clinical outcomes: a systematic review. World J Surg 2013;37:2134-9. 14. Fancellu A, Turner RM, Dixon JM, et al. Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ. Br J Surg 2015;108:883-93. 15. Mansfield SA, Abdel-Rasoul M, Terando AM, et al. Timing of breast cancer surgery—how much does it matter? Breast J 2017;23:444-51. 16. Bleicher RJ, Ruth K, Sigurdson ER, et al. Preoperative delays in the US Medicare population with breast cancer. J Clin Oncol 2012;30:4485-92. 17. Edge SB, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging handbook: from the AJCC cancer staging manual. New York, NY: Springer; 2010. 18. Kirkman TW. Statistics to use. Available at: http://www.physics. csbsju.edu/stats/. 1996. Accessed April 10, 2016. 19. Richards MA, Westcombe AM, Love SB, et al. Influence of delay on survival in patients with breast cancer: a systematic review. Lancet 1999;353:1119-26. 20. Houssami N, Turner R, Morrow M. Preoperative magnetic resonance imaging in breast cancer: meta-analysis of surgical outcomes. Ann Surg 2013;257:249-55. 21. Houssami N, Hayes DF. Review of preoperative magnetic resonance imaging (MRI) in breast cancer: should MRI be performed on all women with newly diagnosed, early stage breast cancer? CA Cancer J Clin 2009;59:290-302. 22. de Rijke JM, Schouten LJ, Schouten HC, et al. Age-specific differences in the diagnostics and treatment of cancer patients aged 50 years and older in the province of Limburg, the Netherlands. Ann Oncol 1996;7:677-85. 23. Cardenosa G, Doudna C, Eklund GW. Mucinous (colloid) breast cancer: clinical and mammographic findings in 10 patients. AJR Am J Roentgenol 1994;162:1077-9.
Credits awarded for this enduring activity are designated “SA-CME” by the American Board of Radiology (ABR) and qualify toward fulfilling requirements for Maintenance of Certification (MOC) Part II: Lifelong Learning and Self-assessment. Scan the QR code to access the SA-CME activity or visit http://bit.ly/ACRSACME.
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Journal of the American College of Radiology Volume - n Number - n Month 2017
No Effect of Pretreatment Breast MRI on the Timing of Surgical Treatment of Newly Diagnosed Breast Cancer Brian Pogatchnik, MD, Jessica Kuehn-Hajder, MD, Michael Nelson, MD, Tim Emory, MD Abstract Background: Although breast MRI has been shown to be more sensitive in the diagnosis of breast cancer than conventional mammography, one criticism breast MRI has faced in the preoperative treatment planning is that it can delay treatment. Methods: A retrospective analysis was performed of all women diagnosed and treated for breast cancer over three consecutive years at an American university hospital. The subjects were divided into two groups: those who received preoperative breast MRI and those who did not. There were 189 patients included in this study, of whom 109 (57.67%) received pretreatment breast MRI. Results: Median time to treatment was not significantly different between pretreatment MRI and no pretreatment MRI groups (32 days versus 34.5 days, P ¼ .950). Adjusting for age, detection method, stage, and histology type did not change this conclusion. Conclusions: At this institution, preoperative breast MRI for patients with newly diagnosed breast cancer seemed to have no significant effect on the timing of surgical treatment in cases of newly diagnosed breast cancer. Key Words: Breast, breast MRI, time to treatment, breast cancer, mastectomy rate J Am Coll Radiol 2017;-:---. Copyright 2017 American College of Radiology
INTRODUCTION Breast MRI has repeatedly been shown to be the most sensitive imaging method for the detection and determination of the extent of involvement of newly diagnosed breast cancer. Studies have also shown MRIs increased sensitivity has proven useful in detecting additional foci of ipsilateral or contralateral in situ or invasive malignancy not identified with traditional mammography or ultrasound [1-4]. As such, MRI has become widely accepted as an optional tool for staging evaluation of newly diagnosed breast cancer to define the extent of known cancer and the presence of additional sites of ipsilateral cancer, as well as to screen for the presence of contralateral cancer. However, the use of pretreatment breast MRI in cases of newly detected breast cancer is a controversial topic. Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota. Corresponding author and reprints: Tim Emory, MD, Department of Radiology, University of Minnesota Medical School, MMC 292, 420 Delaware St SE, Minneapolis, MN 55455; e-mail: [email protected]. The authors have no conflicts of interest related to the material discussed in this article.
ª 2017 American College of Radiology 1546-1440/17/$36.00 n http://dx.doi.org/10.1016/j.jacr.2017.06.032
Criticism of its use includes the claim that pretreatment breast MRI does not improve surgical margins and is associated with an increased rate of mastectomies without proof that it impacts survival [5,6]. However, MRI has not been alone in association with increased mastectomy rates; additional commonly cited associations with increased mastectomy rate include higher stage, cancer histology, and age [7,8]. Studies have reported that preoperative breast MRI may delay surgical therapy in patients with breast cancer [9-11]. Delays in therapy have been cited by multiple articles in the surgical and radiological literature as arguments against the use of preoperative breast MRI [12-15]. The time to treatment after the breast cancer diagnosis is made relies on a number of factors in addition to pretreatment breast MRI. Depending on the case, this time includes scheduling and completing consultations with not only the surgeon but often a team of professionals including the medical oncologist, plastic surgeon, radiation oncologist, and genetic counselor, in addition to working around the patient’s own personal schedule [11,15]. Notably, if patients divide their care up between multiple institutions, other time-consuming variables
1
including repetitions of the process may be introduced [16]. The delay in treatment due to repetitions of the process when patients seek care from multiple sites has not been accounted for in prior studies that link preoperative MRI with treatment delays [9-11]. We hypothesized that pretreatment MRI did not delay surgery in patients who were biopsied and treated at our single academic institution. We reviewed the records of patients who fit these criteria in this regard, and we evaluated our patients with respect to our detection rates of additional foci of cancer, mastectomy rates, histologic subtypes, and age.
Because the primary outcome variable was time to treatment, methods of survival analysis were applied: Kaplan-Meier curves and proportional hazards [Cox] regression using SAS version 9.3 (SAS Institute Inc; Cary, NC, USA). For dichotomous data, the Fisher test was used on data where at least one cell had a value of less than 5 (because a c2 test assumes an expected frequency of 5 or greater) and c2 tests were performed on everything else. Online calculators from the Physics Department at The College of St Benedict/St John’s University were used to calculate the c2 test [18]. An alpha value of 0.05 was used to signify statistical significance.
MATERIALS AND METHODS After obtaining approval by the Institutional Review Board, a retrospective study was carried out using the breast center biopsy log, the institutional breast MRI list, and patients’ charts. The medical records of consenting women with newly diagnosed breast cancer over three consecutive years were studied. For this study, patients were included who had their diagnostic imaging workup, breast biopsy diagnosis of primary breast cancer, possible pretreatment MRI and any subsequent MRI-related workup, and eventual breast cancer surgery all performed at our institution. The patient’s age, type of surgery, pathologic findings from biopsies and surgery, and imaging findings from the diagnostic workup were all recorded. Time to treatment, cancer histopathology, cancer stage, additional lesions detected by pretreatment MRI with workup including biopsies, and mastectomy rates were tabulated for pretreatment MRI and no pretreatment MRI groups. Excluded from our cohort were patients who had their diagnostic workup or surgery elsewhere. Patients who were treated initially with neoadjuvant therapy were excluded. Patients who had metastatic disease at presentation were excluded. And patients who had their initial breast cancer diagnosed at screening MRI were excluded. The study cohort consisted of 189 patients who met these criteria. Time to treatment was calculated as the number of days between the day of initial diagnosis and the day of surgery. Patient age was the age at the time of initial biopsy. Cancer histopathology was from the surgery pathology report. Method of cancer detection was taken from the medical record including diagnostic imaging workup. Staging was performed by synthesizing the pathology reports from each patient and calculating a stage based on the 2010 American Joint Committee on Cancer staging manual [17].
RESULTS
2
Age Characteristics Of the 189 patients who met inclusion criteria, 109 (57.67%) received a pretreatment breast MRI study. The mean age of the patients in this study was 57.92 years with a range of 28 to 86 years. Those who had a pretreatment MRI were on average 10 years younger (53.65 years, SD ¼ 10.06 years) compared with those without pretreatment MRI (63.74 years, SD ¼ 11.59 years, P < .001). Women who underwent mastectomy were on average 4 years younger than those who underwent breast-conserving surgery (BCS) (P ¼ .028). Detection Characteristics Overall, screening mammography and patients’ selfdetection were the most common ways to first detect their breast cancer. Patients with self-detected breast cancer were far more likely to undergo preoperative breast MRI (37.61% versus 20%, P ¼ .028, Table 1). Additional methods of detection included physical examination by a physician, CT scan, and PET/CT scans. Cancer Characteristics Regarding histologic subtypes, invasive ductal carcinoma not otherwise specified made up a significantly greater percentage of the MRI cohort (68.81%) versus the non-MRI group (57.50%), whereas ductal carcinoma in situ (DCIS) made up a significantly smaller share of the MRI cohort than the non-MRI cohort (12.88% versus 23.75%, P ¼ .023, Table 2). Other histopathologic types of breast cancer found included mucinous, papillary, metaplastic, and neuroendocrine tumors. They comprised a smaller percentage of those in the MRI cohort than the non-MRI cohort (4.59% versus 12.50%). Overall, there was no significant difference in the distribution of cancer stage in the MRI versus non-MRI groups (P ¼ .311). Journal of the American College of Radiology Volume - n Number - n Month 2017
Table 1. Methods of cancer detection based on whether the patient underwent pretreatment MRI Pretreatment MRI %
Method of Detection
n
Screening mammography Patient detected Mass found by physician PET/CT CT
62 41 4 2 0
56.88 37.61 3.67 1.84 0
No Pretreatment MRI n % 60 16 1 1 2
P Value
75.00 20.00 1.25 1.25 2.50
.028
MRI Findings Of the patients who underwent MRI, 45 (41.3%) had a new lesion detected by MRI (Fig. 1). Seven of these were not biopsied because they had benign imaging characteristics such as simple cysts. One of these lesions was felt to be indeterminate, but the decision was made to not proceed with a biopsy because the patient planned on undergoing bilateral mastectomies. On final pathology, the additional lesion was found to be malignant. Five indeterminate lesions were not followed up. Of the 32 patients who were biopsied, 14 (43.8%) were found to have additional foci of cancer.
Cox regressions (with time to treatment as the outcome) had no effect on this conclusion. Furthermore, there was no indication of interactions of pretreatment MRI with age, histopathology, or cancer detection method as determinants of time to therapy. Additionally, the occurrence of a second lesion requiring an additional biopsy found on their pretreatment MRI also did not indicate any significant delayed surgical treatment (Table 3). Furthermore, there was no indication of an interaction of pretreatment MRI with age, histopathology, or cancer detection method as determinants of time to surgery.
Time to Treatment There was no significant delay in therapy for patients undergoing pretreatment MRI with median time in the pretreatment group 32 days versus 34.5 days in the no pretreatment MRI group (P ¼ .950, Table 3). Controlling for age, histopathology, and cancer detection method in
Surgical Treatment Overall, there was no difference in the mastectomy rate in patients receiving pretreatment breast MRI with those who did not (P ¼ .391, Table 4). In total, 77 (70.64%) of those who underwent pretreatment breast MRI had a BCS in contrast to 61 (76.25%) of those who did not
Table 2. Cancer characteristics based on whether or not the patient underwent pretreatment MRI Cancer Characteristics Histology Ductal carcinoma in situ Invasive ductal carcinoma, not otherwise specified Invasive lobular carcinoma Papillary Mucinous Metaplastic Neuroendocrine IDC and ILC Overall stage In situ I II III
Pretreatment MRI n %
No Pretreatment MRI n %
18 75
16.51 68.81
19 46
23.75 57.50
12 0 1 2 0 1
11.01 0.00 0.92 1.84 0 0.92
6 1 7 0 1 0
7.5 1.25 8.75 0.00 1.25 0.00
18 60 27 4
16.51 55.05 24.77 3.67
19 45 12 4
23.75 56.25 15.00 5.00
P Value .023
.311
One patient in the pretreatment group had both invasive ductal carcinoma and invasive lobular carcinoma and so was counted twice. Furthermore, if the patient had focus of ductal carcinoma in situ in addition to an invasive cancer, only the invasive cancer was recorded. IDC ¼ invasive ductal carcinoma, ILC ¼ invasive lobular carcinoma.
Journal of the American College of Radiology Pogatchnik et al n Pretreatment Breast MRI
3
Total PaƟents N=189
No MRI N=80 (42.3%)
MRI N=109 (57.7%)
No New Lesion Found N=64 (58.7%)
New Lesion Found N= 45 (41.3%)
Biopsy N= 32 (71.1%)
Benign N=18 (56.2%)
No Follow Up N=5 (11.1%)
No Biopsy N= 8 (17.8%)
Malignant N= 14 (43.8%)
Benign N= 7 (87.5%)
Malignant N= 1 (12.5%)
Fig 1. Flowchart showing the results of the additional findings on MRI.
undergo MRI. However, if a patient had a second lesion found on breast MRI shown to be another focus of cancer, she was significantly less likely to undergo BCS (P ¼ .0080). In fact, only 6 of 15 (40.00%) of those with a second malignant lesion found underwent BCS, and 21 (80.77%) of those who had a benign lesion underwent BCS. Of note, one patient elected to undergo mastectomy of her left breast and BCS on her right breast for a newly discovered lesion.
DISCUSSION There was no effect of pretreatment breast MRI on the timing of surgical treatment of newly diagnosed breast
cancer in our group of patients, with the mean time to treatment in the MRI group in our study being 32 days. This is contrary to prior publications. Hulvat et al concluded that multimodality imaging including MRI is likely associated with the increase in time to treatment at their institution, which was 21.8 days in 1998 and 41.1 days in 2008 [11]. Bleicher et al reported a mean time to treatment interval of 56.9 days in the pretreatment MRI group versus 38.1 for patients who did not have MRI [9]. The difference in results of our study compared with prior results may be at least partially explained by including patients who seek surgery at a site different from where they received a diagnosis, especially if those patients had been more likely to receive pretreatment MRI. Controlling for other factors that differ between the pretreatment MRI and no pretreatment MRI groups, which also can affect the time to surgery, did not alter our conclusion regarding the effect of pretreatment MRI. Richards et al in 1999 reported that delays of 3 to 6 months from the onset of symptoms to the initiation of therapy are associated with lower survival [19]. Mansfield et al recently reported that time to treatment of less than 60 days did not influence breast cancer outcomes [15]. Time to treatment in our study was well under that figure, even in the group that had new lesions on their MRI. Thus, with prompt scheduling of MRIs and follow-up if new lesions are discovered, pretreatment breast MRIs do not necessarily delay treatment, which was well within the 60-day time frame. Many aspects of this study were in line with previous investigations. The difference in mean age of those receiving pretreatment MRI has been seen in many studies [20]. Of the 109 women who underwent preoperative breast MRI, an additional 14 biopsyproven synchronous cancers were discovered. The rate of detecting additional lesions was within what had been seen in other studies, as was the diagnostic positive predictive value for biopsied new lesions [21]. Furthermore, de Rijke et al showed that older patients tend to have more contraindications to MRI and prefer less extensive workups [22]. This could also explain some of the discrepancy between histological subtypes and MRI
Table 3. Time to treatment based on whether or not the patient underwent pretreatment MRI Dependent Variable
Pretreatment MRI, Median (95% CI)
No Pretreatment MRI, Median (95% CI)
Time to treatment (days)
32 (29, 34)
34.5 (30, 37)
Time to treatment (days)
New Lesion, Median (95% CI)
No New Lesion, Median (95% CI)
34 (29, 39)
31 (27, 34)
P value .950
.288
CI ¼ confidence interval.
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Table 4. Mastectomy rates with respect to preoperative breast MRI and an additional lesion detected Pretreatment MRI %
Treatment Type
n
Breast-conserving surgery Mastectomy
77 32
No Pretreatment MRI n %
70.64 29.36
61 19
Benign Second Lesion (n ¼ 19) n % Breast-conserving surgery Mastectomy
21 5
Journal of the American College of Radiology Pogatchnik et al n Pretreatment Breast MRI
.391
Malignant Second Lesion (n ¼ 14) n %
80.77 19.23
cohorts. Mucinous cancers are more common with increased age according to a study by Cardenosa et al, and of the eight in this study, seven were in the cohort without pretreatment MRI [23]. The discrepancy could also be that invasive ductal carcinoma not otherwise specified is felt to warrant a greater workup versus the ductal carcinoma in situ that was seen in higher numbers among those who did not receive pretreatment MRI. Furthermore, the MRI cohort tended to have breast cancer discovered through self-reported symptoms, which could indicate a higher degree of selfadvocacy leading to a more intensive workup. Thus, the difference in age and histological subtypes are interesting findings that could point to differences in management outside of MRI alone. MRI has been reported to result in increased mastectomy rates without improvement in outcomes [6,9]. Additional commonly cited associations with increased mastectomy rate include higher stage, cancer histology, and age [7,8]. This study found no significant overall difference in the mastectomy rate for patients with respect to whether they received preoperative MRI, which has also been reported in the surgical literature [11]. The absence of a significant increase in mastectomies was still true even accounting for other variables that were significantly associated with preoperative breast MRI, namely patient age, histopathology, and initial cancer detection method. However, the finding of additional cancer by pretreatment MRI was associated with an increased mastectomy rate in our group. This study did have notable limitations, however. First, it was a retrospective analysis of data. Consequentially, there was no way to limit selection biases for who received pretreatment MRI. Furthermore, the data only represent one site’s experience and may not apply to all populations. In conclusion, this study demonstrated that breast MRI did not necessarily delay treatment in patients with newly diagnosed breast cancer, even when new lesions
72.07 23.75
P Value
6 8
40 60
.008
were detected on MRI. Women who underwent pretreatment breast MRI were on average 10 years younger. This study also demonstrated no significant overall increase in mastectomy rates among those who received pretreatment MRI, although patients with additional cancer detected had a much increased mastectomy rate, which may very well be appropriate. Finally, we hope that this study will remove the assumption that pretreatment MRI in newly diagnosed breast cancer will necessarily delay definitive treatment.
TAKE-HOME POINTS -
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Preoperative breast MRI does not necessarily delay treatment in patients with newly diagnosed breast cancer. There was no significant effect of observing a new lesion on the MRI as a determinant of time to surgery. Of the women who underwent preoperative breast MRI, 12.8% had a synchronous breast cancer detected by MRI. Despite having a significantly younger population, those who underwent preoperative breast MRI did not have a significantly increased mastectomy rate at this facility. The effects of age, histopathology, and cancer detection method did not alter the conclusion that pretreatment MRI had no significant effect on the time to surgery.
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