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MRI in routine breast cancer follow-up: Correlation with clinical outcome
ClinicalRadiology(1999) 54, 459-461
MRI in Routine Breast Cancer Follow-up: Correlation with Clinical Outcome A. COULTHARD,
C. J. B E V E R I D G E ,
A . J. P O T T E R T O N
University Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K. Received: 2 December 1998
Revised: 2 February 1999
Accepted: 9 February 1999
AIM: Magnetic resonance imaging (MRI) of the breast has been shown to be useful as an additional imaging test in patients suspected of having recurrent disease, when clinical examination or mammography are equivocal. This study examines the utility of MRI as a routine test in the follow-up of treated breast cancer patients without equivocal clinical or imaging findings. MATERIALS AND METHODS: Contrast-enhanced breast MRI was performed as part of routine breast cancer follow-up in 26 patients with equivocal clinical or mammographic findings and 33 control patients in whom clinical and imaging findings were consistent with post-treatment changes only. Clinical outcome was assessed at 3 years post MRI. RESULTS: Four patients with equivocal clinical or mammographic findings had abnormal MRI: all MRI abnormalities were subsequently shown to represent benign disease. None of the equivocal group developed local recurrence, although two of 26 developed distant metastases. One of the control group had unsuspected distant metastases detected by MRI: the other 32 patients had no significant abnormality on MRI. Three patients subsequently developed local tumour recurrence. CONCLUSION: A single normal breast MRI examination during follow-up is a poor predictor of subsequent local recurrence. Coulthard, A. et al. (1999) ClinicalRadiology 54, 459-461. Key words: breast; breast neoplasms; breast, MR; magnetic resonance (MR).
Magnetic resonance imaging (MRI) of the breast has been advocated as a useful technique for detection of local recurrence in the post-operative patient [1-4]. MRI is probably of most value as an additional imaging test, in those patients suspected of having recurrent disease but with equivocal clinical or radiological findings. Currently there is little evidence from the literature to support the use of breast MRI as a routine imaging test in patients without equivocal clinical or imaging findings. However, there may be pressure from clinicians to use MRI as part of routine post-treatment follow-up, as breast MRI begins to be perceived as more sensitive than 'conventional' imaging strategies in the detection of breast cancer in this group of patients. When breast MRI first became available at this centre in 1993, there were few guidelines to the appropriate use of breast MRI. To develop our own experience, we agreed to perform breast MRI on consecutive patients attending the breast cancer follow-up clinic. In this study we have reviewed these patients, to determine whether MRI performed as part of breast cancer treatment follow-up has any predictive value on clinical outcome.
Correspondenceto: Dr A. Coulthard,UniversityDepartmentof Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, U.K. 0009-9260/99/070459+03 $12.00/0
MATERIALS AND METHODS
Sixty-three women with treated breast carcinoma attending the breast cancer follow-up clinic between October 1993 and September 1994 were referred for breast MRI. Suspicion of recurrence on clinical examination or mammography was documented at the time of referral. Patients were assigned to two groups: patients with equivocal clinical or mammographic findings ('equivocal' group) and patients considered to have post-operative changes only on clinical and radiographic examination (control group). Contrast-enhanced MRI of both breasts was performed on all patients at 1.0T using a dedicated bilateral breast coil (Siemens, Erlangen). Three-dimensional Fast Low Angle Shot (FLASH) acquisitions were acquired through both breasts in 6 0 - 9 0 s , once before and five times immediately after an intravenous injection of gadolinium DTPA 0.1 mmol/kg. Pixel subtraction was used to identify areas of contrast enhancement. Maximal percentage enhancement of > 100% within the first 3 m in post-injection was regarded as suspicious of malignancy. Clinical outcome at 3 years post breast MRI was documented from the case notes. Information was extracted on surgical treatment, radiotherapy and chemotherapy, histopathological diagnosis and nodal involvement in each case. Development of local or distant recurrent or metastatic disease was recorded. © 1999 The Royal College of Radiologists
460
CLINICALRADIOLOGY
Table 1 - Histological diagnosis of primary pathology
Histology
Equivocal group
Control Total group
Ductal carcinoma Lobular carcinoma Tubular/tubulovillous carcinoma Medullary carcinoma Spindle cell carcinoma Colloid mucous carcinoma Axillary node positive,primary not found Ductal carcinoma in situ Total
20 1 3 0 1 0 0 1 26
22 2 0 2 0 1 1 5 33
42 3 3 2 1 1 1 6 59
RESULTS Full clinical follow-up was available on 59 of 63 women (mean age 54 years, range 30-74). The histology of the primary tumours is given in Table 1. Thirteen of 59 patients had axillary node involvement at the time of surgery. Forty-four patients were treated by wide local excision of the primary turnout: 13 had lumpectomy and two had mastectomy. Fifty-one patients had post-operative radiotherapy. All patients were at least 1 year post-surgery at the time of MRI referral and had attended the follow-up clinic regularly since surgery (median 4 years 7 months, range 15 months-12 years). Twenty-six of 59 patients were assigned to the 'equivocal' group based on clinical and mammographic examination. Thirty-three patients formed the control group. The two groups were similar with regard to age (equivocal group: mean age 64.9, control group: mean age 64.1) and time between surgery and MRI (median 4 years 6 months for both groups). Clinical follow-up at 3 years (median 36 months, range 1 0 47 months) showed that three patients had developed metastatic disease and three patients had developed local recurrence in the ipsilateral breast (Table 2). Twenty-four of the 26 patients in the equivocal group were completely well at follow-up. There were no cases of locally
recurrent disease, but two patients had developed symptomatic metastatic disease: one pulmonary (19 months post MRI: patient A, Table 2) and one pulmonary and bone (35 months: patient B, Table 2). At the time of initial referral, MRI examination had detected four cases with equivocal MRI findings in this group, none of which was subsequently shown to represent recurrent disease (Table 3). None of the patients in the control group had breast MRI findings that were suspicious for locally recurrent disease, although incidental pleural metastases were identified in one patient (patient C, Table 2). However, within this group, three patients subsequently developed locally recurrent disease within the ipsilateral breast. Two asymptomatic recurrences were detected as stellate masses on routine annual mammography. One patient who had excision of a node-negative invasive ductal carcinoma 5 years before MRI presented with an 11 mm spiculated lesion on mammography 21 months postMRI, subsequently shown to be a grade 3 invasive ductal carcinoma (patient D, Table 2). The second patient, who had surgery for a breast mass 2 years prior to MRI (DCIS with fat necrosis) was identified as having a 10 mm spiculated lesion on mammography 29 months post-MRI, representing a grade 1 tubular carcinoma (patient E, Table 2). The third patient, who had surgery for a node-positive invasive ductal carcinoma 10 years before MRI, presented clinically with a palpable breast lump 37 months after MRI, shown at histology to be an 8 mm grade 2 invasive ductal carcinoma (patient F, Table 2). In each case, retrospective review of the initial MRI examination by two radiologists experienced in breast MRI did not reveal any suspicious lesions.
DISCUSSION Most studies of breast MRI in patients who have had previous treatment for breast cancer have recruited those patients in whom conventional assessment findings were equivocal [1-4]. There have been no studies using breast MRI as a
Table 2 - MRI findings in patients with subsequent recurrent or metastatic disease (WLE = Wide local excision; L = lumpectomy; RT -= Radiotherapy)
Patient
Study group
Primary diagnosis
Node status
Treatment
A
Equivocal
Ductal carcinoma
Negative
B
Equivocal
Ductal carcinoma
C
Control
D
Time, diagnosis to MRI
MRI findings
Recurrence
Time, MRI to recurrence
WLE + RT 70 m o n t h s
Non-enhancing scar
Pulmonary
19 months
Negative
WLE
Non-enhancing scar
Pulmonary, bone
35 months
Ductal carcinoma
Negative
WLE + RT 73 months
Plettral + pulmonary deposits
Pleural, pulmonary
0 months
Control
Lobular carcinoma
Negative
WLE+ RT 61 m o n t h s
Non-enhancing scar
Ipsilateral breast
21 months
E
Control
Ductal carcinoma in situ
Not samples
L
26 m o u t h s
Non-enhancing scar
Ipsilateral breast
29 months
F
Control
Ductal carcinoma
Positive
L + RT
122 m o n t h s
Non-enhancingscar
Ipsilateral breast
37 months
12 m o n t h s
MRI IN ROUTINEBREASTCANCER FOLLOW-UP
461
Table 3 - MRI findings and outcome in equivocal group patients with abnormal MRI (WLE = Wide local excision; L = lumpeetomy; RT = Radiotherapy; FNAC = Fine needle aspiration cytology)
Patient
Study group
Primary diagnosis
Node status
Treatment
Time, diagnosis to MRI
MRI findings
Outcome
G
Equivocal
Ductal carcinoma
Negative
WLE + RT
55 months
No abnormal enhancement, ipsilateral breast 5 mm enhancing focus, contralateral breast
Fibroadenoma, contralateral breast
H
Equivocal
Ductal carcinoma
Not sampled
L ÷ RT
108 months
Diffuse enhancement ipsilateral breast
FNAC negative: Well on follow-up (3 years)
I
Equivocal
Ductal carcinoma
Negative
WLE + RT
67 months
Non-enhancing scar
Well on follow-up
J
Equivocal
Ductal carcinoma
Negative
WLE + RT
40 months
Non-enhancing scar
Well on follow-up
screening tool in this situation, even though the relative risk of breast cancer is increased in these patients [5]. Screening studies utilizing MRI in other groups at increased risk of developing breast cancer are beginning to emerge [6]. Given the increased sensitivity of breast MRI over mammography in detection of cancer, there may be a place for a study comparing breast MRI with mammography in post-operative follow-up. This study has compared breast MRI with mammography and clinical examination in patients in whom clinical and mammographic assessment was equivocal and also in patients in whom assessment was considered to be normal. Although the results represent a comparison between MRI and conventional assessment at a single point in time, the extended clinical follow-up period has allowed us to make some observations which may have implications for any proposed longitudinal study of MRI in breast cancer follow-up, None of the 33 patients with unequivocally normal clinical examination and mammography had evidence of locally recurrent disease on MRI, suggesting that the pick-up rate for MRI detection of recurrent breast cancer in the absence of equivocal clinical or mammographic findings is likely to be low. The results also show that little long-term reassurance can be derived from a normal MRI result, as a single normal breast MRI examination is clearly a poor predictor of subsequent local recurrence. In our cohort of 59 patients, three patients with unequivocally normal clinical examination, mammography and breast MRI subsequently developed local recurrence within 3 years, two of which were identified on annual mammography. We can only speculate whether breast MRI would have identified these recurrences at an earlier stage, but there are implications for the frequency of
MRI examination if the latter is to be used routinely in breast cancer follow-up. Of the 26 patients referred with equivocal clinical examination or mammography, four abnormal MRI examinations instigated further investigations before recurrent disease could be excluded and the patients reassured. Although no local recurrences occurred in this group within the follow-up period, two patients developed distant metastases, a reminder that surveillance of the breast with even the most sensitive imaging modality is not the only issue of importance in this group of patients.
REFERENCES 1 Lewis-Jones HG, Whitehouse GH, Leinster SJ. The role of magnetic
2 3
4 5 6
resonance imaging in the assessment of local recurrent breast carcinoma. Clin Radiol 1991;43:197-204. Rieber A, Merkle E, Zeitler H, Gorich J, Kreienherg R, Brambs HJ et al. Value of MR mammography in the detection and exclusion of recurrent breast carcinoma. J Comput Assist Tomog 1997;21:780-784. Mumtaz H, Davidson T, Hall-Craggs MA, Payley M, Walmsley K, Cowley G e t al. Comparison of magnetic resonance imaging and conventional triple assessment in locally recurrent breast cancer. Br J Surg 1997;84:1147-1151. Muller RJB, Sanerwein W, Langer R. Assessment of local recurrence after breast-conserving therapy with MRI. J Comput Assist Tomog 1998;22:408-412. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors and genetics [see comments]. Br Med J 1994;309:1003-1006. MRC breast screening study advisory group. National study of magnetic resonance imaging to screen women at genetic risk of breast cancer. Lancet 1998 (Protocol P7/4: http://www.thelancet.com/newlancet/reg/ author/body.protocol2.html):4.
MRI in Routine Breast Cancer Follow-up: Correlation with Clinical Outcome A. COULTHARD,
C. J. B E V E R I D G E ,
A . J. P O T T E R T O N
University Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K. Received: 2 December 1998
Revised: 2 February 1999
Accepted: 9 February 1999
AIM: Magnetic resonance imaging (MRI) of the breast has been shown to be useful as an additional imaging test in patients suspected of having recurrent disease, when clinical examination or mammography are equivocal. This study examines the utility of MRI as a routine test in the follow-up of treated breast cancer patients without equivocal clinical or imaging findings. MATERIALS AND METHODS: Contrast-enhanced breast MRI was performed as part of routine breast cancer follow-up in 26 patients with equivocal clinical or mammographic findings and 33 control patients in whom clinical and imaging findings were consistent with post-treatment changes only. Clinical outcome was assessed at 3 years post MRI. RESULTS: Four patients with equivocal clinical or mammographic findings had abnormal MRI: all MRI abnormalities were subsequently shown to represent benign disease. None of the equivocal group developed local recurrence, although two of 26 developed distant metastases. One of the control group had unsuspected distant metastases detected by MRI: the other 32 patients had no significant abnormality on MRI. Three patients subsequently developed local tumour recurrence. CONCLUSION: A single normal breast MRI examination during follow-up is a poor predictor of subsequent local recurrence. Coulthard, A. et al. (1999) ClinicalRadiology 54, 459-461. Key words: breast; breast neoplasms; breast, MR; magnetic resonance (MR).
Magnetic resonance imaging (MRI) of the breast has been advocated as a useful technique for detection of local recurrence in the post-operative patient [1-4]. MRI is probably of most value as an additional imaging test, in those patients suspected of having recurrent disease but with equivocal clinical or radiological findings. Currently there is little evidence from the literature to support the use of breast MRI as a routine imaging test in patients without equivocal clinical or imaging findings. However, there may be pressure from clinicians to use MRI as part of routine post-treatment follow-up, as breast MRI begins to be perceived as more sensitive than 'conventional' imaging strategies in the detection of breast cancer in this group of patients. When breast MRI first became available at this centre in 1993, there were few guidelines to the appropriate use of breast MRI. To develop our own experience, we agreed to perform breast MRI on consecutive patients attending the breast cancer follow-up clinic. In this study we have reviewed these patients, to determine whether MRI performed as part of breast cancer treatment follow-up has any predictive value on clinical outcome.
Correspondenceto: Dr A. Coulthard,UniversityDepartmentof Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, U.K. 0009-9260/99/070459+03 $12.00/0
MATERIALS AND METHODS
Sixty-three women with treated breast carcinoma attending the breast cancer follow-up clinic between October 1993 and September 1994 were referred for breast MRI. Suspicion of recurrence on clinical examination or mammography was documented at the time of referral. Patients were assigned to two groups: patients with equivocal clinical or mammographic findings ('equivocal' group) and patients considered to have post-operative changes only on clinical and radiographic examination (control group). Contrast-enhanced MRI of both breasts was performed on all patients at 1.0T using a dedicated bilateral breast coil (Siemens, Erlangen). Three-dimensional Fast Low Angle Shot (FLASH) acquisitions were acquired through both breasts in 6 0 - 9 0 s , once before and five times immediately after an intravenous injection of gadolinium DTPA 0.1 mmol/kg. Pixel subtraction was used to identify areas of contrast enhancement. Maximal percentage enhancement of > 100% within the first 3 m in post-injection was regarded as suspicious of malignancy. Clinical outcome at 3 years post breast MRI was documented from the case notes. Information was extracted on surgical treatment, radiotherapy and chemotherapy, histopathological diagnosis and nodal involvement in each case. Development of local or distant recurrent or metastatic disease was recorded. © 1999 The Royal College of Radiologists
460
CLINICALRADIOLOGY
Table 1 - Histological diagnosis of primary pathology
Histology
Equivocal group
Control Total group
Ductal carcinoma Lobular carcinoma Tubular/tubulovillous carcinoma Medullary carcinoma Spindle cell carcinoma Colloid mucous carcinoma Axillary node positive,primary not found Ductal carcinoma in situ Total
20 1 3 0 1 0 0 1 26
22 2 0 2 0 1 1 5 33
42 3 3 2 1 1 1 6 59
RESULTS Full clinical follow-up was available on 59 of 63 women (mean age 54 years, range 30-74). The histology of the primary tumours is given in Table 1. Thirteen of 59 patients had axillary node involvement at the time of surgery. Forty-four patients were treated by wide local excision of the primary turnout: 13 had lumpectomy and two had mastectomy. Fifty-one patients had post-operative radiotherapy. All patients were at least 1 year post-surgery at the time of MRI referral and had attended the follow-up clinic regularly since surgery (median 4 years 7 months, range 15 months-12 years). Twenty-six of 59 patients were assigned to the 'equivocal' group based on clinical and mammographic examination. Thirty-three patients formed the control group. The two groups were similar with regard to age (equivocal group: mean age 64.9, control group: mean age 64.1) and time between surgery and MRI (median 4 years 6 months for both groups). Clinical follow-up at 3 years (median 36 months, range 1 0 47 months) showed that three patients had developed metastatic disease and three patients had developed local recurrence in the ipsilateral breast (Table 2). Twenty-four of the 26 patients in the equivocal group were completely well at follow-up. There were no cases of locally
recurrent disease, but two patients had developed symptomatic metastatic disease: one pulmonary (19 months post MRI: patient A, Table 2) and one pulmonary and bone (35 months: patient B, Table 2). At the time of initial referral, MRI examination had detected four cases with equivocal MRI findings in this group, none of which was subsequently shown to represent recurrent disease (Table 3). None of the patients in the control group had breast MRI findings that were suspicious for locally recurrent disease, although incidental pleural metastases were identified in one patient (patient C, Table 2). However, within this group, three patients subsequently developed locally recurrent disease within the ipsilateral breast. Two asymptomatic recurrences were detected as stellate masses on routine annual mammography. One patient who had excision of a node-negative invasive ductal carcinoma 5 years before MRI presented with an 11 mm spiculated lesion on mammography 21 months postMRI, subsequently shown to be a grade 3 invasive ductal carcinoma (patient D, Table 2). The second patient, who had surgery for a breast mass 2 years prior to MRI (DCIS with fat necrosis) was identified as having a 10 mm spiculated lesion on mammography 29 months post-MRI, representing a grade 1 tubular carcinoma (patient E, Table 2). The third patient, who had surgery for a node-positive invasive ductal carcinoma 10 years before MRI, presented clinically with a palpable breast lump 37 months after MRI, shown at histology to be an 8 mm grade 2 invasive ductal carcinoma (patient F, Table 2). In each case, retrospective review of the initial MRI examination by two radiologists experienced in breast MRI did not reveal any suspicious lesions.
DISCUSSION Most studies of breast MRI in patients who have had previous treatment for breast cancer have recruited those patients in whom conventional assessment findings were equivocal [1-4]. There have been no studies using breast MRI as a
Table 2 - MRI findings in patients with subsequent recurrent or metastatic disease (WLE = Wide local excision; L = lumpectomy; RT -= Radiotherapy)
Patient
Study group
Primary diagnosis
Node status
Treatment
A
Equivocal
Ductal carcinoma
Negative
B
Equivocal
Ductal carcinoma
C
Control
D
Time, diagnosis to MRI
MRI findings
Recurrence
Time, MRI to recurrence
WLE + RT 70 m o n t h s
Non-enhancing scar
Pulmonary
19 months
Negative
WLE
Non-enhancing scar
Pulmonary, bone
35 months
Ductal carcinoma
Negative
WLE + RT 73 months
Plettral + pulmonary deposits
Pleural, pulmonary
0 months
Control
Lobular carcinoma
Negative
WLE+ RT 61 m o n t h s
Non-enhancing scar
Ipsilateral breast
21 months
E
Control
Ductal carcinoma in situ
Not samples
L
26 m o u t h s
Non-enhancing scar
Ipsilateral breast
29 months
F
Control
Ductal carcinoma
Positive
L + RT
122 m o n t h s
Non-enhancingscar
Ipsilateral breast
37 months
12 m o n t h s
MRI IN ROUTINEBREASTCANCER FOLLOW-UP
461
Table 3 - MRI findings and outcome in equivocal group patients with abnormal MRI (WLE = Wide local excision; L = lumpeetomy; RT = Radiotherapy; FNAC = Fine needle aspiration cytology)
Patient
Study group
Primary diagnosis
Node status
Treatment
Time, diagnosis to MRI
MRI findings
Outcome
G
Equivocal
Ductal carcinoma
Negative
WLE + RT
55 months
No abnormal enhancement, ipsilateral breast 5 mm enhancing focus, contralateral breast
Fibroadenoma, contralateral breast
H
Equivocal
Ductal carcinoma
Not sampled
L ÷ RT
108 months
Diffuse enhancement ipsilateral breast
FNAC negative: Well on follow-up (3 years)
I
Equivocal
Ductal carcinoma
Negative
WLE + RT
67 months
Non-enhancing scar
Well on follow-up
J
Equivocal
Ductal carcinoma
Negative
WLE + RT
40 months
Non-enhancing scar
Well on follow-up
screening tool in this situation, even though the relative risk of breast cancer is increased in these patients [5]. Screening studies utilizing MRI in other groups at increased risk of developing breast cancer are beginning to emerge [6]. Given the increased sensitivity of breast MRI over mammography in detection of cancer, there may be a place for a study comparing breast MRI with mammography in post-operative follow-up. This study has compared breast MRI with mammography and clinical examination in patients in whom clinical and mammographic assessment was equivocal and also in patients in whom assessment was considered to be normal. Although the results represent a comparison between MRI and conventional assessment at a single point in time, the extended clinical follow-up period has allowed us to make some observations which may have implications for any proposed longitudinal study of MRI in breast cancer follow-up, None of the 33 patients with unequivocally normal clinical examination and mammography had evidence of locally recurrent disease on MRI, suggesting that the pick-up rate for MRI detection of recurrent breast cancer in the absence of equivocal clinical or mammographic findings is likely to be low. The results also show that little long-term reassurance can be derived from a normal MRI result, as a single normal breast MRI examination is clearly a poor predictor of subsequent local recurrence. In our cohort of 59 patients, three patients with unequivocally normal clinical examination, mammography and breast MRI subsequently developed local recurrence within 3 years, two of which were identified on annual mammography. We can only speculate whether breast MRI would have identified these recurrences at an earlier stage, but there are implications for the frequency of
MRI examination if the latter is to be used routinely in breast cancer follow-up. Of the 26 patients referred with equivocal clinical examination or mammography, four abnormal MRI examinations instigated further investigations before recurrent disease could be excluded and the patients reassured. Although no local recurrences occurred in this group within the follow-up period, two patients developed distant metastases, a reminder that surveillance of the breast with even the most sensitive imaging modality is not the only issue of importance in this group of patients.
REFERENCES 1 Lewis-Jones HG, Whitehouse GH, Leinster SJ. The role of magnetic
2 3
4 5 6
resonance imaging in the assessment of local recurrent breast carcinoma. Clin Radiol 1991;43:197-204. Rieber A, Merkle E, Zeitler H, Gorich J, Kreienherg R, Brambs HJ et al. Value of MR mammography in the detection and exclusion of recurrent breast carcinoma. J Comput Assist Tomog 1997;21:780-784. Mumtaz H, Davidson T, Hall-Craggs MA, Payley M, Walmsley K, Cowley G e t al. Comparison of magnetic resonance imaging and conventional triple assessment in locally recurrent breast cancer. Br J Surg 1997;84:1147-1151. Muller RJB, Sanerwein W, Langer R. Assessment of local recurrence after breast-conserving therapy with MRI. J Comput Assist Tomog 1998;22:408-412. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors and genetics [see comments]. Br Med J 1994;309:1003-1006. MRC breast screening study advisory group. National study of magnetic resonance imaging to screen women at genetic risk of breast cancer. Lancet 1998 (Protocol P7/4: http://www.thelancet.com/newlancet/reg/ author/body.protocol2.html):4.