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Does preoperative MRI influence the extent of surgical resection in conservative breast cancer surgery?
The Breml (1999J8, X4-88 0 1999 Harcourt Brace & Co. Ltd
ORIGINAL ARTICLE
Does preoperative MRI influence the extent of surgical resection in conservative breast cancer surgery? M. Douek,* T. Davidson,* M. A. Hall-Craggs,+ S. R. Lakhani,’ M. Baum* and I. Taylor* Departments of “Surgery, tRadiology and *Histopathology, 7LD, UK
University College London Medical School, London WlP
S U M M A R I’. We assessed prospectively the impact of preoperative breast magnetic resonance (MRI) on the extent of surgical resection. Of 131 breast cancers treated with breast conservation over 18 months, 41 underwent preoperative MRI. Scans were shown to the operating surgeon to indicate the location of lesions and their local extent. Clinical information and histological assessment of wide local excision specimens were compared between those patients who underwent preoperative MRI and those who did not. There was no significant difference between the MRI group (n=41) and no-MRI group (n=90) in average specimen weight (P = 0.72) or circumferential margin status (P = 0.17). Logistic regression analysis demonstrated a positive correlation between margin status and patient age (P = 0.045), younger patients being more likely to have involved margins, and a negative correlation with MRI status (P = 0.006) these women having an MRI being more likely to have negative margins. Preoperative MRI does not currently influence the extent of surgical resection in breast conservation surgery.
INTRODUCTION
provides accurate information on tumour size,’ which correlates closely with histological measurements.8’9 However, since clinical assessment often overestimates tumour size” and incorrectly stages breast cancer patients,” the wider availability of MRI may influence surgeons to alter the amount of tissue removed during breast conservation. The aim of our study was to assess prospectively the impact of preoperative MRI on extent of surgical resection.
The availability of magnetic resonance imaging (MRI) and its application to novel anatomical sites has increased dramatically in the UK over the last decade.’ Breast MRI, introduced in the mid 198Os,* is now increasingly used as an additional imaging modality in the management of breast cancer. However, since both its clinical indications in patient management and pre-operative planning of surgery have not yet been adequately clarified, it remains a modality which requires further evaluation. Additional enhancing foci on MRI are frequently noted adjacent to the main tumour. Although these may represent foci of in situ or invasive cancer,3 their clinical relevance has been questioned4 and it remains uncertain whether excision margins need to be extended in cases where such additional foci are detected. In breast cancer detection, the sensitivity of MRI approaches 1OO%5but its specificity is relatively 10w.~ MRI
PATIENTS Patients
Over a period of 18 months (September 1996-March 1998), 190 breast cancer patients with 193 breast cancers (three patients with bilateral tumours) were diagnosed by triple assessment (clinical examination, mammography and fine needle aspiration cytology). Of these, 131 cancers (67.9%) were treated by breast conservation surgery (wide local excision or quadrantectomy) with postoperative radiotherapy, and comprised the study group. Patients undergoing excisional biopsies were excluded. Breast MRI was offered to any eligible pre-operative patient according to availability of the MRI scanner. Patients were unselected but those with known claustrophobia (n=l), obesity (n=l), poor mobility (n=l), metal implants (n=2), or those who refused (n=2), were included in the no-MRI group for analysis.
Address correspondence to: I. Taylor, Professor of Surgery, Royal Free and University College Medical School, University College London, Department of Surgery, Charles Bell House, 67-73 Riding House Street, London WlP 7LD, UK. Fax: +44 171 636 5176 An abstract of our findings has been presented at the Surgical Society (SRS) Meeting in Dublin (2-3 July 1998).
AND METHODS
Research
84
Preoperative MRI influence on extent of surgical resection
85
Breast MRI
Statistical analysis
Breast MRI was performed using a high resolution transverse Tl-weighted three dimensional (3D) FLASH sequence (TR=18 ms, TE=7 ms, FA=40”; TA=4 m 56 s, FOV=410 mm) with a 1.0 T (Siemens Magneton Scanner 42 SP with dedicated breast coil) during the initial 8 months. The scanner was then upgraded and a dynamic transverse Tl-weighted three dimensional (3D) FLASH sequence (TR=8.1 ms, TE=4 ms, FA=20”; TA=l m 18 s, FOV=410 mm) with a 1.5 T (Siemens Magneton Vision) scanner, was used thereafter. Scans were performed before and after an intravenous bolus hand injection of dimeglumine gadopentetate (Magnevist, 0.2 mL/kg).
Statistical analysis was performed using the Independent Sample T-Test for comparing mean specimen weights between the MRI and no-MRI groups. Multiple regression analysis was used to identify variables, which correlate with the ratio of tumour volume to specimen weight. Logistic regression analysis was used to identify factors which correlated with circumferential margin status.
Surgical management MRI scans were not used for decision-making on type of surgery (conservative surgery vs mastectomy) but hard copies of matched pre- and post-contrast images were shown immediately before surgery to the operating surgeon to indicate the location of lesions, size and local extent. The written report was supplemented by comments from an experienced observer (M H-C or MD). It is standard practice for deep excision to include the pectoral fascia in patients undergoing wide local excision or quadrantectomy. The extent of conservative breast resection was decided upon by the surgeon (TD, MB, IT). Intraoperatively, all specimens were orientated using sutures and sent fresh for histological assessment.
Histopathological
RESULTS Clinical and pathological characteristics of the 131 patients studied are summarized on Table 1. Of those patients who underwent MRI, four had a primary tumour represented by only a few small enhancing foci and two had multifocal primary tumours (Fig. 1). Additional enhancing foci away from the primary tumour (Fig. 2) were identified and reported in eight patients. None of the patients who underwent MRI was subsequently converted to a mastectomy as a result of MRI findings. No significant difference between the MRI group (n=41) and no-MRI group (n=90) was seen in average specimen weight (Table 2a) or resection margin status (Table 2b). Multiple regression analysis was performed using the ratio of tumour size to specimen weight as the grouping variable; Table 1 Characteristics of breast cancer preoperative MRI and those who did not
assessment
A single breast pathologist (SL), who was unaware of the MRI findings, performed the histopathological assessment. Specimens were weighed, inked and sectioned in a transverse plane. The largest tumour cross-section was processed whole as a large block. Additional small blocks were taken for estimation of closest margins. Excision margins were classified as positive (invasive carcinoma present at an inked margin); close (invasive carcinoma 1 mm from an inked margin); negative (no invasive carcinoma within 1 mm from an inked margin) or indeterminate (not measured). Circumferential margin status was determined by excluding deep margin involvement. Breast specimen weights and excision margin status were used to estimate the actual volume of tissue removed and were compared between those patients who underwent preoperative MRI and those who did not. A ratio of tumour volume over specimen weight (4/3 x II x r’/specimen weight; r = tumour radius) was used as a measure of extent of surgical excision, using specimen weight as an estimate of actual specimen volume. This takes account of the relative volume of specimen required to remove a tumour of a particular size.
Age (years) Axillary
node surgery
Tumour
grade
Tumour
size (cm)
Vascular
invasion
Values
in parenthesis
Meanksd Range Clearance Sampling None I II 111 <2 2-s >5
patients
who underwent
MRI (n=4 1)
No-MRI (n=90)
50.2kl4.2 2X-84 27 (65.9) 2 (4.9) 12 (29.3) 5/3l (16.1) 13131 (41.9) 13/31 (41.9) 14132 (43.8) 17/32 (53.1) l/32 (3.1) 13141 (31.7)
56.3kl4.5 28-87 52 (57.8) 4 (4.4) 34 (37.8) 1 l/80 (13.8) 39/80 (48.8) 30/80 (37.5) 37/83 (44.6) 43/83 (5 1.8) 3/83 (3.6) 31/90 (34.4)
are percentages.
Fig. 1 Pre- (A), post- (B) and subtracted (C) contrast-enhanced MRI scan of a multifocal breast tumour. Two distinct enhancement foci (small arrows) were detected away from the primary tumour (large arrow).
86
The Breast Table 3 Multiple regression influence the ratio of tumour specimen weight)
Age Margin MRUNo
status MRI
SE: standard
Comparison
of specimen
weight
(a) and resection
margin
SE of Coefficient
P
2.108 -51.981 31.580
1.367 28.878 43.020
0.126 0.075 0.465
error
(a)
Age Tumour Tumour MRUNo
and age, MRI (performed/not performed) and resection margin status, as explanatory variables. There was no statistically significant correlation with the explanatory variables (Table 3). When close margins were regarded as positive, a logistic regression model demonstrated a positive correlation between resection margin status and patient age (younger patients being more likely to have involved margins) and a negative correlation between resection margin status and MRI status (patients having MRI being more likely to have negative margins) (Table 4a). These correlations were not present when close margins were regarded as negative (Table 4b). Re-excision for histologically confirmed residual disease was performed in 11 patients. Of these, three patients underwent preoperative MRI and eight did not. 2
Coefficient
Table 4 Results of fitting a logistic regression model to determine which variables independantly correlate with resection margin status. Close margins were regarded as positive (a) or negative (b).
Fig. 2 Pre- (A) and post- (B) contrast-enhanced breast MRI showing a breast tumour (large arrow) which was also clinically palpable. The smaller enhancing focus (small arrow) away from the index quadrant was an incidental finding. The surgeon decided not to attempt to remove this lesion and follow-up MRI was recommended.
Table
analysis to determine which factors volume to specimen weight (4/3pr’/
diameter volumelspeciment MRI
weight
Coefficient
SE
P
0.032 -0.049 -0.007 -1.261
0.016 0.030 0.002 0.550
0.036 0.098 0.653 0.022
Coefficient
SE
P
0.038 -0.083 0.003 -0.263
0.022 0.040 0.003 0.681
0.091 0.038 0.23 1 0.699
(b)
Age Tumour Tumour MRI/No
diameter volumekpeciment MRI
weight
DISCUSSION The detection of additional small enhancing foci away from the primary tumour by MRI represents a clinical problem4 since it may lead to more extensive wide local excisions or
status (b) between
patients
who underwent
preoperative
MRI
and those who did not.
(a)
Specimen weight (g)
Mean SD
MRI (n=41)
No-MRI (n=90)
Mean Difference
SE of Difference
95% CI for SE of Difference
2 Tail P*
98.8 84.1
93.4 78
-5.40
15.16
-35.4,
0.72
*T: test for equality of the means. CI: confidence interval; SE: standard
24.6
error.
@I
Margin status (distance resection margin)
of invasive
carcinoma
from
nearest
Circumferential margin status (distance of invasive margin nearest resection margin other than the deep margin)
Circumferential disease from
*Chi
from
margin status (distance of in situ or invasive nearest resection margin other than the deep margin)
square test with 2 DF (indeterminate
cases were excluded).
MRI (n=41)
No-MRI (n=90)
P*
Positive (0 mm) Close (G 1 mm) Negative (> 1 mm) Indeterminate
8 8 23 2
(19.5%) (19.5%) (56.1%) (4.9%)
15 28 44 3
(16.7%) (31.1%) (48.9%) (3.3%)
0.41
Positive (0 mm) Close (< 1 mm) Negative (> 1 mm) Indetermine
4 4 31 2
(9.8%) (9.8%) (75.6%) (4.9%)
10 21 56 3
(11.1%) (23.3%) (62.2) (3.3%)
0.17
Positive (0 mm) Close (= I mm) Negative (> 1 mm) Indeterminate
6 3 31 1
(14.6%) (7.3%) (75.6%) (2.4%)
16 24 48 2
(17.8%) (26.7%) (53.3%) (2.2%)
0.06
Preoperative MRI influence on extent of surgical resection even unnecessary mastectomies. It is essential therefore to determine the impact of MRI on patient management as well as the clinical significance of additional small enhancing foci by prospective comparative studies. However, as a result of the rapid expansion of MRI in the UK (Fig. 3), breast MRI may become widely used before the results of such trials are available. In this prospective study we evaluated whether MRI currently influences the extent of surgical resection in conservative breast surgery. We used resection margin status and specimen weight as surrogate markers of the actual volume of tissue removed during surgery. The deleterious effects of large resections on cosmesis are well recognised.“,‘” Smaller resections are reported by some to lead to higher positive margin and local recurrence rates.” Resection margin closeness or involvement by tumour does represent a risk factor for the development of local recurrence,‘5.‘h especially in the absence of radiotherapy,12,” and it is therefore important to ensure negative resection margins during breast conservation. Positive and close margin rates vary between different studies depending on the pathological technique used for assessment,‘8 the pathological criteria used,” and whether or not the deep margin (pectoral fascia) is included in the assessment. However, deep margin involvement is less clinically significant since an adequate conservative resection includes the pectoral fascia and when the pectoral fascia is involved, it does not appear to be a risk factor for recurrence, even following mastectomy.‘” In this study we compared resection margin status between the groups using the deep as well as circumferential margins. Our margin positive rates compared favourably with those of other surgical studies.“-‘” Ten of 41 patients who underwent MRI had enhancing foci away from the primary lesion. Although these may
87
represent in situ or invasive cancer foci,5 long-term followup is necessary to determine their natural history and clinical significance. When mastectomy specimens are sampled extensively, cancer foci are seen throughout the breast in up to 60% of cases.” However, large clinical studies have shown that up to 90% of local recurrences following breast conservation occur in the operated quadrant and consequently the significance of these cancer foci has been questioned.h Since there is no evidence to suggest that subclinical enhancing foci on MRI, if left surgically untreated, lead to poor local control, resecting them may not be necessary. In this prospective study we have demonstrated that knowledge of breast MRI findings preoperatively does not appear to significantly influence the extent of surgical resection. The negative correlation between margin status and having an MRI suggests that preoperative MRI may increase tumour clearance margins if close margins are regarded as unacceptable (Table 4a). This may ultimately result in larger resections although we have not demonstrated this in our patient series. Advances in real time 3D-breast MRIz8 and interventional biopsy techniques” may influence surgical management in the future but these techniques are still at the experimental stage. At present, surgeons are primarily guided by clinical and mammographic assessment of local tumour extent in deciding how much tissue to excise at the time of breast conservation.
Acknowledgement This project is supported Hospital Trustees.
by a research
grant from
the Middlesex
References I
2.
3.
4.
5.
6. 7.
Fig. 3 Cumulative were obtained from
total and yearly MR installations in the UK (figures the MRI Evaluation Centre Database’)
8.
De Wilde J. MRI Evaluation Centre for the Medical Devices Agency (MagNET) Database. Electrical Engineering Department, Imperial College of Science Technology and Medicine, London. El Yousef S J, Duchesneau R H. Magnetic resonance imaging of the human breast: A phase 1 trial. Radio1 Clin North Am 1984; 22: 859-868. Davis P L, McCarty K S Jr. Sensitivity of enhanced MRI for the detection of breast cancer: new, multicentric, residual, and recurrent. Eur Radio1 1997; 7 Suppl 5: 289-298. Heywang-Kobrunner S H. Veiweg P, Heinig A, Kuchler C. Contrast-enhanced MRI of the breast: accuracy. value. controversies. solutions. Eur J Radio1 1997; 24(2): 94-108. Douek M. Vaidya J S, Lakhani S R, Hall-Craggs M A, Baum M. Taylor I. Can magnetic resonance imaging help elucidate the natural history of breast cancer multicentricity? Lancet 1998; 351: 801-802. Baum M, Vaidya J S, Mittra 1. Multicentricity and recurrence of breast cancer. Lancet 1997; 349: 208. Davis P L, Staiger M J, Harris K B, et al. Breast cancer measurements with magnetic resonance imaging, ultrasonography. and mammography. Breast Cancer Res Treat 1996; 37(l): l-9. Yang W T, Lam W W, Cheung H, Suen M, King W W, Metreweli C. Sonographic, magnetic resonance imaging, and mammographic
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The Breast assessments of preoperative size of breast cancer. J Ultrasound Med 1997; 16(12): 791-797. Mumtaz H, Hall-Craggs M A, Davidson T, et al. Staging of symptomatic primary breast cancer with MR imaging. Am J Roentgen01 1997 Aug; 169(2): 417424. Pain J A, Ebbs S R, Hem R P, Lowe S, Bradbeer J W. Assessment of breast cancer size: a comparison of methods. Em J Surg Oncol 1992; 18( 1): 44-48. Dixon J M, Senbanjo R 0, Anderson T J, Forrest A P, Elton R A. Clinical assessment of tumour size in primary breast carcinoma. Clin Oncol 1984; 10(2): 117-121. Veronesi U, Luini A, Galimberti V, Zurrida S. Conservative approaches for the management of stage I/II carcinoma of the breast: Milan Cancer Institute trials. World J Surg 1994; 18: 70-75. Liauw S H, Sanfilippo L J, Santoro E. Breast size versus cosmesis and local control in stages I and II breast carcinoma. N J Med 1987; 84: 706-710. Vicini F A, Eberlein T J, Connolly J L et. al. The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy. Ann Surg 199 1; 214(3): 200-205. Noguchi S, Koyama H, Kasugai T, et al. A case-control study on risk factors for local recurrences or distant metastases in breast cancer patients treated with breast-conserving surgery. Oncology 1997; 54(6): 4688474. Kurtz J M, Jacquemier J, Amalric R, et al. Risk factors for breast recurrence in premenopausal and postmenopausal patients with ductal cancers treated by conservation therapy. Cancer 1990; 65(8): 1867-1878. Renton S C, Gazet J C, Ford H T, Corbishley C, Sutcliffe R. The importance of the resection margin in breast conservative surgery for beast cancer. Eur J Surg Oncol 1996; 22(l): 17-22. Guidi A J, Connolly J L, Harris J R, Schnitt S J. The relationship between shaved margin and inked margin status in breast excision specimens. Cancer 1997; 79(8): 1568-1573. Fisher E R, Costantino J, Fisher B, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol
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B-17. Five-year observations concerning lobular carcinoma in situ. Cancer 1996; 78(7): 1403-1416. Mentzer S J, Osteen R T, Wilson R E. Local recurrence and the deep resection margin in carcinoma of the breast. Surg Gynecol Obstet 1986; 163(6): 513-517. Umpleby H, Royle G, Herbert A, Taylor I. Wide excision of primary breast cancer: the incidence of residual carcinoma at the site of excision. Annals of the Royal College of Surgeons 1988; 70: 246-248. MacMillan R D, Purushotham A D, Mallon E, Ramsay G, George W D. Breast-conserving surgery and tumour bed positivity in patients with breast cancer. Br J Surg 1994; 81: 56-58. Chinyama C N, Davies J D, Rayter Z, Farndon J R. Factors affecting surgical margin clearance in screen-detected breast cancer and the effect of cavity biopsies on residual disease. European Journal of Surgical Oncology 1997; 23: 123-127. Spivack B, Khanna M M, Tafra L, Juillard G, Giuliano A E. Margin status and local recurrence after breast conserving surgery. Arch Surg 1994; 952-957. Macmillan R D, Purushotham A D, Mallon E, Love J G, George W D. Tumour bed positivity predicts outcome after breast conservation surgery. Br J Surg 1997; 84: 159-1562. Fisher E R, Anderson S, Redmond C, Fisher B. Ipsilateral breast tumour recurrence and survival following lumpectomy: pathological findings from the NSABP protocol B-06. Semin Surg Oncol 1992; 8(3): 161-166. Vaidya J S, Vyas J, Chinoy R F, Merchant N H, Sharma 0 P, Mittra I. Multicentricity of breast cancer: whole organ analysis and clinical implications. Br J Cancer 1996; 74: 820-824. Daniel B L, Jeffrey S S, Birdwell R L, Ikeda D M, Sawyer-Glover A M, Herlkens R J. Three-dimensional shaded-surface rendering of MR images of the breast: technique, applications, and impact on surgical management of breast disease. Radiographics 1998; 18(2): 483-496. Gould S W, Lamb G, Lomax D, Gedroyc W, Darzi A J. Interventional MR-guided excisional biopsy of breast lesions. Magn Reson Imaging 1998; 8( 1): 26-30.
ORIGINAL ARTICLE
Does preoperative MRI influence the extent of surgical resection in conservative breast cancer surgery? M. Douek,* T. Davidson,* M. A. Hall-Craggs,+ S. R. Lakhani,’ M. Baum* and I. Taylor* Departments of “Surgery, tRadiology and *Histopathology, 7LD, UK
University College London Medical School, London WlP
S U M M A R I’. We assessed prospectively the impact of preoperative breast magnetic resonance (MRI) on the extent of surgical resection. Of 131 breast cancers treated with breast conservation over 18 months, 41 underwent preoperative MRI. Scans were shown to the operating surgeon to indicate the location of lesions and their local extent. Clinical information and histological assessment of wide local excision specimens were compared between those patients who underwent preoperative MRI and those who did not. There was no significant difference between the MRI group (n=41) and no-MRI group (n=90) in average specimen weight (P = 0.72) or circumferential margin status (P = 0.17). Logistic regression analysis demonstrated a positive correlation between margin status and patient age (P = 0.045), younger patients being more likely to have involved margins, and a negative correlation with MRI status (P = 0.006) these women having an MRI being more likely to have negative margins. Preoperative MRI does not currently influence the extent of surgical resection in breast conservation surgery.
INTRODUCTION
provides accurate information on tumour size,’ which correlates closely with histological measurements.8’9 However, since clinical assessment often overestimates tumour size” and incorrectly stages breast cancer patients,” the wider availability of MRI may influence surgeons to alter the amount of tissue removed during breast conservation. The aim of our study was to assess prospectively the impact of preoperative MRI on extent of surgical resection.
The availability of magnetic resonance imaging (MRI) and its application to novel anatomical sites has increased dramatically in the UK over the last decade.’ Breast MRI, introduced in the mid 198Os,* is now increasingly used as an additional imaging modality in the management of breast cancer. However, since both its clinical indications in patient management and pre-operative planning of surgery have not yet been adequately clarified, it remains a modality which requires further evaluation. Additional enhancing foci on MRI are frequently noted adjacent to the main tumour. Although these may represent foci of in situ or invasive cancer,3 their clinical relevance has been questioned4 and it remains uncertain whether excision margins need to be extended in cases where such additional foci are detected. In breast cancer detection, the sensitivity of MRI approaches 1OO%5but its specificity is relatively 10w.~ MRI
PATIENTS Patients
Over a period of 18 months (September 1996-March 1998), 190 breast cancer patients with 193 breast cancers (three patients with bilateral tumours) were diagnosed by triple assessment (clinical examination, mammography and fine needle aspiration cytology). Of these, 131 cancers (67.9%) were treated by breast conservation surgery (wide local excision or quadrantectomy) with postoperative radiotherapy, and comprised the study group. Patients undergoing excisional biopsies were excluded. Breast MRI was offered to any eligible pre-operative patient according to availability of the MRI scanner. Patients were unselected but those with known claustrophobia (n=l), obesity (n=l), poor mobility (n=l), metal implants (n=2), or those who refused (n=2), were included in the no-MRI group for analysis.
Address correspondence to: I. Taylor, Professor of Surgery, Royal Free and University College Medical School, University College London, Department of Surgery, Charles Bell House, 67-73 Riding House Street, London WlP 7LD, UK. Fax: +44 171 636 5176 An abstract of our findings has been presented at the Surgical Society (SRS) Meeting in Dublin (2-3 July 1998).
AND METHODS
Research
84
Preoperative MRI influence on extent of surgical resection
85
Breast MRI
Statistical analysis
Breast MRI was performed using a high resolution transverse Tl-weighted three dimensional (3D) FLASH sequence (TR=18 ms, TE=7 ms, FA=40”; TA=4 m 56 s, FOV=410 mm) with a 1.0 T (Siemens Magneton Scanner 42 SP with dedicated breast coil) during the initial 8 months. The scanner was then upgraded and a dynamic transverse Tl-weighted three dimensional (3D) FLASH sequence (TR=8.1 ms, TE=4 ms, FA=20”; TA=l m 18 s, FOV=410 mm) with a 1.5 T (Siemens Magneton Vision) scanner, was used thereafter. Scans were performed before and after an intravenous bolus hand injection of dimeglumine gadopentetate (Magnevist, 0.2 mL/kg).
Statistical analysis was performed using the Independent Sample T-Test for comparing mean specimen weights between the MRI and no-MRI groups. Multiple regression analysis was used to identify variables, which correlate with the ratio of tumour volume to specimen weight. Logistic regression analysis was used to identify factors which correlated with circumferential margin status.
Surgical management MRI scans were not used for decision-making on type of surgery (conservative surgery vs mastectomy) but hard copies of matched pre- and post-contrast images were shown immediately before surgery to the operating surgeon to indicate the location of lesions, size and local extent. The written report was supplemented by comments from an experienced observer (M H-C or MD). It is standard practice for deep excision to include the pectoral fascia in patients undergoing wide local excision or quadrantectomy. The extent of conservative breast resection was decided upon by the surgeon (TD, MB, IT). Intraoperatively, all specimens were orientated using sutures and sent fresh for histological assessment.
Histopathological
RESULTS Clinical and pathological characteristics of the 131 patients studied are summarized on Table 1. Of those patients who underwent MRI, four had a primary tumour represented by only a few small enhancing foci and two had multifocal primary tumours (Fig. 1). Additional enhancing foci away from the primary tumour (Fig. 2) were identified and reported in eight patients. None of the patients who underwent MRI was subsequently converted to a mastectomy as a result of MRI findings. No significant difference between the MRI group (n=41) and no-MRI group (n=90) was seen in average specimen weight (Table 2a) or resection margin status (Table 2b). Multiple regression analysis was performed using the ratio of tumour size to specimen weight as the grouping variable; Table 1 Characteristics of breast cancer preoperative MRI and those who did not
assessment
A single breast pathologist (SL), who was unaware of the MRI findings, performed the histopathological assessment. Specimens were weighed, inked and sectioned in a transverse plane. The largest tumour cross-section was processed whole as a large block. Additional small blocks were taken for estimation of closest margins. Excision margins were classified as positive (invasive carcinoma present at an inked margin); close (invasive carcinoma 1 mm from an inked margin); negative (no invasive carcinoma within 1 mm from an inked margin) or indeterminate (not measured). Circumferential margin status was determined by excluding deep margin involvement. Breast specimen weights and excision margin status were used to estimate the actual volume of tissue removed and were compared between those patients who underwent preoperative MRI and those who did not. A ratio of tumour volume over specimen weight (4/3 x II x r’/specimen weight; r = tumour radius) was used as a measure of extent of surgical excision, using specimen weight as an estimate of actual specimen volume. This takes account of the relative volume of specimen required to remove a tumour of a particular size.
Age (years) Axillary
node surgery
Tumour
grade
Tumour
size (cm)
Vascular
invasion
Values
in parenthesis
Meanksd Range Clearance Sampling None I II 111 <2 2-s >5
patients
who underwent
MRI (n=4 1)
No-MRI (n=90)
50.2kl4.2 2X-84 27 (65.9) 2 (4.9) 12 (29.3) 5/3l (16.1) 13131 (41.9) 13/31 (41.9) 14132 (43.8) 17/32 (53.1) l/32 (3.1) 13141 (31.7)
56.3kl4.5 28-87 52 (57.8) 4 (4.4) 34 (37.8) 1 l/80 (13.8) 39/80 (48.8) 30/80 (37.5) 37/83 (44.6) 43/83 (5 1.8) 3/83 (3.6) 31/90 (34.4)
are percentages.
Fig. 1 Pre- (A), post- (B) and subtracted (C) contrast-enhanced MRI scan of a multifocal breast tumour. Two distinct enhancement foci (small arrows) were detected away from the primary tumour (large arrow).
86
The Breast Table 3 Multiple regression influence the ratio of tumour specimen weight)
Age Margin MRUNo
status MRI
SE: standard
Comparison
of specimen
weight
(a) and resection
margin
SE of Coefficient
P
2.108 -51.981 31.580
1.367 28.878 43.020
0.126 0.075 0.465
error
(a)
Age Tumour Tumour MRUNo
and age, MRI (performed/not performed) and resection margin status, as explanatory variables. There was no statistically significant correlation with the explanatory variables (Table 3). When close margins were regarded as positive, a logistic regression model demonstrated a positive correlation between resection margin status and patient age (younger patients being more likely to have involved margins) and a negative correlation between resection margin status and MRI status (patients having MRI being more likely to have negative margins) (Table 4a). These correlations were not present when close margins were regarded as negative (Table 4b). Re-excision for histologically confirmed residual disease was performed in 11 patients. Of these, three patients underwent preoperative MRI and eight did not. 2
Coefficient
Table 4 Results of fitting a logistic regression model to determine which variables independantly correlate with resection margin status. Close margins were regarded as positive (a) or negative (b).
Fig. 2 Pre- (A) and post- (B) contrast-enhanced breast MRI showing a breast tumour (large arrow) which was also clinically palpable. The smaller enhancing focus (small arrow) away from the index quadrant was an incidental finding. The surgeon decided not to attempt to remove this lesion and follow-up MRI was recommended.
Table
analysis to determine which factors volume to specimen weight (4/3pr’/
diameter volumelspeciment MRI
weight
Coefficient
SE
P
0.032 -0.049 -0.007 -1.261
0.016 0.030 0.002 0.550
0.036 0.098 0.653 0.022
Coefficient
SE
P
0.038 -0.083 0.003 -0.263
0.022 0.040 0.003 0.681
0.091 0.038 0.23 1 0.699
(b)
Age Tumour Tumour MRI/No
diameter volumekpeciment MRI
weight
DISCUSSION The detection of additional small enhancing foci away from the primary tumour by MRI represents a clinical problem4 since it may lead to more extensive wide local excisions or
status (b) between
patients
who underwent
preoperative
MRI
and those who did not.
(a)
Specimen weight (g)
Mean SD
MRI (n=41)
No-MRI (n=90)
Mean Difference
SE of Difference
95% CI for SE of Difference
2 Tail P*
98.8 84.1
93.4 78
-5.40
15.16
-35.4,
0.72
*T: test for equality of the means. CI: confidence interval; SE: standard
24.6
error.
@I
Margin status (distance resection margin)
of invasive
carcinoma
from
nearest
Circumferential margin status (distance of invasive margin nearest resection margin other than the deep margin)
Circumferential disease from
*Chi
from
margin status (distance of in situ or invasive nearest resection margin other than the deep margin)
square test with 2 DF (indeterminate
cases were excluded).
MRI (n=41)
No-MRI (n=90)
P*
Positive (0 mm) Close (G 1 mm) Negative (> 1 mm) Indeterminate
8 8 23 2
(19.5%) (19.5%) (56.1%) (4.9%)
15 28 44 3
(16.7%) (31.1%) (48.9%) (3.3%)
0.41
Positive (0 mm) Close (< 1 mm) Negative (> 1 mm) Indetermine
4 4 31 2
(9.8%) (9.8%) (75.6%) (4.9%)
10 21 56 3
(11.1%) (23.3%) (62.2) (3.3%)
0.17
Positive (0 mm) Close (= I mm) Negative (> 1 mm) Indeterminate
6 3 31 1
(14.6%) (7.3%) (75.6%) (2.4%)
16 24 48 2
(17.8%) (26.7%) (53.3%) (2.2%)
0.06
Preoperative MRI influence on extent of surgical resection even unnecessary mastectomies. It is essential therefore to determine the impact of MRI on patient management as well as the clinical significance of additional small enhancing foci by prospective comparative studies. However, as a result of the rapid expansion of MRI in the UK (Fig. 3), breast MRI may become widely used before the results of such trials are available. In this prospective study we evaluated whether MRI currently influences the extent of surgical resection in conservative breast surgery. We used resection margin status and specimen weight as surrogate markers of the actual volume of tissue removed during surgery. The deleterious effects of large resections on cosmesis are well recognised.“,‘” Smaller resections are reported by some to lead to higher positive margin and local recurrence rates.” Resection margin closeness or involvement by tumour does represent a risk factor for the development of local recurrence,‘5.‘h especially in the absence of radiotherapy,12,” and it is therefore important to ensure negative resection margins during breast conservation. Positive and close margin rates vary between different studies depending on the pathological technique used for assessment,‘8 the pathological criteria used,” and whether or not the deep margin (pectoral fascia) is included in the assessment. However, deep margin involvement is less clinically significant since an adequate conservative resection includes the pectoral fascia and when the pectoral fascia is involved, it does not appear to be a risk factor for recurrence, even following mastectomy.‘” In this study we compared resection margin status between the groups using the deep as well as circumferential margins. Our margin positive rates compared favourably with those of other surgical studies.“-‘” Ten of 41 patients who underwent MRI had enhancing foci away from the primary lesion. Although these may
87
represent in situ or invasive cancer foci,5 long-term followup is necessary to determine their natural history and clinical significance. When mastectomy specimens are sampled extensively, cancer foci are seen throughout the breast in up to 60% of cases.” However, large clinical studies have shown that up to 90% of local recurrences following breast conservation occur in the operated quadrant and consequently the significance of these cancer foci has been questioned.h Since there is no evidence to suggest that subclinical enhancing foci on MRI, if left surgically untreated, lead to poor local control, resecting them may not be necessary. In this prospective study we have demonstrated that knowledge of breast MRI findings preoperatively does not appear to significantly influence the extent of surgical resection. The negative correlation between margin status and having an MRI suggests that preoperative MRI may increase tumour clearance margins if close margins are regarded as unacceptable (Table 4a). This may ultimately result in larger resections although we have not demonstrated this in our patient series. Advances in real time 3D-breast MRIz8 and interventional biopsy techniques” may influence surgical management in the future but these techniques are still at the experimental stage. At present, surgeons are primarily guided by clinical and mammographic assessment of local tumour extent in deciding how much tissue to excise at the time of breast conservation.
Acknowledgement This project is supported Hospital Trustees.
by a research
grant from
the Middlesex
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Fig. 3 Cumulative were obtained from
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