Use of (routine) preoperative MRI in breast cancer: current evidence Joint Hospital Surgical Grand Round 22 Oct 2011.

Use of (routine) preoperative MRI in breast cancer:

current evidence

Joint Hospital Surgical Grand Round 22 Oct 2011

Presentation outline

Introduction Literature review Our own data

Introduction

Traditional triple assessment gives limited data on precise tumor size, location and margin

And whether there are multifocal (=several foci of tumors in the same quadrant) /multicentric (=foci of tumors in different quadrant) /contralateral disease

Breast magnetic resonance imaging (MRI) is emerging as a new clinical adjunct in this respect

Better surgical planning theoretically translates into less local recurrence and improved survival

BI-RADS (= Breast Imaging Reporting and Data System) 5

Radiology (2007) 244, 356-378

BI-RADS 2

Radiology (2007) 244, 356-378

MR Spectroscopy

Total choline (tCho) peak

Radiol Clin N Am (2010) 48, 1013-1042

Diffusion Weighted Imaging (DWI)

Radiol Clin N Am (2010) 48, 1013-1042

Clinical outcomes

Short term Sensitivity and specificity Alteration in management Re-excision rate

Long term Recurrence and survival

Three reviews conducted by Nehmat Houssami

Concluded that “ Evidence consistently shows that MRI changes surgical management, usually from breast conservation to more radical surgery; however there is no evidence it improves surgical care or prognosis”

J Clin Oncol (2008) 26, 3248-3258J Clin Oncol (2009) 27, 5640-5649CA Cancer J Clin (2009) 59, 290-302

(1) Accuracy and Surgical Impact of MRI in Breast Cancer Staging: Systemic Review and Meta-Analysis in Detection of Multifocal and Multicentric Cancer

19 studies with n=2610 MRI detected additional disease in 16%

(interquartile range 11-24%) of women with breast cancer

Summary PPV 66% (95%CI, 52-77%) TP: FP ratio 1.91 (95%CI, 1.09-3.34) Conversion due to MRI

Wide local excision (WLE) to mastectomy 8.1% WLE to more extensive surgery 11.3%

Unnecessary conversion due to MRI (histology negative) WLE to mastectomy 1.1% WLE to more extensive surgery 5.5% J Clin Oncol (2008)

26, 3248-3258

(2) MRI Screening of the Contralateral Breast in Women with Newly Diagnosed Breast Cancer: Systematic Review and Meta-Analysis of Incremental Cancer Detection and Impact on Surgical Management

22 studies with n=3253 Additional contralateral disease detected by

MRI 9.3% (interquartile range 3.8-13.9%) Summary PPV 47.9% (95%CI, 31.8-64.6%) TP:FP ratio 0.92 (95%CI, 0.47-1.82) No data on pooled management alteration

J Clin Oncol (2009) 27, 5640-5649

(3) Review of Preoperative MRI in Breast Cancer. Should MRI be Performed on All Women with Newly Diagnosed, Early Stage Breast Cancer? RCTs showed equivalent survival between breast

conservation therapy (WLE + radiotherapy) and mastectomy for early stage cancer

Vast majority of MRI detected additional disease are within same quadrant as the index tumor, which can be successful treated with post operative radiotherapy

COMICE trial and two additional observational studies did not show reduction in re-excision rate and on contrary higher mastectomy rate

Average of 22.4 days delay in workup

CA Cancer J Clin (2009) 59, 290-302

Only two observational studies provided data on long term outcome Fischer et al study limited by imbalance of

treatment between two groups Solin et al study

Local recurrence in 8 years (MRI+ vs. MRI-ve, 3% vs. 4%, p=0.51)

Overall survival in 8 years (86% vs. 87%, p=0.51)

Significant false positive rate caused additional cost and procedure; potential impact on cosmetic outcome

CA Cancer J Clin (2009) 59, 290-302

Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial

Multi-center, randomised 1623 women with biopsy proven breast

cancer scheduled for WLE after triple therapy MRI (n=816) vs. no further imaging (n=807)

Lancet (2010) 375, 563-571

19% 19%

Reoperation rate within 6 months 19% MRI group vs. 19% in no MRI group(odds ratio 0.96, 95%CI 0.75-1.24, p=0.77)

Cost: MRI group £5508.4 vs. No MRI group £5213.5 (p=0.075)

Our own data No previous study conducted in Asian population

whom breast density was considered higher Retrospective review Consecutive 712 biopsy proven breast cancer

patients underwent operation by a single surgeon in Hong Kong Sanatorium and Hospital during the period 1 January 2006 till 31 December 2009

Exclusion criteria (1) prior surgery to ipsilateral breast except excisional

biopsy for diagnosis (n=14) (2) neoadjuvant chemo/hormonal therapy (n=37) (3) missing data (n=2)

Total 659 cases for analysis MRI+ 147 vs. MRI- 512

Table 1 Indications for MRI

　 Percentage (n=147)

Nodular breast on clinical examination 7.5

MMG showed multiple pleomorphic microcalcification 4.1

MMG showed dense tissue 2.0

USG showed ill-defined border 19.0

USG showed multiple indeterminate shadows 53.1

Suspicion for multi-tumor on CNB 2.0

Discordance between clinical, imaging and histological finding 6.1

To locate occult primary focus with positive axillary LN 0.7

To search for residual tumor after excisional biopsy 4.8

Previous injection mammoplasty 0.7

Total 100.0

MMG=mammogram, USG=Ultrasound

Table 2 Characteristics of the patients included in the study

　 　 MRI-(n= 512)

MRI+(n = 147)

p value

Age (years)

Mean ± SD 52 ± 12 48 ± 7 <0.0011

Median 50 47

Range 25 - 91 30 - 70

Menopausal state <0.0012

Premenopausal 290 (56.6%) 113 (76.9%)

Postmenopausal 222 (43.4%) 34 (23.1%)

Family history 0.7922

No 413 (80.7%) 120 (81.6%)

Yes 99 (19.3%) 27 (18.4%)

Breast density on MMG <0.0012

<=50% 211 (41.2%) 45 (30.6%)

>50% 234 (45.7%) 93 (63.3%)

　 Missing data 67 (13.1%) 9 (6.1%) 　Student's t test for continuous variables1

Chi Squared test for categorical variables2

Table 3 Pathological characteristics of the included malignancies

　 　 MRI- (n = 512 )

MRI+ (n = 147)

p value

Size (cm) 0.2131

Mean ± SD 2.3 ± 1.4 2.1 ± 1.7

Median 2.2 1.8

Range 0.01 - 13.00 0.1 - 10.00

Grade 0.4022

I 104 (20.3%) 30 (20.4%)

II 136 (26.6%) 41(27.9%)

III 171 (33.4%) 35 (23.8%)

Missing 101 (19.7%) 41(27.9%)

Invasive/In situ 0.0222

Invasive present 423 (82.6%) 109 (74.1%)

Only in situ tumor 89 (17.4%) 38 (25.9%)

Focality <0.0012

Unifocal 456 (89.1%) 101 (68.7%)

Multifocal 56 (10.9%) 46 (31.3%)

Estrogen receptor score (H score) 0.9411

Mean ± SD 165 ± 104 165 ± 149

Median 190 180

Range 0-300 0-300

Progesterone receptor score (H score) 0.1541

Mean ± SD 111 ± 103 125 ± 107

Median 100 115

Range 0-300 0-300

Ki67 index (%) 0.3061

Mean ± SD 24 ± 51 20 ± 22

Median 11 9

Range 0-9 0-90

CerbB2 Score 0.5142

Negative 247 (48.2%) 80 (54.4%)

Indeterminate 149 (29.1%) 38 (25.9%)

Positive 107 (20.9%) 29 (19.7%)

　 Missing 9 (1.8%) 0 (0%) 　Student's t test for continuous variables1

Chi Squared test for categorical variables2

Table 4 Rate of re-excisions and completion mastectomies in patient undergoing BCT

　 MRI- (n = 349) MRI+ (n = 89) p value

Re-excision of tumor bed 28 (8.0%) 5 (5.6%)

Completion mastectomy 29 (8.3%) 11 (12.4%)

Total 57 (16.3%) 16 (18.0%) 0.71*

Chi Squared test*

Table 5 Rate of final mastectomies

MRI- (n = 512) MRI+ (n = 147) p value

163 (31.8%) 58 (39.5%) 0.085*

Chi Squared test*

Management alteration with MRI

66.0% (97 out of 147) had change in extent of operation From lumpectomy to wider lumpectomy (23 out of

97) to mastectomy (47 out of 97) to bilateral lumpectomy (15 out of 97) to others (12 out of 97)

Within 97 alterations in management, 12 were considered inappropriately extensive due to false positive finding on MRI

MRI detection of multifocal/ multicentric/ contralateral disease

False positive rate = 12.8% False negative rate = 7.5% Sensitivity = 95.3% Specificity = 80.3%

Conclusion

High sensitivity and moderate specificity Neither alter short term outcome e.g. re-

excision rate Nor sufficient evidence to alter long term

recurrence or survival No concrete evidence to support its routine

use