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,

BI-RADS 2 Radiology (2007) 244,

MR Spectroscopy Total choline (tCho) peak Radiol Clin N Am (2010) 48,

Diffusion Weighted Imaging (DWI) Radiol Clin N Am (2010) 48,

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, J Clin Oncol (2009) 27, CA Cancer J Clin (2009) 59,

(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, ) 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,

(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 %) Summary PPV 47.9% (95%CI, %) TP:FP ratio 0.92 (95%CI, ) No data on pooled management alteration J Clin Oncol (2009) 27,

(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,

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,

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,

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

Cost: MRI group £ vs. No MRI group £ (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 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 ± SD52 ± 1248 ± 7< Median5047 Range Menopausal state< Premenopausal290 (56.6%)113 (76.9%) Postmenopausal222 (43.4%)34 (23.1%) Family history No413 (80.7%)120 (81.6%) Yes99 (19.3%)27 (18.4%) Breast density on MMG< <=50%211 (41.2%)45 (30.6%) >50%234 (45.7%)93 (63.3%) Missing data67 (13.1%)9 (6.1%) Student's t test for continuous variables 1 Chi Squared test for categorical variables 2

Table 3 Pathological characteristics of the included malignancies MRI- (n = 512 ) MRI+ (n = 147) p value Size (cm) Mean ± SD2.3 ± ± 1.7 Median Range Grade I104 (20.3%)30 (20.4%) II136 (26.6%)41(27.9%) III171 (33.4%)35 (23.8%) Missing101 (19.7%)41(27.9%) Invasive/In situ Invasive present423 (82.6%)109 (74.1%) Only in situ tumor89 (17.4%)38 (25.9%) Focality< Unifocal456 (89.1%)101 (68.7%) Multifocal56 (10.9%)46 (31.3%) Estrogen receptor score (H score) Mean ± SD165 ± ± 149 Median Range0-300

Progesterone receptor score (H score) Mean ± SD111 ± ± 107 Median Range0-300 Ki67 index (%) Mean ± SD24 ± ± 22 Median11 9 Range CerbB2 Score Negative247 (48.2%) 80 (54.4%) Indeterminate149 (29.1%) 38 (25.9%) Positive107 (20.9%) 29 (19.7%) Missing9 (1.8%) 0 (0%) Student's t test for continuous variables 1 Chi Squared test for categorical variables 2

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 bed28 (8.0%)5 (5.6%) Completion mastectomy29 (8.3%)11 (12.4%) Total57 (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