Original Study
MRI-Guided Breast Biopsy: Outcomes and Effect on Patient Management Kelly S. Myers, Ihab R. Kamel, Katarzyna J. Macura Abstract Magnetic resonance imaging (MRI)-guided breast biopsies are commonly performed for indeterminant breast lesions only visualized using MRI. At our institution, the pathology outcomes of 215 eligible lesions that underwent MRI-guided biopsy from March 2006 to May 2012 were reviewed and correlated with MRI characteristics. Malignancy rate was associated with lesion size, washout kinetics, and marked background enhancement of the breast parenchyma but was not associated with any clinical history characteristics. In patients with a new diagnosis of breast cancer who underwent an MRI-guided breast biopsy, the biopsy changed the surgical plan in 19 of 67 patients [28%]. Introduction: The purpose of this study was to correlate the pathology results of MRI-guided breast biopsies at our institution with MRI findings and patient clinical history characteristics. The effect of MRI-guided breast biopsies on surgical management in patients with a new diagnosis of breast cancer was also assessed. Patients and Methods: In this Health Insurance Portability and Accountability Act-compliant study we retrospectively reviewed all MRI-guided breast biopsies performed from March 2006 to May 2012. Clinical history, MRI features, and pathology outcomes were reviewed. In patients who underwent breast MRI to evaluate extent of disease, any change in surgical management resulting from the MRI-guided biopsy was recorded. Statistical analysis included binary logistic regression and independent Student t test. Results: Two-hundred fifteen lesions in 168 patients were included, of which 23 (10.7%) were malignant, 43 (20%) were high-risk, and 149 (69.3%) were benign. No clinical characteristic was associated with malignancy in our cohort. MRI features associated with malignancy were: larger size (mean 2.6 cm vs. 1.3 cm; P ¼ .046), washout kinetics (18% malignancy rate; P ¼ .02), and marked background parenchymal enhancement (40% malignancy rate; P < .001-.03). Nineteen (28%) of the 67 patients with a new diagnosis of breast cancer who underwent MRI-guided breast biopsy had a change in surgical management based on the biopsy result. Conclusion: Malignancy rate was associated with lesion size, washout kinetics, and marked background enhancement of the breast parenchyma but was not associated with any clinical history characteristics. Preoperative MRIguided breast biopsies changed surgical management in 28% of women with a new diagnosis of breast cancer. Clinical Breast Cancer, Vol. 15, No. 2, 143-52 ª 2015 Elsevier Inc. All rights reserved. Keywords: Breast MRI, Core biopsy, MRI-guided biopsy, Pre-operative breast MRI
Introduction Breast magnetic resonance imaging (MRI) is commonly used for breast cancer screening in high-risk patients and to evaluate the extent of disease in patients with a new diagnosis of breast cancer. Although MRI has a high reported sensitivity for breast cancer of 0.90 (95% confidence interval, 0.88-0.92), it has a lower specificity Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Hospital, Baltimore, MD Submitted: Jun 28, 2014; Revised: Oct 27, 2014; Accepted: Nov 3, 2014; Epub: Nov 10, 2014 Address for correspondence: Kelly S. Myers, MD, Memorial Sloan Kettering Cancer Center e West Harrison, 500 Westchester Ave, West Harrison, NY 10604 E-mail contact:
[email protected] 1526-8209/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clbc.2014.11.003
of 0.72 (95% confidence interval, 0.67-0.77), and biopsy is often required to establish a diagnosis.1,2 When a lesion is visible only on MRI, MRI-guided biopsy is a fast and safe option for diagnosis. The reported malignancy rate of MRI-guided breast biopsies varies from 18% to 60%, with most studies reporting malignancy rates of 20% to 35%.3-11 The variation is probably related to differences in patient populations, study designs, and radiologist thresholds for recommending biopsy. Per the American College of Radiology BI-RADS Atlas 2013, the benchmark for the malignancy rate of MRI-guided biopsies performed (also known as the biopsy yield of malignancy or positive predictive value [PPV], 3) is 20% to 50%.12 Magnetic resonance imaging-guided breast biopsies are often performed in women with a new diagnosis of breast cancer,
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MRI-Guided Breast Biopsy although the role of breast MRI in this patient population is controversial. Although several studies have demonstrated that preoperative breast MRI changes surgical management in 10% to 34% of cases,13-17 some argue that this change in surgical plan does not change patient outcomes.18-20 Additional studies to evaluate the role of breast MRI in this patient population and its subsequent clinical effect are needed. The purpose of this study was to correlate the pathology results of MRI-guided breast biopsies at our institution with MRI findings and patient clinical history characteristics. The effect of MRI-guided breast biopsies on surgical management in patients with a new diagnosis of breast cancer was also assessed.
Patients and Methods Subjects This Health Insurance Portability and Accountability Actcompliant study was approved by the institutional review board at Johns Hopkins Hospital. A database search for all MRI-guided breast biopsy examinations from March 2006 to May 2012 was performed, which identified 261 potentially eligible lesions. To be eligible, lesions must have been successfully biopsied using MRI guidance (MRI-guided core biopsy or MRI-guided localization with subsequent surgical biopsy), have available images from the MRI examination on which the biopsy was recommended, and have available pathology results. Forty-six lesions were excluded for the following reasons: images were from an MRI-guided biopsy performed at an outside institution (n ¼ 15), biopsied lesions were identified on outside images that were not available (n ¼ 15), the procedure was MRI-guided clip placement without direct pathology (n ¼ 6), unsuccessful biopsy attempts (n ¼ 6), or examinations of localizations for known cancers or lesions that had already undergone biopsy (n ¼ 4). This study included Breast Imaging-Reporting and Data System (BI-RADS) 4 or 5 lesions that were only visualized using MRI. Therefore, lesions detected using MRI for which second look ultrasound and subsequent ultrasound-guided biopsy were performed were excluded. For the 215 eligible lesions, the original breast MRI that identified the lesion to undergo MRI-guided breast biopsy was then identified.
Magnetic Resonance Imaging-Guided Breast Biopsy
144
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Patients were scanned on a 1.5-Tesla MRI system (Intera, Philips Medical Systems, Best, The Netherlands) in the prone position using a bilateral 7-channel phased array breast coil (InVivo, Orlando, FL). As part of the patient preparation for a unilateral MRI-guided breast biopsy, we applied compression on the examined breast and for patients who presented for bilateral biopsies, compression was applied to both breasts. The MRI protocol included a high spatial resolution scan for 2.5 minutes before and 10 seconds after contrast administration, followed by an additional high spatial resolution scan to assess the delayed phase of enhancement. High spatial resolution, 3-D, T1weighted spoiled gradient echo scans with fat suppression were acquired in the transverse plane (repetition time/echo time: 7.08/3.56; flip angle ¼ 10 ; slice thickness ¼ 2 mm; field of view ¼ 35 35 cm; and matrix size ¼ 512 512) before and after intravenous administration of gadobenate dimeglumine (Gd-BOPTA, Multihance; Bracco Imaging Spa, Milan, Italy) at a
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rate of 0.2 mL/s and a dose of 0.1 mM/kg. Postprocessing with subtraction of precontrast images from postcontrast images was performed after lesion localization and placement of an introducer to the target as previously reported.21 Biopsies were performed with a 10-gauge vacuum-assisted core biopsy device (Vacora, Bard, AZ) with an average of 6 core biopsies per lesion. Biopsies were performed by 1 of 4 radiologists with an average experience of 4 years (range, 2-12 years).
Data Collection and Analysis A retrospective chart review was performed for the 215 eligible lesions in 168 patients. Clinical information including age, risk factors for breast cancer, previous or current diagnosis of breast cancer, and indication for the MRI was recorded. For patients with a new diagnosis of breast cancer who underwent breast MRI for evaluation for extent of disease, the surgical plan before the breast MRI and after the MRI-guided breast biopsy were recorded. The magnetic resonance images were originally interpreted by 1 of 4 radiologists with an average experience of 4 years (range, 2-12 years). When the eligible breast MRI examinations were identified, a second reader retrospectively characterized all lesions reported during the original interpretation according to the BIRADS lexicon, and also recorded lesion kinetics, lesion T2 signal, comparison to the previous MRI examinations, background parenchymal enhancement, and breast density. Lesion T2 signal was categorized as low, intermediate, or high signal compared with background parenchymal T2 signal. Background parenchymal enhancement was subjectively assessed according to the BI-RADS definitions.22 The second reader was blinded to pathology outcomes. The lesion characterization recorded by the second reader was used for all statistical analyses. The number of months of MRI follow-up for all lesions was also recorded. Pathology from the MRI-guided core biopsy and surgery were recorded, with the final pathology that reflected surgery pathology, when available. High-risk lesions on core biopsy that showed malignancy at surgery were considered to be upgraded. During the time of this study (March 2006 to May 2012), lesions at core biopsy that were considered to be high risk at our institution and for which surgical excision was considered included: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), atypia not otherwise specified, atypical vascular proliferation, lobular carcinoma in situ, papilloma, micropapilloma, complex sclerosing lesion, and radial scar.
Statistical Analysis Correlations between malignancy rate and clinical information, and malignancy rate and imaging features were assessed using binary logistic regression for categorical variables. A generalized linear model with general estimating equations was used to account for within-patient correlations of lesions. Correlations between malignancy rate and lesion size, and malignancy rate and patient age were assessed using independent Student t tests.
Results Patients A retrospective review yielded 261 potentially eligible MRIguided breast biopsies with 46 lesions excluded, resulting in 215
Kelly S. Myers et al eligible lesions in 168 patients. The mean age was 51 years (range, 21-76 years), with no association of age with malignancy (mean age 51 9.9 years), for benign lesions versus 53 10 years for malignant lesion (P ¼ .43). The indication for breast MRI was: extent of disease (86/168; 52%), high-risk screening (49/168; 29%), diagnostic work-up of an indeterminant imaging or physical examination finding (14/168; 8%), follow-up (9/168; 5%), nipple discharge (4/168; 2%), pain (2/168; 1%), research study participant (1/168; 1%), or unknown primary cancer site (1/168; 1%), with the indication unknown in 2 of 168 (1%). In those with available clinical history, there was a strong family history of breast cancer in 33 of 140 (24%) and personal history of atypia in 22 of 144 (15%). In our cohort, there was no association with any clinical characteristic and malignancy (Table 1), other than a greater malignancy rate in patients in whom the original MRI was
performed for short-term follow-up compared with high-risk screening.
Histopathology of MRI-Guided Core Biopsy Magnetic resonance imaging-guided core biopsies were performed on 200 lesions (Figure 1), of which 16 of 200 (8.0%) were malignant: 9 of 200 (4.5%) were invasive ductal carcinoma (IDC), 5 of 200 (2.5%) were ductal carcinoma in situ (DCIS), and 2 of 200 (1%) were invasive mammary carcinoma with mixed ductal and lobular features (Table 2). Thirty-nine (19.5%) of the 200 core biopsied lesions were high-risk, with the predominant pathologies being ALH (7/200; 3.5%), ADH (7/200; 3.5%), papilloma (10/200; 5%), and complex sclerosing lesion (5/200; 2.5%). Benign findings were seen in 72.5% of the core biopsies, with fibrocystic change (62/200; 31%), benign breast tissue
Table 1 Clinical Characteristics of Patients Who Underwent MRI-Guided Biopsy Characteristic
n
Malignant
OR (95% CI)
P
Indication High-risk screeninga Extent of disease Follow-up
60
3/60 (5%)
NA
NA
115
15/115 (13%)
2.9 (0.8-10.4)
.1
9
3/9 (33%)
8.1 (1.4-48.4)
.02
Diagnostic work-up
18
1/18 (6%)
1.1 (0.11-11.5)
.93
Other
13
1/13 (8%)
1.6 (0.15-16.6)
.7
135
19/135 (14%)
3.2 (0.73-14.0)
.12
41
2/41 (5%)
NA
NA
79
12/79 (15%)
2.0 (0.82-5.1)
.12
112
9/112 (8%)
NA
NA
143
13/143 (9%)
0.4 (0.13-1.22)
.11
NA
NA
Strong Family History of Breast Cancerb No Yesa Any Family History of Breast Cancer No a
Yes
Family History of Ovarian Cancer No Yesa
25
5/25 (20%)
154
19/154 (12%)
4.2 (0.53-33.7)
.17
31
1/31 (3%)
NA
NA
126
15/126 (12%)
1.35 (0.50-3.65)
.55
66
6/66 (9%)
NA
NA
136
17/136 (13%)
History of Atypia No a
Yes
History of Benign Biopsy No Yesa Current Hormonal Treatment No
Underpowered
Estrogen and/or progesterone
14
1/14 (7%)
Adjuvant hormonal therapy
25
1/25 (4%)
148
18/148 (12%)
NA
NA
30
1/30 (3%)
1.66 (0.59-4.69)
.34
Ethnicity Caucasiana African-American Hispanic
a
4
2/4 (50%)
Asian
12
1/12 (8%)
Indian
2
0/2 (0%)
Arab
2
Other
15
1/2 (50%) 0/15 (0%)
Reference category, comparison accounted for within-correlation of within-patient lesions. Strong family history was defined as a first-degree, premenopausal, female relative, or a first-degree male relative of any age.
b
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MRI-Guided Breast Biopsy Figure 1 Flowchart of Lesion Outcomes. Two Hundred Fifteen Lesions Underwent Magnetic Resonance (MR)-Guided Biopsy At Our Institution Between March 2006 and May 2012 (200 Underwent MR-Guided Core Biopsy and 15 Underwent MR-Guided Localization or Clip Placement With Surgical Biopsy). The Malignancy Rate At Core Biopsy Was 8.0%. The Malignancy Rate of MR-Guided Localizations Was 20%. The Final Malignancy Rate After Surgery Was 10.7%
261 Potentially eligible lesions 46 Ineligible 215 Eligible lesions
200 MR-Guided core biopsies
39/200 (19.5%) High risk lesions -10 Papilloma -7 ADH -7 ALH -5 CSL -10 Other
2/16 Lost to follow-up
12/39 Lost to follow-up / No Surgery Performed
5/16 No direct pathology available (satellite lesions)
4/39 Surgery Performed but no direct Pathology available
Total
Surgical pathology
Core biopsy
16/200 (8.0%) Malignant -9 IDC -2 IMC -5 DCIS
9/16 Malignant -8 Invasive -1 DCIS
23/215 (10.7%) Malignant -15 Invasive -8 DCIS
145/200 Benign (72.5%) -62 Fibrocystic change -31 Benign breast tissue -16 Stromal fibrosis -36 Other
15 MR-Guided localizations -7 MR-Guided needle localizations -8 MR-Guided clip placements
142/145 No surgery Performed
23/39 Surgery Performed with available Pathology -1 IDC -3 DCIS -19 High risk lesions
3/145 Discordant, Surgery Performed -1 ADH -1 Papilloma -1 Fibrocystic change
43/215 (20%) High risk -24 Atypical
3/15 Malignant -2 Invasive -1 DCIS
6/15 High risk -3 ADH -3 ALH
6/15 Benign
149/215 (69.3%) Benign
Abbreviations: ADH ¼ atypical ductal hyperplasia; ALH ¼ atypical lobular hyperplasia; CSL ¼ complex sclerosing lesion; DCIS ¼ ductal carcinoma in situ; IDC ¼ invasive ductal carcinoma; IMC ¼ invasive mammary carcinoma.
(31/200; 15.5%), and stromal fibrosis (16/200; 8%) being the most common.
Histopathology at Surgery
146
-
Rather than undergoing core biopsy, 15 lesions seen on breast MRI underwent surgical biopsy after MRI-guided needle localization (n ¼ 7) or MRI-guided clip placement with subsequent
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mammographic wire localization (n ¼ 8). Three (20%) of the 15 were malignant (IDC, n ¼ 1), carcinoma (n ¼ 1), and DCIS (n ¼ 1), 6 of 15 (40%) were high-risk ALH (n ¼ 3) and ADH (n ¼ 3), and 6 of 15 (40%) were benign (fibrocystic change, n ¼ 3), stromal fibrosis (n ¼ 2), and benign breast tissue (n ¼ 1). In total, 59 lesions underwent surgery, including the 15 lesions that had a surgical biopsy and 44 lesions that had a previous
Kelly S. Myers et al Table 2 Pathology of Lesions That Underwent MRI-Guided Biopsy Pathology
Pathology
MRI-Guided Core Biopsy
MRI-Guided Needle Localization
MRI-Guided Clip Placement With Mammographic Localization
n
n
n
n
Final %
Malignant IDC
9
1
0
12
DCIS
5
1
0
8
3.7
Mammary carcinoma
2
0
0
1
0.5
Infiltrating carcinoma
0
0
0
1
0.5
Carcinoma
0
0
1
1
0.5
Total
16/200 (8%)
5.6
23/215
10.7 6.0
Atypical ALH
7
2
1
12
ADH
7
2
1
7
3.3
Atypia NOS
2
0
0
3
1.4
Atypical vascular proliferation
1
0
0
0
0.0
LCIS
1
0
0
1
0.5
ADH and ALH
1
0
0
1
0.5
Total
19/200 (9.5%)
24/215
11.2 4.7
High-Risk Without Atypia Papilloma without atypia
10
0
1
10
Complex sclerosing lesion
5
0
0
4
Micropapilloma
4
0
0
4
Radial scar
1
0
0
1
Total
20/200 (10%)
19/215
1.9 0.5 9.3
Benign Fibrocystic change
63
0
3
65
30.2
Benign breast tissue
31
1
0
32
14.8
Stromal fibrosis
16
0
2
18
8.4
Sclerosing adenosis
10
0
0
10
4.7
Fibroadenoma
9
0
0
9
4.2
Fibroadenomatoid change
5
0
0
5
2.3
PASH
4
0
0
4
1.9
Fat necrosis
3
0
0
3
1.4
Nodules of adenosis
1
0
0
1
0.5
Chronic inflammation
1
0
0
1
0.5
Dense stromal tissue
1
0
0
1
0.5
1
0
0
Fat Total Total
145/200 (72.5%) 200
7
9
0
0.0
148/215
69.4
215
100.0
Abbreviations: ADH ¼ atypical ductal hyperplasia; ALH ¼ atypical lobular hyperplasia; DCIS ¼ ductal carcinoma in situ; IDC ¼ invasive ductal carcinoma; LCIS ¼ lobular carcinoma in situ; MRI ¼ magnetic resonance imaging; NOS ¼ not otherwise specified; PASH ¼ pseudoangiomatous stromal hyperplasia.
MRI-guided core biopsy. The 44 core-biopsied lesions that underwent surgery included: 14 of 16 malignant lesions on core biopsies (1 patient had surgery elsewhere, another patient was lost to followup), 27 of 39 high-risk lesions on core biopsy, with 8 patients who chose to forego surgery and 4 patients who were lost to followup, and 3 benign lesions, which were interpreted as discordant. At surgery, direct pathology was not available for 4 of 27 highrisk lesions due to the lesion being included in a larger specimen (lumpectomy or mastectomy) without direct pathology reported for
the excised high-risk lesion. Two (8.7%) of the 23 high risk lesions were lesions that did not contain atypia on core biopsy and were found to contain atypia at surgical excision. Four (17.4%) of the 23 high-risk lesions were upgraded to malignancy at surgery (3 to DCIS, 1 to IDC). One (20%) of the 5 DCIS lesions on core biopsy was upgraded to IDC. Of the 3 lesions with benign core biopsy pathology that were interpreted as discordant, 1 was a papilloma at surgical excision, 1 contained ADH, and 1 was fibrocystic change. Including all lesions that underwent MRI-guided biopsy or
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MRI-Guided Breast Biopsy Table 3 Imaging Characteristics of MRI Findings for Which Biopsy Was Recommended Imaging Characteristic
n
Malignant
OR (95% CI)
Pa
NA
NA
Finding Type Massb
79
9/79 (11%)
Nonmass enhancement
96
10/96 (10%)
0.86 (0.25-3.0)
.82
Focus
40
4/40 (10%)
0.96 (0.28-3.2)
.94
Round
20
2/20 (10%)
0.79 (0.14-4.45)
.79
Oval
17
3/17 (18%)
1.6 (0.30-7.95)
.6
Lobulated
9
0/9 (0%)
NA
NA
Irregularb
34
4/34 (12%)
NA
NA
Smooth
30
2/30 (7%)
0.16 (0.026-0.995)
Irregular
36
3/36 (8%)
0.20 (0.39-1.073)
.06
Spiculatedb
13
4/13 (31%)
NA
NA
Shape of Mass
Margin of Mass .049
T2 Signal of Mass or Focus Low
10
2/10 (20%)
3.6 (0.61-21.5)
.16
Intermediate
30
6/30 (20%)
3.6 (0.99-13.4)
.51
Highb
79
5/79 (6%)
NA
NA
Focal
45
5/45 (11%)
2.1 (0.23-19.7)
.51
Linearb
18
1/18 (6%)
NA
NA
Segmental
19
2/19 (10%)
2.0 (0.17-24.1)
.59
9
2/9 (22%)
4.8 (0.35-66.3)
.24
1.25 (0.23, 6.9)
Distribution of Nonmass Enhancement
Other (regional, multifocal, diffuse) Internal Enhancement Characteristics of Nonmass Enhancement Homogeneous
41
5/41 (12%)
Heterogeneous
11
2/11 (18%)
2.0 (0.25, 15.8)
.51
Stippled/punctate
19
1/19 (5%)
0.5 (0.04, 5.8)
.58
20
2/20 (10%)
b
Clumped
NA
.8
NA
Dynamic Contrast Enhancement Kinetics No color
5
0/5 (0%)
Persistent
28
0/28 (0%)
3.1 (1.2-7.7)
.02
Plateau
68
7/68 (10%)
Washoutb
82
15/82 (18%)
Yesb
29
3/29 (10%)
No
13
3/13 (23%)
0.39 (0.07-2.2)
Minimal
55
8/55 (14%)
0.26 (0.07-0.89)
.03
Mild
71
3/71 (4%)
0.07 (0.02-0.03)