DOI: 10.1148/rg.27si075503
RadioGraphics 2007;27:S165-S182
© RSNA, 2007
Breast Cancers Detected with Imaging Screening in the BRCA Population: Emphasis on MR Imaging with Histopathologic Correlation1
Petrina A. Causer, MD,
Roberta A. Jong, MD,
Ellen Warner, MD,
Kimberley Hill, BA,
John W. Wong, MD,
Belinda N. Curpen, MD, and
Donald B. Plewes, PhD
1 From the Department of Medical Imaging (P.A.C., R.A.J., B.N.C.), Division of Medical Oncology, Department of Medicine (E.W., K.H.), Department of Anatomic Pathology (J.W.W.), and Imaging Research and Department of Medical Biophysics (D.B.P.), Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, MG166, Toronto, ON, Canada M4N 3M5. Presented as an education exhibit at the 2006 RSNA Annual Meeting. Received February 5, 2007; revision requested March 20 and received May 24; accepted June 21. Supported by the Canadian Breast Cancer Research Initiative, the Terry Fox Foundation of the National Cancer Institute of Canada, the Ontario Research and Development Challenge Fund, and Amersham Health, Oakville, Ontario, Canada. R.A.J. collaborates on research with General Electric, Fairfield, Conn; all other authors have no financial relationships to disclose.
Address correspondence to P.A.C. (e-mail: Petrina.causer{at}sunnybrook.ca).
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Abstract
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The benefit of screening with breast magnetic resonance (MR) imaging for certain patient populations at high risk for breast cancer, most notably patients with a genetic mutation in the BRCA1 or BRCA2 gene, has been established in numerous studies and is now becoming part of routine clinical practice. Despite the lower sensitivity of mammography compared with that of MR imaging, the former remains the standard of care for screening any patient population. In the BRCA1 and BRCA2 populations, the inferior sensitivity and specificity of ultrasonography (US) limit its role as a screening tool, but US remains a vital diagnostic tool because of its ability to provide guidance for biopsy of many suspicious lesions detected with MR imaging. Important features of a screening program with breast MR imaging include the following: optimization of the MR imaging technique, an awareness of the imaging features of invasive and noninvasive breast cancers detected with MR imaging, an understanding of the limitations of the various imaging modalities in both the initial screening and subsequent diagnostic work-up evaluations, and the requirement for MR imaging–guided biopsy.
© RSNA, 2007
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Introduction
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Approximately 1% of women are at very high risk for developing breast cancer due to a proved or suspected genetic predisposition, and 5%–10% of all breast cancer is hereditary (1,2). Known mutations in the BRCA1 and BRCA2 genes account for about 50% of these hereditary breast cancers (3). 
BRCA1 and BRCA2 mutation carriers face a lifetime breast cancer risk as high as 85% and develop breast cancer at an early age, approximating 50% by 50 years (1,4).
Consensus guidelines have until recently recommended screening with annual mammography and semiannual clinical breast examination beginning at age 25–35 years. The results have been discouraging, with very few cases of ductal carcinoma in situ (DCIS) reported; invasive cancers were often larger than 1 cm with lymph node involvement (up to 78% and 56%, respectively); and interval cancer rates were as high as 50% (5–8).
The most recent results of four large magnetic resonance (MR) imaging screening studies evaluating women at high risk for breast cancer, including large numbers of known BRCA1 and BRCA2 mutation carriers, have been published (9–12). Screening MR imaging offers high sensitivity in detecting breast cancer, superior to conventional surveillance with mammography, clinical breast examination, and ultrasonography (US), most notably for BRCA1 and BRCA2 patients.
This article provides a summary of the results of screening MR imaging in the BRCA1 and BRCA2 populations. Recommended breast MR imaging protocol requirements and the MR imaging techniques of our study are reviewed. We also describe the imaging appearances of screening-detected breast cancers, both invasive and in situ, with histopathologic correlation. The limitations of the various imaging modalities, most notably of mammography and US, that we have encountered in our high-risk patient screening study, both in screening and diagnostic lesion detection, are reviewed. In the context of the limitations of mammography and US, the necessity for MR imaging–guided biopsy in a screening program is highlighted along with an overview of how we perform biopsy.
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Breast Cancer Screening with MR Imaging in BRCA1 and BRCA2 Patients
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The four largest screening studies reported to date varied with respect to the enrollment inclusion criteria, with breast cancer risk levels of the patient population ranging from moderate (15% or greater lifetime risk) to very high (a documented mutation in the BRCA1 or BRCA2 gene) (9–12). The number of BRCA1 or BRCA2 mutation carriers enrolled in these studies has ranged from 43 to 354 patients (8%–100% of the enrolled study patients).
As anticipated, cancer detection rates were highest in the patients with BRCA1 or BRCA2 mutations, ranging from 2.6% to 4.8%, compared with overall high-risk patient rates of 1.1%–2.5%. Compared with other investigated methods of surveillance either alone or in combination specifically with mammography, clinical breast examination, and US, MR imaging offered superior sensitivity in detecting breast cancer (Table 1). The specificity of MR imaging, calculated according to the number of biopsy results, was lower than that of mammography and about equivalent to that of US. In some studies, the sensitivity and specificity of MR imaging were higher for the BRCA mutation carriers, particularly for the BRCA1 group, than for the other risk groups (9,10).
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Table 1. Sensitivity and Specificity Based on Biopsy Results in Four Large, Prospective, MR Imaging Screening Studies of Women at High Risk for Breast Cancer
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Not only is the sensitivity of MR imaging superior to those of mammography and US for detecting invasive cancer, but MR imaging can provide a similar sensitivity benefit for DCIS detection. The higher DCIS detection rates in single-center studies compared with multicenter studies likely reflect an interpretation learning curve (Table 2).
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Table 2. DCIS Detection Results in Four Large, Prospective, MR Imaging Screening Studies of Women at High Risk for Breast Cancer
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Because the studies have consistently proved the benefit of screening MR imaging for very high-risk patients, especially BRCA mutation carriers, screening MR imaging for such patient populations is now gaining acceptance outside of research protocols. Recommendations have recently begun appearing supporting breast MR imaging screening for high-risk women, including BRCA mutation carriers and women not tested for the mutation but with a history highly suggestive of being a carrier (13–16). Given such support, it is important that breast MR imaging has become a screening study that many insurance providers will reimburse in such a high-risk population.
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Breast MR Imaging Technique
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Minimum Requirements
There are a variety of breast MR imaging techniques that are successfully used. Despite variations, basic minimum technical requirements should be fulfilled, as outlined by Rausch and Hendrick (17) and the American College of Radiology (18), to optimize diagnostic accuracy. Technical requirements are summarized in Table 3.
Our Screening and Diagnostic MR Imaging Protocols
Premenopausal patients are scheduled for MR imaging screening during week 2 of the menstrual cycle. The breast MR imaging screening protocol is summarized in Table 4.
Once an indeterminate lesion is identified at screening MR imaging as requiring further assessment, diagnostic unilateral breast MR imaging with both high temporal and high spatial resolution is performed 1–3 months after the initial screening examination, also timed to week 2 of the menstrual cycle for premenopausal patients. The diagnostic MR imaging study is similar in principle to spot compression or magnification mammographic views to work up a mammographic abnormality. Its purpose is both to determine if a nonmass lesion is due to transient physiologic enhancement, based on its resolution, and to further characterize the enhancement and morphology of persisting lesions according to the BI-RADS breast MR imaging lexicon (19). The unilateral MR imaging protocol is summarized in Table 5.
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Overview of Multimodality Screening Program
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Between November 1997 and May 2005, 355 female BRCA1 (n = 189) or BRCA2 (n = 166) mutation carriers (mean age, 44 years; age range, 25–65 years), irrespective of breast density, were screened annually with mammography, clinical breast examination, US, and MR imaging, performed on the same day. All women completed one round of screening, 266 (75%) two rounds, 193 (54%) three rounds, 121 (34%) four rounds, 75 (21%) five rounds, and five (1%) six rounds, totaling 1015 rounds of screening.
Forty-one cancers (invasive and DCIS) were detected in 40 women. The highest number of cancers (36 [88%]) was detected with MR imaging. Eleven cancers (27%) were detected with mammography, and 14 cancers (34%) were detected with US. The sensitivity of mammography and MR imaging combined was 95%. The specificity (based on biopsy results) of each modality was 88% for MR imaging, 98% for mammography, and 96% for US. Table 6 outlines the histopathologic type, size, and lymph node status according to detection during prevalent and incident screening rounds.
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Table 6. Histopathologic Type, Mean Size, and Lymph Node Status of Breast Cancers Detected during Prevalent and Incident Screening Rounds
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In the general population, the sensitivity of mammography, when screening is performed with only mammography, has been found to be inversely proportional to mammographic breast density (80% sensitivity for fatty breasts compared with 30% for dense breasts) (20,21). We have found that the mammographic sensitivity in the BRCA population, when being simultaneously screened with MR imaging, is also higher for lower breast density (defined as <50%) at 43% compared with 21% sensitivity for higher breast density (
50%) (22). However, given the relative low sensitivity of mammography regardless of breast density, it is inadequate to serve as a sole screening tool in this population.
Our current breast imaging screening study for BRCA mutation carriers includes annual mammography and MR imaging. Screening US was discontinued due to its limited additional benefit over the combination of mammography and MR imaging.
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Imaging Detection and Findings of Breast Cancers in the BRCA1 and BRCA2 Populations with Histopathologic Correlation
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Initiating a breast MR imaging screening program requires organization of breast imaging resources and an awareness of the limitations of the imaging tools available. Knowledge of the likelihood of cancers in BRCA1 or BRCA2 patients being visible with different imaging modalities may ultimately optimize the efficiency of the diagnostic work-up by limiting unnecessary tests.
Despite a screening study being prospectively classified as negative, cancers detected with any given modality can sometimes be identified in a retrospective review of the imaging study initially deemed negative. As the sensitivity of MR imaging is much higher than that of mammography or US, mammographic rereview or more often targeted US evaluation, even in the context of a negative screening US study, may allow identification of the MR imaging–visible lesion in question. Often the finding could not have been prospectively classified as suspicious, but its visibility remains important. Identifying such lesions can help by educating the radiologist about the more subtle signs of cancer; also important, it can serve as a faster and cheaper method of biopsy guidance by using US or stereotactic guidance as opposed to MR imaging guidance.
An illustrative imaging overview with histopathologic correlation of cancers in the BRCA1 and BRCA2 populations follows. Both MR imaging screening detected and undetected categories are included. The visibility of the cancers in a retrospective review of the screening study and after a diagnostic work-up with targeted US is also reviewed.
Cancers Detected with MR Imaging Screening
Until May 2005, 41 cancers in 40 patients were detected with screening, 36 of which were detected with MR imaging screening. The numbers of MR imaging screening detected cancers identified also at screening US and mammography or visible retrospectively at review of mammography or with targeted US are given in Table 7.
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Table 7. Breast Cancers Detected with MR Imaging Screening: Detection at Screening Mammography and US and Retrospective Visibility at Mammography and Targeted US
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Cancers Visible Only at MR Imaging.—
Cancers visible only with MR imaging are documented in the literature. A report specifically evaluating second-look US in MR imaging detected, mammographically occult suspicious lesions found a 14% predictive value of malignancy for such lesions not visible at US (23). In our study, a relatively high number of cancers (13 of 33 [39%]) remained visible only at MR imaging even after second-look US. Eight of the 13 cancers (62%) visible only at MR imaging were invasive ductal carcinoma (IDC) (Fig 1), and the remaining five (38%) were DCIS (Fig 2).
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Figure 1a. IDC of the left breast detected only at MR imaging in a 49-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided localization and surgical excision biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 8-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (hematoxylin-eosin [H-E] stain) shows high-grade IDC (horizontal arrows), which corresponds to the mass seen at MR imaging. Vertical arrows = associated DCIS.
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Figure 1b. IDC of the left breast detected only at MR imaging in a 49-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided localization and surgical excision biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 8-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (hematoxylin-eosin [H-E] stain) shows high-grade IDC (horizontal arrows), which corresponds to the mass seen at MR imaging. Vertical arrows = associated DCIS.
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Figure 1c. IDC of the left breast detected only at MR imaging in a 49-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided localization and surgical excision biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 8-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (hematoxylin-eosin [H-E] stain) shows high-grade IDC (horizontal arrows), which corresponds to the mass seen at MR imaging. Vertical arrows = associated DCIS.
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Figure 2a. DCIS of the left breast detected only at MR imaging in a 50-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided vacuum-assisted biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows a spiculated 5-mm mass (arrow) with a type I enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing intermediate-grade DCIS (arrows), which corresponds to the mass seen at MR imaging.
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Figure 2b. DCIS of the left breast detected only at MR imaging in a 50-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided vacuum-assisted biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows a spiculated 5-mm mass (arrow) with a type I enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing intermediate-grade DCIS (arrows), which corresponds to the mass seen at MR imaging.
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Figure 2c. DCIS of the left breast detected only at MR imaging in a 50-year-old BRCA1 patient. The cancer was diagnosed with MR imaging–guided vacuum-assisted biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows a spiculated 5-mm mass (arrow) with a type I enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing intermediate-grade DCIS (arrows), which corresponds to the mass seen at MR imaging.
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Cancers Visible at MR Imaging and US But Occult at Mammography.—
Six of the 36 MR imaging screening detected cancers (17%) were mammographically occult and US screening detected. Despite negative results at screening US, nine additional mammographically occult MR imaging detected cancers were visible at second-look US. Three of the 36 US undetected cancers were also initially detected with mammographic screening and did not undergo a second targeted US study. In total, 15 of 33 cancers (45%) were visible at both MR imaging and US, similar to the results of a previous report by LaTrenta et al (23), in which nine of 19 (47%) mammographically occult MR imaging detected cancers had a US correlate. Twelve of the 15 cancers (80%) were invasive (IDC) (Fig 3), and the remaining three (20%) were DCIS (Fig 4). The fact that additional cancers are detected at targeted US highlights the difference between this examination, where subtle features of cancers can be observed, and screening US.
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Figure 3a. IDC and DCIS of the left breast detected at MR imaging and US screening in a 53-year-old BRCA1 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows an irregular 9-mm mass (horizontal arrow) with a type III enhancement curve. There is surrounding clumped ductal enhancement (vertical arrows). (b) Normal left mediolateral oblique mammogram shows low mammographic breast density. (c) US image shows the irregular 9-mm mass (arrow). (d) Low-power photomicrograph (H-E stain) shows the lobulated tumor composed of high-grade IDC (arrows), which corresponds to the mass seen at MR imaging and US. The arrowhead indicates DCIS, which corresponds to the ductal enhancement visible only at MR imaging.
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Figure 3b. IDC and DCIS of the left breast detected at MR imaging and US screening in a 53-year-old BRCA1 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows an irregular 9-mm mass (horizontal arrow) with a type III enhancement curve. There is surrounding clumped ductal enhancement (vertical arrows). (b) Normal left mediolateral oblique mammogram shows low mammographic breast density. (c) US image shows the irregular 9-mm mass (arrow). (d) Low-power photomicrograph (H-E stain) shows the lobulated tumor composed of high-grade IDC (arrows), which corresponds to the mass seen at MR imaging and US. The arrowhead indicates DCIS, which corresponds to the ductal enhancement visible only at MR imaging.
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Figure 3c. IDC and DCIS of the left breast detected at MR imaging and US screening in a 53-year-old BRCA1 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows an irregular 9-mm mass (horizontal arrow) with a type III enhancement curve. There is surrounding clumped ductal enhancement (vertical arrows). (b) Normal left mediolateral oblique mammogram shows low mammographic breast density. (c) US image shows the irregular 9-mm mass (arrow). (d) Low-power photomicrograph (H-E stain) shows the lobulated tumor composed of high-grade IDC (arrows), which corresponds to the mass seen at MR imaging and US. The arrowhead indicates DCIS, which corresponds to the ductal enhancement visible only at MR imaging.
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Figure 3d. IDC and DCIS of the left breast detected at MR imaging and US screening in a 53-year-old BRCA1 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (50/4.2, 50° flip angle) shows an irregular 9-mm mass (horizontal arrow) with a type III enhancement curve. There is surrounding clumped ductal enhancement (vertical arrows). (b) Normal left mediolateral oblique mammogram shows low mammographic breast density. (c) US image shows the irregular 9-mm mass (arrow). (d) Low-power photomicrograph (H-E stain) shows the lobulated tumor composed of high-grade IDC (arrows), which corresponds to the mass seen at MR imaging and US. The arrowhead indicates DCIS, which corresponds to the ductal enhancement visible only at MR imaging.
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Figure 4a. DCIS of the left breast, detected only at MR imaging screening and visible at second-look US, in a 41-year-old BRCA2 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 11-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) US image shows the irregular, isoechoic mass (arrow) and heterogeneous dense background echotexture. (d) Low-power photomicrograph (H-E stain) shows a focus of high-grade DCIS (arrows), which corresponds to the mass seen at MR imaging. * = fibrocystic changes, which were present throughout the breast at pathologic analysis.
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Figure 4b. DCIS of the left breast, detected only at MR imaging screening and visible at second-look US, in a 41-year-old BRCA2 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 11-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) US image shows the irregular, isoechoic mass (arrow) and heterogeneous dense background echotexture. (d) Low-power photomicrograph (H-E stain) shows a focus of high-grade DCIS (arrows), which corresponds to the mass seen at MR imaging. * = fibrocystic changes, which were present throughout the breast at pathologic analysis.
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Figure 4c. DCIS of the left breast, detected only at MR imaging screening and visible at second-look US, in a 41-year-old BRCA2 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 11-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) US image shows the irregular, isoechoic mass (arrow) and heterogeneous dense background echotexture. (d) Low-power photomicrograph (H-E stain) shows a focus of high-grade DCIS (arrows), which corresponds to the mass seen at MR imaging. * = fibrocystic changes, which were present throughout the breast at pathologic analysis.
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Figure 4d. DCIS of the left breast, detected only at MR imaging screening and visible at second-look US, in a 41-year-old BRCA2 patient. The cancer was diagnosed with US-guided core biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an irregular 11-mm mass (arrow) with a type III enhancement curve. (b) Left mediolateral oblique mammogram shows a normal appearance. (c) US image shows the irregular, isoechoic mass (arrow) and heterogeneous dense background echotexture. (d) Low-power photomicrograph (H-E stain) shows a focus of high-grade DCIS (arrows), which corresponds to the mass seen at MR imaging. * = fibrocystic changes, which were present throughout the breast at pathologic analysis.
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Cancers Visible at MR Imaging and Mammography.—
Breast cancer in BRCA mutation carriers, particularly BRCA1 carriers, occurs in a younger age group compared with sporadic cancers. Mammographic breast density is also generally inversely proportional to age (24). Potential factors accounting for the poor sensitivity of mammography in BRCA mutation carriers include the elevated breast density in younger patients, which obscures mass lesions, and a reported unique histopathology of BRCA1-related cancers, which includes high cellularity, round pushing margins, and less associated DCIS; therefore, the cancer is less likely to appear as distortion, spiculation, or microcalcifications at mammography (24–27).
Three of the 36 (8%) MR imaging detected cancers were also detected with mammographic screening. Two of the three cancers (67%) were IDC (Fig 5), and the remaining cancer was DCIS (Fig 6). All mammographically visible cancers in this category appeared as mammographic microcalcifications.
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Figure 5a. IDC and DCIS of the right breast detected at MR imaging and mammography in a 55-year-old BRCA1 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows 25-mm linear enhancement (arrow) with a type III enhancement curve. (b) Magnification mammographic view of the right breast shows new faint pleomorphic calcifications (arrow), which represent only a small portion of the malignancy. (c) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the linear enhancement seen at MR imaging and the calcifications seen at mammography. Arrow = surrounding DCIS. Calcifications demonstrated within the IDC at histopathologic analysis are not shown.
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Figure 5b. IDC and DCIS of the right breast detected at MR imaging and mammography in a 55-year-old BRCA1 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows 25-mm linear enhancement (arrow) with a type III enhancement curve. (b) Magnification mammographic view of the right breast shows new faint pleomorphic calcifications (arrow), which represent only a small portion of the malignancy. (c) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the linear enhancement seen at MR imaging and the calcifications seen at mammography. Arrow = surrounding DCIS. Calcifications demonstrated within the IDC at histopathologic analysis are not shown.
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Figure 5c. IDC and DCIS of the right breast detected at MR imaging and mammography in a 55-year-old BRCA1 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows 25-mm linear enhancement (arrow) with a type III enhancement curve. (b) Magnification mammographic view of the right breast shows new faint pleomorphic calcifications (arrow), which represent only a small portion of the malignancy. (c) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the linear enhancement seen at MR imaging and the calcifications seen at mammography. Arrow = surrounding DCIS. Calcifications demonstrated within the IDC at histopathologic analysis are not shown.
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Figure 6a. DCIS of the right breast detected at MR imaging and mammography in a 46-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (150/4.2, 50° flip angle) shows a new 1.3-cm focal area of clumped enhancement (vertical arrow) with a type III enhancement curve. Horizontal arrows = stable background stippled enhancement. (b) Magnification mammographic view of the right breast shows new clustered, coarse, heterogeneous calcifications (arrow). (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing high-grade DCIS (arrows), which corresponds to the focal enhancing area seen at MR imaging and the calcifications seen at mammography. * = surrounding fibrocystic changes.
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Figure 6b. DCIS of the right breast detected at MR imaging and mammography in a 46-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (150/4.2, 50° flip angle) shows a new 1.3-cm focal area of clumped enhancement (vertical arrow) with a type III enhancement curve. Horizontal arrows = stable background stippled enhancement. (b) Magnification mammographic view of the right breast shows new clustered, coarse, heterogeneous calcifications (arrow). (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing high-grade DCIS (arrows), which corresponds to the focal enhancing area seen at MR imaging and the calcifications seen at mammography. * = surrounding fibrocystic changes.
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Figure 6c. DCIS of the right breast detected at MR imaging and mammography in a 46-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (150/4.2, 50° flip angle) shows a new 1.3-cm focal area of clumped enhancement (vertical arrow) with a type III enhancement curve. Horizontal arrows = stable background stippled enhancement. (b) Magnification mammographic view of the right breast shows new clustered, coarse, heterogeneous calcifications (arrow). (c) Low-power photomicrograph (H-E stain) shows an involved cluster of ducts containing high-grade DCIS (arrows), which corresponds to the focal enhancing area seen at MR imaging and the calcifications seen at mammography. * = surrounding fibrocystic changes.
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Cancers Visible at MR Imaging, US, and Mammography.—
Five of the 36 cancers (14%) were screening detected with all three modalities and were all IDC at pathologic analysis (Fig 7). Including the mammographically occult cancers, US was able to depict 20 (56%) of the 36 MR imaging screening detected cancers.
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Figure 7a. IDC of the right breast detected at MR imaging, mammography, and US screening in a 46-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an oval 9-mm mass with smooth margins (arrow) and a type III enhancement curve. (b) Mediolateral oblique mammogram of the right breast shows the oval low-density mass (arrow) surrounded by minimal scattered fibroglandular density. (c) US image shows the isoechoic oval mass with microlobulated margins and an echogenic halo (arrow). (d) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the mass seen at MR imaging, mammography, and US.
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Figure 7b. IDC of the right breast detected at MR imaging, mammography, and US screening in a 46-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an oval 9-mm mass with smooth margins (arrow) and a type III enhancement curve. (b) Mediolateral oblique mammogram of the right breast shows the oval low-density mass (arrow) surrounded by minimal scattered fibroglandular density. (c) US image shows the isoechoic oval mass with microlobulated margins and an echogenic halo (arrow). (d) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the mass seen at MR imaging, mammography, and US.
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Figure 7c. IDC of the right breast detected at MR imaging, mammography, and US screening in a 46-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an oval 9-mm mass with smooth margins (arrow) and a type III enhancement curve. (b) Mediolateral oblique mammogram of the right breast shows the oval low-density mass (arrow) surrounded by minimal scattered fibroglandular density. (c) US image shows the isoechoic oval mass with microlobulated margins and an echogenic halo (arrow). (d) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the mass seen at MR imaging, mammography, and US.
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Figure 7d. IDC of the right breast detected at MR imaging, mammography, and US screening in a 46-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows an oval 9-mm mass with smooth margins (arrow) and a type III enhancement curve. (b) Mediolateral oblique mammogram of the right breast shows the oval low-density mass (arrow) surrounded by minimal scattered fibroglandular density. (c) US image shows the isoechoic oval mass with microlobulated margins and an echogenic halo (arrow). (d) Low-power photomicrograph (H-E stain) shows high-grade IDC (*), which corresponds to the mass seen at MR imaging, mammography, and US.
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Cancers Undetected with MR Imaging Screening
Until May 2005, five (12%) mammographic and/or US screening detected cancers were not prospectively diagnosed with MR imaging. One additional patient presented with an interval cancer (2%). In diagnostic MR imaging studies, the negative predictive value of MR imaging has ranged from 85% in multicenter studies to 100% at single institutions (28–31). The numbers of MR imaging screening undetected cancers, their method of detection, and their visibility at retrospective screening MR imaging are given in Table 8.
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Table 8. Breast Cancers Undetected with MR Imaging Screening: Detection at Mammography and US and Retrospective Visibility at MR Imaging
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Cancers Detected Only with US Screening.—
Two of the five (40%) MR imaging undetected cancers were detected only with screening breast US, including one IDC and one invasive lobular cancer at pathologic analysis (Fig 8). At retrospective review of the imaging studies, both cancers were visible at MR imaging but remained occult at mammography.
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Figure 8a. Invasive lobular cancer of the left breast detected only at US screening in a 60-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) US image from the screening examination shows a 5-mm hypoechoic, spiculated mass (arrow). (b) Image from the second dynamic series of contrast-enhanced T1-weighted subtracted GRE imaging (18.4/4.3, 40° flip angle) shows the minimally enhancing, irregular 5-mm mass (arrow) with a type I enhancement curve; the mass was visible in retrospect. Note the black lines at tissue interfaces (arrowheads), an appearance due to motion artifact. (c) Normal left mediolateral oblique mammogram shows a heterogeneously dense breast. (d) Low-power photomicrograph (H-E stain) shows a focus of invasive lobular cancer (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 8b. Invasive lobular cancer of the left breast detected only at US screening in a 60-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) US image from the screening examination shows a 5-mm hypoechoic, spiculated mass (arrow). (b) Image from the second dynamic series of contrast-enhanced T1-weighted subtracted GRE imaging (18.4/4.3, 40° flip angle) shows the minimally enhancing, irregular 5-mm mass (arrow) with a type I enhancement curve; the mass was visible in retrospect. Note the black lines at tissue interfaces (arrowheads), an appearance due to motion artifact. (c) Normal left mediolateral oblique mammogram shows a heterogeneously dense breast. (d) Low-power photomicrograph (H-E stain) shows a focus of invasive lobular cancer (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 8c. Invasive lobular cancer of the left breast detected only at US screening in a 60-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) US image from the screening examination shows a 5-mm hypoechoic, spiculated mass (arrow). (b) Image from the second dynamic series of contrast-enhanced T1-weighted subtracted GRE imaging (18.4/4.3, 40° flip angle) shows the minimally enhancing, irregular 5-mm mass (arrow) with a type I enhancement curve; the mass was visible in retrospect. Note the black lines at tissue interfaces (arrowheads), an appearance due to motion artifact. (c) Normal left mediolateral oblique mammogram shows a heterogeneously dense breast. (d) Low-power photomicrograph (H-E stain) shows a focus of invasive lobular cancer (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 8d. Invasive lobular cancer of the left breast detected only at US screening in a 60-year-old BRCA2 patient. The cancer was diagnosed with US-guided biopsy. (a) US image from the screening examination shows a 5-mm hypoechoic, spiculated mass (arrow). (b) Image from the second dynamic series of contrast-enhanced T1-weighted subtracted GRE imaging (18.4/4.3, 40° flip angle) shows the minimally enhancing, irregular 5-mm mass (arrow) with a type I enhancement curve; the mass was visible in retrospect. Note the black lines at tissue interfaces (arrowheads), an appearance due to motion artifact. (c) Normal left mediolateral oblique mammogram shows a heterogeneously dense breast. (d) Low-power photomicrograph (H-E stain) shows a focus of invasive lobular cancer (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Cancer Detected with Mammographic and US Screening.—
One of the five (20%) MR imaging undetected cancers was screening detected with both mammography and US, a large invasive ductal cancer, which was retrospectively visible at MR imaging (Fig 9).
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Figure 9a. IDC of the right breast detected with US and mammographic screening in a 60-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot compression view of the right breast shows a persisting asymmetry and distortion (arrows). (b) US image from the screening examination shows a 2-cm hypoechoic, lobulated mass with smooth margins and posterior acoustic enhancement (arrow). (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows the irregular 2.5-cm mass (arrow) with a type II enhancement curve; the mass was visible in retrospect. Note that the mass enhances to a greater degree than the surrounding parenchyma (*). (d) Low-power photomicrograph (H-E stain) shows a focus of IDC (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 9b. IDC of the right breast detected with US and mammographic screening in a 60-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot compression view of the right breast shows a persisting asymmetry and distortion (arrows). (b) US image from the screening examination shows a 2-cm hypoechoic, lobulated mass with smooth margins and posterior acoustic enhancement (arrow). (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows the irregular 2.5-cm mass (arrow) with a type II enhancement curve; the mass was visible in retrospect. Note that the mass enhances to a greater degree than the surrounding parenchyma (*). (d) Low-power photomicrograph (H-E stain) shows a focus of IDC (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 9c. IDC of the right breast detected with US and mammographic screening in a 60-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot compression view of the right breast shows a persisting asymmetry and distortion (arrows). (b) US image from the screening examination shows a 2-cm hypoechoic, lobulated mass with smooth margins and posterior acoustic enhancement (arrow). (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows the irregular 2.5-cm mass (arrow) with a type II enhancement curve; the mass was visible in retrospect. Note that the mass enhances to a greater degree than the surrounding parenchyma (*). (d) Low-power photomicrograph (H-E stain) shows a focus of IDC (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Figure 9d. IDC of the right breast detected with US and mammographic screening in a 60-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot compression view of the right breast shows a persisting asymmetry and distortion (arrows). (b) US image from the screening examination shows a 2-cm hypoechoic, lobulated mass with smooth margins and posterior acoustic enhancement (arrow). (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows the irregular 2.5-cm mass (arrow) with a type II enhancement curve; the mass was visible in retrospect. Note that the mass enhances to a greater degree than the surrounding parenchyma (*). (d) Low-power photomicrograph (H-E stain) shows a focus of IDC (arrows), which corresponds to the mass seen at US and retrospectively visible at MR imaging.
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Cancers Detected Only with Mammography.—
Two (40%) cancers, both DCIS, that appeared as microcalcifications were screening detected only with mammography. One case was visible retrospectively at MR imaging (Fig 10); the other remained occult at MR imaging.
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Figure 10a. DCIS of the left breast detected only at mammographic screening in a 39-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Magnification mammographic image shows a cluster of new mildly pleomorphic calcifications (arrow). (b) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows a 5-mm focal enhancing area (arrow) with a type I enhancement curve; the enhancing area was visible in retrospect. (c) Low-power photomicrograph (H-E stain) shows foci of DCIS (arrows), which correspond to several involved clusters of ducts, the area of calcifications seen at mammography, and the nonmass enhancement retrospectively visible at MR imaging. The calcifications (arrowheads) are stromal in location.
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Figure 10b. DCIS of the left breast detected only at mammographic screening in a 39-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Magnification mammographic image shows a cluster of new mildly pleomorphic calcifications (arrow). (b) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows a 5-mm focal enhancing area (arrow) with a type I enhancement curve; the enhancing area was visible in retrospect. (c) Low-power photomicrograph (H-E stain) shows foci of DCIS (arrows), which correspond to several involved clusters of ducts, the area of calcifications seen at mammography, and the nonmass enhancement retrospectively visible at MR imaging. The calcifications (arrowheads) are stromal in location.
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Figure 10c. DCIS of the left breast detected only at mammographic screening in a 39-year-old BRCA2 patient. The cancer was diagnosed with stereotactic biopsy. (a) Magnification mammographic image shows a cluster of new mildly pleomorphic calcifications (arrow). (b) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) shows a 5-mm focal enhancing area (arrow) with a type I enhancement curve; the enhancing area was visible in retrospect. (c) Low-power photomicrograph (H-E stain) shows foci of DCIS (arrows), which correspond to several involved clusters of ducts, the area of calcifications seen at mammography, and the nonmass enhancement retrospectively visible at MR imaging. The calcifications (arrowheads) are stromal in location.
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Interval Cancer.—
One interval cancer was detected 7 months after the prior screening round. It was visible at mammography, US, and MR imaging at the time of presentation (Fig 11) and was visible retrospectively at screening MR imaging and mammography.
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Figure 11a. Interval cancer (IDC and DCIS of the right breast) in a 40-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot magnification view of the right breast, obtained at clinical presentation, shows a persisting asymmetry with distortion and associated pleomorphic clustered calcifications (arrow). (b) US image obtained at presentation shows a 2-cm hypoechoic, irregular mass (arrow) with internal echogenic foci, which correspond to calcifications. (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) obtained at presentation shows the rim-enhancing 1.5-cm mass (arrow) with a type III enhancement curve and surrounding clumped ductal enhancement (arrowheads). Note that the mass and the nonmass lesions enhance to a greater degree than the surrounding parenchyma (*). (d) Contrast-enhanced screening MR image obtained 7 months earlier shows a portion of the clumped nonmass enhancement (arrowhead), which was visible in retrospect and also enhanced to a greater degree than the significant background parenchymal enhancement (*). (e) Low-power photomicrograph (H-E stain) shows a focus of IDC (*), which corresponds to the mass seen at US; the asymmetry, distortion, and calcifications seen at mammography; and the mass retrospectively visible at MR imaging. Arrow = associated DCIS and clumped ductal enhancement visible only at MR imaging.
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Figure 11b. Interval cancer (IDC and DCIS of the right breast) in a 40-year-old BRCA1 patient. The cancer was diagnosed with US-guided biopsy. (a) Spot magnification view of the right breast, obtained at clinical presentation, shows a persisting asymmetry with distortion and associated pleomorphic clustered calcifications (arrow). (b) US image obtained at presentation shows a 2-cm hypoechoic, irregular mass (arrow) with internal echogenic foci, which correspond to calcifications. (c) Contrast-enhanced T1-weighted subtracted GRE image (18.4/4.3, 40° flip angle) obtained at presentation shows the rim-enhancing 1.5-cm mass (arrow) with a type III enhancement curve and surrounding clumped ductal enhancement (arrowheads). Note that the mass and the nonmass lesions enhance to a greater degree than the surrounding parenchyma (*). (d) Contrast-enhanced screening MR image obtained 7 months earlier shows a portion of the clumped nonmass enhancement (arrowhead), which was visible in retrospect and also enhanced to a greater degree than the significant background parenchymal enhancement (*). (e) Low-power photomicrograph (H-E stain) shows a focus of IDC (*), which corresponds to the mass seen at US; the asymmetry, distortion, and calcifications seen at mammography; and the mass retrospectively visible at MR imaging. Arrow = associated DCIS and clumped ductal enhancement visible only at MR imaging.
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Abstract
Introduction
