Detection of Breast Cancer: Screening of Asymptomatic Patients

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CHAPTER 1 Detection of Breast Cancer: Screening of Asymptomatic Patients

Breast cancer is the most common malignancy and the second leading cause of cancer deaths among American women. In 2005, it is estimated that more than 211,000 new cases will be diagnosed, and more than 40,000 women will die of the disease.¹ Breast carcinoma mortality in the United States has declined substantially over the past 30 years, from 31.4 deaths per 100,000 women per year in 1975 to 25.9 deaths per 100,000 women per year in 2001.² More recent analysis by the CDC of 1999–2003 data from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) study and the CDC National Program of Cancer Registries (NPCR) indicated that age-adjusted incidence rates for invasive breast cancer decreased each year from 1999 to 2003, with the greatest decrease (6.1%) occurring from 2002 to 2003. For in situ cancers, rates increased each year from 1999 to 2002 and then decreased from 2002 to 2003, although the percentage decrease (2.7%) was smaller than that for invasive cancers (6.1%). In addition to advances in treatment options, the combination of increasing utilization of screening mammography and improved mammographic quality, allowing detection of cancers at an earlier stage, is likely to account for the reduction in breast cancer mortality.^3–⁴

Mammography is currently the only screening test proven to reduce mortality from breast cancer in women of average risk. Other modalities, including ultrasound and dynamic contrast enhanced MRI (DCE-MRI), have demonstrated improved cancer detection in select subgroups of women. They have not been examined in women of low risk. In addition, in contrast to screening mammography, studies of these newer modalities have not evaluated mortality as an end point. Therefore, it has been assumed that improved detection rates for ultrasound and MRI will translate to a reduction in mortality.

SCREENING MAMMOGRAPHY

To date, the benefits from screening mammography for women 40 to 70 years of age have been proven in eight randomized controlled trials (RCTs) conducted in Europe and the United States during the past 40 years.⁵^–¹¹ Reported reductions in breast cancer mortality range from 20% to 45%. Because of the relatively small numbers of women aged 40 to 49 years in the individual trials, the benefit from screening in this age range has been controversial. However, in 1997, a meta-analysis of women aged 40 to 49 years in all five Swedish trials found a 30% reduction in breast cancer deaths.¹² In addition, long-term follow-up of three trials (Health Insurance Plan Project [HIP], Gothenburg, and Malmö) each found statistically significant reductions in breast cancer mortality.¹³^–¹⁵ Therefore, for average risk women, most professional organizations in the United States recommend screening mammography beginning at the age of 40 years. For screening women younger than the age of 40 years, there are few RCT data. Therefore, decisions concerning screening practice in this age group must be based on less rigorous evidence and on a more individual basis. Given that younger women have a longer life expectancy and that cancers tend to grow more rapidly in younger women, earlier detection of these cancers may theoretically be advantageous. However, this must be balanced by the limitations of screening mammography in younger women, which include a lower frequency of breast cancer, reduced sensitivity of mammography, slightly increased radiation risk, and higher recall rates. Screening of younger women will be of most benefit in women at high risk, especially those known to carry the BRCA1 or BRCA2 gene mutation. Methods for estimating risk based on medical and family history include the Gail, Claus, and BRCAPRO mathematical models. Observational studies of high-risk women aged 30 to 39 years show a cancer detection rate similar to that for women aged 40 to 49 years.^16–¹⁷ In general, screening of women aged less than 40 years is restricted to high-risk subgroups (women with a 20% lifetime breast cancer risk at or before the age of 30 years or breast cancer risk at a given age equivalent to that of the average woman at the age of 40 years). These include BRCA1 or BRCA2 gene mutation carriers, women with a personal history of breast cancer, women with a prior diagnosis of atypical ductal or lobular hyperplasia, women with previous radiation therapy to the chest before the age of 30 years, and women with a strong family history of breast cancer (usually involving one or more first-degree relatives with premenopausal breast cancer or breast cancer before the age of 50 years).

LIMITATIONS OF MAMMOGRAPHY

Although there have been significant improvements in mammographic technique over the past 50 years, fundamental limitations remain. These include the low inherent contrast differences between tissue structures in the breast and the fact that mammographic detection of breast cancer (sensitivity) relies on the ability to visualize cancer through the background of overlying normal tissue (Figure 1). Mammographic specificity relies on the ability to distinguish benign from malignant breast lesions based on their margins and morphologic features.^18–¹⁹ However, malignant and benign lesions may have similar appearances, thereby reducing specificity. Data from the Breast Cancer Surveillance Consortium demonstrated that on average, screening mammography programs had a callback rate of 6.4% to 13.3% and a positive predictive value of 3.4% to 6.2%.²⁰ The mean cancer detection rate was 4.7 per 1000, and the mean size of invasive cancers was 13 mm. The main mammographic signs of breast cancer include clustered microcalcifications, masses, architectural distortions, and asymmetrical densities. Comparison to prior mammograms is essential because some cancers may only be detected by perceiving them as a subtle change from prior studies. In addition, the availability of prior mammograms for comparison can reduce the number of unnecessary callbacks for stable benign findings.²¹

FIGURE 1 A 58-year-old asymptomatic woman undergoing yearly screening mammography. A, A spiculated mass is seen in the medial left breast on the CC view, isodense to breast parenchyma. On biopsy, this proved to be an invasive ductal carcinoma. B, In retrospect, the mass is evident on the study 2 years before, but is difficult to differentiate from glandular tissue.

DIGITAL MAMMOGRAPHY AND COMPUTER-AIDED DETECTION

Screen-film mammography (SFM) has been the standard method used for breast cancer screening since the end of xeromammography some 20 years ago. Advances in screen-film technology and film-processing techniques have contributed to major improvements in the quality of mammographic images. In addition to high contrast, the strength of SFM lies in its extremely high spatial resolution, often greater than 10 line pairs per millimeter (lp/mm). This allows the detection of exceedingly small clusters of microcalcifications, one of the earliest signs of breast cancer. The limitations of SFM include the detection of subtle soft tissue lesions, especially in the presence of dense glandular tissues, and the fact that the film serves simultaneously as the image receptor, display medium, and long-term storage medium. Recent technologic advances have led to the development of full-field digital mammography (FFDM). One of the initial concerns of FFDM is its inherent lower spatial resolution of 5 to 10 lp/mm. However, several studies have demonstrated that despite the limited spatial resolution, the visibility of calcifications on FFDM is not significantly different from that on SFM.²²^–²⁴ The higher contrast resolution of FFDM may account for its comparable detection rates. In a recent multicenter trial of 49,528 women, Pisano and colleagues²⁴ reported that the overall diagnostic accuracy of FFDM was comparable to SFM as a means of screening for breast cancer. The study also found that digital mammography was more accurate in women younger than 50 years, women with radiographically dense breasts, and premenopausal or perimenopausal women.

Digital mammography has the potential to overcome the inherent limitations of SFM. By directly converting the detected x-ray photons to numerical values, the process of x-ray photon detection is decoupled from the image display. The digital images can be processed by a computer, displayed in multiple formats, and fed directly to computer-aided detection (CAD) software programs. In addition, there are logistical and financial advantages of FFDM, including faster patient throughput, no film or processing costs, the ability to transmit images, and the ability to perform telemammography.

CAD programs were developed to assist a radiologist in the interpretation of screening mammograms, so that cancer detection rates could be improved. These programs rely on neural networks to analyze the images and highlight potentially suspicious findings that may have been overlooked by the radiologist. Several studies have shown improved cancer detection by radiologists using CAD versus radiologists alone, without significantly increasing callback rates.²⁴^–²⁷ However, other studies have shown less promising results.^28–²⁹ A recent study by Fenton and colleagues²⁹ reported that CAD decreased the accuracy of screening mammogram interpretation. This was not due to a decrease in cancer detection, but rather to an increase in false-positive results. To be effective, CAD programs should not increase callback rates and should not significantly prolong interpretation times for screening mammograms. It is important to remember that CAD programs are tools that must be used in an appropriate manner. They should not be used to override a suspicious finding detected by a radiologist. In general, these systems tend to be more helpful for low-volume or inexperienced readers.

MAGNETIC RESONANCE IMAGING

Dynamic, contrast-enhanced MRI of the breast has been shown to be extremely sensitive in the detection of invasive breast cancer and is not limited by the density of the breast tissue. However, because the reported sensitivity of MRI for ductal carcinoma in situ (DCIS) ranges between 45% and 100%, MRI is currently not recommended as a replacement for mammography.³⁰ A more recent single institution study suggests that MRI may have a higher sensitivity than mammography for DCIS than previously thought, particularly for high-grade DCIS.³¹ The use of MRI in the general population has been limited by its moderate specificity. Therefore, its use has been focused on studying patients in whom the yield from MRI is likely to be higher. Multiple studies have shown that MRI is a useful tool as an adjuvant to screening mammography in women at high risk for breast cancer.³²^–³⁴ The American Cancer Society (ACS) recommends annual screening MRI for women with a 20% to 25% lifetime risk for breast cancer.³⁵ This includes women with the BRCA1 or BRCA2 breast cancer genes, as well as women with multiple family members with breast or ovarian cancer, and women who have undergone mediastinal irradiation for Hodgkin’s disease. Women whose benefit from screening MRI was considered questionable by the ACS because of insufficient data included women with a personal history of breast cancer, prior biopsy yielding atypia, or extremely dense breasts on mammography. The decision to perform screening MRI in these women should be made on a case-by-case basis. Several models may be used to calculate lifetime risk for breast cancer, including the Gail, Claus, and Tyrer-Cusick models.

ULTRASOUND

Early studies of breast ultrasound for cancer screening were disappointing because of its poor detection of small cancers and excessively high false-positive rates.³⁶^–⁴⁰ With the advent in the early 1990s of technical improvements in ultrasound, including improved spatial and contrast resolution utilizing higher-megahertz (MHz) transducers, the potential of whole-breast ultrasound as a screening tool has been revisited. Several recent singleinstitution studies have demonstrated a prevalence detection rate of 3 to 4 mammographically occult cancers per 1000 women screened.⁴¹^–⁵⁰ However, the biopsy positive predictive values were less than 20%, lower than accepted for mammography.⁵¹ These initial studies have focused mainly on women with mammographically higher-density breasts. Screening ultrasound appears to be more sensitive in detecting early invasive cancer, whereas mammography is more sensitive in the detection of DCIS. Of the invasive cancers, ultrasound found a higher percentage of invasive lobular carcinomas than that usually found on mammography. Therefore, whole-breast ultrasound should supplement mammographic screening, rather than replace it.

Despite these promising early results, the use of screening ultrasound in general has not been recommend by professional organizations because of concerns regarding the scientific validity of these initial studies and the lack of randomized controlled trials.

The initial studies were performed mostly by radiologists with a high ultrasound skill level and in some studies were not blinded to the mammographic findings. Therefore, the initial results of screening ultrasound may not extrapolate to its use in general clinical practice.⁵² Other concerns include the lack of standardized exam techniques, interpretation criteria, false-positive results, and unnecessary biopsies. In addition, most of the initial studies on whole-breast ultrasound have evaluated prevalence (initial) detection rates, rather than incidence (subsequent) detection rates. The benefit from subsequent yearly screening ultrasound is uncertain, but likely to be less. The American College of Radiology Imaging Network (ACRIN) is currently conducting a randomized multicenter trial evaluating whole-breast bilateral screening ultrasound in high-risk, asymptomatic women with dense breasts. The study will evaluate both prevalence (year 1) and incidence (years 2 and 3) screening ultrasound detection rates as compared with mammography. Interpretation of the examinations will be performed by radiologists trained in mammographic and ultrasound interpretation, using standardized interpretive criteria.

Although ultrasound is less sensitive than MRI, because of its lower cost and availability, it is likely that whole-breast ultrasound will play an increasing role as a supplemental screening modality in women with dense breasts. Current postprocessing algorithms, including spatial compounding and harmonic imaging, as well as newer techniques such as elastography, may help to improve the specificity of breast ultrasound and decrease the number of false-positive results and unnecessary biopsies. In addition, automated whole-breast ultrasound systems, currently being developed by several manufacturers, may help to standardize and streamline whole-breast ultrasound.

MOLECULAR IMAGING

Previous attempts of breast imaging using ^99mTc sestamibi and ¹⁸F fluorodeoxyglucose (FDG) positron emission tomography (PET) were limited by the use of relatively low-resolution whole-body systems. However, newer high-resolution dedicated breast imaging systems have been developed. Breast-specific gamma imaging (BSGI) and positron emission mammography (PEM) allow high-resolution imaging of the breast based on metabolism, rather than anatomic changes. Their use as screening tests has not been established. Variability of uptake in primary breast tumors, as well as moderate specificities, has limited their potential. Randomized control trials are needed to evaluate their possible role as an adjuvant screening tool in certain subgroups of women.

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CASE 1 Breast cancer presenting as a small new mass on mammography

An asymptomatic 57-year-old woman underwent screening mammography, which showed a new finding of a 6-mm round mass in the anterior upper outer quadrant (UOQ) of the left breast (Figures 1 and 2). The patient had undergone a prior benign left breast needle biopsy with placement of a marker clip in the posterior upper outer left breast. Ultrasound confirmed the presence of a somewhat ill-defined 6-mm solid mass (Figure 3). Ultrasound-guided core needle biopsy yielded a diagnosis of low-grade ductal carcinoma in situ.

FIGURE 1 Mediolateral oblique (MLO) (A) and cranial-caudal (CC) (B) views show a small, 6-mm, low-density round mass in the anterior upper outer quadrant (arrows).

FIGURE 2 Close-up view demonstrates that the margins of the mass are ill defined.

FIGURE 3 Ultrasound confirms a hypoechoic mass with internal echoes. Although this could represent a cyst with debris or thick fluid, it does not meet the criteria for a simple cyst. Therefore, it must be considered solid until proved otherwise.

The patient was treated surgically with lumpectomy alone. Final histologic diagnosis was a 6-mm low- to intermediate-grade ductal carcinoma in situ with negative margins.

TEACHING POINTS

Mammographic signs of breast cancer may manifest as subtle new findings. The ability to compare to prior mammograms can facilitate the detection of subtle changes. Because the finding in this case represented a new mass, workup proceeded directly to ultrasound for evaluation. This could have represented a benign cyst. Any new solid mass requires tissue biopsy. Therefore, mammographic magnification views to analyze the margin features of this mass would not have changed clinical management.

CASE 2 Breast cancer presenting as a new mass on mammography

A new left lower inner quadrant mass with ill-defined margins was identified on a screening mammogram performed on an asymptomatic 67-year-old woman (Figure 1). Sonography confirmed a suspicious, 1 cm, irregularly marginated, hypoechoic, solid mass, which was taller than wide (Figure 2). A mammographically questioned second abnormality, architectural distortion in the left upper breast, had no sonographic confirmation. MRI was recommended to further assess the question of possible multicentric disease. The suspected cancer mass was highly suspicious by MRI criteria, showing irregular margination (Figures 3 and 4) and a washout pattern of enhancement (Figure 5). No correlate was found on MRI for the questioned left upper architectural distortion. There was no evidence of multicentricity by MRI.

FIGURE 1 MLO (A) and CC (B) mammograms show heterogeneous increased breast parenchymal density. There is a mass with indistinct margins in the lower inner quadrant of the left breast. Although the mass is of similar density to the breast tissue, it is readily visualized in an area where the breast is relatively fatty. Mammography also raised a question of architectural distortion in the left upper breast at 12 o’clock, where more locally increased parenchymal density can be seen.

FIGURE 2 The mass is highly suspicious on ultrasound. It is solid, very hypoechoic, and taller than wide, and it has irregular, angular margins. No sonographic correlate for the questioned left upper breast architectural distortion was found.

FIGURE 3 T2-weighted axial MRI shows the mass to be posterior and surrounded by fatty tissue, with an irregular margin and relatively hypointense signal intensity. Most breast cancers are hypointense on T2-weighted MRI. A fluid signal, round, cystic structure in the right chest represented a known pericardial cyst.

FIGURE 4 Enhanced subtracted axial breast MRI shows the mass to enhance intensely heterogeneously. The margin is irregular. Scattered, tiny punctate foci of enhancement are also noted throughout both breasts.

FIGURE 5 Three minutes later, the left breast mass enhancement has markedly declined. This washout suggests malignancy.

Subsequent image-guided biopsy of the mass confirmed invasive ductal carcinoma (IDC). Clinical and imaging evaluation suggested stage 1 disease, and the patient was treated surgically with partial mastectomy. The pathology showed a 1.5-cm invasive ductal carcinoma, estrogen receptor and progesterone receptor positive and HER-2/neu positive, with clear margins. Two sentinel lymph nodes were negative for malignancy.

Radiation therapy was administered after surgery, and hormonal therapy (initially tamoxifen, subsequently switched to anastrozole [Arimidex]) was begun afterward.

TEACHING POINTS

Mammographic detection of the new mass in the posterior lower inner quadrant of the left breast was greatly aided by the fact that it arose in a region where the patient’s breast is relatively fatty. The mass is similar in density to the breast parenchyma and would have been more difficult to identify if it occurred in an area of greater breast density. The question raised on mammography of a second abnormality, with possible architectural distortion in the upper left breast, needed to be settled before a decision could be made regarding suitable surgical treatment for this patient. The lack of an ultrasound correlate was somewhat reassuring, but greater reassurance is provided by the absence of a corresponding abnormality on MRI, with its high sensitivity for invasive neoplasia. The background pattern of tiny scattered enhancing foci is commonly encountered, especially in premenopausal women, and is presumed related to hormonal effects. These findings are minimized by imaging, when possible, in the second week of the menstrual cycle. Even when they cannot be eliminated, it is generally possible to “read around” these findings when they are fairly diffuse and symmetric.

The use of breast MRI in this case increases the confidence level that this patient’s tumor is unifocal and that she is a suitable candidate for breast conservation surgery.

CASE 3 Small growing breast cancer presenting as a contour change on mammography

Routine digital screening mammography in an asymptomatic 62-year-old woman suggested an interval change compared with prior years’ studies, with a 1-cm upper outer quadrant mass suggested (Figure 1). This persisted on spot compression, and ultrasound identified a corresponding suspicious 9-mm hypoechoic, solid mass, with irregular margins (Figure 2).

FIGURE 1 MLO (A) and CC (B) right digital mammograms show scattered fibroglandular density. A subtle contour change on the MLO view in the right upper breast tissue suggested the possibility of a developing mass (arrows). C, For comparison, a prior year’s MLO mammograms.

FIGURE 2 Ultrasound shows a highly suspicious corresponding mass that is taller than wide and very hypoechoic, with irregular and lobular margins. The mass is surrounded by echogenic fibrous tissue, as on mammography.

Ultrasound-guided core needle biopsy proved the lesion was an infiltrating ductal carcinoma (IDC). Ultrasound-guided needle localization was performed before lumpectomy. The pathology showed a 1.1-cm IDC, estrogen receptor and progesterone receptor positive, with negative margins and negative sentinel node sampling. Chemotherapy and radiation were administered subsequently.

TEACHING POINTS

Interval change can be the only sign of malignancy on screening mammograms and can be very subtle. This growing mass was largely concealed by adjacent parenchymal density, with only a subtle contour bulge suggesting its presence. Little increased density, architectural distortion, or other visual clue to the presence of this mass was seen. In this case, only systematic comparison, density for density, between current and prior mammograms enabled this IDC to be picked up at a small size and early stage (stage 1, T1N0).

CASE 4 Slow-growing microlobulated colloid carcinoma

An asymptomatic 65-year-old female underwent screening mammography, which showed an enlarging circumscribed mass in the central right breast (Figures 1 and 2). Ultrasound demonstrated a corresponding hypoechoic solid mass (Figure 3). Subsequent ultrasound-guided core needle biopsy was performed and yielded a diagnosis of invasive colloid carcinoma.

FIGURE 1 Right CC mammographic view shows a mass in the central right breast (arrow).

FIGURE 2 Close-up view of the mass demonstrates partially circumscribed margins and microlobulations.

FIGURE 3 Ultrasound demonstrates a hypoechoic solid mass with mildly irregular margins, corresponding to the mammographic mass.

TEACHING POINTS

This case illustrates the importance of prior mammograms in the evaluation of subtle change. A new or enlarging mass should prompt further workup. In this case, because this is an enlarging mammographic mass, the workup can proceed directly to ultrasound. Evaluation of the margins of the mass on magnification mammographic views would not change clinical management. Any new or enlarging solid mass should prompt a biopsy, regardless of its appearance mammographically. The role of ultrasound in this instance is to determine whether the finding represents a cyst or solid mass. In this case, the mass was solid and demonstrated a relatively benign appearance. Some cancers, including colloid carcinoma, papillary carcinoma, and medullary carcinoma, may have relatively smooth margins.

CASE 5 Breast cancer presenting as a new posterior mass on mammography: Importance of inclusion of posterior breast tissue on mammography

A 70-year-old woman with a prior history of stage II ovarian carcinoma was noted on a routine screening mammogram to have a partially visualized, asymmetric density in the posterior right breast, seen only on the MLO view (Figure 1). She was recalled for additional evaluation. On spot compression, a mass was confirmed, with ill-defined margins (Figure 2). The mass was sufficiently far posterior that it was difficult to visualize entirely by mammography. Ultrasound showed highly suspicious characteristics, including being taller than wide, with irregular, angular margins (Figure 3). Ultrasound-guided core needle biopsy of the mass proved that the lesion was infiltrating mammary carcinoma. MRI confirmed that the lesion was solitary, without evidence of additional disease sites (Figure 4). Surgical therapy consisted of partial mastectomy and sentinel lymph node sampling. Final pathology showed a 1.8-cm infiltrating ductal carcinoma, with clear margins and one negative sentinel lymph node.

FIGURE 1 Screening mammographic views show breast parenchyma of heterogeneous increased density. On the right MLO view (A), overlying the inferior pectoral muscle, is a new, partially visualized density. No corresponding abnormality is seen on the craniocaudal view (B), probably because of the far posterior position of the lesion. Visualized margins appear indistinct and spiculated. The patient was recalled for additional views.

FIGURE 2 Spot compression [MLO (A) and exaggerated CC (B)] confirms the abnormality, but the far posterior position precludes complete visualization of the posterior margins. The visualized margins are irregular, with spiculation.

FIGURE 3 Ultrasound demonstrates the corresponding lesion well and displays multiple malignant features. The mass is intensely hypoechoic and taller than wide, and the margins are irregular and angular. The lesion is readily visualized and more accessible than with mammography; thus, ultrasound guidance was selected for histologic sampling.

FIGURE 4 Maximum intensity projection (MIP) of a subtracted data set from the enhanced dynamic breast MRI shows the tumor to enhance intensely and early. It displays features of malignancy on MRI, including spiculated margins and rim enhancement. Both breasts show a fairly symmetric pattern of lower-level fibrocystic-type enhancement, consisting of innumerable scattered tiny foci of enhancement. Enhancement of normal-sized lymph nodes (including one projecting posterior to the mass) and internal mammary vessels is also demonstrated bilaterally here.

TEACHING POINT

This case illustrates graphically the answer to the perennial patient question about the mammogram: “Why do they pull so hard?” Inclusion of as much of the breast tissue as possible is critical to optimal breast cancer screening with mammography. Abnormalities in unimaged breast tissue cannot be identified on screening. Abnormalities such as this, in a far posterior position, which may be difficult to image entirely with mammography, may be readily visualized on other modalities, if seen even partially at screening. Critique of image quality, regarding positioning and complete inclusion of the breast tissue, is an ongoing process at both the technologist and physician review levels and should include comparison with the coverage achieved on prior studies in the same patient.

CASE 6 DCIS presenting as a microcalcification cluster

A new microcalcification cluster was identified on screening mammography in this 82-year-old woman. Magnification views showed pleomorphic forms (Figure 1), and stereotactic biopsy was recommended. Specimen radiography confirmed that the calcifications were sampled, and histology identified infiltrating ductal carcinoma and comedo ductal carcinoma in situ (DCIS). The patient opted for surgical therapy with mastectomy and was treated with tamoxifen for 5 years thereafter.

FIGURE 1 A and B, Magnification views of the calcifications in question show pleomorphism, with the clustered calcifications varying from one another in size, shape, and density.

TEACHING POINTS

Quality control in performance of image-guided biopsies takes place at many levels. Two essential quality assurance components of stereotactic-guided biopsy programs are specimen radiography and pathology correlation. Specimen radiographs should routinely be obtained when performing stereotactic biopsy for microcalcifications and may occasionally be useful after biopsy of masses. It can be difficult, because of the presence of lidocaine and particularly if bleeding develops, to be certain with stereotactic images that microcalcifications have been obtained. This is particularly true when sampling small microcalcification clusters, especially with larger (e.g., 8-gauge Mammotome) vacuum-assisted devices.

Correlation of the pathology results with the imaging features of the biopsied lesion is also critical. For any sampled lesion, there is an acceptable range of possible pathologic results, and insistence on internal consistency between the histologic diagnosis and the imaging features of the abnormality is a basic safeguard against sampling error.

CASE 7 DCIS presenting as multiple microcalcification clusters along a ductal ray

New microcalcification clusters were noted in the medial left breast on routine mammographic screening of a 61-year-old asymptomatic woman. The most recent comparison mammogram was 3 years earlier. A suspicious, segmental distribution of the microcalcifications was noted, and magnification was performed to better visualize them. Magnification views of the medial breast confirmed three separate, suspicious clusters of pleomorphic microcalcifications, aligned along an axis toward the nipple (Figure 1). Stereotactic biopsy was performed on two of the three clusters, including the most anterior and posterior (Figure 2). Intermediate- to high-grade ductal carcinoma in situ (DCIS), with necrosis, was obtained from both sites. Pathology commented that the DCIS obtained from the posterior site was variably associated with microcalcifications. Based on the distance between the sampled sites (4 cm), it seemed likely that there was extensive intraductal disease, suggesting the patient was not a suitable candidate for breast-conserving surgery. Breast MRI was performed to assess for additional, mammographically occult disease (Figure 3). No MRI findings particularly suggestive of unsuspected or occult invasive disease were seen.

FIGURE 1 Magnification views in 90-degree lateral (A) and CC (B) projections show three clusters of microcalcifications (arrows) in the medial breast, aligned in an axis toward the nipple. The morphology of the calcifications is irregular, variable, and pleomorphic. The findings were new compared with a mammogram performed 3 years earlier. The benign-appearing mass also noted in these views was proved by ultrasound to be a simple cyst.

FIGURE 2 Post–stereotactic biopsy films [90-degree lateral (A) and CC (B)] show clips at the two sampled sites (arrows), corresponding to the most anterior and posterior of the three clusters. The measured distance between the sampled sites, both of which yielded DCIS, is at least 4 cm.

FIGURE 3 A, Enhanced subtracted bilateral breast MRI shows a thin rim of enhancement corresponding to the anterior biopsy site from which DCIS was obtained in the medial left breast. Nipple enhancement is also noted, which is a frequently seen normal finding. B, At another level, the second, more posterior biopsy site is seen. The rim enhancement at the lateral aspect of the biopsy cavity is less smooth, with slightly nodular foci of enhancement. C, Fat-saturated, unenhanced T1-weighted gradient echo sagittal view shows hyperintense blood products within the two small postbiopsy cavities. D, A delayed (about 5 minutes after injection) enhanced subtracted sagittal image shows rim enhancement of the two postbiopsy cavities. Parenchymal enhancement is now seen above the posterior biopsy cavity.

The patient underwent mastectomy and sentinel lymph node sampling. The mastectomy specimen pathology showed residual foci of intermediate-grade cribriform DCIS with central necrosis, including four foci (ranging in size from < 1 mm to 4 mm) adjacent to the anterior biopsy site and one 2-mm residual focus adjacent to the posterior biopsy site. Four sentinel lymph nodes were negative for malignancy.

TEACHING POINTS

This case provides many interesting lines of inquiry for discussion. In an ideal world (in which there are no constraints of time, room availability, or waiting patients), all three of these suspicious microcalcification clusters might have been sampled. In the real world, in which many patients are not able to tolerate the prone position required for stereotactic sampling long enough to perform three biopsies, the next best option is to choose sites for biopsy with the greatest potential yield in terms of decision making. In this case, the clusters were equally suspicious, but the most anterior and posterior clusters were larger and likelier to yield a higher number of calcifications in the sampling. In addition, the smaller, middle cluster was fairly close to the most posterior cluster. Sampling the farthest apart clusters is the most efficient approach when histologic confirmation of suspected multifocal disease is desired. The similar-appearing middle cluster would be presumed to be the same histology.

Breast MRI can be very helpful in the assessment of the breast for additional or occult invasive disease. In this particular case, breast MRI did not show any separate or unsuspected sites of disease, indicating that the calcifications seen on mammography were the best imaging “map” of the extent of disease. Unfortunately, even that cannot be depended on to demonstrate the full disease extent, because the histologic sample from the posterior cluster noted that not all of the identified DCIS was associated with microcalcifications. The negative breast MRI result is not surprising in this case because the volume of residual disease found at mastectomy was small (although multiple foci of DCIS were found, the largest focus was 4 mm). In addition, DCIS as a histology can be variable in enhancement, the process on which MRI visualization depends.

There are a variety of factors influencing surgical decision making between breast-conserving lumpectomy and mastectomy. The goals of breast conservation can be summarized as surgical removal of all identifiable disease with good cosmesis. The tumor size and location in relation to the breast size must be taken into account. In this case, even if the mammographic calcifications were an accurate reflection of the distribution of the DCIS, complete surgical extirpation would have required removal of much of a quadrant, making a pleasing cosmetic result difficult to achieve.

CASE 8 Breast cancer presenting as architectural distortion in extremely dense breasts

A 46-year-old woman with very dense breasts was called back for bilateral magnification views of microcalcifications noted on screening mammography. These proved to be widely scattered, with morphology consistent with milk of calcium. However, right upper outer quadrant (UOQ) increased breast density was noted with architectural distortion (Figure 1), and ultrasound was performed for further evaluation. Sonography showed a 1.2-cm hypoechoic, shadowing, irregularly marginated mass in the UOQ, corresponding to the mammogram (Figure 2). Ultrasound-guided core needle biopsy confirmed infiltrating ductal carcinoma (IDC). Because of the extreme density of the patient’s breast parenchyma, breast MRI was performed as an aid to presurgical staging. The known IDC was visualized as a spiculated, enhancing 1.5-cm mass in a background of diffuse fibrocystic enhancement, with innumerable scattered small foci of less intense enhancement (Figures 3, 4, 5).

FIGURE 1 Architectural distortion (arrow) was suspected on the right, best seen in an exaggerated CC spot view.

FIGURE 2 Ultrasound of the area in question shows a corresponding abnormality, with an intensely hypoechoic, taller-than-wide, irregularly marginated mass concealed within a band of hyperechoic, dense fibrous tissue. Margins show angularity and spiculations, features of malignancy. Biopsy with ultrasound guidance confirmed IDC.

FIGURE 3 Maximum intensity projection (MIP) of an early, enhanced, fat-saturated volumetric dynamic acquisition shows a dominant enhancing mass with irregular margins in the right lateral breast, which is readily visualized despite the extensive background of diffuse fibrocystic foci of enhancement. MIP views provide an overview of a volumetric data set and can be useful as a visual “shorthand” form of communication when presenting a case in conference or discussing it with a clinician, but should never be relied on for primary interpretation.

FIGURE 4 A single slice from early in the dynamic enhanced series better shows the malignant MRI features of the IDC. Margin spiculation and rim enhancement are seen.

FIGURE 5 Importance of imaging early during dynamic enhanced breast MRI is well demonstrated in this patient. The lesion becomes less conspicuous with progressive enhancement of the parenchyma by 4 minutes after the contrast injection.

After ultrasound-guided needle localization (Figure 6, specimen radiograph), a partial mastectomy was performed. The pathology showed a 1.5-cm IDC with mucinous and clear cell features, without angiolymphatic invasion, estrogen receptor and progesterone receptor positive, with margins clear for invasion and notable only for a focal close (1 mm) inferior medial margin for DCIS. Five sentinel lymph nodes were negative.

FIGURE 6 The mammographic characteristics of the IDC are best demonstrated on the specimen radiograph, which shows the spiculated mass adjacent to the localizing wire, placed under ultrasound guidance. Microcalcifications are seen throughout the specimen.

The final stage was stage I, T1N0M0 disease. The patient was treated with four cycles of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) chemotherapy and radiation therapy, with a boost to the lumpectomy bed. Tamoxifen was started after completion of chemotherapy.

TEACHING POINTS

This case raises a variety of points for additional discussion. The patient was called back for calcifications, which were benign in morphology. Fortunately, the callback provided an opportunity for the mammographically subtle finding of architectural distortion to be suspected. In dense breasts like these, the threshold for imaging with other modalities, especially with ultrasound, of questionable areas should be low. The ultrasound is unequivocally suspicious and shows well how the position of the suspicious spiculated mass, concealed within dense fibrous tissue, enables the abnormality to be nearly occult on mammography.

The breast MRI of this patient shows a dramatic example of hormonal effects, manifested as innumerable enhancing foci, which are regularly encountered in performing breast MRI, particularly in younger and premenopausal women. Even with such expected findings, breast MRI is useful in evaluating women with dense breast tissue. The timing of performance of enhanced, subtracted dynamic imaging is particularly important in these patients. The early, intense enhancement of tumors capitalizes on angiogenesis and is best visualized in the first 1 to 2 minutes after intravenous contrast administration, when the greatest differential in enhancement between tumors with angiogenesis and normally enhancing breast tissue is encountered. With greater delays, the progressive enhancement of normal tissue will decrease the conspicuity of neoplastic lesions, as is well demonstrated here.

Another issue raised by this case is the use of specimen radiography after ultrasound-guided needle localization. Although specimens can be sonographically imaged after removal, this is less frequently used in practice. Radiography of specimens obtained after sonographic localization is used sporadically, often on a case-by-case basis, particularly if the localized abnormality, residual lesion, or clip is difficult to visualize and additional assurance is desired that the abnormality has been removed. In this case, the specimen radiograph provides the first unobstructed mammographic look at the malignant features of the lesion. Specimens should be scrutinized for the presence of localizing wires and clips as well as for the presence and position within the specimen of the abnormality. In addition to assessing the completeness of the excision, the relation of the abnormality to the margins of the specimen is assessed to determine whether to obtain additional tissue.

CASE 9 ILC presenting as a growing amorphous density

An asymptomatic 61-year-old woman underwent screening mammography over a 14-year period. Over the course of the patient’s screening examinations, an amorphous density and focal asymmetry developed within the upper outer right breast (Figures 1, 2, 3, and 4). Although this was recalled for spot compression views, the finding was interpreted as asymmetric glandular tissue because it partially dispersed on compression and contained fat density areas (Figure 5). The area subsequently became palpable, prompting an ultrasound examination. The ultrasound demonstrated an irregular solid mass with posterior acoustic shadowing (Figure 6). Needle biopsy of the mass revealed an invasive lobular carcinoma (ILC).

FIGURE 1 Bilateral MLO mammographic views from 1992. The breasts are mixed fat and fibroglandular density. There are no apparent abnormalities.

FIGURE 2 Bilateral MLO views performed in 1996. In retrospect, there is the subtle beginning of a developing asymmetry in the upper outer right breast (arrow).

FIGURE 3 Bilateral MLO views from 2001. The asymmetry (arrow) in the right breast has increased in size and density since the prior examination.

FIGURE 4 Bilateral MLO views performed in 2004. The asymmetry in the right breast continued to enlarge (arrow). At this point, the finding on screening mammography prompted a callback for additional evaluation.

FIGURE 5 An MLO spot compression view demonstrates the asymmetry to partially disperse and to contain areas of fat. This was thought to represent asymmetrical normal glandular tissue, and the patient was returned to annual screening.

FIGURE 6 In 2006, the patient presented complaining of a palpable mass in the area of mammographic asymmetry in the upper outer right breast. Ultrasound reveals a large irregular hypoechoic mass with posterior shadowing, corresponding to the palpable finding. Subsequent needle biopsy revealed an invasive lobular carcinoma.

TEACHING POINTS

This case illustrates several teaching points. It is important to compare screening mammograms with several prior years’ mammograms. As in this case, a slowly growing cancer may not appear to change much from year to year. Comparing the current mammogram with films from several years before may reveal a developing mass. Although the mammographic finding could have been asymmetric glandular tissue, an unexplained enlarging density should prompt a biopsy. In this case, we see that invasive lobular carcinoma can mimic normal tissue, and ultrasound can help in differentiation. Invasive lobular carcinoma represents about 10% of invasive breast cancers.

CASE 10 Small cancer in implant patient, well seen only on implant-displaced views

An asymptomatic 51-year-old woman with bilateral silicone implants underwent annual screening mammography. The right standard views showed no definite abnormality (Figure 1). The implantdisplaced MLO view demonstrated a focal asymmetry in the upper right breast (Figure 2). Spot compression MLO view confirmed a spiculated mass in the upper right breast (Figure 3). Ultrasound showed a corresponding irregular 11-mm solid mass in the 12-o’clock position (Figure 4). Subsequent biopsy confirmed an invasive ductal carcinoma.

FIGURE 1 Right breast mammographic views [MLO (A) and CC (B)] show subglandular implants and moderate parenchymal density. No definite abnormality is seen.

FIGURE 2 With implant displacement, a focus of increased density and architectural distortion is seen adjacent to the implant (arrow).

FIGURE 3 MLO spot compression confirms a small, suspicious, spiculated mass adjacent to the implant.

FIGURE 4 Ultrasound of the right upper breast confirms a corresponding suspicious mass that is hypoechoic, taller than wide, with irregular, angular margins.

TEACHING POINTS

This case demonstrates the need for supplemental views in patients with implants undergoing screening mammography. These include implant push-back or displacement views to better compress the breast tissue anterior to the implants. Other views may include laterally exaggerated craniocaudal views and 90-degree ML views.

CASE 11 Importance of a complete workup of new mammographic masses

A screening mammogram on an asymptomatic 49-year-old woman showed bilateral, similar-appearing upper outer quadrant breast masses (Figure 1), which were new from a prior mammogram taken 2 years earlier. Ultrasound was performed to further evaluate these masses (Figures 2 and 3). On the right, where mammography suggested two masses, ultrasound confirmed two simple cysts. On the left, where mammography showed a single new mass (similar in appearance to the right-sided findings), sonography identified a vascular, solid mass with indeterminate features. Biopsy was recommended. Excision of the lesion demonstrated a 1.4-cm infiltrating ductal carcinoma. In addition to lumpectomy and a negative sentinel lymph node sampling, the patient was treated with radiation therapy.

FIGURE 1 Screening mammography [MLO (A) and CC (B)] shows heterogeneous breast parenchymal density and bilateral, similar-appearing breast masses (arrows). Where the margins can be visualized, they appear circumscribed, suggesting cysts. Other margins are obscured by dense adjacent parenchyma. Because the masses were new compared with a mammogram taken 2 years earlier, and the patient had never been demonstrated to have cysts, sonography was recommended to characterize the masses.

FIGURE 2 Ultrasound of the right breast (A and B) confirms two simple cysts, accounting for the right mammographic findings. These display all the hallmarks of simple cysts (sharp back wall, anechoic, and enhanced through-transmission).

FIGURE 3 Ultrasound of the left breast shows a solid, vascular, taller-than-wide mass, without ultrasound features to suggest benignity. Although the mass shows lobular borders, it is not surrounded by the thin echogenic pseudocapsule that can often be demonstrated in benign solid masses, such as fibroadenomas. Biopsy was recommended and confirmed infiltrating ductal carcinoma.

TEACHING POINTS

The case illustrates the importance of complete workups. Mammographers often refer to the “rule of multiplicity,” which suggests that if there are multiple breast masses, they are all likely benign. It is difficult to correlate sonographic to mammographic masses, one for one, when the lesions are numerous. However, at least when beginning screening, it is useful to clearly establish by ultrasound that a patient with multiple masses has multiple cysts, multiple solid masses, or some combination. With this information, subsequent mammographic changes, such as waxing and waning of multiple cysts, can be more accurately assessed. However, development of a new mass or masses in a patient without such prior findings warrants a sonographic evaluation. In this case, virtually identical new bilateral mammographic findings resulted in a diagnosis of benign cysts on one side and cancer on the other.

CASE 12 MRI high-risk screening for occult breast cancer

A 35-year-old woman who tested positive for the BRCA1 gene mutation was followed with yearly mammograms and breast MRI after treatment 4 years earlier for right breast cancer. The tumor was a stage I, T1N0M0, node-negative 1.9-cm medullary carcinoma, treated with lumpectomy, chemotherapy, and radiation. The patient underwent hysterectomy and bilateral salpingo-oophorectomy after treatment for breast cancer.

An intensely enhancing small (5-mm) left breast nodule was noted to be new on high-risk screening MRI (Figure 1). After a 3-month delay during which a prior comparison MRI was obtained from another facility (confirming the lesion to be new), a sonographic correlate was identified and biopsied, confirming infiltrating ductal carcinoma (IDC) (Figure 2). By ultrasound, the mass measured 8 × 6 mm. The patient elected to undergo bilateral mastectomies for treatment and received postoperative chemotherapy with docetaxel (Taxotere) and cyclophosphamide (Cytoxan), as well as chest wall and supraclavicular radiation therapy. The left mastectomy specimen showed a 1.6-cm, T1N1 tumor with angiolymphatic invasion and negative margins, with one of 19 lymph nodes positive. No additional tumor was found on the right.

FIGURE 1 Axial, enhanced, subtracted slice from bilateral high-risk screening breast MRI shows a solitary enhancing sub-centimeter nodule with irregular margins in the left posterior breast, new from a prior year’s study. Based on MRI, this was localized at 5 o’clock.

FIGURE 2 Ultrasound of the left breast identifies the correlate at 3 o’clock as an indeterminate, hypoechoic, solid mass with no well-defined capsule. Biopsy with ultrasound guidance confirmed IDC.

TEACHING POINTS

This case provides a convenient launching point for a discussion of imaging surveillance of patients at high risk for breast cancer. Who is considered high risk? Patients with a genetic predisposition to breast cancer include those with genetic mutations (BRCA1 and BRCA2) and those with a family history of breast cancer in one or more first- or second-degree relatives (mother, sister, daughter, maternal aunt), especially if the relative’s breast cancer was premenopausal. Other patients who are considered at high risk include those with a prior personal history of breast cancer and those with prior histologic diagnoses of lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), and atypical ductal hyperplasia (ADH).

The high lifetime risk for developing breast cancer faced by women with the BRCA1 and BRCA2 gene mutations is well recognized. Lifetime breast cancer risks of up to 85% have been predicted for BRCA mutation patients. As illustrated by this case, there is a substantial risk (30%) in these patients of developing a contralateral breast cancer within 5 years after diagnosis of breast cancer.

The breast cancers developing in BRCA mutation patients tend to occur early, in younger patients with dense breasts who are more difficult to screen with mammography. The tumors also tend to be more rapidly growing and aggressive. This is suggested in this case by noting the discrepancy between the apparent size of the new small mass on MRI (5 mm), its ultrasound correlate 3 months later (8 mm), and the 1.6-cm IDC found in the mastectomy specimen, suggesting interval growth in the 5 months that elapsed between the initial identification of the lesion and its excision.

BRCA mutation patients should undergo multipronged surveillance, with twice-yearly clinical breast examinations and yearly imaging screening, which traditionally consisted of mammography. Because of the difficulty of screening younger women with dense breast tissue with mammography, a number of investigators have reported in recent years on the use of breast MRI to supplement the imaging surveillance of these patients. These studies support the use of breast MRI as a more sensitive modality than mammography for earlier diagnosis of smaller, earlier-stage, occult breast cancers. The largest series reported to date was a prospective trial from the Netherlands by Kriege and colleagues, in which 1909 women with a cumulative lifetime breast cancer risk of 15% or greater were screened every 6 months with clinical breast examination and yearly with mammography and breast MRI. The study population included 358 patients with genetic mutations. Fifty-one cancerous lesions were identified over a median follow-up period of 2.9 years, including 44 invasive cancers, 6 cases of DCIS, 1 lymphoma, and 1 LCIS. Sensitivity for identification of invasive breast cancer with clinical breast examination (CBE) was 18%, compared with 33% for mammography and 80% for breast MRI, with specificities of 98%, 95%, and 90%, respectively. The invasive cancers identified by MRI were smaller, with a lower incidence of positive axillary nodes, than those identified by mammography.

A Canadian study of 236 BRCA mutation patients by Warner and associates reported similar results and included ultrasound in the comparison between modalities and CBE. In this study, CBE was performed every 6 months. Once a year, patients underwent mammography, breast ultrasound, breast MRI, and CBE on the same day. Each modality was interpreted independently, and all breast imaging reporting and data system (BI-RADS) 4 (suspicious) and 5 (highly suspicious) abnormalities detected by any modality underwent biopsy. The sensitivity and specificity of each modality were calculated, as well as the sensitivity of all four modalities together compared with mammography and CBE. Twenty-two cancers were identified, including 16 invasive cancers and 6 cases of DCIS. The sensitivity of breast MRI was 77%, compared with 36% for mammography, 33% for ultrasound, and 9% for CBE. The four screening modalities together had a sensitivity of 95%, compared with 45% for mammography and CBE together. Overall sensitivity of the combined modalities dropped to 86% with ultrasound excluded. A third of the detected cancers (7 of 22, or 32%) were demonstrated on MRI alone. Mammography and ultrasound each found two cancers not identified on other modalities.

These data suggest several approaches to the imaging surveillance of BRCA mutation and other high-risk patients. On the one hand, in an ideal world (with no constraints on costs), all three imaging modalities would be employed to maximize cancer detection. Because their strengths in diagnosing breast cancers derive from different approaches to imaging, it is to be expected that there will be cancers picked up on one modality that go undetected on others. An additional price to be paid with this approach would be an increase in false-positive results and additional biopsies. A more cost-effective approach might be to screen yearly with mammography and breast MRI, with ultrasound used to further evaluate abnormalities and guide biopsies when abnormalities are identified. A case can also be made for yearly performance of mammography and breast MRI, alternating every 6 months.

This case also reminds us not to be rigid about lesion localization in the breast when looking for ultrasound correlates for breast MRI abnormalities. By MRI, the new focus of enhancement was judged to be at 5 o’clock, whereas its correlate on ultrasound was found at 3 o’clock. The mobility of breast tissue and positioning differences (prone versus supine or supine oblique positioning between breast MRI and ultrasound) introduces considerable variability in apparent position of corresponding lesions. It probably is a good idea to examine with ultrasound at least a quadrant’s worth of breast tissue on either side of the clock position of any concerning lesion identified on MRI.

TEACHING POINTS

There is no established role for breast MRI in screening of the general population. However, breast MRI has gained credence in recent years for screening of higher-risk patients. Recently published American Cancer Society guidelines recommend annual screening MRI as an adjuvant to mammography in high-risk patients. High-risk women were defined as women with an approximately 20% to 25% or greater lifetime risk for breast cancer. These patients include those with BRCA genetic mutations, strong family history (especially premenopausal breast cancer or breast cancer in two or more primary relatives), or prior treatment for Hodgkin’s disease. Increased breast density has recently been recognized as an independent risk factor for development of breast cancer and limits the efficacy of mammographic screening, as in this case. It should be emphasized that MRI is recommended as an adjuvant rather than a replacement for mammography. Given the variable sensitivity of MRI for DCIS, mammography may find areas of DCIS not detected by MRI. Conversely, because DCIS may not be calcified in up to two thirds of cases, MRI can identify DCIS that is mammographically occult.

CASE 14 Breast cancer presenting as a growing small mass on screening MRI

A 57-year-old woman who was due for routine screening mammography requested breast MRI as an alternative because of concerns about radiation. She had previously had a benign right stereotactic breast biopsy for new microcalcifications, 1.5 years before.

The breast MRI showed small, scattered bilateral enhancing nodules, thought to be benign (Figure 1). The largest was 8 × 6 mm in the right lower outer quadrant (LOQ), with a similar lesion in the left LOQ (Figure 2). A workup with bilateral mammography and ultrasound showed no suspicious findings or definite corresponding lesions. A repeat breast MRI in 6 months was recommended.

FIGURE 1 Axial maximal intensity projection (MIP) from the first minute of an enhanced, subtracted dynamic MRI series shows a background of innumerable, scattered, tiny foci of fibrocystic enhancement. Bilateral, solitary, sub-centimeter, benign-looking masses are noted in the lateral aspects of both breasts.

FIGURE 2 Source images from early in the dynamic series show similar-appearing, oval, benign-appearing bilateral masses, one each in the lower outer quadrants of both breasts [right (A) and left (B)]. With windowing, faint nonenhancing septa were suggested within these masses, which were bright on STIR images. These were thought to be benign, probably fibroadenomas. No correlates were found on mammography or ultrasound, and 6-month follow-up MRI was recommended.

The follow-up breast MRI showed interval growth of both of the lower outer quadrant small masses (Figures 3, 4, and 5). They were both subcentimeter in size, and similar in appearance, being bright on short tau inversion recovery (STIR) imaging, with faint nonenhancing internal septa, suggesting fibroadenomas. A sonographic correlate was found on ultrasound for the larger (9 × 9 mm) nodule in the right LOQ (Figure 6). Ultrasound-guided core needle biopsy revealed invasive ductal carcinoma (IDC). Sonographic evaluation of the left breast showed a possible correlate at 3 o’clock, a hypoechoic, round, 7-mm complex cyst versus solid mass (Figure 7). However, it aspirated, proving it was a complex cyst and not a correlate for the enhancing (and thereby solid) nodule on MRI. No solid sonographic correlate was found for the left LOQ lesion, which by MRI was nearly identical in appearance to the contralateral proven cancer.

FIGURE 3 Axial MIP from enhanced, subtracted, dynamic breast MRI, 6 months later, is similar to the prior study, with a single, rounded, benign-appearing mass in each breast, seen against a background of fibrocystic enhancement.

FIGURE 4 Source images from the enhanced subtracted dynamic series, from the 6-month follow-up study, showed nonenhancing septa on windowing within the oval breast masses [right (A) and left (B)]. Both of these lesions showed interval growth. The larger one, on the right, measured 9 × 9 mm, compared with 8 × 6 mm previously.

FIGURE 5 Corresponding STIR axial MRI [right (A) and left (B)] through the same levels show the small bilateral masses to be hyperintense in signal.

FIGURE 6 Ultrasound through the right breast LOQ at 8 o’clock shows a subtle, oval, solid, fairly benign-appearing mass (demarcated by cursors), isoechoic to subcutaneous fat, which seemed to correspond to the MRI finding. Biopsy was performed with ultrasound guidance, identifying IDC.

FIGURE 7 Ultrasound of the left breast at 3 o’clock shows a 7-mm, round, hypoechoic, benign-looking complex cyst versus solid mass, which readily aspirated, proving it was a complex cyst and not a correlate for the enhancing, solid nodule on MRI.

MRI-guided biopsy (Figure 8) of the left LOQ enhancing mass initially returned a diagnosis of cribriform atypical ductal hyperplasia and atypical lobular hyperplasia. A clip was placed to mark the site. The pathologic diagnosis was revised subsequently (after review by Dr. David Page of Vanderbilt) to atypical lobular hyperplasia.

FIGURE 8 A, A fat-saturated, enhanced, gradient echo image from the sagittal localizer series identifies the lobular, sub-centimeter mass in question for biopsy. B, Repeat sagittal fat-saturated series after placement of the localizing obturator shows signal void adjacent to the enhancing nodule, at the posterosuperior margin (arrow). C, Axial fat-saturated image shows the breast in compression, with lateral skin indentations from the localizing grid. The mass is enhanced, and the signal void from the localizing obturator is immediately posterior to it (arrow). D, Repeat sagittal series after sampling with a 9-gauge Suros vacuum-assisted system shows the signal void of the obturator at the superior margin of a small postbiopsy cavity. The enhancing mass is no longer seen. Atypical lobular hyperplasia (ALH) was obtained on analysis of the specimens.

Surgical therapy was accomplished by bilateral ultrasound-guided needle localizations of the residual mass on the right and the clip and postbiopsy hematoma site on the left (Figure 9). A sentinel lymph node procedure was performed on the right.

FIGURE 9 A, Image from the ultrasound-guided needle localization of the proven right breast IDC at 8 o’clock shows the hookwire in place (entering from the left), traversing the residual mass. B, Image from the ultrasound-guided needle localization of the left breast postbiopsy cavity at 3 o’clock shows the needle deep to the collection, entering from the left. The procedure was performed four days after MRI-guided vacuum-assisted biopsy. ALH was again obtained from the excision specimen.

Pathology of the right lumpectomy specimen showed a 7-mm infiltrating ductal carcinoma, with clear margins. The single sentinel lymph node was negative for malignancy. The left excisional biopsy specimen again showed atypical lobular hyperplasia.

An Oncotype DX assay indicated a recurrence score of 19, in the low-intermediate risk group, with the rate of recurrence using the assay estimated at 12% at 10 years. The patient declined chemotherapy and was begun on anastrozole (Arimidex) for her estrogen receptor–positive disease and further treated with radiation therapy.

TEACHING POINTS

There are a variety of teaching and discussion points raised by this case. This patient requested MRI as an alternative to mammography because of concerns about radiation. She had had a prior benign biopsy of calcifications but had no prior pathologic diagnosis of atypical ductal hyperplasia (ADH) or other borderline histology to suggest she was a higher-risk patient. There are no data supporting the use of breast MRI for breast cancer screening in the general (non-high-risk) population. Thus, in a perfect world (in which patients heed the advice of medical professionals), this patient would not have undergone breast MRI as an alternative to mammography, which remains the only imaging modality that excels at detecting microcalcifications as a harbinger of potential malignancy. In cases of extreme patient anxiety (cancer phobia), a better but not completely supportable case could be made for supplementing mammographic surveillance with periodic breast MRI. That said, there likely are patients in many practices who may insist, for radiation-related or other reasons, on having an imaging alternative to mammography. If, after appropriate counseling, these patients cannot be dissuaded, we generally take the view that some imaging screening is better than none.

This patient’s breast MRI showed no dominant mass or highly suspicious findings to suggest an occult invasive breast cancer. Fairly typical, faint, scattered, tiny fibrocystic-type foci of enhancement were noted diffusely. The significance of such foci, less than 5 mm in size and showing progressive enhancement, depends on the context. That is, they are not likely to be significant in a screening population because they are present in 80% of studies in healthy, premenopausal women, but such findings need to be scrutinized with a higher level of suspicion in a cancer patient.

Larger foci, such as the lesions identified in each LOQ of this patient, warrant workup, with mammographic correlation and targeted ultrasound. If corresponding targets are identified (generally on sonography), histologic sampling is recommended.

In this case, the initial workup did not identify targets for sampling, and 6-month follow-up breast MRI was recommended. The overall findings on repeat breast MRI were very similar, with the imaging features of both of the LOQ lesions again suggesting probable fibroadenomas. However, there was interval growth of both lesions, appropriately triggering repeat targeted breast ultrasounds. This time, a subtle, fairly benign-looking ultrasound correlate was found for the larger, right-sided lesion. Biopsy proved this growing mass was a sub-centimeter IDC.

Correlation on the left for the contralateral mirror-image lesion was more problematic. The initially identified correlate proved on aspiration to be a complex cyst, and so could not be the same lesion as this small enhancing (thereby solid) mass. Given the similarity in its MRI appearance and behavior (growth) to the proven IDC in the opposite breast, this prompted further preoperative investigation in the form of MRI-guided biopsy. This proved to be a proliferative lesion with foci of ADH and atypical lobular hyperplasia (ALH), illustrating the nonspecificity of MRI findings. (This histologic diagnosis was subsequently revised to ALH after review by Dr. David Page of Vanderbilt.)

It is also of interest to observe how benign in appearance small breast cancers can be, as this case illustrates. It is important to remember that apparent margins of a lesion seen on MRI are actually a map of enhancement and angiogenesis and do not correspond to actual anatomic borders of a lesion.

Finally, this case illustrates a variety of image-guided procedures used for diagnosis and in needle localization for surgery. Depending on their size, biopsy cavities can be visualized for ultrasound localization for several weeks after a biopsy and may in some cases be easier to relocate and target than clips placed after a biopsy.

CASE 15 CT identification of unknown breast cancer in an asymptomatic patient

An 83-year-old woman had an abdomen and pelvis CT for left lower quadrant (LLQ) pain. An enhancing nodule was noted in the right breast on the most superior image (Figure 1). The patient had not had a mammogram for 4 years. A diagnostic workup was performed, including mammography and ultrasound.

FIGURE 1 Contrast-enhanced image from an abdominal CT scan obtained for LLQ pain shows an enhancing discrete mass in the right breast.

On mammography, extreme breast density was noted, attributable to the patient’s use of conjugated estrogens (Premarin) for more than 40 years (Figure 2). The new mammogram showed a change in contour at the posterior margin of dense retroareolar tissue, suggesting a poorly visualized new mass. Ultrasound readily demonstrated a corresponding suspicious mass (Figure 3). Multiple features of malignancy were noted of the solid, vascular mass, including marked hypoechogenicity, taller-than-wide dimensions, and microlobulation of the margins. Ultrasound-guided biopsy confirmed infiltrating ductal carcinoma (IDC).