CHAPTER 3 Local Staging: Imaging Options and Core Biopsy Strategies
Treatment planning for newly diagnosed breast cancer patients, including local and systemic therapies, is based on tumor type, extent of disease, and accurate staging. Imaging and image-directed needle biopsies play a critical role in establishing the local extent of disease and aid in staging. Surgical decision making, between breast-conserving therapy (also termed lumpectomy or segmental or partial mastectomy) and mastectomy, is primarily based on tumor size, extent and location within the breast, cosmetic implications, and patient preference. Imaging modalities, including mammography, ultrasound, MRI, and molecular imaging, are used to determine the extent of disease. However, disease extent cannot be reliably established solely by imaging. When preoperative imaging suggests more extensive disease than clinical impressions, histologic confirmation is necessary before performing a more extensive surgery.
Imaging is used to locally stage breast cancer. The TNM stage is based on the size of the tumor and whether the cancer has spread (Table 1). Identification of abnormal adenopathy (axillary, supraclavicular, or internal mammary nodes), as well as involvement of the skin, pectoralis muscle, or chest wall, affects staging and therapeutic decision making. Options for local therapies include surgery and radiation therapy, whereas systemic treatments may include chemotherapy, hormone therapy, and biologic therapy. Imaging also is used to identify distant metastases.
Table 1 AMERICAN JOINT COMMITTEE ON CANCER STAGING SYSTEM FOR PATIENTS WITH BREAST CANCER
Primary Tumor (T) | |
TX | Primary tumor cannot be assessed |
T0 | No evidence of primary tumor |
Tis | Carcinoma in situ |
Tis (DCIS) | Ductal carcinoma in situ |
Tis (LCIS) | Lobular carcinoma in situ |
Tis (Paget’s) | Paget’s disease of the nipple with no tumor |
TI | Tumor 2 cm or less in greatest dimension |
T1mic | Microinvasion 0 to 1 cm or less in greatest dimension |
T1a | 0.1 to 0.5 cm |
T1b | >0.5 to 1 cm |
T1c | >1 to 2 cm |
T2 | Tumor >2 to 5 cm in greatest dimension |
T3 | Tumor >5 cm in greatest dimension |
T4 | Tumor of any size with direct extension to chest wall or skin |
T4a | Extension to chest wall, not including pectoral muscle |
T4b | Edema (including peau-d’orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast |
T4c | T4a and T4b |
T4d | Inflammatory carcinoma |
Regional Nodes (N) | |
NX | Regional lymph nodes cannot be assessed (e.g., previously removed) |
N0 | No regional lymph node metastasis |
N1 | Metastasis in movable ipsilateral axillary lymph nodes |
N2 | Metastasis in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis. |
N2a | Metastasis in ipsilateral axillary lymph nodes fixed to one another or to other structures |
N2b | Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis |
N3 | Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent ipsilateral internal mammary node(s) in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement |
N3a | Metastasis in ipsilateral infraclavicular lymph node(s) and axillary lymph node(s) |
N3b | Metastasis in ipsilateral internal mammary lymph node(s) nodes and axillary lymph node(s) |
N3c | Metastasis in ipsilateral supraclavicular lymph node(s) |
Distant Metastasis (M) | |
MX | Distant metastasis cannot be assessed |
M0 | No distant metastasis |
M1 | Distant metastasis |
Selection of the appropriate imaging tests to determine tumor extent and stage are not standardized and are often based on the particulars of each case.
EXTENT OF DISEASE
Most breast cancers are evaluated by mammography, ultrasound, or both modalities. It is important to document the size, location, and distribution of the primary lesion, but also to evaluate for satellite lesions. Preoperative identification of additional lesions improves the likelihood of obtaining clear margins if breast-conserving therapy (BCT) is performed. For masses, it is important to look for associated microcalcifications, which may represent an associated noninvasive (in situ) component. The term extensive intraductal component (EIC) is used to refer to invasive tumors in which ductal carcinoma in situ (DCIS) makes up at least 25% of the neoplasm. Of all invasive ductal carcinomas, 15% to 30% have an EIC.1 Tumors that are predominantly DCIS with focal invasion are also classified as EIC. The presence of EIC may have prognostic implications on the likelihood of obtaining clear margins, as well as the risk for subsequent local recurrence.2,3
As many as 30% to 60% of breast cancers are pathologically multifocal (more than one tumor focus, separated by normal tissue) at the time of diagnosis.4,5 The term multicentric has been variably defined. It generally has been used to describe cancers separated by more than 4 cm or tumors located in different quadrants of the breast. BCT generally is not suitable for multicentric carcinomas because of poor cosmetic results, limitations of radiation therapy, and inability to obtain clear margins.
Synchronous contralateral breast cancer may occur in about 3% to 5% of women with breast cancer.6,7 Identification of these lesions at the time of the contralateral index cancer diagnosis can facilitate treatment in a single surgery, thereby avoiding both delays in diagnosis, as well as the emotional stress of a later diagnosis and second surgery.
MRI is useful to identify residual disease and direct re-excision in patients with positive margins at initial lumpectomy (Figure 1).

FIGURE 1 MRI evaluation can be useful in patients with close or positive surgical margins. A, Post-contrast, subtracted MRI of a right breast shows a focus of residual DCIS (arrow) along the medial aspect of a large lumpectomy cavity. B, Post-contrast, subtracted MRI shows residual invasive tumor (arrow) along the anterior lateral aspect of a small lumpectomy cavity.
EVALUATING ADENOPATHY
Identification of abnormal adenopathy, including axillary, supraclavicular, and internal mammary nodes, is important in staging. Metastatic adenopathy is suspected on imaging when there is cortical thickening (generally >3 mm), loss of the fatty hilum, and enlargement, particularly with increasingly round shapes8 (Figure 2 and Figure 3). However, because many benign processes may cause reactive nodes with similar imaging findings, fine-needle aspiration (FNA) or core needle biopsy is necessary to confirm suspected metastatic nodal disease. Conversely, the absence of suspicious imaging findings, whether on mammography, ultrasound, MRI, or molecular imaging studies, does not exclude metastatic nodal involvement, particularly for micrometastasis. Therefore, in addition to imaging, sampling, either with axillary dissection or sentinel lymph node biopsy, is essential in the staging of breast cancer patients.

FIGURE 2 Sonographic appearance of normal axillary lymph nodes. A, Longitudinal image shows uniform thickness of the hypoechoic cortex, surrounding the echogenic fatty hilus. B, Transverse image of the same lymph node. The cortical thickness of 2 mm is within normal limits (<3 mm). C, Color Doppler image shows vascularity in the hilus.




FIGURE 3 The spectrum of abnormal axillary node sonographic findings (all FNA-proven to have breast cancer metastases). A, Cursors delineate borderline thickening of the hypoechoic cortex. The fatty hilus is preserved. A second, similar-appearing axillary lymph node is seen to the left. These findings are not clearly pathologic by sonographic criteria. Subtle findings on staging MRI, CT, and positron emission tomography (PET) studies (for inflammatory breast cancer) suggested axillary involvement. FNA confirmed metastatic carcinoma. B, Cortical thickening in this case is more eccentric and measures 5 mm. Ultrasound-guided FNA of the axillary lymph node confirmed metastatic carcinoma. C, Axillary node sonography of a 55-year-old woman with locally advanced breast cancer (LABC) shows highly suspicious morphology. The cortex is very hypoechoic, as well as abnormally thickened and nodular. There is a rat-bite, scalloped appearance and mass effect on the echogenic hilus. D, Same case as C, with color Doppler. Increased and abnormal vascularity is seen. Normal lymph node vascularity is seen only at the hilus. E, A 45-year-old woman with a new infiltrating ductal carcinoma (IDC) diagnosis. The cortical mantle of this axillary lymph node is markedly thickened, and the echogenic hilus is nearly completely effaced. F, Although small, this axillary node morphology is quite abnormal. The cortex is very hypoechoic. The node is “thick-waisted,” with nearly complete effacement of the fatty hilus, which is hinted at in profile. G, A 56-year-old woman with a neglected LABC (IDC with secondary inflammation) and multiple abnormal axillary nodes, which were FDG-avid on PET. This lymph node shows diffuse cortical thickening, without hilar effacement. H, Another lymph node of the same patient shows complete hilar loss and an abnormally rounded shape. I, A 41-year-old woman with a large postpartum pregnancy-associated breast cancer. This lymph node is massively enlarged and would be considered abnormal on any modality. Size, the primary criterion for judging normalcy on CT and MRI, is a weaker criterion by which to judge axillary nodes. Other morphologic criteria, including shape, cortical thickening and nodularity, and mass effect on or effacement of the fatty hilus, are more reliable in the assessment of the axillary lymph nodes of breast cancer patients. These more subtle findings are most easily assessed with ultrasound. This lymph node shows many of these features: marked cortical hypoechogenicity, nodularity, and thickening, with partial loss of the fatty hilus. The intracortical and peripheral vascularity is highly abnormal and also suggests malignancy. J, The same lymph node seen transversely shows that the hilus is incompletely effaced. Echogenic remnants are seen surrounded by the grossly thickened hypoechoic cortex. The abnormally increased vascularity, seen on the periphery of the cortex, is highly suggestive of malignancy. K, Even more normal-appearing adjacent lymph nodes, with visible echogenic fatty hila, have borderline thickened cortices and are notable for their ease of visualization and increased number. L, A 49-year-old woman with newly diagnosed, node-positive (five of eight nodes, largest 1.9 cm, with extracapsular extension), 1.8-cm left breast IDC. Her preoperative ultrasound predicted the extracapsular extension. This very hypoechoic axillary lymph node shows no echogenic hilus. The left side is rounded by a cortical nodule, and the right side has frankly angular margins. M, Oblique, noncontrast, T1-weighted MRI of the left axilla shows an abnormal lymph node (arrow), notable for the loss of the fatty hilum and the rounded and expanded shape.
The axillary nodes form a chain from the underarm to the collarbone (Figure 4). The axillary lymph nodes are named in relation to the pectoralis minor muscle, with level I the lowest, lateral to the pectoralis minor muscle. Level I receives the most lymphatic drainage from the breast. Level II axillary nodes are beneath the pectoralis minor muscle. Level III is above and medial to the pectoralis minor muscle. A traditional axillary lymph node dissection usually removes nodes in levels I and II. Sentinel lymph node sampling involves the mapping and removal of the first lymph node or nodes (usually 1 to 3) that drain the involved area of the breast (Figure 5 and Figure 6). Instead of removing 10 or more lymph nodes as performed in a standard dissection, the status of the axilla can be predicted by excision and close pathologic examination of the sentinel node. Sentinel lymph node biopsy has significantly reduced the number of women undergoing standard axillary dissection, avoiding dissection-associated side effects such as arm lymphedema. The identification of abnormal lymph nodes on physical exam or imaging studies favors proceeding directly to axillary dissection over sentinel node biopsy.

FIGURE 4 Schematic of axillary lymph node nomenclature. The axillary lymph nodes ascend from the axilla medially to the clavicle and are named in relation to the pectoralis minor muscle. Level I, the lowest, is lateral to the pectoralis minor; level II, deep to it; and level III, medial to it.

FIGURE 5 Schematic of the technique of sentinel lymph node injection. The breast lymphatics drain to the skin, and there is a rich periareolar network of lymphatics, with one or two major lymphatic channels draining to the axilla. Anatomic studies indicate 75% of the lymphatic drainage of the breast is to the axilla, with 25% to the internal mammary nodes. In this drawing, a peritumoral injection is depicted, but success has been reported for a variety of techniques (including subdermal or intradermal overlying the tumor, and periareolar), presumably owing to the rich network of the breast lymphatic plexus.

FIGURE 6 Lymphoscintigraphy (from left to right: anterior, left anterior oblique, and left lateral) can be performed in conjunction with injections for sentinel lymph node identification. In this example, intense activity is seen at the injection site of the tumor in the left breast. A lymphatic drainage channel extending to the axilla is clearly delineated, as are a faint, more superior secondary channel and the axillary sentinel lymph node. If a sentinel node is identified at imaging, skin marking can save surgical dissection time. Breast cancer sentinel node mapping with lymphoscintigraphy is not universally performed, unlike in melanoma.
The use of molecular imaging studies, CT, or MRI may identify adenopathy in areas other than the axilla (Figure 7). The presence of internal mammary node adenopathy (Figure 8) affects staging and radiation therapy planning. Identification of abnormal Rotter’s nodes (Figure 9), nodes between the pectoralis minor and major muscles, also has staging and therapeutic implications.

FIGURE 7 Schematic of the lymphatic drainage pathways of the breast. By anatomic studies, 75% of the lymphatic drainage is to the axilla, with 25% to the ipsilateral internal mammary nodes. Note lymphatic communications extending across the midline of the chest to contralateral internal mammary nodes and inferiorly extending channels, which communicate with the abdomen.

FIGURE 8 Internal mammary node metastasis. A, Axial postcontrast MRI in a patient with an implant with an abnormally enlarged left internal mammary node (arrow) adjacent to the internal mammary artery and vein, suspicious for involvement. B, Axial postcontrast MRI shows a small (2–3 mm) right internal mammary node (left). The same area, 5 years later, has a chest wall recurrence (arrow), presumably from metastasis to the internal mammary node (right).

FIGURE 9 Rotter’s nodes. A, Oblique T1-weighted (left) and axial fat-saturated, enhanced T1-weighted (right) MRIs of the left axilla show a small Rotter’s node (arrows) between the pectoralis major and pectoralis minor muscles. B, Enhanced CT scan demonstrates a metastasis to a large Rotter’s node (arrow), as well as within the right axilla.
SKIN, PECTORALIS, AND CHEST WALL INVOLVEMENT
Identification of breast edema and skin thickening in patients with invasive breast cancer may represent an inflammatory component (tumor involving the dermal lymphatics). This materially affects staging and therapeutic approach. Skin punch biopsy may be necessary to confirm the diagnosis if the clinical picture is not characteristic. Identification of pectoralis muscle or chest wall involvement also affects treatment planning. Pectoralis muscle involvement should be looked for in women with posterior lesions. The diagnosis on MRI requires not just effacement or obliteration of the pectoralis fascia but also enhancement of the muscle (Figure 10). Identification of either skin or chest wall involvement classifies a tumor as a locally advanced breast carcinoma (LABC). Large (>5 cm) tumors and those with clinically matted or fixed axillary node involvement or involved supraclavicular or internal mammary nodes by imaging are also considered locally advanced. LABC is generally treated with preoperative (neoadjuvant or primary systemic) chemotherapy, which converts some patients into operative candidates. Multiple examples are presented in Chapter 5.

FIGURE 10 Chest wall invasion. Postcontrast axial MRI in a patient with a breast sarcoma, demonstrating enhancement of the pectoralis major muscle and intercostal muscles (arrows). Chest wall involvement is confirmed by identification of intercostal muscle enhancement, whereas the pectoralis muscle is considered part of the breast.
PREOPERATIVE MAGNETIC RESONANCE IMAGING
MRI is becoming increasingly established as a useful modality in patients with known breast cancer. However, patterns of use of preoperative MRI in women with biopsy-proven breast cancer remain highly variable in practice because of the lack of randomized control trials. It has been firmly established that preoperative MRI can detect unsuspected disease and often changes management in women with known breast cancer.9 However, the use of preoperative MRI to alter surgical management has been criticized because of the lack of studies evaluating its effect on tumor recurrence and mortality.10–12 Fischer and colleagues,13 in a study involving more than 40 months of follow-up, reported a reduction in ipsilateral breast tumor recurrence, from 6.8% to 1.2%, in patients who underwent preoperative MRI. However, this study was a retrospective, singleinstitution review of only 346 patients. It has been argued that unsuspected disease detected on MRI and treated with BCT is of little clinical consequence and is controlled by radiation therapy. This argument is primarily based on the fact that 10-year local recurrence rates as low as 10% have been reported in patients with negative surgical margins.14–16 Concerns about the use of preoperative MRI involve the potential for unnecessary biopsies, delays in treatment, and an increase in unnecessary mastectomies. Despite these arguments, there is ongoing evidence and experience accumulating that supports its benefit in preoperative staging, as follows:
FUNCTIONAL (MOLECULAR) BREAST IMAGING: BREAST-SPECIFIC GAMMA IMAGING AND POSITRON EMISSION MAMMOGRAPHY
Functional breast imaging is a growing and evolving field that is assuming a larger role in breast cancer diagnosis, providing complementary information to anatomically based breast imaging modalities. Scintimammography has matured from initial versions using standard gamma cameras, which were limited in resolution and positioning flexibility, to breast-specific gamma imaging (BSGI), which obtains higher-resolution planar images in views emulating mammography.21–25 Similarly, positron emission mammography (PEM) is performed using a small-field-of-view, high-resolution PET scanner that resembles a mammogram unit and acquires tomographic data sets in planes analogous to mammography.26–29 Scintimammography is performed after the intravenous administration of 25 mCi of either 99mTc-sestamibi or 99mTc-tetrofosmin, whereas PEM is performed after an hour’s uptake of 10 mCi of 18F-fluorodeoxyglucose (FDG) admin-istered intravenously. The radiation dose is about the same, about 0.4 rad. Imaging time is also similar. Scintimammography planar views are acquired for 5 to 10 minutes, or at least 150,000 counts, whereas PEM tomographic data sets are acquired for 4 to 10 minutes per projection. The lower limit of BSGI detector resolution is 3 mm (although smaller lesions may be identifiable), whereas the in plane resolution of PEM is on the order of 2 mm (Table 2).
Table 2 FUNCTIONAL BREAST IMAGING COMPARISON CHART
BSGI, breast-specific gamma imaging; PEM, positron emission mammography.
The uptake of sestamibi is dependent on regional blood flow and cellular mitochondrial density. Enhanced blood flow due to tumorinduced neo-angiogenesis results in increased delivery of radiopharmaceutical. Cancer cells have higher cytoplasmic mitochondrial density than normal breast tissue and bind more of the radiopharmaceutical than the surrounding tissue.
PEM is performed with 18F-FDG, a radioactive glucose analogue in wide use as a cancer-imaging agent with whole-body PET. PEM and PET with FDG capitalize on the higher glycolytic rate of cancer cells, with FDG actively transported intracellularly through an up-regulated transmembrane GLUT-1 receptor mechanism. Once intracellular, FDG is phosphorylated by hexokinase like glucose, but because it is not metabolized further, it is trapped intracellularly in proportion to glucose utilization.
At this writing, BSGI is becoming more available, with sites with early experience finding it useful both for problem solving of ambiguous conventional breast imaging findings, and as an adjunct to local staging, looking for multifocality, multicentricity, and contralateral lesions (Figure 11). BSGI does not require a diagnosis of breast cancer for reimbursement, and increasingly is being performed in patients with suspicious conventional breast imaging findings as an aid to biopsy decision making (e.g., deciding how many areas need sampling). Currently, PEM is approved for patients with known or prior breast cancer diagnoses. Several cases incorporating the use of PEM have been included in this chapter. Its performance compared with MRI in preoperative local staging of apparently localized breast cancer is being assessed by a multicenter, prospective clinical trial, which at this writing is accruing patients. Early pilot studies show high sensitivity for depiction of primary breast cancers, on the order of 91%. Similarly high sensitivity for primary tumor depiction is reported for BSGI. Both modes of functional breast imaging appear to have improved specificity compared with MRI, on the order of 87% to 89% for BSGI and 93% for PEM, offering hope that increased use of functional breast imaging in the future may decrease the number of unnecessary benign biopsies now being performed.

FIGURE 11 An 89-year-old woman with a prior right upper outer quadrant benign biopsy (scar marked on mammographic views (arrows)—A, MLO; B, CC). Multiple lobular and circumscribed masses are seen within moderately dense breast tissue, especially in the upper outer quadrant near the scar. Ultrasound of the corresponding area suggested two cysts and one solid mass, for which biopsy was recommended. Breast-specific gamma imaging (BSGI) (C, MLO; D, CC) shows multifocal upper outer quadrant increased activity, with three discrete sites of increased uptake. At surgical pathology, a multilobed mucinous carcinoma, with ductal carcinoma in situ was confirmed.
(Case courtesy of Dilon Technologies)
Currently, no biopsy capability using functional imaging modalities for guidance is readily available, although feasibility studies have been done and this should be available in the near future.
DISTANT METASTASES
Routine imaging with bone scan, CT, and PET is not indicated for early-stage (stage I and II) breast cancers. Patients with limited-stage breast cancer who have symptoms, such as back or bone pain, or right upper quadrant pain; physical examination abnormalities (such as jaundice or hepatomegaly), or laboratory abnormalities can be considered for imaging to exclude distant metastatic disease. Patients with locally advanced breast cancer or evidence of axillary nodal involvement by physical examination or imaging should be considered for systemic imaging after a detailed history, physical exam, and laboratory evaluation.
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2 Schnitt SJ, Connolly JL, Recht A, et al. Breast relapse following primary radiation therapy for early breast cancer. II. Detection, pathologic features and prognostic significance. Int J Radiat Oncol Biol Phys. 1985;11:1277-1284.
3 Bartelink H, Borger JH, van Dongen JA, Peterse JL. The impact of tumor size and histology on local control after breast conserving treatment. Radiother Oncol. 1988;11:297-303.
4 Holland R, Veling SH, Mravunac M, Hendricks JH. Histologic multifocality of Tis, T1–2 breast carcinomas: implications for clinical trials of breast conserving surgery. Cancer. 1985;56:979-990.
5 Wilkinson LS, Given-Wilson R, Hall T, et al. Increasing the diagnosis of multifocal primary breast cancer by the use of bilateral whole-breast ultrasound. Clin Radiol. 2005;60:573-578.
6 Heron DE, Komarnicky LT, Hyslop T, et al. Bilateral breast carcinoma: risk factors and outcomes for patients with synchronous and metachronous disease. Cancer. 2000;88:2739-2750.
7 Liberman L, Morris EA, Kim CM, et al. MR imaging findings in the contralateral breast of women with recently diagnosed breast cancer. AJR Am J Roentgenol. 2003;180:333-341.
8 Yang WT, Chang J, Metreweli C. Patients with breast cancer: differences in color Doppler flow and gray-scale US features of benign and malignant axillary lymph nodes. Radiology. 2000;215:568-573.
9 Bedrosian I, Mick R, Orel SG, et al. Changes in the surgical management of patients with breast carcinoma based on preoperative magnetic resonance imaging. Cancer. 2003;98:468-473.
10 Morrow M. Magnetic resonance imaging in the preoperative evaluation of breast cancer: primum non nocere. J Am Coll Surg. 2004;198:240-241.
11 Morrow M. Magnetic resonance imaging in breast cancer: one step forward, two steps back? JAMA. 2004;292:2779-2780.
12 Morrow M. Magnetic resonance imaging in breast cancer: is seeing always believing? Eur J Cancer. 2005;41:1368-1369.
13 Fischer U, Zachariae O, Baum F, et al. The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Eur Radiol. 2004;14:1725-1731.
14 Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995;76:259-267.
15 Neuschatz AC, DiPetrillo T, Safaii H, et al. Long-term follow-up of a prospective policy of margin-directed radiation dose escalation in breast-conserving therapy. Cancer. 2003;97:30-39.
16 Obedian E, Haffty BG. Negative margin status improves local control in conservatively managed breast cancer patients. Cancer J Sci Am. 2000;6:28-33.
17 Provenzano E, Hopper JL, Giles GG, et al. Histological markers that predict clinical recurrence in ductal carcinoma in situ of the breast: an Australian population-based study. Pathology. 2004;36:221-229.
18 Borg MF. Breast-conserving therapy in young women with invasive carcinoma of the breast. Australas Radiol. 2004;48:376-382.
19 Smitt MCMD, Horst K. Association of clinical and pathologic variables with lumpectomy surgical margin status after preoperative diagnosis or excisional biopsy of invasive breast cancer. Ann Surg Oncol. 2007;14(3):1040-1044.
20 Lehman CD, Gatsonis C, Kuhl CK, et al. ACRIN Trial 6667 Investigators Group. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;356(13):1295-1303.
21 Schillaci O, Buscombe JR. Breast scintigraphy today: indications and limitations. Eur J Nucl Med Mol Imaging. 2004;31(Suppl 1):S35-S45.
22 Brem RF, Schoonjans JM, Kieper DA, et al. High-resolution scintimammography: a pilot study. J Nucl Med. 2002;43:909-915.
23 Brem RF, Rapelyea JA, Zisman G, et al. Occult breast cancer: scintimammography with high-resolution breast-specific gamma camera in women at high risk for breast cancer. Radiology. 2005;237:274-280.
24 Brem RF, Fishman M, Rapelyea JA. Detection of ductal carcinoma in situ with mammography, breast specific gamma imaging, and magnetic resonance imaging: a comparative study. Acad Radiol. 2007;14(8):945-950.
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26 Levine EA, Freimanis RI, Perrier ND, et al. Positron emission mammography: initial clinical results. Ann Surg Oncol. 2003;10:86-91.
27 Rosen EL, Turkington TG, Soo MS, et al. Detection of primary breast carcinoma with a dedicated, large-field-of-view FDG pet mammography device: initial experience. Radiology. 2005;234:527-534.
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CASE 1 Mammography: Extent of disease
A 75-year-old woman presented with a palpable left breast mass. Mammography demonstrated a dense, spiculated breast cancer, corresponding to the palpable mass (Figure 1). Closer review of the mammogram showed a second abnormality distant from the palpable mass, with suspicious linear microcalcifications in the central left breast (Figure 2). Biopsy of the mass revealed invasive ductal carcinoma and stereotactic biopsy of the calcification found intermediate-grade ductal carcinoma in situ (DCIS). Because the two areas of disease involved a large portion of the left breast, mastectomy was performed.

FIGURE 1 CC mammographic view of the left breast: A dense spiculated mass is seen in the medial left breast, corresponding to the palpable finding.

FIGURE 2 Close-up view of the CC mammographic view: An area of suspicious linear microcalcifications is seen (arrows) in the central breast, distant from the palpable mass. These calcifications exhibit classic linear and casting features of DCIS.
TEACHING POINTS
Breast imagers need to constantly guard against “satisfaction of search.” By fully defining the extent of disease, the appropriate surgical therapy can be planned. The occurrence of synchronous ipsilateral or bilateral breast cancer is about 3% to 5%. For localized breast cancer, the 20-year follow-up reports of two pivotal prospective randomized trials demonstrated that survival after a lumpectomy with radiotherapy is equal to survival after mastectomy. However, these studies are based on patients in whom clear margins were obtained. By better defining the extent of disease preoperatively, the likelihood of obtaining clear margins at initial surgery can be improved. Pathologic margin status is the most important predictor of local recurrence after breast conservation with radiation. Even when clear margins are obtained, many patients have remaining foci of disease. The role of radiation therapy is to treat these areas of occult residual tumor. The risk for local recurrence may be diminished if the residual tumor burden after surgery is minimized. This is even more important in patients who undergo partial breast irradiation rather than whole breast irradiation.
Fisher B, Anderson S, Bryant J, et al. Twenty year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241.
Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of Tis, T1–2 breast carcinomas: implications for clinical trials of breast-conserving surgery. Cancer. 1985;56(5):979-990.
Veronesi U, Cascinelli N, Mariani L, et al. Twenty year follow-up of a randomized study comparing breast conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-1232.
Wazer DE, Schmidt-Ullrich RK, Schmid CH, et al. The value of breast lumpectomy margin assessment as a predictor of residual tumor burden. Int J Radiat Oncol Biol Phys. 1997;38(2):291-299.
CASE 2 Use of ultrasound to find invasive disease within extensive microcalcifications; depiction of disease extent by breast MRI versus PEM versus whole-body PET
An asymptomatic 40-year-old woman had extensive new left lateral microcalcifications identified on screening mammography. These showed suspicious linear and branching pleomorphism on magnification views (Figure 1), and extensive ductal carcinoma in situ (DCIS) was suspected. Ultrasound was performed to determine whether an invasive component could be identified for biopsy. Five solid masses were identified in the left lateral breast, ranging up to 1.8 cm in size, as well as a suspicious abnormal axillary lymph node (Figure 2).

FIGURE 1 Lateral (A) and CC (B) magnification views show moderate parenchymal density. Diffuse pleomorphic microcalcifications are present throughout the left lateral breast (arrows).

FIGURE 2 Left lateral breast ultrasound, performed to search for invasive components within suspected extensive DCIS, identified five discrete masses, measuring up to 1.8 cm in size. (A) At 2 o’clock, an oval hypoechoic mass without a well-defined capsule shows tiny punctate foci of hyperechoic calcium. Similar foci within the surrounding parenchyma can also be appreciated (arrows). (B) At 2:30 to 3 o’clock, two additional, similar-appearing, solid, hypoechoic masses with ill-defined margins are seen.
Biopsies with ultrasound guidance of the two largest upper outer quadrant masses at 2 and 3 o’clock confirmed grade 3 infiltrating ductal carcinoma, high-grade DCIS, with comedonecrosis, estrogen receptor and progesterone receptor positive, and HER-2/neu negative, from both sites. Axillary lymph node fine-needle aspiration confirmed metastatic carcinoma.
The patient desired breast conservation, and so extensive staging studies were performed to assess the extent of disease. These included breast MRI (Figure 3), positron emission mammography (PEM) (Figure 4 and Figure 5), and whole-body positron emission tomography (PET) (Figure 6). These studies confirmed multicentric disease with axillary nodal involvement, but showed no distant metastases. Neoadjuvant chemotherapy was given.

FIGURE 3 Axial breast MRI enhanced, subtracted maximal intensity projection view shows diffuse, confluent enhancement of the left lateral breast, corresponding to the distribution of pleomorphic DCIS calcifications on mammography. Within this field can be seen a variety of intensely enhancing masses. The largest display rim enhancement and washout. Eight discrete masses could be delineated on MRI in the left upper and lower outer quadrants. An enlarged left axillary lymph node can also be seen here.

FIGURE 4 Digital mammographic views and comparable PEM views, for correlation: (A) MLO mammogram. (B) MLO “volume” PEM image. Seven discrete foci of intense increased FDG uptake are seen. (C) CC mammogram. (D) CC “volume” PEM image. The most posterior of the seven lesions seen in the MLO projection is not included in the field of view and is not seen. Lower-level uptake of FDG is seen in the upper outer breast, corresponding both to the distribution of parenchyma and the extensive microcalcifications. The mammographic parenchymal density conceals the masses which could be identified by ultrasound, MRI, and PEM.


FIGURE 5 PEM data are a volumetric, tomographic acquisition and are divided into 12 slices: (A) MLO projection. PEM progresses from medial (upper left) to lateral (lower right). With windowing, the largest lesion, projecting above the nipple, shows a rim pattern of uptake. On the edge of the field of view (middle row, upper left, arrow), hypermetabolic axillary lymph nodes can be seen. (B) CC projection PEM is displayed from cranial (upper left) to caudal (lower right).
TEACHING POINTS
Extensive, new, suspicious microcalcifications suggested an extensive intraductal component in this case. Stereotactic biopsy of microcalcifications undoubtedly would have established a diagnosis of DCIS. However, ultrasound can be useful to search for a mass for ultrasound sampling within an area of suspicious microcalcifications, which may enable a diagnosis of invasive disease to be made.
This is a very extensive, multicentric malignancy with an extensive intraductal component. It is interesting to compare the performance of the various modalities in depicting the extent of this neoplasm. The mammogram best depicts the extensive calcified DCIS, diffusely involving the upper and lower outer quadrants, but the breast tissue density obscured the invasive components. Five masses (two proven invasive) were identified by ultrasound within the area encompassed by the microcalcifications. The microcalcifications can be recognized sonographically, but would likely not be recognized prospectively without mammographic correlation.
Both invasive and noninvasive disease components are well depicted by MRI. The DCIS manifested as confluent, segmental enhancement in the lateral breast. Eight intensely enhancing discrete masses with washout could be identified by MRI within this extensive intraductal component. PEM performed nearly as well, depicting seven discrete sites of intense increased fluorodeoxyglucose (FDG) uptake. The intraductal disease (as represented by the distribution of calcifications on mammography) would be difficult to recognize prospectively on PEM, without mammographic correlation. The lower-level segmental FDG uptake seen here in the distribution of the DCIS calcifications also corresponds to the distribution of parenchymal density and so would be difficult to differentiate from background parenchymal uptake.
PEM is essentially a small field of view, high-resolution dedicated breast PET scan. Tomographic volumetric data is acquired with gentle compression (for immobilization, not for tissue thinning) in planes analogous to mammography. Because the detectors (in compression plate-like arrays) on either side of the breast are extremely close to the radioactive source (FDG taken up by glycolytically active tumor), the resolution is considerably higher than in whole-body PET, wherein a patient’s body is surrounded by a ring of detectors. State-of-the-art whole-body PET scanners have a lower limit of resolution today of about 6 mm, whereas resolution on the order of 2 mm can be expected with PEM. This is illustrated in this case. Only the three largest foci of FDG uptake could be visualized within the breast on whole-body PET, as compared with seven discrete lesions on PEM. A limitation of PEM is also illustrated here. Two hypermetabolic axillary nodes are at least partially visualized on PEM. Axillary visualization on PEM is variable, depending on patient anatomy and positioning. Whole-body PET in this patient readily demonstrated three hypermetabolic axillary nodes.
CASE 3 MRI: Extent of disease
A 54-year-old woman presented with a palpable mass in the upper outer left breast. Diagnostic mammographic and ultrasound evaluations demonstrated multiple masses in the upper outer quadrant of the left breast at the site of the palpable abnormality (Figure 1 and Figure 2). Core needle biopsy confirmed invasive ductal carcinoma. Preoperative MRI suggested much more extensive involvement of the left breast, with multiple enhancing masses extending from area of the known cancer toward the nipple (Figure 3). Because of the MRI findings, second-look ultrasound was performed and identified several small masses in the subareolar region (Figure 4). Core needle biopsy confirmed the extensive nature of the patient’s disease, and she was treated surgically with mastectomy and axillary dissection.

FIGURE 1 MLO mammographic view of the left breast: Multiple masses (arrows) are seen in the upper outer quadrant at the site of the patient’s palpable complaint.

FIGURE 2 Ultrasound evaluation of the left breast axillary tail region: A dominant mass is seen corresponding to the patient’s palpable lump. The mass is highly suspicious for malignancy with its irregular shape and margin features.

FIGURE 3 Postcontrast maximum intensity projection MRI: Multiple enhancing masses are demonstrated involving a large portion of the left breast, extending from the left axillary tail to the subareolar region (arrows).
TEACHING POINTS
This case illustrates the use of MRI to evaluate the extent of disease in a patient with a known carcinoma. MRI may detect areas of additional disease unsuspected on mammography and ultrasound. In this case, MRI allowed targeting of ultrasound to identify more subtle additional lesions that could then undergo biopsy to establish the extent and aid in planning the appropriate surgical treatment.
CASE 4 Multicentric IDC and DCIS: Local staging with MRI
A 47-year-old woman was evaluated with mammography and ultrasound for a palpable lump in the right breast upper outer quadrant.
Mammography showed very dense breast tissue, with no correlate for the palpable abnormality (Figure 1). Ultrasound of the palpable lump showed a 2-cm heterogeneous, solid mass, with irregular margins and vascularity and a highly suspicious appearance (Figure 2). An ultrasound-guided core needle biopsy confirmed infiltrating ductal carcinoma (IDC), with high-grade ductal carcinoma in situ (DCIS). At initial surgical consultation, breast conservation therapy with partial mastectomy and radiation was discussed. Because of the mammographic density of the patient’s breasts, the patient was referred for preoperative breast MRI to more fully evaluate her suitability for breast conservation therapy.

FIGURE 1 Mammography [MLO (A), CC (B), and spot compression (C)] shows a marker placed at the level of the palpable lump in the right upper outer quadrant. The breast tissue is very dense, and no correlate is seen.

FIGURE 2 Ultrasound of the right breast palpable lump shows a mildly hypoechoic, solid mass, with lobular and irregular borders, with peripheral vascular flow on color Doppler. Several tail-like areas of suspected ductal extension are depicted.
Bilateral enhanced subtracted breast MRI showed the known right breast carcinoma mass to be intensely enhancing, with irregular margins and spiculation. Multiple smaller, additional foci of enhancement were noted throughout the right breast, markedly asymmetric compared with the left side (Figure 3 and Figure 4). A few of these foci were larger and more morphologically concerning, including an irregular mass at 5 o’clock (Figure 5) and clumped contiguous foci of enhancement at 9 o’clock (Figure 6). A second-look ultrasound was performed of the right breast seeking correlates for biopsy, to prove the patient’s disease was multicentric and that she was not a conservation candidate.

FIGURE 3 Maximal intensity projection from the enhanced, subtracted dynamic breast MRI series shows marked asymmetry between sides. The left shows no concerning finding. The right shows an irregularly marginated, dominant, intensely enhancing mass in the upper outer quadrant. Multiple smaller nodules are noted throughout the breast as well, larger than the tiny (<5 mm) foci frequently seen with physiologic and fibrocystic enhancement.

FIGURE 4 A section from the dynamic enhanced breast MRI series through the upper outer quadrants shows the known right infiltrating ductal carcinoma, with intense peripheral rim enhancement. The margins are irregular, with tiny spiculations.

FIGURE 5 Another enhancing, irregularly bordered mass is seen just below the level of the nipple (partially visualized here). This was reported as being at 12 o’clock. However, the sonographic correlate (see Figure 7) was best seen at 5 o’clock. This discrepancy illustrates the difficulty in lesion localization between modalities, which is due both to the mobility of breast tissue and differences in positioning. This patient had very small breasts, and this is a centrally positioned lesion.

FIGURE 6 Another section from the dynamic enhanced MRI series shows additional concerning findings in the right lateral breast, at about 9 o’clock. Irregular clumped enhancement, with linear extension anteriorly toward the nipple, suggests additional disease.
Ultrasound identified two subtle correlates for biopsy, confirming DCIS at both sites (Figure 7 and Figure 8). With pathologic confirmation of multicentric disease, the surgery treatment was changed to mastectomy.

FIGURE 7 Ultrasound of the right breast at 5 o’clock: This lesion was identified using the MRI as a roadmap and was not recognized prospectively. The correlate is subtle, being minimally hypoechoic. Once located, there are some suspicious sonographic features, including being taller than wide and having marginal angularity. Core needle biopsy confirmed DCIS.

FIGURE 8 Targeted right breast second-look ultrasound at 9 o’clock showed a very subtle correlate. A, A lobular, minimally hypoechoic focus seemed to correlate in shape and location to the MRI findings. B, Because of the lack of conspicuity of this area, a larger-volume, vacuum-assisted sampling was performed, also confirming DCIS. The needle was maneuvered underneath the target. With pathology-proven multicentricity, the surgical treatment was changed to mastectomy.
Final pathology was a 2.1-cm IDC, with associated high-grade (comedo) DCIS extending into lobules. The tumor was noted to be multicentric, with 50% of the gross tumor at the index cancer site, an 8-mm residual focus at 5 o’clock, and microscopic residual at 9 o’clock. Margins were negative, and two sentinel lymph nodes were also negative. Final stage was stage II, T2N0, and the patient was additionally treated with chemotherapy.
TEACHING POINTS
This case illustrates well how a multimodality approach can yield critical additional information to most accurately stage a newly identified breast cancer. Mammography was not particularly useful in this patient, owing to breast density, but confirmed that there were no microcalcifications. Prospectively, ultrasound identified the index tumor and provided guidance to confirm the diagnosis of IDC. However, no additional disease sites were recognized prospectively on ultrasound to suggest multicentric disease. However, with the breast MRI as a roadmap for a directed, second-look ultrasound, more subtle correlates could be discerned and targeted for sampling, confirming two separate sites of DCIS remote from the IDC, indicating that the patient’s disease should be treated surgically with mastectomy.
This case also illustrates ductal extension on ultrasound, a sonographic sign suspect for malignancy, as delineated by Stavros and colleagues. This feature is less frequently seen or recognized than other features of malignancy, such as taller-than-wide shape and shadowing.
CASE 5 Additional disease site identified by PEM
A 46-year-old woman was noted to have a suspicious 1-cm spiculated mass overlying the right pectoral muscle on baseline screening mammography (Figure 1). It was confirmed on spot compression views, and a suspicious sonographic correlate was found (Figure 2), as well as a second concerning ultrasound finding. Both were biopsied with ultrasound guidance, confirming infiltrating ductal carcinoma (IDC) at 12 o’clock and sclerosing adenosis at 10 o’clock.

FIGURE 1 Baseline screening mammogram [MLO (A) and CC (B)] shows moderate parenchymal density. An irregularly marginated mass is seen overlying the pectoral muscle (circled and arrow on MLO view) and on the edge of the field in the CC projection (arrow).

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