CASE 1 LABC (large tumor size)

A 45-year-old woman was noted on routine physical examination by her physician to have an abnormal left breast examination. Although the patient had not noted any discrete masses, an area of induration and irregularity was palpated in the left upper breast, extending from upper inner to upper outer quadrant.

Breast imaging evaluation showed extremely dense breast parenchyma. New clustered microcalcifications were identified in the upper inner quadrant (UIQ). Sonography showed irregular, hypoechoic parenchymal echotexture in the left upper breast at 11 to 12 o’clock with cysts and shadowing (Figure 1), and the region of the microcalcifications was visualized as well. Ultrasound-guided biopsy confirmed infiltrating ductal carcinoma (IDC) with ductal carcinoma in situ (DCIS).

FIGURE 1 A and B, Representative ultrasound images of the 11 to 12 o’clock region show dense shadowing, with irregular anterior margination. The extent of the process is difficult to define and to differentiate from extreme fibrocystic changes.

The patient was evaluated by medical and radiation oncology and surgery for possible breast conservation. All three examiners had difficulty quantifying the size of the palpable abnormality, partly because of the presence of large coexisting cysts. One examiner noted a large area of firm dense tissue extending over 5 to 6 cm at the 12-o’clock level, and was concerned about the true extent of disease, because mammography had shown only a small UIQ microcalcification cluster. A breast MRI was, therefore, ordered to assess the extent of disease.

Breast MRI showed striking asymmetry between the two sides, with findings of a very large, diffusely infiltrating cancer on the left (Figures 2 and 3). The intensely enhancing process, centered at 12 o’clock but spanning 11 to 2 o’clock, showed architectural distortion, with additional extensive clumped enhancement diffusely involving the medial breast. By MRI, the abnormality measured at least 6 cm and involved at least two quadrants extensively, indicating that the patient was not a conservation candidate.

FIGURE 2 Axial enhanced, maximal intensity projection MRI shows extreme asymmetry between sides. The right side shows diffuse low-level, extensive, scattered, tiny fibrocystic foci of enhancement. The left side is dominated by a central mass with architectural distortion, and there is geographic enhancement in the medial breast.

FIGURE 3 Representative axial, subtracted, enhanced images, from above to below. A, Clumped enhancement medially with larger central tumor nodules involves both the upper inner and upper outer quadrants at this level. B, There is intense central enhancement with distortion and segmental clumped medial enhancement at this level. C, The spiculation and distortion of the central enhancing component are well demonstrated on this section. The oval defect within the enhancing spiculated mass represents a cyst, which was surrounded by the enhancing tumor. Clumped segmental medial enhancement, suggesting DCIS, is again seen. D, At the level of the nipple, extensive clumped segmental enhancement is seen medially and centrally, suggesting an extensive intraductal component, which was subsequently confirmed. E, Sagittal, subtracted, enhanced breast MRI shows how extensively the entire upper half of the breast is infiltrated.

Unfortunately, the surgeon did not become aware of this result until the day of the surgery because the study had been ordered by another physician. Fortunately, the radiologist who scanned the patient for performance of ultrasound-guided needle localization on the day of surgery recognized that the surgeon could not have been aware of the results of the MRI. The patient was subsequently apprised of the results and the extremely high likelihood of positive margins if lumpectomy was attempted, and therefore underwent mastectomy.

The mastectomy specimen showed an 8-cm IDC of the central breast extending into the upper inner and lower inner quadrants, with a high-grade DCIS component involving 50% of the lesion (extensive intraductal component). Multifocal satellite tumor nodules were noted within the large tumor. Extensive angiolymphatic involvement was seen, and four sentinel lymph nodes showed metastatic carcinoma (Figure 4). Completion axillary dissection showed no additional axillary disease, for a total of 4 of 20 lymph nodes positive for metastatic disease. The deep mastectomy margin was negative.

FIGURE 4 Coronal short tau inversion recovery (STIR) image of the thorax (obtained with the body coil at the time of breast MRI) shows three adjacent mildly prominent left axillary lymph nodes. Although not prospectively interpreted as suspicious because no one lymph node is particularly large, in retrospect the asymmetry in number from the opposite side is a clue to the axillary involvement.

The patient underwent imaging staging postoperatively, with bone scan, CT, and positron emission tomography (PET) (Figures 5 and 6), which showed only postsurgical changes of the axilla and chest wall and no evidence of distant metastatic disease. Final stage was stage IIIA, with T3N1M0 disease, and the tumor was estrogen receptor and progesterone receptor positive.

FIGURE 5 PET scan, obtained 2 weeks after left mastectomy, shows a left chest wall photopenic collection with a metabolically active rim, consistent with a postoperative seroma.

FIGURE 6 Enhanced chest CT image for correlation with PET shows a left chest wall seroma after mastectomy.

TEACHING POINTS

The extensive nature of this locally advanced, very large IDC became apparent relatively late in this patient’s evaluation and was accurately delineated only by MRI. The clinical examination in this patient confounded multiple examiners. The patient had extremely dense, fibrocystic breasts, with multiple cysts, and examiners found it difficult to delineate the extent of the tumor by palpation. Fortunately, one examiner sensed a discrepancy between the imaging findings and the apparent clinical extent, and breast MRI was ordered. It is not surprising that mammography in a patient with very dense breast tissue and multiple cysts would underestimate the extent of disease. Much of this patient’s extensive intraductal disease was noncalcified, with only a small microcalcification cluster noted in the UIQ at mammographic evaluation. The sonogram identified abnormal echotexture in the involved area, accurately guiding core biopsy for a diagnosis, but the size of the process and the full significance of the sonographic findings, with geographic shadowing and poor margin delineation, were not fully appreciated prospectively.

Accurate and timely communication between specialties is a critical part of the care of the newly diagnosed breast cancer patient, as this case illustrates. Evaluations up to the point of the breast MRI had not shown clear evidence that the patient was not a lumpectomy candidate, and so the treatment planning was proceeding with this expectation. One examiner’s concern that there might be a discrepancy between the imaging findings and the clinical examination led to performance of breast MRI, which confirmed a very large, locally advanced tumor. Unfortunately, this was ordered at the last minute and without the knowledge of the surgeon. Fortunately, the radiologist charged with performing the needle localization on the day of surgery was able to rectify the situation, which was precipitously, but satisfactorily, resolved in favor of the patient undergoing mastectomy.

CASE 2 LABC with axillary and internal mammary involvement; staging with whole-body PET and PEM

A 77-year-old woman was noted on routine physical examination by her primary care physician to have a palpable 3-cm mass on the right at 6 o’clock. Breast imaging evaluations confirmed this mass, which was best seen on ultrasound as a 3.2-cm mass with lobular and irregular margins (Figure 1). On ultrasound, a second suspicious mass, which was not seen mammographically, was noted medial to the dominant mass, at 4 o’clock (Figures 2 and 3). This was a bilobed, hypoechoic mass. A highly suspicious axillary lymph node was also found, measuring 2.3 cm, with complete effacement of the fatty hilus (Figure 4).

FIGURE 1 Ultrasound of the palpable lump on the right at 6 o’clock shows a very hypoechoic, heterogeneous, vascular mass with lobular and irregular margins, with a highly suspicious sonographic appearance. Biopsy confirmed IDC.

FIGURE 2 Ultrasound of the right 4-o’clock level shows a hypoechoic, bilobed, more smoothly marginated mass, resembling an abnormal lymph node in morphology. Biopsy with ultrasound guidance confirmed IDC.

FIGURE 3 Ultrasound shows the relationship between the 4- and 6-o’clock masses, which are 3.5 cm apart by ultrasound. A rounded, sub-centimeter nodule interposed between the two masses (arrow) was not noted prospectively. It corresponds to a smaller satellite lesion, which was FDG avid and seen on both whole-body and dedicated breast PET (PEM).

FIGURE 4 Ultrasound of the right axilla shows a round, completely replaced enlarged axillary lymph node. The fatty hilus is completely effaced.

These three abnormalities were biopsied with ultrasound guidance. Both the 4- and 6-o’clock breast masses were poorly differentiated infiltrating ductal carcinomas (IDC), estrogen receptor and progesterone receptor negative, HER-2/neu negative, grade 8/9. The axillary lymph node fine-needle aspiration showed adenocarcinoma, consistent with metastatic breast carcinoma.

Staging evaluations were obtained because of the patient’s node-positive status, concurrent complaints of back pain, and concern for possible metastatic disease. The patient had a pacemaker, which limited the options for performing MRI. A bone scan and positron emission tomography (PET)/CT scan were obtained. In addition, a positron emission mammography (PEM) scan was obtained of the breasts, immediately after the PET/CT, using the same dose of fluorodeoxyglucose (FDG).

Bone scan suggested an L1 compression fracture as the etiology of back pain (Figure 5). A band of modest increased metabolic activity was seen at the superior end plate of L1 on PET, and CT showed superior end-plate invagination, confirming the bone scan impression of a compression fracture (Figure 6). Three right lower inner quadrant FDG-avid breast masses were seen on whole-body PET/CT, with a small additional FDG-avid nodule seen between the two known IDC masses at 4 and 6 o’clock. The known involved right axillary lymph node was intensely hypermetabolic and was accompanied by several smaller additional metabolically active axillary lymph nodes. Activity was also seen in two internal mammary lymph nodes, which on CT measured 8 mm (Figures 7 and 8).

FIGURE 5 Bone scan images show a band of increased activity at the L1 level. This pattern of activity suggests a compression fracture as the etiology of the patient’s back pain.

FIGURE 6 Coronal CT reconstruction of the lumbar spine shows end-plate invagination of the L1 vertebral body, correlating with the bone scan and consistent with a compression fracture (arrows). Modest PET scan activity was present at this level. Other lumbar levels show discogenic changes and a levoscoliotic curvature.

FIGURE 7 Enhanced chest CT images, from above to below. A, An oval, markedly enlarged axillary lymph node is seen on the right, corresponding to the ultrasound. Scatter artifact from a right chest wall pacemaker is noted. B, A rounded, enlarged right internal mammary lymph node is seen adjacent to the enhanced internal mammary artery (arrow). This was hypermetabolic on PET. The vein is seen over the lateral right sternum. C, A second right internal mammary (IM) lymph node is seen adjacent to the artery and vein (from right to left: IM artery, IM vein, IM lymph node) (arrow). This was also hypermetabolic on PET. D, Through the inferior breasts, two right breast masses are seen. The medial one is the same as the 4-o’clock mass on ultrasound. It has a lobulated contour. No fat plane is seen between it and the muscle. A round smaller mass is seen lateral to it. E, Further inferior, the dominant right 6-o’clock irregularly marginated mass is seen, as well as the inferior aspect of the 4-o’clock mass.

FIGURE 8 PET scan images show three multifocal, FDG-avid right lower inner quadrant breast masses, as well as FDG-avid axillary lymph nodes and internal mammary nodes (not shown). A, Cursors are positioned at the level of the 6-o’clock IDC. A small adjacent FDG-avid nodule is seen on the coronal slice. B, Cursors are positioned at the level of the 4-o’clock IDC. The small satellite mass is partially seen on the axial image.

A PEM study was also obtained in this patient after completion of PET/CT, using the same FDG dose. The proven multifocality of her tumor would ordinarily have been an indication for breast MRI, but the patient could not readily undergo breast MRI because of her pacemaker. The dominant mass on the right at 6 o’clock was seen with exquisite detail on PEM, with intense heterogeneous uptake of FDG (Figure 9). The 4-o’clock mass was not seen on either view. This result was anticipated because of its far posterior position on the chest wall on CT. The small, intermediately positioned satellite tumor mass was visualized on the mediolateral oblique (MLO) projection, which shows more posterior breast tissue. The PEM also permitted more thorough screening of the left breast.

FIGURE 9 PEM scan images [MLO (A) and CC (B, next page)] show heterogeneous FDG uptake within the 6-o’clock IDC. The small, adjacent FDG-avid nodule is seen posterior to the 6-o’clock IDC only on the MLO view, which shows more posterior tissue.

Modified radical mastectomy and axillary lymph node dissection were performed. At surgery, abutment and adherence of tumor focally to the pectoralis muscle was noted, requiring some excision of muscle.

Pathology showed three IDC tumor masses in the right lower inner quadrant, measuring 4.5 cm each at 4 and 6 o’clock and 1 cm in between. There was angiolymphatic invasion, with the 4-o’clock IDC close (0.09 mm) to the deep margin. Metastatic carcinoma was identified in 7 of 12 axillary lymph nodes, with extreme matting noted by pathology.

TEACHING POINTS

This is a locally advanced breast cancer, based on axillary and internal mammary lymph node involvement. This degree of nodal involvement is classified as N3b, making the patient stage IIIC. The internal mammary lymph node involvement does not have to be histologically proven to be considered positive for involvement. In this case, the ease of visualizing these enlarged internal mammary lymph nodes on CT and the FDG avidity seen on PET leave little doubt that they are involved.

This patient’s concurrent back pain raised the specter of metastatic disease. Fortunately, the bone scan abnormality is characteristic of a compression fracture and the PET and CT were entirely consistent. Of course, this does not entirely exclude the possibility of a pathologic compression fracture due to a bone metastasis, but without other evidence of osseous metastases, this seems unlikely. An osteoporotic compression fracture is a commonly encountered benign cause of symptoms and bone scan findings in older women.

It is interesting to note the node-like morphology of the 4-o’clock lesion in this case. It strongly resembles an abnormal lymph node and was positioned on the chest wall, suggesting it may be a completely replaced external mammary lymph node.

Normally, with proven multifocal breast cancer, local staging would often be supplemented with breast MRI, which would effectively screen the other breast. In this case, a pacemaker precluded performance of breast MRI. PEM was utilized to screen the other breast. It is interesting to see some of the strengths and weaknesses of PEM displayed by this case. As in mammography, only tissue that is imaged can be evaluated. Far posterior lesions that cannot be positioned between the detector arrays will not be seen, even sizable ones like the 4-o’clock lesion in this case. Design improvements of future PEM devices may improve detectability of posterior lesions. On the other hand, the detail of the heterogeneous FDG uptake of the 6-o’clock IDC is striking in contrast to the whole-body PET depiction.

The role of PEM in the breast imaging armamentarium is currently being assessed by a prospective, multi-institutional clinical trial comparing the performance of PEM to breast MRI in local staging of newly diagnosed breast cancers. Essentially, PEM is a small-field-of-view, high-resolution PET scanner, with in plane resolution on the order of 2 mm. Resembling a mammogram unit, the compression “plates” consist of an array of detectors. Compression is applied to immobilize the breast, but not to the same degree as in mammography. As PEM is a tomographic technique, there is no need to thin the breast to the same degree as in mammography.

CASE 3 LABC with nipple skin involvement

A 56-year-old woman noted new right nipple inversion 4 months before presenting for breast imaging evaluation for a newly developed right palpable axillary lump. Mammography and ultrasound showed a dominant 12-o’clock mass with nipple retraction and localized skin thickening, as well as axillary lymphadenopathy (Figures 1, 2, and 3). Ultrasound-guided biopsy of the dominant mass confirmed invasive ductal carcinoma (IDC), and ultrasound-guided axillary node fine-needle aspiration confirmed metastatic disease. Periareolar dusky erythema was noted, and skin punch biopsy was performed, which was negative. Local staging was completed with breast MRI (Figures 4, 5, 6, 7, and 8).

FIGURE 1 Ultrasound of the right upper outer quadrant shows a hypoechoic, taller-than-wide, sonographically suspicious mass with irregular and angular margins.

FIGURE 2 Ultrasound of the retracted right nipple shows unusual increased periareolar vascularity.

FIGURE 3 Ultrasound of the right axilla shows two adjacent, highly abnormal lymph nodes: both are rounded, with very hypoechoic, thickened cortices. Nodular mass effect is exerted on the echogenic fatty hila, which are partially effaced. No increased vascularity is identified.

FIGURE 4 Maximal intensity projection of enhanced, subtracted, axial gradient echo data set shows an intensely enhancing, dominant mass in the central right breast. Numerous linear spicules extend anteriorly toward the nipple. There are enlarged, draining veins on the right, and enlarged, enhancing right axillary lymph nodes.

FIGURE 5 Axial breast MR images through the dominant right IDC (A, enhanced, subtracted, T1-weighted gradient echo; B, STIR) show rim enhancement and spiculation of the mass. Linear spicules extend anteriorly toward the nipple and posteriorly toward the pectoral muscle. The periareolar skin is thickened and edematous, and enhances. A rounded, low-lying axillary or intramammary lymph node enhances intensely in the posterolateral right breast.

FIGURE 6 Sagittal, subtracted, contrast enhanced MRI of the right breast showing the enhancing linear tendrils extending to the nipple, as well as the periareolar skin enhancement.

FIGURE 7 Kinetic information (A, DynaCAD color map; B, enhancement curve) showing washout from portions of the IDC mass.

FIGURE 8 Axial STIR images of the axilla. A, An enlarged right axillary level I lymph node is seen lateral to the pectoralis major and minor muscles (arrow). B, An enlarged interpectoral (Rotter’s) lymph node is seen on the right, between the pectoralis major muscle in front and pectoralis minor muscle behind (arrow).

Systemic staging with positron emission tomography (PET)/CT showed fluorodeoxyglucose (FDG) avidity of the known right breast cancer and axillary lymphadenopathy, but no additional disease. Neoadjuvant chemotherapy was given, consisting of four cycles each of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) and paclitaxel (Taxol). The nipple inversion resolved, and there was marked clinical regression of the dominant mass. Modified radical mastectomy and axillary dissection were performed. A 4.5-cm residual lesion of admixed IDC and normal breast tissue remained. Margins were negative, and 5 of 13 lymph nodes showed metastatic tumor. Chest wall, supraclavicular, and posterior axillary boost radiation therapy were given, and the patient was placed on anastrozole (Arimidex).

TEACHING POINTS

In this case, the localized periareolar skin thickening, edema, and enhancement probably represented secondary inflammation and involvement by a locally advanced breast cancer (LABC), rather than being a manifestation of primary inflammatory breast cancer.

CASE 6 PABC, treated with neoadjuvant chemotherapy with complete pathologic response

A 33-year-old pregnant patient noted a palpable right breast lump at about 18 weeks of gestation. This was confirmed by her obstetrician, who performed a fine-needle aspiration. No diagnosis or fluid was obtained. Ultrasound identified a suspicious 2.2-cm mass, as well as an abnormal and enlarged axillary lymph node (Figures 1 and 2). Ultrasound-guided core needle biopsy of the breast mass revealed high-grade infiltrating ductal carcinoma, and fine-needle aspiration (FNA) of the axillary lymph node showed metastatic carcinoma, consistent with breast primary.

FIGURE 1 Ultrasound of the right LOQ palpable lump shows highly sinister features of malignancy: extreme hypoechogenicity, taller-than-wide shape; angry-looking, angular margins; and shadowing. Biopsy with ultrasound guidance confirmed IDC.

FIGURE 2 Sonography of the axilla [gray scale (A) and color Doppler (B)] shows abnormal lymph node morphology. A large cortical nodule occupies one half of the lymph node, effacing a portion of the fatty hilus, which remains visible in the other half. Color Doppler shows markedly increased, abnormal vascularity of the cortical nodule. FNA identified metastatic cells.

On palpation, the mass was large, in the lower outer quadrant, estimated at 6 to 8 cm in size, and thought to be too large to attempt breast conservation. A 2-cm axillary lymph node was also palpable and mobile. The patient was interested in breast preservation and in continuing with her pregnancy, and so neoadjuvant chemotherapy was performed with four cycles of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC).

Breast MRI was obtained to assess the extent of disease, given the discrepancy between physical examination and ultrasound. It showed a large, dominant, irregularly marginated mass occupying most of the lower outer quadrant (LOQ) and measuring 8.1 cm in maximal dimension (Figures 3, 4, 5, 6, and 7). Clinical stage was stage III, T3N1, estrogen receptor and progesterone receptor low positive, HER-2/neu positive.

FIGURE 3 Axial maximal intensity projection view from enhanced, dynamic, subtracted breast MRI series shows marked asymmetry, with diffuse increased enhancement in the right lateral breast. Generalized lower-level enhancement of both breasts is attributable to the hormonal effects of pregnancy.

FIGURE 4 Enhanced, subtracted, axial MRI through the inferior breasts shows irregular mass enhancement occupying much of the right LOQ.

FIGURE 5 A more superior slice, through the nipple, shows that the clumped and multifocal mass enhancement is extensive. No focal or concerning left breast enhancement is seen.

FIGURE 6 Sagittal, enhanced, subtracted images of the right breast (A, through the nipple; B, laterally) obtained about 5 to 6 minutes after contrast administration show the extensive process as nearly confluent enhancement.

FIGURE 7 Coronal STIR image of the thorax (obtained with the body coil) shows both breasts to be very engorged and fluid in signal intensity. An enlarged axillary lymph node is seen on the right.

The patient was treated with four cycles of AC, with delivery of the baby planned for 36 weeks’ gestation, with paclitaxel (Taxol) and trastuzumab (Herceptin) therapy afterward for HER-2/neu positive disease. After the four AC cycles, the mass was no longer palpable. The patient was induced and delivered a healthy baby at about 33 weeks’ gestation.

Her chemotherapy was resumed after delivery, with weekly Taxol and Herceptin for 12 weeks, with Herceptin planned weekly for 40 additional weeks (1 year total). Mid-chemotherapy restaging studies were obtained, showing a smaller ultrasound residual mass, now 1.2 cm, and resolution of the abnormal axillary findings (Figure 8). Given the marked imaging regression of the tumor, the patient underwent ultrasound-guided clip placement into the residual for future localization (Figure 9). Repeat breast MRI showed marked regression of the mass, reduced to a linear residual (Figure 10).

FIGURE 8 Repeat breast ultrasound, after completion of four cycles of chemotherapy with AC, shows evidence of a response. The sonographically visible component of the mass is smaller.

FIGURE 9 Sonographic images from ultrasound-guided clip placement (A, with needle in place; B, final image, with clip deployed). A clip was placed because of the marked regression of the tumor in response to neoadjuvant chemotherapy, to ensure the region could be localized in case complete imaging resolution were to ensue.

FIGURE 10 Repeat breast MRI, after four cycles of chemotherapy with AC, shows only a minimal linear residual at the site.

Staging studies were repeated 2 months later, after completion of Taxol therapy, and showed further regression, with only minimal residuals on both ultrasound and MRI (Figures 11 and 12). The patient was treated surgically with a partial mastectomy, which showed no invasive carcinoma and negative margins. A limited axillary dissection removing six lymph nodes was performed, and there was no evidence of metastatic tumor in the sampled nodes. Radiation therapy was subsequently administered to the breast and supraclavicular region.

FIGURE 11 Final breast ultrasound, 2 months later, after completion of neoadjuvant chemotherapy with four cycles of AC and 12 weekly doses of Taxol and Herceptin, shows no residual mass. A minimal hypoechoic collar outlines the clip (in box).

FIGURE 12 Final breast MRI, 2 months later, after completion of neoadjuvant chemotherapy with four cycles of AC and 12 weekly doses of Taxol and Herceptin, shows linear enhancement at the site, in a slightly different pattern than that seen previously. The sharp definition of the edges suggests an iatrogenic etiology, namely enhancement around the clip placed since the prior MRI.

TEACHING POINTS

This case well illustrates the typical features of breast cancers diagnosed during pregnancy, which tend to be large and node-positive and may be inoperable. Pregnancy-associated breast cancer (PABC) is generally defined as breast cancer diagnosed during pregnancy or within a year of delivery. PABC tends to be advanced at diagnosis, with contributions from physician and patient-related delays in diagnosis. The difficulty of physical examination in pregnancy and lactation-engorged breasts is thought to contribute to delayed diagnosis.

Although PABC is generally regarded as rare, complicating 1 in 3000 pregnancies in the United States, the actual number of PABCs is about what would be predicted based on the incidence of breast cancer in women of reproductive age and the expected pregnancy rate in these women.

Ultrasound is an excellent first imaging choice in assessing a palpable mass in a pregnant patient. If ultrasound did not identify a mass or satisfactory explanation for a palpable lump, the imaging evaluation could safely be extended to include mammography, based on an estimated fetal dose of 500 μGy from two-view film screen mammography with abdominal shielding.

Breast MRI is another viable imaging option for use during pregnancy, preferably after the first trimester. Particularly in such a case as this, when a diagnosis of breast cancer is established, breast MRI can be considered for local staging and assessment of the extent of disease. Although hormonal engorgement of the breasts is expected, as seen in this case, in general such changes and increased density are not an issue for breast MRI.

In formulating a treatment plan for a pregnant patient with breast cancer, the usual approach is to treat the cancer while allowing the pregnancy to proceed. Both surgery and chemotherapy can be safely performed during pregnancy, whereas radiation is preferentially given after delivery. In this case, the patient was initially considered for mastectomy while pregnant, but her excellent response to neoadjuvant chemotherapy during pregnancy enabled successful lumpectomy, performed after induced delivery.

This patient had a dramatic imaging response to neoadjuvant chemotherapy, with virtually complete resolution by imaging of what had been a very sizable tumor. Although this correlates well in this case with the complete pathologic response that was obtained, it has been well documented in the literature that a complete response by imaging does not exclude microscopic residual disease on pathology.

CASE 7 Postpartum LABC, with multiple axillary nodes involved; excellent response to neoadjuvant chemotherapy

A 41-year-old woman, 4 months postpartum and tapering breast-feeding, noted a left axillary lump. She also noted left breast tenderness and swelling. A massively enlarged and vascular axillary lymph node was found on ultrasound, which also showed a region in the left upper outer quadrant (UOQ) of parenchymal hypoechogenicity (Figures 1, 2, 3, and 4). Core needle biopsy with ultrasound guidance of the left UOQ showed infiltrating ductal carcinoma (IDC), estrogen receptor negative, progesterone receptor weakly positive, HER-2/neu negative. Ultrasound-guided fine-needle aspiration (FNA) of the axillary lymph node showed a mixed population of lymphocytes, but no malignant cells. Clinically and morphologically, the axilla was suspected to be involved, despite the negative FNA. Physical examination of the breast noted a large area of nodularity and induration, estimated at 5 cm in size, but difficult to precisely define.

FIGURE 1 Ultrasound of the left UOQ shows heterogeneous, hypoechoic echotexture, which differed in appearance from other regions.

FIGURE 2 Ultrasound of the palpable left axillary lump shows a massively enlarged and vascular lymph node, with dramatic cortical thickening.

FIGURE 3 Transverse view of the same lymph node shows nearly complete effacement of the echogenic fatty hilum. Abnormal (nonhilar) vascularity is demonstrated, and the cortex is massively thickened.

FIGURE 4 Additional sonographic view of the left axilla shows multiple additional, abnormal lymph nodes. One is very hypoechoic, is rounded and lobular in shape, and shows complete hilar loss. Even the two more normal-appearing lymph nodes shown here are more subtly abnormal. Although their fatty hila remain, their cortices are abnormally thickened.

Breast MRI was obtained to better define the extent of the tumor (Figures 5 and 6). It showed a much larger area of involvement, spanning 8 cm in the left lateral breast. This consisted of multiple intensely enhancing masses, with clumped, linear, and ductal enhancement, oriented along a ductal ray.

FIGURE 5 Dynamic contrast-enhanced, subtracted views of both breasts (A above B) show intense, multifocal enhancement in the left lateral breast, with a large, irregularly shaped posterior mass, and multiple smaller masses and clumped linear and ductal enhancement extending in a ductal ray anteriorly. Note also the fine linear enhancement at the posterior and lateral aspects of the dominant mass. No abnormalities are seen in the right breast.

FIGURE 6 Axial STIR images (A above B, at the same levels as Figure 5) show the lateral region of the left breast to be hypointense compared with the edematous, engorged appearance of the remainder of the breast. The appearance is in striking contrast to the right breast, which shows localized retroareolar ductal ectasia only. The lateral left breast skin is thickened and edematous, but showed no abnormal enhancement.

Positron emission tomography (PET)/CT and enhanced CT scans were obtained to systemically stage the patient. These showed intense multifocal hypermetabolism in the left lateral breast and in multiple left axillary enlarged lymph nodes (Figures 7, 8, 9, 10, and 11). No evidence of stage IV disease was seen.

FIGURE 7 PET scan images show intense hypermetabolism in the lateral left breast, as well as in multiple left axillary lymph nodes. Normal, low-level, physiologic uptake is seen in the right breast.

FIGURE 8 Axial PET/CT images through the axilla show multiple enlarged and hypermetabolic left axillary nodes.

FIGURE 9 The corresponding enhanced chest CT shows enlarged, nearly confluent left level I (lateral to the pectoralis minor [PM] muscle) and II (under the muscle) axillary lymph nodes.

FIGURE 10 Axial PET/CT images through the breasts show intense, multifocal hypermetabolic activity in the left lateral breast.

FIGURE 11 Contrast-enhanced chest CT images of the breasts (A above B) show multifocal, ill-defined enhancement in the left lateral breast, poorly delineated from normal parenchyma. The left lateral breast skin is thickened.

Neoadjuvant chemotherapy was recommended, owing to the large size of the tumor. Four cycles each of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) and docetaxel (Taxotere) were given. Restaging with breast ultrasound and MRI (Figures 12, 13, and 14) and PET/CT was performed after four cycles of AC and again after 4 cycles of Taxotere (Figures 15 and 16). Restaging showed an excellent imaging response, with dramatic shrinkage and decreased enhancement of the tumor and axillary lymph nodes, and resolution of the PET uptake.

FIGURE 12 Restaging lateral left breast ultrasound, 3 months later after four cycles of AC chemotherapy. A, At 2 o’clock, there is a vascular hypoechoic residual mass. B, Persistent hypoechoic echotexture is seen at 3 o’clock. C, The axillary lymph node, which was massively enlarged previously, is markedly improved but shows persistent cortical thickening (4 mm).

FIGURE 13 Restaging breast MRI, 3 months later, after four cycles of AC chemotherapy. A, Axial STIR shows a much more normal and symmetrical pattern of signal intensity. B, Axial, dynamic, enhanced, subtracted MRI shows dramatic improvement. A linear array of enhancing foci is seen in the lateral left breast where the extensive multifocal masses were previously. C, A more inferior image from the same series. D, No washout is now seen. The curve shows slow uptake, with plateauing enhancement.

FIGURE 14 Mammogram, after four cycles of AC chemotherapy, shows heterogeneously dense breast parenchyma [MLO (A) and CC (B)]. There is a suggestion of architectural distortion (arrows) on the MLO view. A marker has been placed at the site of palpable induration.

FIGURE 15 Restaging lateral left breast ultrasound, 6 months after diagnosis and after four cycles each of AC and Taxotere chemotherapy. A, An ill-defined hypoechoic residual mass is seen at 2 o’clock. B, The axillary lymph node has further normalized in appearance. Cortical thickness is now borderline.

FIGURE 16 Restaging breast MRI, 6 months after diagnosis and after four cycles each of AC and Taxotere chemotherapy. A, Axial maximal intensity projection (3 minutes after contrast injection) shows only a few foci of enhancement at the lateral left breast site of treated IDC. B, Only slow, persistent enhancement can now be identified.

The left UOQ residual was needle-localized for surgery with two wires, and a residual, mildly abnormal-appearing left axillary lymph node was also needle-localized with ultrasound guidance. Pathology showed multifocal microscopic foci of atypical cells, consistent with residual carcinoma. The anterior margin was close (<1 mm). The extent of the residual tumor was estimated at 1.5 cm. The localized axillary lymph node was enlarged and fibrotic, with no evidence of neoplasm. A wide breast re-excision specimen showed no residual malignancy.

The patient began tamoxifen, and radiation therapy to the breast and peripheral lymphatics was given.

TEACHING POINTS

These axillary lymph nodes were so enlarged at presentation, a “plumbing problem” can be suspected to underlie the unusual pattern of edema and engorgement seen in the remainder of the left breast. The linear enhancing strands seen extending from the multifocal breast neoplasm toward the axilla suggest tumor-engorged lymphatics. The skin thickening and edema in the left lateral breast, best seen on STIR MRI and on chest CT, is not accompanied by enhancement, and so probably is part of the generalized engorgement and edema. Skin thickening with enhancement would be concerning for an inflammatory component.

Another potentially contributory factor to the markedly engorged appearance of the left breast at presentation was the patient’s lactational status. She was 4 months postpartum and had been breast-feeding; at presentation she was actively weaning her child (breast-feeding one-half of the day). However, the marked asymmetry between breasts argues for obstructed lymphatics as the dominant factor.

This patient had a very extensive tumor. This is a locally advanced breast cancer (LABC), based both on size (>5 cm) and the extensive axillary involvement. The only imaging modality that accurately delineated the true extent of this LABC was MRI. This tumor can also be considered a pregnancy-associated breast cancer (PABC), defined as breast cancer diagnosed during pregnancy or within the first year after delivery. In the developed world, PABC constitutes about 1% of all breast cancers.

By both imaging and pathology, this patient had a good response to primary systemic chemotherapy. At presentation, she had been inclined to undergo a mastectomy, but was persuaded that preoperative chemotherapy was advisable because of the size of the tumor. Downsizing of the tumor to a degree at which breast conservation became a viable option was an unexpected benefit of neoadjuvant therapy in this case.

CASE 8 IDC treated with neoadjuvant chemotherapy with incomplete imaging response, but complete pathologic response

A 47-year-old woman presented with a growing palpable lump, noted initially a year before evaluation. Mammographic evaluation showed development since the prior year of a new upper outer quadrant (UOQ) right breast mass, which was 4 cm, spiculated, and associated with pleomorphic calcifications (Figure 1). Additional suspicious microcalcifications were seen medial and caudal to the dominant mass. Palpation-guided biopsy by a breast surgeon was suspicious with atypia, but not conclusive. Subsequently, ultrasound demonstrated a 2.9-cm mass (Figure 2), with highly suspicious features, and core needle biopsy with ultrasound guidance confirmed moderately differentiated infiltrating ductal carcinoma (IDC), estrogen receptor and progesterone receptor positive, HER-2/neu negative.

FIGURE 1 Mammographic spot compression views [MLO (A) and CC (B)] show a dominant, dense mass with spiculated margins, which was palpable. (Note adjacent marker on the MLO projection.)

FIGURE 2 Ultrasound of the palpable lump in the right UOQ shows a highly suspicious appearance, being very hypoechoic, with shadowing and irregular, angular margins.

Breast MRI showed the mass to be larger than previously suspected, measuring 5 cm (Figures 3 and 4). The patient opted for neoadjuvant chemotherapy to downsize the tumor. The mass shrank in response, as assessed on follow-up mammograms and MRI (Figures 5 and 6). By MRI, the dominant mass declined in size from 5 cm pretreatment to 3 cm post-treatment, with an adjacent 1-cm mass inferomedially. Mammography showed a decline in size of the visible mass from 4 cm to 1.5 cm. However, sampling of the unchanged microcalcifications was now recommended, because of their location in the lower outer quadrant (LOQ), separate from the known IDC in the UOQ. Stereotactic biopsy confirmed the calcifications represented ductal carcinoma in situ (DCIS), and with two quadrants involved, the patient was deemed unsuitable for breast conservation.

FIGURE 3 Staging breast MRI axial images (A, T2-weighted; B, enhanced, subtracted T1-weighted gradient echo) show the right breast to be larger than the left. The dominant mass in the right lateral breast is hypointense on T2-weighted images and shows rim enhancement on subtracted enhanced images.

FIGURE 4 Signal intensity–time enhancement curve shows a suspicious pattern, with rapid uptake of contrast, and washout, indicating angiogenesis.

FIGURE 5 Restaging breast MRI images (A, T2-weighted; B, enhanced, subtracted T1-weighted gradient echo), after neoadjuvant chemotherapy, show shrinkage of the mass, which is still visible as a contracted residual on both views.

FIGURE 6 Sagittal enhanced, subtracted, T1-weighted gradient echo views. A, Before neoadjuvant chemotherapy. B, After chemotherapy, for comparison.

Accordingly, the patient underwent a mastectomy and sentinel lymph node sampling. No residual IDC was found in the mastectomy specimen. There was residual cribriform and solid DCIS in the LOQ measuring 1.8 cm. The margins were negative, and one lymph node was negative as well.

Additional therapy given included radiation therapy to the chest wall and supraclavicular fossa, and the patient was started on tamoxifen.

TEACHING POINTS

Good responses to neoadjuvant chemotherapy may convert a nonoperable patient into operability with mastectomy, or can convert a mastectomy candidate to eligibility for breast-conserving lumpectomy. However, as this case shows, even a good response to neoadjuvant chemotherapy may still necessitate treatment with a mastectomy. This tumor was considered a locally advanced breast cancer based on the large size of lesion (>5 cm). It can be easier to perform mastectomy with clear margins after shrinking a tumor with neoadjuvant chemotherapy, and no difference in recurrence rates has been demonstrated for administration of chemotherapy preoperatively compared with postoperatively.

CASE 10 Complete imaging response to neoadjuvant chemotherapy

A 54-year-old postmenopausal woman with a family history of breast cancer underwent routine screening mammography, which identified developing asymmetrical density and possible architectural distortion in the right upper outer quadrant (UOQ). Mammographic spot compression confirmed the suspected abnormality, and ultrasound showed corresponding ill-defined shadowing in the 9- to 10-o’clock region (Figure 1). Stereotactic biopsy was recommended because the abnormality seemed to be better visualized mammographically than sonographically. However, the lesion could not be satisfactorily visualized for stereotactic biopsy, presumably because of the less effective compression achievable with stereotactic procedures. The hypoechoic shadowing correlate was biopsied with ultrasound guidance, confirming infiltrating ductal carcinoma (IDC).

FIGURE 1 Ill-defined shadowing emanates from the right lateral breast, in the region of the mammographic abnormality. The margins and precise dimensions are difficult to delineate. The process distorts the normal breast tissue planes. Biopsy with ultrasound guidance confirmed IDC.

On surgical, medical oncology, and radiation oncology evaluations, no palpable mass was identified. Because the size of the lesion and true extent of disease were difficult to estimate accurately based on clinical breast exam, mammography, and ultrasound, breast MRI was requested.

MRI suggested more advanced disease than suspected to that point (Figures 2, 3, 4, and 5). Multiple intensely enhancing right axillary lymph nodes were identified, which were up to 1.1 × 1.8 cm in size. The index lesion was larger than previously demonstrated, with maximal dimension estimated to be 4 cm (prior estimate by ultrasound was 2 cm). The skin of the right breast was noted to be asymmetrically thickened and edematous, with enhancement. Nearly concurrent with this, the patient noted new faint erythema of the right breast, and a tender right axillary lymph node was now palpable. She was placed on antibiotics for a possible infection. The erythema persisted, but no peau d’orange changes were ever noted. A punch skin biopsy was performed to assess for a possible inflammatory component, but showed only perivascular inflammation, with no dermal or intralymphatic carcinoma seen.

FIGURE 2 Axial STIR breast MRI shows marked skin asymmetry. The right breast skin is thick and edematous. However, little increased edema is seen within the breast itself.

FIGURE 3 Axial enhanced, subtracted, T1-weighted, gradient echo images show irregularly marginated, intense enhancement in the right lateral breast, corresponding to the known IDC. In this plane, the size correlated fairly well with the ultrasound estimate of index lesion size.

FIGURE 4 Another section, through the axilla, shows an intensely enhancing and enlarged right axillary lymph node.

FIGURE 5 Sagittal, subtracted breast MRI of the right lateral breast shows the craniocaudal extent of disease. The process appears more extensive and larger than previously suspected. Enhancing right axillary lymph nodes are also depicted. The thickened supra-areolar skin shows enhancement, suggesting a possible inflammatory component.

Although the patient had initially been interested in breast conservation therapy, the more extensive nature of her tumor suggested by these evaluations led to a decision to begin neoadjuvant chemotherapy after clip placement (under ultrasound guidance) into the mass. While undergoing this, the patient had BRCA gene testing and was confirmed to be BRCA2 positive. Her family history of breast cancer included a sister diagnosed at age 48 and mother diagnosed at age 65, with death at age 67 from metastatic breast cancer. After this information became available, the patient decided to undergo bilateral mastectomies after completing neoadjuvant chemotherapy.

After four cycles of chemotherapy with doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC), breast MRI was repeated (Figures 6 and 7). This showed a response, with the enhancing tumor reduced in size and a marked decline in intensity of enhancement. Only slow progressive enhancement was now identified. The enhancing axillary lymph nodes also resolved.

FIGURE 6 Repeat breast MRI, 3 months later, after four cycles of AC chemotherapy, shows decreased size of the enhancing mass [axial (A) and sagittal (B)], with a contracted, strandy residual remaining. The enhancement is much less intense. These findings completely resolved on repeat breast MRI, performed after completion of chemotherapy (not shown).

FIGURE 7 The signal intensity–time curve shows only slow, progressive, low-level enhancement now. These minimal findings were completely resolved on the next follow-up, after four cycles of Taxotere.

After four cycles of docetaxel (Taxotere), restaging breast studies were obtained. By MRI, there was a complete response, with no residual enhancement identified. The patient’s right breast skin was noted to be persistently thickened and edematous, but without abnormal enhancement. No residual disease was demonstrable by mammography or ultrasound.

The patient elected surgical treatment with bilateral mastectomies. On the right, a sentinel lymph node was positive for malignancy, and so axillary dissection was performed. Two of four axillary lymph nodes showed tumor. The right mastectomy specimen contained residual IDC, spread over a 1.3-cm expanse. There was angiolymphatic invasion. The skin and margins were uninvolved. The left mastectomy specimen showed fibrocystic changes only.

Right chest wall, supraclavicular, and posterior axillary boost radiation was given, and the patient was started on anastrozole (Arimidex).

TEACHING POINTS

This case reminds us that complete imaging responses to neoadjuvant chemotherapy are not equivalent to complete pathologic response. Although no imaging evidence of disease remained after chemotherapy, there was microscopic residual IDC. The converse can also occur: Complete pathologic responses can be seen in patients whose tumorous imaging findings do not completely resolve.

CASE 11 IDC with cystic component; mixed response to neoadjuvant chemotherapy

A 28-year-old woman noted a palpable left breast lump while in the shower, which was subsequently confirmed by her primary care physician’s physical examination in the upper outer quadrant (UOQ). Ultrasound showed a 2.9-cm complex mass with cystic and solid components (Figure 1). Biopsy was recommended and accomplished with ultrasound guidance. The solid component was sampled with 14-gauge core needle biopsy technique and the cystic component aspirated, with the bloody aspirate sent for cytologic analysis. Pathology showed poorly differentiated invasive ductal carcinoma (IDC), estrogen receptor and progesterone receptor negative, HER-2/neu negative, and the fluid cytology showed malignant cells.

FIGURE 1 Ultrasound images of the palpable left upper outer quadrant mass. A, Anechoic cystic component shows a sharp back wall and enhanced through-transmission, with a deceptively benign appearance at first glance. B, Another ultrasound section shows mural thickening and a solid component on the right side of the cystic portion. C, This image, through the solid component, does not look innocent. Although the margins are lobular and relatively circumscribed, there is no well-defined capsule. The solid component is heterogeneous in echotexture, and there is peripheral vascularity, all features suggesting this needs to be sampled. Biopsy confirmed high-grade IDC.

Breast MRI was obtained next and showed the left UOQ known IDC to be partially cystic (Figure 2). By MRI, the maximal dimension was 3.7 cm. An unsuspected 1-cm, intensely enhancing, circumscribed mass was found in the posterior right lateral breast (Figure 3). Subsequent workup with diagnostic mammography and ultrasound was performed. On the right, ultrasound found a 1.0- × 0.3-cm hypoechoic, oval, benign-appearing mass against the chest wall, which seemed to correspond to the MRI finding (Figure 4). Subsequent right ultrasound-guided core needle biopsy confirmed a diagnosis of fibroadenoma.

FIGURE 2 MRIs of the known left UOQ IDC mass. A, Axial STIR shows a cystic mass in the left lateral breast. A septation or focal mural thickening is seen within this cystic component posterolaterally. Fluid between the mass and the pectoral muscle may be related to the preceding biopsy. A mildly prominent left axillary lymph node with suggestive cortical mantle thickening is seen. Ultrasound-guided left axillary fine-needle aspiration was negative for malignancy, as was sentinel node evaluation after neoadjuvant chemotherapy. B, A more inferior axial STIR image shows a more heterogeneous, multilocular cystic and solid appearance of the left lateral IDC. C, Enhanced, subtracted image of the left IDC shows peripheral, thick-walled enhancement of the cystic component, with solid mural components, particularly posterolaterally. D, Unsubtracted, enhanced, T1-weighted, gradient echo image through the inferior portion of the left IDC shows papillary peripheral enhancement of the partially cystic mass. E, Enhanced, subtracted, sagittal image shows the solid mural components projecting into the lumen of the partially cystic mass.

FIGURE 3 MRIs of a previously unsuspected right breast mass. A, A small (about 1 cm) hyperintense mass is seen against the posterior chest wall in the right lateral breast on axial STIR. B, Unsubtracted, enhanced, fat-saturated, T1-weighted, gradient echo image of the right mass shows smooth lobular contours. C, Detail of the right mass shows faint, nonenhancing internal septa within. D, Sagittal, subtracted, enhanced view of the same right mass. E, Kinetic analysis shows progressive enhancement of the mass. These characteristics suggest this represents a benign fibroadenoma, which was confirmed by subsequent ultrasound-guided core biopsy. i, Color map. ii, Signal intensity change–time curve.

FIGURE 4 Ultrasound of the right breast shows an oval, circumscribed, benign-appearing mass against the pectoral muscle, corresponding to the enhancing abnormality on MRI. This was confirmed by ultrasound core needle biopsy to be a fibroadenoma.

Initial consultations with surgery, medical oncology, and radiation oncology noted the tumor to be large relative to the patient’s breast size. The patient desired breast conservation, and so neoadjuvant chemotherapy with four cycles of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) and four cycles of docetaxel (Taxotere) was elected. Preliminary staging studies with positron emission tomography (PET)/CT and enhanced body CT scans showed hypermetabolism of the peripheral solid left IDC components, but no evidence of nodal or distant metastatic disease (Figure 5). Ultrasound and breast MRI studies obtained during and at the conclusion of neoadjuvant chemotherapy showed a waxing and waning response, with improvement midway through therapy (after four cycles of AC), but partial regrowth after four cycles of Taxotere (Figures 6, 7, 8, 9, and 10). The final imaging evaluations did show overall improvement in comparison with the staging studies, despite the partial regression of the response demonstrated midway through therapy.

FIGURE 5 Enhanced axial chest CT images (A above and B below) and PET/CT (C) for correlation with MRI. A, At this level, the mass is complex cystic in appearance with thick and irregular solid enhancement posterolaterally. B, An even more suspicious appearance is seen at the inferior margin of the mass, with multilocularity, enhancing septa, and papillary projections. C, Axial PET/CT images show a C-shaped rim of intense hypermetabolism corresponding to the solid rim component of this multiloculated cystic neoplasm. No nodal or distant metastatic disease was identified on these studies.

FIGURE 6 Interim ultrasound (US) examinations, obtained during chemotherapy to assess the response. A, After two cycles of AC chemotherapy, the mass contracted, with decrease in the size of the cystic component. B, After four cycles of AC, further contraction is seen. The cystic component resolved. The residual solid component is irregularly marginated and vascular.

FIGURE 7 Repeat breast MRI, after completion of four cycles of AC neoadjuvant chemotherapy. A, Enhanced, subtracted axial image from minute 1 of the dynamic series shows early enhancement of a smaller solid component. The cystic component of the mass was no longer evident on this examination. B, Enhanced, subtracted axial image from minute 3 of the dynamic series shows less intense, more delayed plateauing enhancement of the rest of the solid residual. Overall size has decreased to 2 cm in maximal dimension. C, DynaCAD kinetic color map (i) showing the differential enhancement of the residual solid mass. A 1-cm component anteriorly (red and yellow) shows washout, whereas the larger posterior component shows a plateauing enhancement pattern. ii, Graph (signal intensity–time curve) from the early enhancing 1-cm anterior component (in red on color map). iii, Graph (signal intensity–time curve) from the delayed, plateauing posterior enhancing component (in blue on color map).

FIGURE 8 Third breast MRI, obtained at the conclusion of neoadjuvant chemotherapy (four cycles of AC and four cycles of Taxotere), shows a waxing and waning, mixed response. Despite improvement seen after the four cycles of AC, this study shows recurrence of the cystic component, with overall increase in size resulting. In addition, angiogenesis is demonstrable from the nodular rim of the mass. A, Axial enhanced, subtracted view of the left IDC shows a change in appearance, with reaccumulation of cyst fluid. The rim is thick, nodular, and irregular. B, Sagittal, enhanced, subtracted view of the same for correlation. The enhancing rim is not smooth, but nodular and variable in thickness. C, Color kinetic map also shows interval change. A region of interest has been placed on the nodular medial component (colored yellow). D, Curve (signal intensity–time curve) shows intense early enhancement with plateauing.

FIGURE 9 Final ultrasound, obtained at the conclusion of neoadjuvant chemotherapy, also reflects the waxing and waning variable appearance of this tumor. Partial reaccumulation of a cystic component is seen, with persistent solid tissue peripherally and vascularity.

FIGURE 10 Axial early (minute 1) enhanced, subtracted, maximal intensity projection images from the dynamic series of three breast MRIs, for comparison. A, At initial diagnosis, before neoadjuvant chemotherapy. The dominant left lateral IDC is large relative to the patient’s overall breast size. A lobular, biopsy-proven fibroadenoma is seen in the posterior right lateral breast against the pectoral muscle. B, Midway through chemotherapy, after four cycles of AC, the left breast IDC appears considerably improved. An early, enhancing 1-cm component is seen, with a stable appearance of the known right breast fibroadenoma. C, Final breast MRI, after four cycles of AC and four cycles of Taxotere, shows regrowth of the left IDC on Taxotere, partly because of reaccumulation of cyst fluid. The overall mass is still smaller than the pretreatment baseline. The right fibroadenoma is unchanged.

The patient was successfully treated with a lumpectomy, followed by radiation therapy to the breast and supraclavicular region (owing to the high position of the index lesion). Final pathology of the partial mastectomy specimen showed a 1.8-cm residual high-grade (grade 9/9) IDC, with negative margins. One sentinel lymph node was negative for tumor. Final stage was stage II, T2N0M0.

TEACHING POINTS

This case is interesting from multiple vantage points. Because of the patient’s youth, the workup of the palpable mass started with ultrasound, as is appropriate. At first glance with ultrasound, the cystic portions of this mass are deceptively innocent looking. However, the identification of solid components mandates further evaluation. The sonographic differential includes malignancies (intracystic carcinoma, papillary carcinoma) and benign diagnoses (post-traumatic resolving hematoma or seroma, abscess, papilloma and complex cyst). How best to sample such a complex mass, with both cystic and solid components? Options to consider include excision, cyst aspiration under ultrasound guidance, core needle biopsy with ultrasound guidance or some combination, as was performed here. Considerations at the time of image-guided sampling include whether and in which order to sample the fluid and the solid components. In this case, the solid component was sampled with 14-gauge core needle biopsy technique, followed by aspiration of the fluid, which was bloody. If aspiration was performed first, many advocate stopping the aspiration before completion if bloody fluid is obtained, with consideration of placing a marker clip if there is no visible residual. Aspiration alone with cytologic evaluation of the fluid runs the risk of a false-negative result, indicating the need for sampling of the solid component.

Performance of bilateral breast MRI effectively screens the opposite breast for cancer, but as in this case, runs the risk of identifying additional findings that may or may not be significant and that may engender additional workups and biopsies. Here, the right breast MRI findings were suggestive of a fibroadenoma, and an ultrasound correlate with a corresponding appearance is also consistent with that diagnosis, as was subsequently proved by biopsy.

This case also demonstrated a waxing and waning response to neoadjuvant chemotherapy. The initial response to AC was encouraging, but repeat imaging after completion of four cycles of Taxotere showed evidence of regrowth. There was nevertheless an overall decline in the size of the mass, making the patient a better candidate for breast conservation, which was successfully achieved with lumpectomy to clear margins.

CASE 12 LABC, unresponsive to neoadjuvant chemotherapy

A 46-year-old premenopausal woman presented with a palpable periareolar lump for 1 month, with nipple retraction. Mammography identified a 2- to 3-cm spiculated mass at 6 o’clock (Figure 1), and ultrasound showed a corresponding shadowing 2.1-cm mass (Figure 2). Ultrasound-guided core needle biopsy confirmed invasive carcinoma with tubular and lobular features.

FIGURE 1 Mammograms [MLO (A) and CC (B)] obtained for evaluation of a palpable lump and nipple retraction on the right (marked) show a spiculated dominant mass behind the nipple.

FIGURE 2 Ultrasound of the right palpable lump shows a highly suspicious corresponding mass: shadowing, hypoechoic, with irregular margins and disruption of the normal breast architecture.

Breast MRI showed the mass to be even larger than previously suspected, with the maximal dimension estimated to be 6 cm (Figure 3). Initial surgical assessment was that the patient was probably not a suitable breast conservation candidate because of the size of the palpable lump and proximity to the nipple. However, the patient desired an attempt at lumpectomy, and opted for neoadjuvant chemotherapy. After four cycles of chemotherapy with doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC), imaging re-evaluation with breast MRI was obtained. Only a modest response was noted, with the maximal dimension of the persistent spiculated mass estimated at 4.5 cm. Repeat breast MRI, 2 months later after three cycles of docetaxel (Taxotere), showed no change, with a persistent, intensely enhancing residual 4.5-cm mass (Figures 4, 5, and 6). By physical examination, the mass size was estimated at 2 cm. Mastectomy was again recommended, and declined. Following ultrasound-guided needle localization, a lumpectomy was performed. The specimen contained a 3.3-cm mixed infiltrating ductal carcinoma (IDC) with ductal and lobular features, estrogen receptor positive, progesterone receptor negative, and HER-2/neu negative. The medial margin was positive, and multiple additional margins were close. One of two lymph nodes was positive, with a 2-mm focus of tumor.

FIGURE 3 Prechemotherapy breast MRI shows a large, dominant, intensely enhancing spiculated central right breast mass.

FIGURE 4 Repeat breast MRI (maximal intensity projection view), 5 months later after neoadjuvant chemotherapy, shows little change, with a persistent, large, intensely enhancing residual mass.

FIGURE 5 Axial T2-weighted images from the prechemotherapy (A) and postchemotherapy (B) breast MRI show hypointense architectural distortion and mass, little changed over the two examinations.

FIGURE 6 Enhanced subtracted sagittal views, prechemotherapy (A) and postchemotherapy (B), show little change.

Subsequent mastectomy showed two microscopic foci of IDC (largest, 2 mm) and negative margins. Right chest wall, supraclavicular, and peripheral lymphatics were radiated subsequently. The patient was started on tamoxifen, which was not well tolerated, and switched to anastrozole (Arimidex) and subsequently to exemestane (Aromasin). No evidence of recurrence has been identified 2.5 years after diagnosis.

TEACHING POINTS

Not every patient responds to neoadjuvant chemotherapy with significant tumor shrinkage, as this case illustrates. Approximately 70% to 75% of patients do respond. There is prognostic information portended by the response to chemotherapy, with patients with large residual masses like this having significantly poorer prognoses than those who respond well.