DOI: 10.1148/rg.245035062
RadioGraphics 2004;24:1269-1285
© RSNA, 2004
Thoracic Manifestations of Breast Cancer and Its Therapy1
Jung Im Jung, MD,
Hak Hee Kim, MD,
Seog Hee Park, MD,
Sun Wha Song, MD,
Myeong Hee Chung, MD,
Hyeon Sook Kim, MD,
Ki Jun Kim, MD,
Myeong Im Ahn, MD,
Soon Beom Seo, MD and
Seong Tai Hahn, MD
1 From the Department of Radiology, St Mary’s Hospital, College of Medicine, Catholic University of Korea, 62 Yeouido-dong, Youngdungpo-gu, Seoul 150–713, South Korea (J.I.J., S.H.P., S.W.S., M.H.C., H.S.K., K.J.K., M.I.A., S.T.H.); and the Department of Radiology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea (H.H.K., S.B.S.). Presented as an education exhibit at the 2002 RSNA scientific assembly. Received March 13, 2003; revision requested June 3 and final revision received December 19; accepted December 23. All authors have no financial relationships to disclose. Address correspondence to J.I.J. (e-mail: jijung@catholic.ac.kr).
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Abstract
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Breast cancer is the second most common cause of cancer-related death in women. In most patients, imaging demonstrates thoracic changes resulting from either treatment, complications of treatment, or tumor recurrence or metastasis. The postsurgical imaging appearance of the chest wall depends on the surgical method used (radical mastectomy, modified radical mastectomy, breast-conserving surgery, breast reconstruction). The most common surgery-related complication is seroma. Radiation therapy frequently causes radiation pneumonitis, which occurs approximately 4–12 weeks after the completion of therapy and is characteristically limited to the field of irradiation. Chemotherapy-related complications include cardiotoxicity, pneumonitis, and infection. Ultrasonography and computed tomography are more sensitive than physical examination for detecting local and regional recurrence. The thorax is a common site of metastasis, which may affect the lymph nodes, bone, lung, pleura, or heart and pericardium. Bone metastasis is usually evaluated with bone scintigraphy and may cause spinal cord compression, a serious complication that requires early diagnosis. Intrapulmonary metastasis may manifest as single or multiple pulmonary nodules, airspace pattern metastasis, lymphangitic metastasis, or endobronchial metastasis. Pleural metastasis usually manifests as pleural effusion, with or without a pleural mass. Familiarity with the spectrum of radiologic findings in breast cancer patients allows accurate image interpretation and correct diagnosis.
© RSNA, 2004
Index Terms: Breast, diseases, 00.32 • Breast, surgery • Breast neoplasms, 00.32 • Breast neoplasms, metastases, 00.32 • Breast neoplasms, postoperative • Breast neoplasms, surgery • Breast neoplasms, therapy • Chemotherapy, complications • Lung neoplasms, metastases, 60.33 • Lymphatic system, neoplasms, 99.33 • Radiations, injurious effects • Surgery, complications, 00.458
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LEARNING OBJECTIVES FOR TEST 2
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After reading this article and taking the test, the reader will be able to:
- Describe the changes in chest wall anatomy after breast cancer surgery.
- Discuss the radiologic features of a variety of treatment-related thoracic complications of breast cancer.
- Recognize the common imaging features of thoracic metastasis in breast cancer.
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Introduction
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Breast cancer is a common cancer in women and is second only to lung cancer as a cause of cancer-related death in women (1). Thoracic imaging changes resulting from either treatment or tumor recurrence are seen in most patients with breast cancer, and the thorax is a common site of metastasis. Treatment options including surgical resection, radiation therapy, and chemotherapy often produce thoracic abnormalities. In this article, we review the variety of thoracic manifestations that can be encountered by radiologists involved in the treatment of patients with breast cancer. These manifestations include those related to treatment or complications of treatment (surgery, radiation therapy, chemotherapy), to tumor recurrence, or to metastasis to lymph nodes, bone, lung, pleura, or heart and pericardium.
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Treatment-related Manifestations
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Surgery
Surgical treatment is used primarily for potentially curable cancer that is confined to the breast and regional lymph nodes. The approach to operable breast cancer has changed dramatically over the past century. Improved detection with screening mammography and heightened clinical awareness on the part of physicians and women have led to a dramatic decrease in the size of tumors at detection and thus have significantly altered the surgical management of breast cancer. In addition, the realization that 90% of treatment failures are attributable to systemic or visceral recurrences has led surgical oncologists to explore alternatives to radical mastectomy as an initial approach for treating operable breast cancer. Therefore, there has been a trend toward breast-conserving surgery (BCS) in this setting (2).
Radical Mastectomy.—
In radical mastectomy, the breast and underlying pectoralis muscles are removed, leaving a bare chest wall (Fig 1). Regional lymph nodes along the axillary vein up to the costoclavicular ligament are also removed. Extended radical mastectomy is standard radical mastectomy that also includes en bloc removal of internal mammary nodes. However, extended radical mastectomy is no longer performed because it failed to provide evidence of improved clinical outcome (2).
Modified Radical Mastectomy.—
Modified radical mastectomy (MRM) combines total mastectomy with removal of axillary lymph nodes in continuity with the mastectomy specimen. It is the most widely used procedure for treating operable breast cancer and is the alternative to BCS (2). MRM leaves the pectoralis major muscle intact, providing a soft-tissue covering over the chest wall and a normal-appearing junction at the shoulder (2). There are two forms of MRM: the Patey procedure (3) (and its modifications as described by Scanlon [4]), and the procedure described by Auchincloss (5).
Patey (3) developed a procedure in which the pectoralis major muscle is preserved and the underlying pectoralis minor muscle and apical nodes in the axilla are removed. Results of the large number of Patey procedures that have been performed indicate that patients have a survival rate similar to that of patients who undergo radical mastectomy. With the Patey procedure, the lateral pectoral nerve is occasionally injured, resulting in denervation and atrophy of the pectoralis major muscle (Fig 2) (6). Scanlon (4) modified the Patey procedure by dividing but not removing the pectoralis minor muscle, thus allowing the removal of apical nodes and preservation of the lateral pectoral nerves to the major muscle.
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Figure 2a. Right-sided modified Patey procedure. CT scans demonstrate absence of the pectoralis minor muscle ( in a) and atrophy of the pectoralis major muscle (arrows in b) on the right side. Note also the metastatic pleural masses on the right side.
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Figure 2b. Right-sided modified Patey procedure. CT scans demonstrate absence of the pectoralis minor muscle ( in a) and atrophy of the pectoralis major muscle (arrows in b) on the right side. Note also the metastatic pleural masses on the right side.
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The procedure described by Auchincloss (5) differs from the Patey procedure in that the pectoralis minor muscle is not removed or divided (Fig 3). This modification limits the complete removal of the highest axillary nodes but is justified by Auchincloss, who calculated that only 2% of patients would potentially benefit from removal of these nodes. The Auchincloss mastectomy method was the most popular surgical procedure for breast cancer treatment during the past decade (2).
Breast-conserving Surgery.—
BCS is defined as excision of the primary breast tumor and adjacent breast tissue (Fig 4). BCS is also commonly referred to as lumpectomy, partial mastectomy, or segmental mastectomy. In modern practice, these more limited surgical procedures are performed as part of a multidisciplinary approach to breast cancer treatment and usually include postoperative radiation therapy (7). BCS may or may not be accompanied by axillary lymph node dissection, depending on histologic findings in the tumor (invasive cancer vs carcinoma in situ) (7,8). Axillary node metastasis occurs in fewer than 5% of patients with ductal carcinoma in situ and is likely due to the presence of unrecognized invasive carcinoma. Hence, axillary node dissection is not routinely performed in patients with ductal carcinoma in situ (8). In patients with invasive cancer, axillary node dissection is accomplished with a separate incision. Recently, sentinel node biopsy (sentinel lymph node dissection) has become popular as an alternative to axillary node dissection (7). Lymphatic mapping for sentinel node dissection can be accomplished with 1% isosulfan blue dye or radiolabeled colloids. Typically, a combination of technetium-99m sulfur colloid and dye is used (7). Lymphoscintigraphy shows a sentinel node as a "hot spot" preoperatively (9).
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Figure 4a. Left-sided BCS. CT scans show volume loss of glandular tissue and adjacent linear strands at the lumpectomy site (arrow in a) and loss of soft tissue at the left axillary node dissection site (arrow in b).
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Figure 4b. Left-sided BCS. CT scans show volume loss of glandular tissue and adjacent linear strands at the lumpectomy site (arrow in a) and loss of soft tissue at the left axillary node dissection site (arrow in b).
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Generally, BCS or breast preservation in patients with invasive breast cancer involves wide local excision of the primary tumor, whole breast irradiation, and a separate axillary node dissection (2).
Breast Reconstruction.—
The techniques of breast reconstruction have evolved and matured over the past 25 years. Recent studies have proved the benefit of breast reconstruction for breast cancer patients (10). Methods of breast reconstruction include implant reconstruction and autologous tissue reconstruction.
Breast reconstruction with use of implants is the simplest technique. Permanent implants are placed beneath the pectoralis muscle and laterally beneath the anterior aspect of the serratus anterior muscle after tissue expansion. The permanent implants may be filled with either saline solution or silicone gel. Over the past 10 years, the majority of breast reconstruction procedures have involved saline solution implants (10).
The latissimus dorsi myocutaneous flap technique was the method of choice for autologous tissue breast reconstruction until the introduction of the transverse rectus abdominis musculocutaneous (TRAM) flap technique. The latissimus dorsi muscle with an overlying skin ellipse can be transferred from the back to the breast area. An implant placed beneath the flap is usually necessary to provide adequate bulk for the breast reconstruction (11).
Currently, the TRAM flap technique is the most commonly used procedure for autologous tissue breast reconstruction (10). The advantage of the TRAM flap procedure is that it provides adequate soft-tissue bulk to allow breast reconstruction without the use of implants. Subcutaneous fat from the abdominal wall and all or part of one or both rectus abdominis muscles are transferred to the chest wall to reconstruct the breast as a pedicle or free flap (12).
CT findings in the TRAM flap technique have been reported (13). The shape of the TRAM flap is the same as that of the native breast. However, fat attenuation is predominant in the TRAM flap at CT, as opposed to the irregular soft-tissue attenuation of fibroglandular tissue mixed with fat seen in the native breast. The thin, curvilinear soft-tissue band seen within the reconstructed breast represents de-epithelialized skin from the abdominal wall. The fat-attenuation tissue superficial to this band represents adipose tissue in the native chest wall, and the fat-attenuation tissue deep to the band represents adipose tissue transposed from the abdominal wall (Fig 5). The thin band that extends to the skin surface represents the transition from full-thickness TRAM flap skin to the de-epithelialized skin that is tunneled under the native chest wall skin and subcutaneous tissue. Although this band may appear thick within a month of surgery, persistent thickening or the development of new thickening should raise suspicion for infection, inflammation, or recurrent breast cancer (13).
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Figure 5. TRAM flap reconstruction of the right breast after MRM for breast cancer in a 38-year-old woman. CT scan shows the breast with fat attenuation. Note the thin, curvilinear soft-tissue band (arrows), which represents skin from the abdominal wall.
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Surgery-related Complications
Complications secondary to surgery include seroma, infection, hemorrhage, flap necrosis, lymphedema, and axillary contracture (14,15).
Seroma is a serous fluid collection in the axillary dead space or over the anterior chest wall; it is the most common complication of breast surgery, with reported rates as high as 60% (16,17). Seroma appears as an anechoic fluid collection at ultrasonography (US) and as a low-attenuation mass at CT (Fig 6). Seroma is generally treated with aspiration performed once or twice. Long-standing seromas are reported to develop a serosal lining that prevents healing and dead space closure (18). Although not life threatening or serious, seromas can and do hinder the recovery phase of a patient and may even delay continued care.
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Figure 6a. Seroma in a 43-year-old woman who had undergone BCS 2 months earlier. (a) CT scan shows a well-defined, ovoid, low-attenuation mass at the surgery site. (b) US image reveals that the lesion is an anechoic fluid collection. Clear, yellowish fluid was aspirated.
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Figure 6b. Seroma in a 43-year-old woman who had undergone BCS 2 months earlier. (a) CT scan shows a well-defined, ovoid, low-attenuation mass at the surgery site. (b) US image reveals that the lesion is an anechoic fluid collection. Clear, yellowish fluid was aspirated.
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Wound infection is the second most common complication (14). In one large series, the overall infection rate was 3.6% (19), with thin skin flaps and compromised lymphatic drainage produced by axillary node dissection predisposing the wound to infection. Infection was characterized by either cellulitis or tissue suppuration. Staphylococcus aureus and S epidermidis were seen in cultures. Cellulitis always responded to antibiotic therapy. Abscess secondary to a necrotizing infection was relatively minor, and aggressive wound management resulted in healing of the abscess (14,15).
At US, cellulitis manifests as diffuse soft-tissue swelling with a linear pattern of entrapped fluid; at CT, it can manifest as diffuse linear strands of soft tissue. At US, abscess manifests as a complex, predominantly cystic structure with internal echogenicity that exhibits through transmission. At CT, abscess manifests as a low-attenuation fluid collection with thick, shaggy, irregular enhancing walls. A mild degree of enhancement can be noted in the tissue around an inflamed abscess (Fig 7).
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Figure 7. Right breast cancer in a 59-year-old woman who had undergone BCS 1 month earlier. The patient complained of swelling, with local heat and redness of the surgical wound. Contrast material-enhanced CT scan shows a low-attenuation fluid collection with an air-fluid level and diffuse, thick wall enhancement. S aureus was seen in the culture of the aspirated pus specimen.
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Radiation Therapy– related Complications
Radiation therapy is widely used in postoperative breast cancer patients to reduce the risk of locoregional recurrence and to decrease the tumor volume in advanced cases (20–22). Radiation pneumonitis usually occurs approximately 4–12 weeks after completion of radiation therapy. Initially, diffuse haziness develops in the irradiated region. Patchy consolidations appear and coalesce to form an area with a relatively sharp edge that conforms to the shape of the treatment portals. These manifestations may gradually clear or completely disappear but may lead to fibrous changes, which take 6–24 months to evolve but usually remain stable after 2 years (23).
The radiographic changes in radiation pneumonitis are generally confined to the field of irradiation, although there have been reports of extensive radiation pneumonitis occurring outside the treatment portals (24,25). There are three radiation portals that induce radiation pneumonitis in breast cancer patients: the tangential beam portal, the supraclavicular portal, and the internal mammary portal (26).
Tangential beam radiation portals are frequently used to irradiate the chest wall. Typically, a 1.5–3-cm strip of underlying peripheral lung is included in the irradiated filed. Radiation pneumonitis occurs in the peripheral lung anterolaterally, has a characteristic shape, and is better visualized at CT than at chest radiography (Fig 8) (27,28).
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Figure 8a. Left breast cancer in a 31-year-old woman who had undergone BCS and irradiation. (a) Portal radiograph demonstrates a tangential beam radiation field. (b) Radiograph obtained 4 months after completion of radiation therapy shows ill-defined haziness in the lateral part of the left midlung (arrow). (c) CT scan obtained 4 months after the radiograph in b demonstrates consolidation with a sharp posterior margin peripherally in the left upper lobe (arrows) that conforms to the shape of the tangential beam radiation field.
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Figure 8b. Left breast cancer in a 31-year-old woman who had undergone BCS and irradiation. (a) Portal radiograph demonstrates a tangential beam radiation field. (b) Radiograph obtained 4 months after completion of radiation therapy shows ill-defined haziness in the lateral part of the left midlung (arrow). (c) CT scan obtained 4 months after the radiograph in b demonstrates consolidation with a sharp posterior margin peripherally in the left upper lobe (arrows) that conforms to the shape of the tangential beam radiation field.
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Figure 8c. Left breast cancer in a 31-year-old woman who had undergone BCS and irradiation. (a) Portal radiograph demonstrates a tangential beam radiation field. (b) Radiograph obtained 4 months after completion of radiation therapy shows ill-defined haziness in the lateral part of the left midlung (arrow). (c) CT scan obtained 4 months after the radiograph in b demonstrates consolidation with a sharp posterior margin peripherally in the left upper lobe (arrows) that conforms to the shape of the tangential beam radiation field.
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The supraclavicular portal is positioned with the inferior border at the first or second intercostal space. The medial border is 1 cm across the midline, extending upward and following the medial border of the sternocleidomastoid muscle to the thyrocricoid groove. The lateral border appears as a vertical line at the level of the anterior axillary fold (26). When supraclavicular portals are used, radiation-induced change occurs in the apex of the lung; the resulting lesions are similar to those seen in pulmonary tuberculosis (Fig 9) (23).
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Figure 9a. Left breast cancer in a 66-year-old woman who had undergone MRM and irradiation. (a) Portal radiograph demonstrates a supraclavicular field. (b) Radiograph obtained 4 months following completion of radiation therapy shows ill-defined consolidation in the left apex (arrows). (c) CT scan shows ill-defined patchy consolidations in the left apex. (d) Follow-up chest radiograph shows some linear areas of increased opacity in the left apex (arrow), a finding that mimics tuberculous scar. (e) CT scan obtained 15 months later shows regression of the areas of increased opacity in d into a dense, bandlike fibrosis.
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Figure 9b. Left breast cancer in a 66-year-old woman who had undergone MRM and irradiation. (a) Portal radiograph demonstrates a supraclavicular field. (b) Radiograph obtained 4 months following completion of radiation therapy shows ill-defined consolidation in the left apex (arrows). (c) CT scan shows ill-defined patchy consolidations in the left apex. (d) Follow-up chest radiograph shows some linear areas of increased opacity in the left apex (arrow), a finding that mimics tuberculous scar. (e) CT scan obtained 15 months later shows regression of the areas of increased opacity in d into a dense, bandlike fibrosis.
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Figure 9c. Left breast cancer in a 66-year-old woman who had undergone MRM and irradiation. (a) Portal radiograph demonstrates a supraclavicular field. (b) Radiograph obtained 4 months following completion of radiation therapy shows ill-defined consolidation in the left apex (arrows). (c) CT scan shows ill-defined patchy consolidations in the left apex. (d) Follow-up chest radiograph shows some linear areas of increased opacity in the left apex (arrow), a finding that mimics tuberculous scar. (e) CT scan obtained 15 months later shows regression of the areas of increased opacity in d into a dense, bandlike fibrosis.
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Figure 9d. Left breast cancer in a 66-year-old woman who had undergone MRM and irradiation. (a) Portal radiograph demonstrates a supraclavicular field. (b) Radiograph obtained 4 months following completion of radiation therapy shows ill-defined consolidation in the left apex (arrows). (c) CT scan shows ill-defined patchy consolidations in the left apex. (d) Follow-up chest radiograph shows some linear areas of increased opacity in the left apex (arrow), a finding that mimics tuberculous scar. (e) CT scan obtained 15 months later shows regression of the areas of increased opacity in d into a dense, bandlike fibrosis.
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Figure 9e. Left breast cancer in a 66-year-old woman who had undergone MRM and irradiation. (a) Portal radiograph demonstrates a supraclavicular field. (b) Radiograph obtained 4 months following completion of radiation therapy shows ill-defined consolidation in the left apex (arrows). (c) CT scan shows ill-defined patchy consolidations in the left apex. (d) Follow-up chest radiograph shows some linear areas of increased opacity in the left apex (arrow), a finding that mimics tuberculous scar. (e) CT scan obtained 15 months later shows regression of the areas of increased opacity in d into a dense, bandlike fibrosis.
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Internal mammary lymph nodes are irradiated with an anteroposterior or oblique beam angle to match the medial tangential beam portal. The medial border of the internal mammary field is the midline. The lateral border is usually 5 cm lateral to the midline, the superior border abuts the inferior border of the supraclavicular field, and the inferior border is at the xiphoid process (26). When internal mammary portals are used, radiation-induced change occurs in the paramediastinal region (Fig 10) (27).
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Figure 10a. Recurrent breast cancer in the chest wall in a 39-year-old woman who had undergone MRM. (a) Chest radiograph obtained 3 months following completion of radiation therapy shows ill-defined consolidations in the medial portion of the right lung that conform to the internal mammary field. (b) Follow-up chest radiograph obtained 1 month later shows resolution of the pneumonia and some residual linear areas of increased opacity.
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Figure 10b. Recurrent breast cancer in the chest wall in a 39-year-old woman who had undergone MRM. (a) Chest radiograph obtained 3 months following completion of radiation therapy shows ill-defined consolidations in the medial portion of the right lung that conform to the internal mammary field. (b) Follow-up chest radiograph obtained 1 month later shows resolution of the pneumonia and some residual linear areas of increased opacity.
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When pulmonary areas of increased opacity are seen at follow-up radiography in patients treated with radiation therapy, the differential diagnosis includes radiation pneumonitis, local recurrence, lymphangitic tumor spread, and infectious pneumonitis (29,30).
Chemotherapy-related Complications
The major cytotoxic agents used to treat breast cancer are cyclophosphamide, methotrexate, 5-fluorouracil, and doxorubicin (31). Signs and symptoms of toxicity are usually short-lived and include nausea, vomiting, mucositis, alopecia, and neutropenia, most of which resolve spontaneously on completion of treatment. Other pathologic conditions can have more of an impact on decisions regarding adjuvant treatment and include thromboembolic disease, cardiac dysfunction from anthracyclines, cognitive dysfunction, leukemia, premature menopause, and neuropathy (32).
Cardiotoxicity from doxorubicin is dose dependent, and its prevalence varies from 1% to 5% if the cumulative dose is limited to less than 500 mg/m2. Cardiotoxicity may manifest as acute, subacute, or chronic cardiomyopathy effects. Acute effects are usually associated with the infusion of doxorubicin and include supraventricular arrhythmias, ventricular premature beats, and reversible ST segment increases. Subacute effects are rarely seen but can be severe or even fatal and are associated with transient episodes of severe left ventricular (LV) dysfunction or a pericarditis-myocarditis syndrome (Fig 11). Chronic effects include late-onset ventricular dysfunction and arrhythmias, which manifest years to decades after treatment with doxorubicin has been completed (33–35).
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Figure 11a. Doxorubicin-induced cardiotoxicity in a 46-year-old woman who had undergone left MRM and adjuvant chemotherapy that included four cycles of doxorubicin. (a) Chest radiograph shows enlargement of the cardiac silhouette. (b) Chest CT scan shows global enlargement of the cardiac chambers and a small amount of pericardial effusion (arrows). Echocardiography demonstrated a decreased LV ejection fraction (25%) with severe LV dysfunction and LV dilatation, as well as enlargement of both atria. The total cumulative dose of doxorubicin was 360 mg/m2.
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Figure 11b. Doxorubicin-induced cardiotoxicity in a 46-year-old woman who had undergone left MRM and adjuvant chemotherapy that included four cycles of doxorubicin. (a) Chest radiograph shows enlargement of the cardiac silhouette. (b) Chest CT scan shows global enlargement of the cardiac chambers and a small amount of pericardial effusion (arrows). Echocardiography demonstrated a decreased LV ejection fraction (25%) with severe LV dysfunction and LV dilatation, as well as enlargement of both atria. The total cumulative dose of doxorubicin was 360 mg/m2.
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High-dose chemotherapy with autologous bone marrow transplantation is now being widely used to treat advanced or metastatic breast cancer. Pulmonary complications after bone marrow transplantation include infections (Fig 12), pneumonitis caused by chemotherapy or radiation therapy, diffuse alveolar hemorrhage, and idiopathic interstitial pneumonitis. Pulmonary drug toxicity occurs in 31%–58% of patients who undergo high-dose chemotherapy with autologous bone marrow transplantation (36,37). Dyspnea, cough, and fever are also common and, on average, develop 60–70 days following bone marrow reinfusion. Chest radiographs are normal in many of these patients, although CT reveals parenchymal abnormalities in 3%–65% of cases. The most common CT manifestations of pulmonary drug toxicity are peripheral ground-glass attenuation or consolidation that occasionally appears nodular or mass-like (36).
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Figure 12a. Pneumonia in a 46-year-old woman with breast cancer who had undergone high-dose chemotherapy and autologous bone marrow transplantation. (a) Chest radiograph shows ill-defined consolidation in the right cardiophrenic angle. (b) CT scan shows a triangular enhancing consolidation with round, well-defined, low-attenuation necrosis in the right middle lobe, findings that suggest pneumonia with abscess formation. The white blood cell count was 1200/mm3. The causative organism was not identified. (c) Radiograph obtained after empirical treatment with antibiotics shows complete resolution of the pneumonia.
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Figure 12b. Pneumonia in a 46-year-old woman with breast cancer who had undergone high-dose chemotherapy and autologous bone marrow transplantation. (a) Chest radiograph shows ill-defined consolidation in the right cardiophrenic angle. (b) CT scan shows a triangular enhancing consolidation with round, well-defined, low-attenuation necrosis in the right middle lobe, findings that suggest pneumonia with abscess formation. The white blood cell count was 1200/mm3. The causative organism was not identified. (c) Radiograph obtained after empirical treatment with antibiotics shows complete resolution of the pneumonia.
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Figure 12c. Pneumonia in a 46-year-old woman with breast cancer who had undergone high-dose chemotherapy and autologous bone marrow transplantation. (a) Chest radiograph shows ill-defined consolidation in the right cardiophrenic angle. (b) CT scan shows a triangular enhancing consolidation with round, well-defined, low-attenuation necrosis in the right middle lobe, findings that suggest pneumonia with abscess formation. The white blood cell count was 1200/mm3. The causative organism was not identified. (c) Radiograph obtained after empirical treatment with antibiotics shows complete resolution of the pneumonia.
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Local and Regional Recurrence and Metastases
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Local and regional sites constitute the most common sites of soft-tissue recurrence of breast cancer. The most common distant sites of metastasis are bone and lung. Intrathoracic metastasis from breast cancer commonly involves the lungs, pleura, mediastinum, and airway (38).
Local recurrence is the reappearance of tumor at the surgical site. Regional recurrence is defined as the appearance of metastases in the lymph nodes that drain the breast, including the supraclavicular, axillary, and internal mammary nodes. The likelihood of local or regional recurrence is greater in patients who have not received postoperative radiation therapy and in those with large primary tumors, positive margins, multiple cancers at the time of initial presentation, and positive lymph nodes (38,39).
Local recurrence is evaluated primarily with physical examination that includes the surgical site, axilla, supraclavicular fossa, and neck. Mammography is an important adjunct to physical examination in the follow-up of breast cancer patients who have been treated with BCS. However, the ability of mammography to help detect local recurrence is compromised by the presence of postoperative distortion and the increased density of the irradiated breast. Mammography is able to help detect only two-thirds of recurrences in postlumpectomy patients (39). Rissanen et al (40) evaluated the usefulness of mammography and US for the diagnosis of local recurrence following mastectomy. The sensitivity of US was 91%, whereas the sensitivities of clinical examination and mammography were 79% and 45%, respectively.
CT has been shown to delineate more clearly than physical examination the extent of recurrent breast carcinoma following mastectomy and is of great value in treatment planning (41–43). CT findings in local recurrence include focally thickened skin to a depth greater than 1 cm (soft-tissue window); dense, mass-like accumulation of soft tissue within the subcutaneous fat; and obvious masses within the chest wall muscles (Fig 13). Contour irregularities or CT inhomogeneity of the muscle can indicate recurrence (43). Sometimes residual muscle also mimics local recurrence (Fig 14).
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Figure 13a. Local recurrence in a 55-year-old woman who had undergone MRM and irradiation 2 years earlier. (a) Chest CT scan shows a 1.5-cm enhancing nodule in the right pectoralis major muscle at the mastectomy site (arrow). (b) US image shows an irregular hypoechoic nodule (arrows). The mass was not palpated at physical examination.
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Figure 13b. Local recurrence in a 55-year-old woman who had undergone MRM and irradiation 2 years earlier. (a) Chest CT scan shows a 1.5-cm enhancing nodule in the right pectoralis major muscle at the mastectomy site (arrow). (b) US image shows an irregular hypoechoic nodule (arrows). The mass was not palpated at physical examination.
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Figure 14. Residual pectoralis muscle mimicking local recurrence in a 54-year-old woman who had undergone radical mastectomy. CT scan shows a residual pectoralis muscle (arrow). Note the small effusion in the dependent portion of the right side of the thorax, which proved to be reactive fluid.
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Lindfors et al (41) reported that in most patients CT not only allowed more accurate determination of disease extent than did physical examination, but also demonstrated additional, clinically unsuspected disease in 49% of patients. The most common site of clinically unsuspected disease was the internal mammary nodal chain.
The normal internal mammary lymph nodes are less than 5 mm in diameter and lie within 3 cm of the edge of the sternum, in the fat and areolar tissue on the endothoracic fascia of the spaces between the costal cartilages. Metastasis to internal mammary lymph nodes is not easily detected at physical examination, mammography, or US because of overlying muscular, cartilaginous, and osseous structures. Normal internal mammary nodes are not routinely identified at CT. Therefore, a lymph node greater than 6 mm in diameter visualized at CT in a patient with breast cancer can suggest malignant lymphadenopathy (Fig 15) (44).
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Figure 15. Chest wall recurrence in a 44-year-old woman who had undergone left MRM. CT scan shows chest wall recurrence (short arrows) in contiguity with right internal mammary lymph node metastasis (long arrow).
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Lymphatic drainage to the internal mammary nodal chain is an important pathway of disease spread, both at the time of initial diagnosis and following primary treatment of breast cancer. The prognosis for patients with internal mammary and axillary node metastases is significantly worse than that for patients with only axillary node disease, which suggests that the internal mammary nodal chain is a channel for more widespread dissemination of disease (45,46).
Lymph Nodes
Metastasis of breast cancer to intrathoracic nodes occurs frequently. An autopsy series by Thomas et al (47) of women who had died of disseminated breast cancer revealed metastatic involvement of intrathoracic lymph nodes in 71% of cases. Lymph node involvement was more extensive in the mediastinum ipsilateral to the primary breast cancer than in the contralateral mediastinum (46).
CT has been the main modality used to evaluate intrathoracic nodes (Fig 16), but this imaging technique, in which size is the main criterion used to assess nodal status, is limited by its poor sensitivity.
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Figure 16. Mediastinal lymph node metastasis in a 63-year-old woman who had undergone left MRM. CT scan shows enlarged lymph nodes in the anterior mediastinum in contiguity with internal mammary lymph nodes.
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Bone
The second most common site of distant metastasis is bone, and bone metastasis is detected in 31% of all patients with metastasis (38). Bone metastases cause considerable morbidity, including pain, impaired mobility, hypercalcemia, pathologic fracture, spinal cord or nerve root compression, and bone marrow infiltration (48).
At radiology, skeletal metastases can be lytic or sclerotic lesions or a combination of both. Radionuclide imaging is often performed to evaluate for possible skeletal metastases because it is more sensitive than radiology for the detection of these lesions (48). Widespread bone metastases from breast cancer can occasionally give rise to a uniform distribution of 99mTc methylene diphosphonate, resulting in a superficially normal-appearing bone scan. These "superscans" are recognizable by the high ratio of bone to soft-tissue activity, the absence of focal lesions in the axial skeleton, and, usually, the absence of renal activity (Fig 17) (49).
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Figure 17a. Bone metastasis in a 36-year-old woman with breast cancer. (a) Chest radiograph shows sclerosis of the ribs, clavicles, and vertebral bodies. (b) 99mTc methylene diphosphonate-labeled bone scintigram shows pronounced skeletal uptake and absent renal activity (superscan).
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Figure 17b. Bone metastasis in a 36-year-old woman with breast cancer. (a) Chest radiograph shows sclerosis of the ribs, clavicles, and vertebral bodies. (b) 99mTc methylene diphosphonate-labeled bone scintigram shows pronounced skeletal uptake and absent renal activity (superscan).
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The development of back pain in a cancer patient that coincides with an abnormality on a spine radiograph should serve as a warning of the possible development of spinal cord compression. Cord compression from malignant epidural disease requires early diagnosis and therapy, since the outcome is clearly better when treatment is started promptly (48). Breast cancer is the most common cause of cord compression in women (50). The most likely site of metastatic breast cancer to the spine with resulting cord compression is at the thoracic or lumbar level (51). Hence, the radiologist should be alert for a developing epidural mass at routine follow-up CT performed to evaluate for recurrence or metastasis (Fig 18). CT can accurately demonstrate epidural metastasis but is limited in the evaluation of vertebral involvement and parenchymal metastasis (eg, cerebrospinal fluid seeding or intramedullary involvement). Magnetic resonance imaging is the examination of choice for cancer patients with suspected spinal cord compression (52).
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Figure 18. Spinal cord compression from bone metastasis in a 55-year-old woman with breast cancer. Chest CT scan shows bone metastasis to the thoracic vertebrae manifesting as an epidural mass that compresses the spinal cord.
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Lung
Solitary Pulmonary Nodule.—
Development of a solitary pulmonary nodule in patients previously treated for breast cancer may represent something other than recurrent disease. Casey et al (53) found that 52% of breast cancer patients presenting with a solitary pulmonary nodule had primary lung cancer, 43% had metastatic breast cancer, and 5% had benign lesions. Histologic confirmation is necessary for appropriate staging and treatment (Fig 19).
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Figure 19. Solitary metastatic nodule in a 34-year-old woman who had undergone BCS 25 months earlier. Precontrast CT scan shows a solitary pulmonary nodule in the lingular segment of the left upper lobe. Wedge resection of the nodule revealed metastatic breast cancer.
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Multiple Pulmonary Nodules.—
Multiple pulmonary nodules are common findings in lung metastasis from breast cancer (38). They occur by means of hematogenous tumor spread. In general, metastatic lesions are spheric or ovoid, vary in size, are sharply marginated, and are located mostly in the periphery of the lung (Fig 20) (54–57).
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Figure 20. Multiple metastatic nodules in a 46-year-old woman with breast cancer. CT scan shows multiple round metastatic nodules. Note the cavitation of two of the nodules (arrows).
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Cavitation of metastatic nodules is rarely seen at radiography. However, cavitation in metastatic adenocarcinoma (including breast cancer) is frequently encountered at CT (Fig 20) (57,58). Chemotherapy occasionally induces cavitation in metastatic pulmonary nodules (59). The exact mechanism is usually difficult to determine, but the cause is presumed to be either tumor necrosis or a check-valve mechanism that develops by tumor infiltration of bronchial air-containing structures (58).
Airspace Pattern Metastasis.—
Metastases from an adenocarcinoma may spread into the lung along the intact alveolar walls (lepidic growth) in a fashion similar to a bronchioloalveolar carcinoma (60). The radiologic features of this tumor growth pattern can mimic pneumonia, especially in metastases from adenocarcinoma of the gastrointestinal tract (61). An airspace pattern of metastasis from breast cancer is infrequent but can occur. In one report, 9.4% of all breast cancers that metastasized to lung had a bronchioloalveolar carcinoma pattern at imaging (Fig 21) (60).
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Figure 21. Airspace pattern metastasis in a 55-year-old woman. Contrast-enhanced CT scan shows lobar consolidation with an air bronchogram of the left lower lobe (arrow) mimicking pneumonia. Biopsy revealed a metastatic tumor from breast cancer.
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Lymphangitic Metastasis.—
In an autopsy series by Connolly et al (56) of women who had died of disseminated breast cancer, 83% of patients had pulmonary lymphangitic metastases. Kreisman et al (62) reported that lymphangitic metastasis was the most frequently observed pulmonary manifestation in patients with thoracic metastases from breast cancer.
Radiologically demonstrable lymphangitic disease is rare compared with the results of large autopsy series. Radiographic findings in lymphangitic metastasis include reticular or reticulonodular interstitial markings, usually with an irregular contour, and thickening of the interlobar septa (Kerley B lines). Bilateral involvement is more common than unilateral lymphangitic spread (54). However, unilateral involvement occurs more frequently in breast cancer than in other malignancies (47,63).
High-resolution CT is the most sensitive imaging tool for the detection of lymphangitic metastasis. High-resolution CT shows irregular, sometimes nodular thickening of the interlobar septa and the peribronchovascular sheaths and thickening of the core structures in the central portions of the secondary pulmonary lobules (Fig 22) (64).
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Figure 22. Lymphangitic metastasis in a 47-year-old woman with breast cancer. High-resolution CT scan shows nodular thickening of the interlobular septa with prominent centrilobular structures.
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Endobronchial Metastasis.—
Breast cancer is the most common tumor causing endobronchial metastasis, accounting for approximately 63% of all such metastases (65). There are five possible routes for the pathogenesis of endobronchial metastasis: (a) mediastinal or hilar metastasis with bronchial extension, (b) parenchymal metastasis with bronchial involvement, (c) bronchial aspiration of tumor cells, (d) direct lymphatic metastasis to the bronchial wall, and (e) direct hematogenous metastasis to the bronchial wall (66). Endobronchial metastasis has the same clinical and radiologic appearance as primary bronchogenic carcinoma. Affected patients present with symptoms such as cough or dyspnea with or without radiologic findings of pulmonary nodules, pneumonitis, atelectasis, pleural effusion, and hilar lymphadenopathy. Although CT may not always demonstrate intraluminal lesions, it may reveal other manifestations of metastatic breast cancer such as hilar or mediastinal lymphadenopathy and single or multiple pulmonary metastatic deposits (Fig 23) (57).
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Figure 23. Endobronchial metastasis in a 47-year-old woman who had undergone left MRM. CT scan shows a lobulated endobronchial mass obstructing the left main bronchus (arrowhead), resulting in total collapse of the left lung. Pleural effusion is also seen (arrows), a finding that suggests pleural metastasis.
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Pleura
The pleura is a frequent target of metastatic breast cancer. Thomas et al (47) found metasta-ses to the visceral and parietal pleura in 75% and 50% of cases, respectively. Pleural effusion is the most common manifestation of pleural metastasis in patients with breast cancer. The effusion is more commonly unilateral and ipsilateral to the primary tumor (56). Thomas et al (47) explained that the laterality of pleural metastasis is due to lymphatic dissemination in breast cancer: The cancer spreads from the ipsilateral internal mammary nodes by lymphatic communications, and the lung, pleura, and pericardium become secondarily involved by lymphatic communications from metastatic mediastinal nodes. It would be expected that ipsilateral mediastinal nodes would become involved sooner than contralateral nodes because of the delay in tumor embolization or permeation across the mediastinum.
Chest radiography, CT, and US usually demonstrate free or loculated pleural effusion without any specific features in the effusion itself. Thoracentesis combined with pleural biopsy provides a diagnosis of malignant effusion. The fluid is usually an exudate with a glucose concentration lower than the corresponding serum value. The fluid may be bloody and contain a variable number of malignant cells. The size of the effusion may help suggest metastatic disease, with larger effusions more likely to be malignant (Fig 24a) (67).
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Figure 24a. Pleural metastasis. (a) Chest CT scan obtained in a 43-year-old woman with right breast cancer who presented with dyspnea shows a large amount of right pleural effusion with mass effect and total collapse of the right lung. Note the thin, even enhancement of the parietal pleura. (b) Chest CT scan obtained in a 44-year-old woman who had undergone left MRM and mammoplasty shows left pleural effusion and irregular plaquelike pleural enhancement (arrows).
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Figure 24b. Pleural metastasis. (a) Chest CT scan obtained in a 43-year-old woman with right breast cancer who presented with dyspnea shows a large amount of right pleural effusion with mass effect and total collapse of the right lung. Note the thin, even enhancement of the parietal pleura. (b) Chest CT scan obtained in a 44-year-old woman who had undergone left MRM and mammoplasty shows left pleural effusion and irregular plaquelike pleural enhancement (arrows).
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Pleural nodularity, irregular pleural thickening, and plaque are less common findings in pleural metastases and rarely occur without an accompanying pleural effusion (Figs 24a, 24b) (56).
Heart and Pericardium
Breast cancer is the most common extrathoracic primary neoplasm causing metastatic involvement of the heart and pericardium (67). Connolly et al (56) found pericardial and myocardial metastases in 18% and 5% of cases, respectively. Metastatic involvement of the pericardium is most commonly recognized when there is associated pericardial effusion. Chest radiographs most commonly show cardiomegaly in the absence of pulmonary vascular congestion. Echocardiography is the most sensitive and cost-effective method for detecting pericardial fluid. CT also easily demonstrates the presence of pericardial effusion, regardless of the amount, and may be the best alternative in patients in whom echocardiography is technically impossible because of pulmonary disease, obesity, or thoracic musculoskeletal deformities (68). When the pericardium is invaded by tumor, it becomes thickened, and generalized thickening or discrete nodular masses may be recognized at CT (Fig 25) (67).
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Figure 25. Pericardial metastasis in a 34-year-old woman who had undergone MRM. CT scan shows pericardial enhancement (arrows). Pericardial effusion had been drained earlier, and cytologic analysis of the aspirate revealed metastasis. Note the pleural metastasis in the left side of the thorax.
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Conclusions
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Abstract
LEARNING OBJECTIVES FOR TEST...
