Most breast cancer patients with intrathoracic metastases are asymptomatic, the exception being those with significant pleural effusions. Therefore, unless pleural, parenchymal, or nodal metastases are demonstrated at initial staging, thoracic metastases are most commonly found at the time of follow-up imaging. A significant number are found on chest x-rays done for other reasons. Isolated involvement of the lung or pleural space occurs in 15% to 25% of women with metastatic breast cancer.¹

Pulmonary metastases are typically peripheral,² and, if large enough, may be discovered on preoperative chest radiographs. Because of its low cost, chest radiography may be a reasonable choice as a baseline study or in follow-up; however, the extremely low yield, false-positive results, inferior sensitivity compared with CT, and lack of data supporting an outcome benefit limit routine use in follow-up.

CT is the preferred modality for investigation of thoracic metastases. CT has proven efficacy for detecting local, regional, and distant disease. Normal-sized internal mammary nodes are not visualized on CT, so a patient in whom CT identifies a node or nodes larger than 6 mm is at risk for malignant involvement.³ Because of the recognized problem of relying on size only to diagnose disease, positron emission tomography (PET)/CT is presently considered the modality of choice for assessing internal mammary nodes (Figure 1). In women who die from disseminated breast cancer, intrathoracic nodal metastases may occur in more than 70% of patients.⁴ As with internal mammary nodes, using size as the major criterion for disease identification reduces both sensitivity and specificity. Magnetic resonance imaging (MRI) can detect most lesions larger than 5 mm, does not expose the patient to ionizing radiation, and has acceptable imaging times; however, it is generally viewed as complementary to CT, rather than as a replacement for CT (Figure 2).^5–9 Cardiac and respiratory motion, reduced sensitivity for lesions smaller than 5 mm (compared with CT), calcified metastases, and suboptimal ability to assess lymphangitic spread are recognized limitations of MRI in the thorax.¹⁰

FIGURE 1 PET/CT images from an initial staging study of a 77-year-old woman with newly identified locally advanced infiltrating ductal carcinoma (IDC). Internal mammary nodal involvement is seen on the right. Normal internal mammary lymph nodes are not usually visualized on chest CT. This enlarged node, measuring 8 mm, is readily seen on CT and is hypermetabolic on PET. Although not biopsy proven, these imaging features are strong presumptive evidence of internal mammary nodal involvement. Seven of 12 axillary nodes were involved with tumor at surgery.

FIGURE 2 A, Breast MRI of a neglected, locally advanced left breast cancer with chest wall, skin, and nipple involvement shows a lung nodule on the right, suggesting possible stage IV disease (arrow). B, Chest CT confirmed a lung nodule, with an additional tiny subpleural nodule seen on this slice as well (arrowhead).

PET using fluorodeoxyglucose (FDG), an analogue of glucose, has assumed a primary role as a whole-body survey examination in many types of cancer, including breast. PET, and more recently PET/CT, excels at identifying the metabolic status of intrathoracic nodes, including internal mammary nodes, and solitary pulmonary nodules. Metabolic changes, resulting in pathologic or increased uptake on PET scan, can occur months before changes in size or shape. Additionally, it is now well recognized that lymph nodes larger than 10 mm may be benign or reactive, and lymph nodes smaller than 10 mm may represent metastases. With one important caveat, PET does not rely on the size of a lymph node or nodule to characterize it as benign or malignant. The caveat relates to the sensitivity of the PET/CT system based on lesion size. Presently, most scanners in clinical practice are able to reliably identify hypermetabolic foci down to about 8 mm. The addition of CT capability in PET/CT combination units will in many cases further improve sensitivity by allowing relatively precise image registration. The ability to confirm hypermetabolic activity in very small lesions may complicate reliance on the standardized uptake value (SUV). This calculated value is a measure of radioactivity in a lesion divided by the average value of radioactivity in the body, corrected for body weight. Many centers use a cut-off value of 2 to 2.5 or higher to indicate malignancy, with values less than 2 as evidence for benignity. The SUV is dependent on a multitude of factors, including serum glucose at the time of FDG injection, time between injection and imaging, and lesion size. Many investigators believe that any uptake above background in small (i.e., 5 to 7 mm) lesions should be regarded as suspicious for malignancy.

In one series of 73 patients who underwent FDG PET and CT for recurrent or metastatic disease, PET proved more sensitive (85% versus 50%) and specific (90% versus 83%) than CT. Also, PET uptake in mediastinal and internal mammary nodes was 2 times more prevalent than enlarged nodes on CT.¹¹ FDG PET has been shown to be significantly more accurate in staging the mediastinum in patients with non–small cell lung cancer, using histology as the gold standard.^12–13 Extrapolation of these data to patients with breast cancer may be problematic. It has been recognized that certain subtypes of breast cancer (e.g., invasive lobular, tubular, carcinoma in situ) show relatively low FDG uptake, resulting in reduced sensitivity compared with infiltrating ductal carcinoma (IDC) primary tumors.^14–15 Theoretically, patients whose initial staging FDG PET is negative in these tumor subtypes (especially if the primary has not been excised) may demonstrate reduced sensitivity for detection of metastases, including within the chest, on restaging studies.

Pleural involvement may be suspected based on clinical signs on physical examination or symptoms (e.g., cough, shortness of breath, pleuritic-type chest pain, orthopnea), the discovery of a pleural effusion on plain radiography or CT, or the identification of pleural abnormalities on CT or FDG PET (Figure 3). Pleural effusion is often unilateral and on the same side as the breast primary.¹⁶ The effusion can be confirmed by chest radiography, CT, or even ultrasound. Thoracentesis may be performed for both diagnostic and therapeutic purposes. If the result is nondiagnostic, or negative with a strong clinical suspicion of malignancy, consideration may be given to FDG PET imaging (preferably, PET/CT).

FIGURE 3 PET/CT axial images of a breast cancer patient with bilateral pleural metastases, more extensive on the left than the right. The pleural spaces extend far inferiorly, so that hypermetabolic pleural metastases appear to project in the periphery of the abdomen, overlapping the liver and spleen. The coronal projection image also shows a large, hypermetabolic left axillary lymph node.

FDG PET commonly identifies more pleural involvement than other imaging modalities and may be especially helpful in delineating the caudal extent of disease. The effusion itself tends to be only mildly positive on PET or frankly negative, presumably owing to the paucity of malignant cells relative to the volume of the effusion.

Many special circumstances exist with respect to the thoracic manifestations of breast cancer, reviewed in depth by Jung and associates.¹⁷ One important consideration is radiation therapy–related complications. Radiation pneumonitis typically occurs within 3 months of radiation therapy and progresses from diffuse haziness to coalescence of areas of consolidation to fibrous changes on chest x-ray or CT. Findings in the irradiated field may persist for months to years (Figure 4). Although PET/CT has demonstrated efficacy in separating scar from active tumor in many malignancies, its use following radiation therapy in the irradiated field may be problematic for months to 1 year or more. The heightened metabolic activity of activated monocytes at sites of radiation pneumonitis can last for a variable period of time, especially in the lung and with head and neck tumors. A negative FDG PET study at a site of postirradiation change on chest x-ray or CT is reassuring; however, a positive study must be interpreted with caution and reassessed or further investigated before initiation of additional tumor-targeted therapy.

FIGURE 4 Axial lung window chest CT image from a 56-year-old woman, 4 years after treatment for a high-risk IDC involving 19 of 26 lymph nodes with lumpectomy, axillary dissection, systemic chemotherapy, and radiation to the breast, axillary, and supraclavicular nodal basins, shows asymmetrical right apical radiation fibrosis. This was stable on imaging, corresponded to the radiation field, and showed stable, low-level activity on FDG PET.

The development of a solitary pulmonary nodule in patients who have been treated for breast cancer should not be assumed to be a breast recurrence without histologic proof. About half of these patients will have lung cancer, and a small percentage of cases will be benign.¹⁸ These patients are excellent candidates for PET/CT. Hypermetabolic uptake in the nodule directs the patient to tissue sampling (sometimes obviated by the finding of widespread metastases). Absent FDG uptake, as well as an otherwise negative study, may allow watchful waiting with short-term CT follow-up (e.g., 3 to 6 months). Recall the limitations of PET with respect to histology and lesion size.

Lymphangitic metastases are extremely common in women who die from breast cancer.¹⁹ CT is the imaging modality of choice for the identification of this process, which is most often bilateral (Figure 5). Findings include irregular thickening of the interlobar septa and peribronchovascular sheaths as well as thickening of the structures in the central regions of the secondary pulmonary lobules.²⁰

FIGURE 5 Axial lung window chest CT image from a 63-year-old woman with bone, thoracic, and brain metastases shows a large right pleural effusion. The lung parenchyma, particularly on the right, shows bronchovascular thickening and a finely nodular appearance of the interstitium, highly suggestive of lymphangitic tumor spread.