PET and PET-CT Imaging of Breast Cancer: Initial Staging

PET and PET-CT imaging of Breast Cancer: Initial Staging

queline C. Brunetti, MD
Director of Radiology, Holy Name Hospital, Teaneck, NJ, and Associate Clinical Professor of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY.
Dr. Brunetti discloses a relationship with GE Healthcare, Chalfont St. Giles, U.K., as a member of their PET Board of Directors and also as a research grant recipient. She also receives research grant support from Siemens Healthcare, Malvern, PA.

There is minimal value in performing whole-body PET or PET-CT in patients with early-stage disease in whom the likelihood of metastatic disease is extremely low. The American Cancer Society reports the 5-year–survival rate for patients diagnosed at stages 0 and I is 100%. Current practice guidelines recommend breast conservation surgery followed by breast irradiation and hormonal blockade. In this patient group, imaging guidance for establishment of surgical margins and exclusion of multifocal disease is critical. Although MRI has been the standard in this scenario, PEM can also be utilized for presurgical planning to reduce the risk of positive margins due to DCIS or satellite lesions in those patients who are candidates for breast-conserving surgery.

For patients diagnosed with stage II disease, the 5-year survival is 86% with further reduction in survival to 57% at stage III and 20% at stage IV. These patients will frequently undergo preoperative chemotherapy, lumpectomy or total mastectomy with axillary lymph node dissection (ALND) followed by adjuvant chemotherapy. Tumor size, axillary lymph node status and histologic grade are 3 factors that determine prognosis in breast cancer. Positive lymph nodes are defined as those with metastatic foci >0.2 mm. Consequently, no currently available imaging modality is sufficiently accurate for axillary node staging. Some authors suggest, however, that when axillary nodes are demonstrated to be positive on PET and PET-CT, the positive-predictive value is sufficiently high to obviate the need for sentinel lymph node biopsy in those patients who are ALND dissection candidates.[16,17] As false-positive findings in the axilla can be seen in sarcoidosis, tuberculosis, rheumatoid arthritis and other inflammatory conditions, obtaining an accurate and complete patient history, along with careful evaluation of the size and biologic activity of the primary lesion as well as the pattern of nodal involvement is required before a confident diagnosis of axillary-nodal metastasis can be made. (Figure 3)

In patients who present with locally invasive disease, i.e., stage IIB and greater, PET-CT performed as part of an initial staging workup may alter therapy as a result of identification of distant metastatic disease. Fuster et al. compared preoperative PET-CT in patients with large (>3 cm) breast tumors with breast MRI, chest CT, liver ultrasonography and bone scan.[18] The sensitivity and specificity of PET-CT in detecting distant metastatic disease were 100% and 98%. For conventional imaging the sensitivity and specificity were 60% and 83%. The findings on PET-CT led to a change in staging in 42% of patients. Additional data supporting the use of PET in initial staging is reported by Cermik et al. in a prospective study of 271 patients with newly diagnosed breast cancer.[19] Extra-axillary nodal involvement was detected in 22 patients and distant metastatic disease in the absence of axillary metastasis was discovered in 5 patients. In 9.2% of patients, the tumor node metastasis (TNM) system stage was upgraded.

Heusner et al. have developed a single-session breast cancer staging protocol utilizing whole-body PET-CT and prone PET-CT mam-mography.[20] The authors compared the integrated PET-CT protocol with the diagnostic accuracy of a multimodality algorithm including MRI, axillary ultrasound, SLNB, bone scan, chest radiography and abdominal ultrasound for the initial staging of breast cancer in 40 patients. Findings relating to the primary tumor, ipsilateral nodes, distant metastases, extra-axillary nodes and management changes were evaluated. The sensitivity for detection of the primary breast tumor was 100% for MRI and 95% for PET-CT. PET-CT was more accurate in determining focality and correctly predicted the pattern in 26 of 33 patients, whereas MRI was correct in 24 of 33. PET-CT detected 80% of ipsilateral nodes compared to 70% discovered with clinical exam and ultrasound. In 3 patients PET-CT identified extra-axillary nodes missed by conventional imaging and correctly identified distant metastatic lesions in 10 patients, while conventional imaging identified 7 of 10. PET-CT findings resulted in therapeutic management change due to the detection of distant metastases in 5 patients, and synchronous colon and lung cancers in 2 patients.

The prognostic implications of the pattern of FDG uptake in breast cancer are an intriguing research topic as the relationship between FDG uptake and biologic behavior of breast cancer may provide a method of risk stratification. The number of viable tumor cells per volume, histologic subtype, tumor grade, microvessel density and proliferative activity, as well as the expression of GLUT-1 transporter and hexokinase I, all influence FDG uptake in breast cancer.[21] There is data to suggest that a poorer prognosis is associated with higher tumor SUVmax.[22–24] An association exists between FDG accumulation and key cellular factors that indicate cellular aggressiveness. Shimoda et al. compared SUVmax and the immunohistochemcal and pathological factors of 37 patients with breast carcinoma.[25] The authors found a strong correlation between FDG uptake and mitotic counts; and the percentage of cells positive for the Ki-67 protein, which is a product of the MKI67 gene, and nuclear grade. Whereas standard prognostic indicators of tumor size, histology, ER, PR and HER2/neu over-expression did not. Recently, Basu et al. reported a 100% sensitivity in detection of triple-negative [ER-/PR-/HER2/neu-] cancers utilizing dual–time-point FDG-PET imaging and higher uptake of FDG in comparison to ER+/PR+/HER2/neu-lesions.[26] Further investigation is needed to explore the clinical impact of these findings.