MEDLINE Abstracts: PET Scanning and the Management of Breast Cancer

October 23, 2003

This feature showcases the latest breakthroughs in the use of positron emission tomographic (PET) scanning to diagnose and help manage breast cancer. For a snapshot in time of what the literature has to offer relating to this swiftly evolving technology, please navigate this collection of recent MEDLINE abstracts compiled by the editors at Medscape Radiology.

Baslaim MM, Bakheet SM, Bakheet R, Ezzat A, El-Foudeh M, Tulbah A
World J Surg. 2003 Aug 18

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. It can be diagnosed based on a clinical or pathologic basis. We evaluated the usefulness of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scans for diagnosing and staging IBC. We retrospectively reviewed the medical records of seven consecutive patients with IBC who underwent FDG-PET scanning for the initial staging. Four patients had follow-up PET scans after chemotherapy. All seven patients presented with diffuse breast enlargement, redness, and peau d'orange for 1 to 5 months' duration. In addition, four patients had a palpable breast mass, and three had axillary lymph node enlargement. Mammography showed diffuse, increased parenchymal density and skin thickening in 85% and parenchymal distortion in 43%. There was no evidence of distant metastasis on computed tomography of the chest or abdomen. Pathologic examination of breast biopsy specimens showed infiltrating ductal carcinoma in six patients, and one had lobular carcinoma. All patients had prechemotherapy whole-body PET scans that showed diffuse FDG uptake in the breast with superimposed intense foci in the primary tumor. Furthermore, there was skin enhancement in 100%, axillary lymph node in 85%, and skeletal metastases in 14% of the patients, confirmed by bone scintigraphy. Postchemotherapy FDG-PET scans performed in four patients showed response in the primary tumor, axillary lymph nodes, and skeletal metastases. The FDG-PET scan is thus useful for displaying the pattern of FDG breast uptake that reflects the extent of the pathologic involvement in IBC (i.e., diffuse breast involvement and dermal lymphatic spread). It can also detect the presence of lymph node and skeletal metastases, demarcating the extent of the disease locally as well as distally.

Nakamoto Y, Osman M, Wahl RL
Clin Nucl Med. 2003;28:302-307

Purpose: The aim of this retrospective study was to report the prevalence and imaging characteristics of bone metastases detected with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and, when possible, compare these findings with the performance of bone scans in the same patients.
Methods: The reports of 403 patients with histologically proved malignant disease who underwent a PET scan for initial or post-therapeutic staging were reviewed for the presence of possible bone metastases. Based on the final diagnosis confirmed by histopathologic analysis or clinical follow-up, the PET findings of patients with positive bone metastases were evaluated in terms of location, intensity, and patterns. When the PET scan was positive, the PET results were compared with the findings of available bone scans.
Results: PET studies suggested the presence of bone metastases in 38 patients (9%). No follow-up data were available for 9 patients, and the remaining 29 were evaluated further. Of these patients, 6 had false-positive findings, whereas bone metastatic involvement was clinically confirmed in 23 patients. The primary malignant findings included lung cancer (n = 9), esophageal cancer (n = 3), lymphoma (n = 2), melanoma (n = 2), thyroid cancer (n = 2), breast cancer (n = 1), colon cancer (n = 1), prostate cancer (n = 1), testicular cancer (n = 1), and nasopharyngeal cancer (n = 1). On PET, 5 patients had a solitary metastatic focus (22%), and the remaining 18 patients had multiple lesions (78%). The vertebrae were the most frequently involved bones (74%), followed by pelvic bones (70%), ribs (65%), upper extremities including the scapula (48%), sternum (43%), and lower extremities (43%). The patterns of abnormal uptake were classified into three groups: focal (15 patients, 65%), diffuse (2 patients, 9%), and a mixed pattern (6 patients, 26%). Most of the lesions showed intense abnormal uptake (18 patients, 78%); 5 patients had both intense and moderate FDG uptake. Thirteen of the 23 patients with confirmed bone metastases also had a bone scan, which revealed positive bone disease in all of these patients. However, PET consistently revealed more metastatic foci than did the bone scan on a lesion basis.
Conclusions: The most frequent pattern of detectable bone metastases with FDG-PET imaging was multiple foci of intense uptake. PET revealed more lesions than did bone scanning, independent of the type of cancer or location of bone involvement, in patients who were accurately diagnosed by FDG-PET imaging.

Zimny M, Siggelkow W
Curr Opin Obstet Gynecol. 2003;15:69-75

Purpose of Review: Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose represents a noninvasive functional imaging modality that is based on metabolic characteristics of malignant tumors. The recent findings of this technique in breast cancer, cervical cancer, ovarian cancer, and other gynecologic malignancies are discussed.
Recent Findings: In breast cancer, positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose is more accurate than conventional methods for the staging of distant metastases, enables early assessment of treatment response in patients undergoing primary chemotherapy. The diagnostic accuracy for axillary lymph node staging depends on the tumor load of the lymph nodes. The sensitivity of this technique in detecting primary breast cancer is limited in small breast lesions and invasive lobular cancer. In cervical cancer it is the most accurate noninvasive method for lymph node staging and it can accurately depict recurrent ovarian cancer in patients with elevated CA125 levels. False negative findings in well differentiated adenocarcinoma and borderline lesions as well as false positive findings in benign conditions limit the role of positron emission tomography scanning for the differential diagnosis of adnex tumors.
Summary: Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose reveals unique information about tumor metabolism in gynecologic malignancies and breast cancer. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the early assessment of treatment response in breast cancer and the detection of recurrent disease in ovarian cancer. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance.

Vranjesevic D, Filmont JE, Meta J, et al
J Nucl Med. 2002;43:325-329

This study was conducted to determine the ability of (18)F-FDG PET and conventional imaging (CI) to predict the outcomes in breast cancer patients who have previously undergone primary treatment.
Methods: The study population consisted of 61 female patients (median age, 54 y; range, 32--91 y) who were reevaluated with (18)F-FDG PET and CI after treatment. The median interval between the last treatment and PET was 0.4 y (range, 0--16 y). PET was performed within 3 mo of CI (median interval, 25 d; range, 2--84 d). To determine the independent impact of PET on outcome, PET images were reinterpreted in a blind fashion. Availability of clinical information after PET scanning (21 plus minus 12 mo) was required for study inclusion. Study endpoints were clinical evidence of progression of disease or death.
Results: Of 61 patients, 19 (31.1%) had no clinical evidence and 38 (62.3%) had evidence of residual or recurrent disease by the end of follow-up. Four patients (6.6%) had died. The positive and negative predictive values (PPV and NPV, respectively) of PET were 93% and 84%, respectively. CI yielded a PPV of 85% and an NPV of 59%. The prognostic accuracy of single whole-body PET was superior to that of multiple procedures with CI (90% vs. 75%; P < 0.05). Kaplan--Meier estimates of disease-free survival in patients with negative PET findings compared with those with positive PET findings revealed a significant difference between the 2 curves (log-rank test = 0.001). Kaplan--Meier estimates of disease-free survival stratified by CI results showed a marginally significant difference between CI-positive and CI-negative patients (log-rank test = 0.04).
Conclusion: FDG PET can be used to improve prediction of the clinical outcome of previously treated breast cancer patients relative to what is achievable through CI alone.

Czernin J, Phelps ME
Annu Rev Med. 2002;53:89-112

Whole-body positron emission tomography (PET) imaging with (18)F deoxyglucose (FDG) is a molecular imaging modality that detects metabolic alterations in tumor cells that are common to neoplastic cells. FDG-PET has recently been approved by the Health Care Finance Administration for Medicare reimbursement for diagnosing, staging, and restaging lung cancer, colorectal cancer, lymphoma, melanoma, head and neck cancer, and esophageal cancer. This review discusses the scientific evidence that led to the emergence of PET imaging as an accepted clinical tool in patients with solitary pulmonary nodules, lung cancer, colorectal cancer, melanoma, lymphoma, breast cancer, and other cancers. When possible, we compare the performance of PET to that of anatomical imaging. We discuss future clinical applications of this imaging modality.

Kelemen PR, Lowe V, Phillips N
Clin Breast Cancer. 2002;3:73-77

Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.

Burcombe RJ, Makris A, Pittam M, Lowe J, Emmott J, Wong WL
Eur J Cancer. 2002;38:375-379

To determine whether [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) can predict complete pathological response (pCR) in patients achieving a good clinical response to neoadjuvant chemotherapy for primary breast cancer, 10 patients underwent FDG PET scanning prior to definitive breast surgery. Scan reports were compared with histopathological findings. No abnormal uptake at the primary tumour site was visualised in any patient. 9 of the 10 patients had residual invasive carcinoma at operation, ranging from 2 to 20 mm in maximum dimension. One patient achieved a complete pathological response. Of the 5 patients who underwent axillary surgery, no axillary FDG uptake was seen preoperatively although 3 of the 5 were histologically node-positive. FDG PET did not reliably identify residual disease in this series of good clinical responders to neoadjuvant chemotherapy, and its discriminatory power as a tool to predict complete pathological response therefore appears to be inadequate for clinical use in this setting.

Blum R, Prince HM, Hicks RJ, Patrikeos A, Seymour J
Am J Clin Oncol. 2002;25:368-370

Positron emission Tomography (PET) is commonly used to stage malignancies and monitor response to treatment. This report describes two patients, one with metastatic breast cancer and the other with aggressive non-Hodgkin's lymphoma (NHL) whose responses to treatment were monitored by serial computed tomography and PET scans. In both cases after completion of systemic chemotherapy, repeat PET scanning revealed residual metabolically active tissue at the base of the neck. Because of differential therapeutic response, the possibility of different pathologic lesions was raised. In each case, further investigation with an ultrasound scan and needle biopsy revealed carcinoma of the thyroid. Both patients were subsequently treated with definitive surgery. In both described cases, a second primary malignancy was found that affected further management and in the second patient altered prognosis. This report concludes that residual metabolically active tissue on PET scans after treatment is not necessarily resistant primary disease. A mixed response requires further investigation, particularly in the case of persisting solitary abnormalities in the neck.

O'Sullivan JM, Cook GJ
Q J Nucl Med. 2002;46:152-159

Bone scintigraphy has provided valuable data in the assessment and management of neoplastic disease since being first described in the early 1960s. There have been many developments in imaging techniques and radiopharmaceuticals over the years allowing more reliable detection of metastatic spread to bone. Other imaging modalities are also evolving roles in the detection of metastatic spread including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Despite this, isotope bone scans continue to have a central role in detection and surveillance of bone metastases in breast and prostate cancer. Paralleling developments in imaging there have been enormous changes in the treatment options available for cancers of the breast and prostate that have metastasised to bone. Bone specific treatments including radionuclides and bisphosphonates as well as high dose chemotherapy provide potential improvement in disease control. There is also evidence that earlier treatment of bone metastases may prolong survival. This increases the need for efficient methods of detection and monitoring of disease. In this article we discuss the efficacy of bone scintigraphy in breast and prostate cancer from the point of view of staging, systematic follow-up of asymptomatic patients, evaluation of symptomatic patients and the assessment of response to therapy.

Gennari A, Donati S, Salvadori B, et al
Clin Breast Cancer. 2000;1:156-161; discussion 162-163

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.

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