FDG-PET and Tumour Marker Tests for the Diagnosis of Breast Cancer

Abstract

Circulating tumour markers for breast cancer can be classified in different groups: mucins such as CA 15.3, CA 27.29 and CA 549, carcinoembryonic antigen (CEA), cytokeratins (TPA, TPs, Cyfra 21.1), enzymes (LDH), hormones and their subunits. All of them have been proposed over the years for the diagnosis and monitoring of breast cancer at different stages. It is well known that tumour marker tests lack in sensitivity at the earliest stage of cancer and also in specificity. False-negative results are rare in patients with advanced disease and metastases; on the contrary they are most frequent in the first stages. Besides this, false-positive results can be due to different nonmalignant conditions. At present CA 15.3 is the most widely used tumour marker in breast cancer patients. Its use follows the general concepts everywhere accepted for mucinic markers: the CA 15.3 test is not useful in screening and early diagnosis; it has an established role in the diagnosis of recurrences; it has an established role in therapy monitoring, alone or in association with other diagnostic tools; it is still under study as a predictor of response to therapy. Several international guidelines help physicians in using tumour markers giving practical recommendations for the appropriate interpretation of circulating tumour markers. CEA and cytokeratins markers are so far less specific than mucinic markers; therefore, they are sometimes tested for evaluating breast cancer patients.

The association of tumour marker tests with a diagnostic imaging modality such as FDG-PET today is of great interest, because sometimes the patients present with a tumour marker increase and do not show clinical symptoms or signs of cancer, or on the contrary some others subjects present with some doubtful symptoms or signs of cancer, and the association with a biochemical test for malignancy can be helpful to make the final diagnosis. FDG-PET is known as a metabolic imaging modality, that, contrary to radiological techniques, reveals cancer not on the basis of morphology like the radiological methods, but because of the uptake and/or processing of a radioactive tracer in cancer tissue. The visualization of cancer by PET depends on the viability and activity of the tumour, and this requirement is very close to the function of synthesis and secretion of tumour markers as products of cell metabolism. One can say that FDG-PET and tumour marker tests describe cancer activities in different ways, and their diagnostic added value takes advantage of this combination.

This chapter overviews the results of the association of FDG-PET with elevated or progressively increasing tumour markers. Tumour-marker-guided PET has demonstrated a diagnostic effectiveness in detecting cancer lesions with variable sensitivity, both at presentation (staging) and during the follow-up (discovery of relapses, metastases and re-staging). It is well known that tumour marker increase is a reliable signal of the presence of occult disease, and this suspicion can be explored by FDG-PET. For this reason some authors have proposed that whole body PET may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. The recent development of hybrid systems, allowing the concomitant examination of the patient by combining PET with CT, has increased the accuracy of diagnostic imaging, and several papers support the evidence that PET/CT is able to add incremental diagnostic confidence to PET and detects more lesions than CT or PET alone. A discussion is still open about the question if FDG-PET or PET/CT can substitute the entire battery of tests routinely used for staging breast cancer or detecting relapse in all breast cancer patients. At present, it is very difficult to draw a final conclusion, since one should consider the cost of the test, the non-complete availability of this examination in all clinical centres, and the problem of the limited sensitivity of PET in early stages, which is not able to rule out the microscopic metastases. There is still a need for further prospective clinical trials for evaluating the impact of this approach on patient management and survival, according to the different risk groups. However, in spite of several controversies in this field, there is no doubt that the association of tumour marker tests with PET or PET/CT seems to provide useful information, and this approach is indicated, mainly in the follow-up of patients at risk, in re-staging patients with symptoms and in evaluating the response to treatments.

The authors have written this paper on behalf of the Group of Immunometric Assays of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN).