Metastatic Breast Cancer—Opportunities from Novel Diagnostic Modalities

US Oncology Review, 2005;1(1):1-5

Abstract:

Reference Section a report by Paolo Morandi, MD and Massimo Cristofanilli, MD, FACP Visiting Scientist and Associate Professor of Medicine, Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center Breast cancer remains the most frequent type of cancer in women,with approximately 212,600 new cases (1,300 male) diagnosed each year in the US. Breast cancer is among the leading causes of cancer death in women (15% of all cancer deaths in women) with an estimated 40,200 cancer-related deaths (400 male) in 2003.1

Citation US Oncology Review, 2005;1(1):1-5

Despite years of clinical research, the odds of achieving complete resolution of metastatic disease with current treatment strategies remain low.2-4 The majority of patients with advanced disease achieve various degrees of objective remission, usually transient, with conventional treatments, and develop evidence of progressive disease within 12 to 24 months of initiating treatment.4 For these patients, systemic treatment has rarely translated into a significant improvement in survival3 but has generally substantially improved the quality of life. The identification of these patients at the time of their initial diagnosis of metastatic disease remains a challenge.A few retrospective studies have demonstrated that these long- term survivors are usually young, have an excellent performance status and, more importantly, have limited metastatic disease.5-7 Several clinical factors have been proposed that would help in predicting long-term outcome and efficacy of treatments. These include a greater number of involved nodes at diagnosis, visceral metastases, primary tumor measuring >2cm, and performance status of the patients.8-10 The use of an intense follow-up program in women with high risk of breast cancer has been advocated in the past, based on the criteria that the early detection and consequent treatment of asymptomatic disease could have translated into a survival benefit for the patients.However, two large randomized trials investigating the relationship between an intensive follow-up policy using standard imaging and routine tests (including bone scans, liver ultrasound, chest X-rays, and blood routine tests) and overall survival failed to detect any advantage for the more aggressive approach.11,12 For the asymptomatic patient, current universally adopted guidelines recommend a regular history, an annual mammography, and physical examination every three to six months for two years,then every six to 12 months for three years, and then annually.

In the asymptomatic patient, or when a recurrence is suspected, complete and accurate non-invasive imaging data are needed to improve clinical management. The advent of more sensitive functional imaging modalities raises the issue of the possible value of early detection of metastatic disease and possibility of more effective systemic treatments in that setting. One example is represented by positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) that allows metabolic and functional imaging of tumor cells. FDG PET has been shown to improve detection of distant relapses over conventional imaging obtained with computed tomography (CT) and magnetic resonance imaging (MRI).13 However,the limited accuracy of lesion localization using PET alone impairs its clinical value, particularly with those patients in whom a precise re- staging is necessary.A hybrid PET/CT scanner has been recently developed for the simultaneous acquisition of anatomic (CT) and functional (PET) data. The superimposition of CT with high spatial resolution improves the localization of areas of increased uptake in PET by directly combining functional and morphological information, allowing more reliable anatomical lesion definition. A definite gain in diagnostic accuracy for neoplastic lesions ranging from approximately 20% to 40% can be achieved with the use of integrated PET/CT compared with PET alone.The potential of PET/CT to become a widespread diagnostic tool and to improve clinical efficacy needs to be properly addressed and evaluated in well designed, prospective, randomized clinical trials.

The increasing availability of laboratory techniques able to detect the presence of cancer cells,or new predictive or surrogate markers in several tissue and body fluids, offer the opportunity to evaluate microscopic disease (MCD) in breast cancer.The detection of MCD in breast cancer has been evaluated in lymph nodes, bone marrow (primary breast cancer), and peripheral blood (metastatic disease).The majority of these studies have demonstrated that the detection of MCD in breast cancer patients contributes prognostic information and, in selected cases, it can predict the efficacy of treatments. In primary breast cancer the detection of microscopic disease in lymph nodes and bone marrow contributed to describe the role of minimal residual disease in this disease. In patients with metstatic breast cancer (MBC) these novel approaches have demonstrated unique features and could significantly Metastatic Breast Cancer - Opportunities from Novel Diagnostic Modalities Paolo Morandi, MD Massimo Cristofanilli, MD, FACP Paolo Morandi, MD, is a Visiting Scientist at the Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center.

He is also Senior Staff Member and Deputy-Director of the Medical Oncology Division at the San Bortolo General Hospital in Vicenza, Italy. He is a member of the Breast Cancer Executive Board of the Michelangelo Foundation at Milan National Cancer Institute, Italy. He has participated in different clinical research projects in close collaboration with investigators of the Milan National Cancer Institute and other national and international Cooperative Groups. He is member of ASCO and ESMO.