Abstract
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide [1]. It is a heterogeneous disease with distinct molecular and genetic subtypes, each with characteristic clinical-biological behavior and imaging patterns. A substantial proportion of tumor markers or biomarkers, both fluid and tissue based, are currently used in the management of patients with breast cancer. Serum biomarkers, such as CA 15–3 and carcinoembryonic antigen (CEA), are not recommended in any senological guidelines due to a lack of sensitivity for early disease and a lack of specificity [2]. Rather, genetic tests are regularly performed in populations at high risk of developing breast cancer. By means of a minimally invasive blood test, women are told whether a germ line mutation in cancer susceptibility genes is present (BRCA). Being diagnosed with a BRCA 1 or 2 gene mutation has a dramatic impact on the life course of a woman. About 5–10 % of all breast cancers are caused by germ line mutations in the two breast cancer susceptibility genes, BRCA-1 and BRCA-2, and women carrying BRCA1 or BRCA2 mutations have an increased risk of developing breast cancer of approximately 50–80 % at 70 years of age [3–5]. Various histopathological and immunohistochemical staining-derived features of breast cancer are used to clinically establish the prognostically relevant subtype, including hormonal receptor expression, architectural growth patterns, and nuclear grades (low, intermediate, or high). Subsequently, the individual management of breast cancer patients is adapted according to these subtypes. Despite the enormous advances in breast imaging, the aforementioned clinically relevant subtyping of breast lesions is still based on invasive procedures, such as core needle biopsy or surgery. However, imaging is increasingly used to assess not only the morphologic features of the pathological process but also to assess the function of tumor tissues or to characterize individual phenotypes for targeted drug therapies, building on developments in genomics and molecular biology features [6–9]. Imaging biomarkers can be defined as any anatomic, physiologic, biochemical, or molecular parameter that is detectable with one or more imaging methods used to help establish the presence and/or severity of disease. The specific term “quantitative imaging biomarkers” corresponds to parameters that are objectively and quantitatively measured noninvasively, are less susceptible to subjective judgment, and are resolved spatially and temporally [10]. Moreover, prerequisites for the effective use of imaging biomarkers are standardization and validation [10–12]. The aim of this chapter is to describe breast imaging biomarkers and their objective, quantifiable features. We consider here only imaging biomarkers that require an element of quantification and standardization, to demonstrate their contribution in the management of breast cancer patients. First, we briefly summarize the heterogeneous group of subtypes of breast cancer, both invasive and noninvasive, to give the reader a synopsis of the complexity of this disease and an insight into the molecular biomarkers of breast cancer. However, a complete overview of the different histologic breast cancer subtypes is beyond the aim of this chapter. Second, we discuss the role of breast imaging biomarkers in terms of risk prediction for the development of breast cancer. These include quantitative imaging techniques for the assessment of breast density based on mammography and the measure of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) based on magnetic resonance imaging (MRI). Third, we will explain the central role of MRI in noninvasively providing quantitative information about tissue characteristics, such as cell density, tumor angiogenesis, and metabolism, leading to an improved differentiation of benign and malignant breast lesions and to a better management of breast cancer patients in monitoring and predicting response to treatment. Finally, we discuss the potential of other imaging techniques, and emerging techniques, which could improve diagnostic accuracy and have the potential for the development of new imaging biomarkers.
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Marino, M.A., Pinker, K., Baltzer, P., Helbich, T.H. (2017). Use Case III: Imaging Biomarkers in Breast Tumours. Development and Clinical Integration. In: Martí-Bonmatí, L., Alberich-Bayarri, A. (eds) Imaging Biomarkers. Springer, Cham. https://doi.org/10.1007/978-3-319-43504-6_17
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