Abstract:
Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related
deaths worldwide. Timely decision-making that enables implementation of the most appropriate
therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While
clinicopathologic characteristics and immunohistochemistry have traditionally been used in decisionmaking,
these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to
tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial
or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor
lesions or between lesions at a single time point while temporal variations are seen as tumor lesions
evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive
biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES
PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standardof-
care imaging methods are often unable to image a myriad of other molecular pathways associated
with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals
targeting other molecular pathways and processes. In this review, we discuss validated and potential
roles of these standard-of-care and novel molecular approaches. These approaches’ relationships
with patient clinicopathologic and immunohistochemical characteristics as well as their influence on
patient management will be discussed in greater detail. This paper will also introduce and discuss
the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers
of PARP expression/upregulation.
