Background

Effect

In 2012, 1.7 million women were diagnosed with breast cancer worldwide, and about 0.52 million women died from the disease. [Torre et al 2015] Breast cancer alone accounts for 25% of all cancer cases and 15% of all cancer deaths among females.[Torre et al 2015] Early detection and accurate diagnosis are crucial for optimizing survival chances with appropriate therapy. X-ray mammography, the only technique found sensitive enough for screening has a low positive predictive value (PPV) with unnecessary secondary investigations including biopsies. It has been estimated that 20-50% of abnormal mammograms in screening will prove to be negative. [Stout et al 2014] Most patients referred to a specialized breast cancer care center after a positive screening will have benign disease. [Kopans 2006]

Diagnosis

The paradigm in diagnosis is to establish whether a screening-detected lesion is a cancerous mass or a benign process, leading to vastly different therapeutic decisions. Diagnosis is performed using x-ray imaging, ultrasonography and image-guided needle biopsy. [Kopans 2006] Depending on availability, Magnetic Resonance Imaging (MRI) may be used in case of uncertain findings in x-ray imaging and ultrasound imaging. [Kuhl 2007]

Weak points

Despite advancements, these clinical imaging modalities suffer from serious shortcomings. X-ray imaging suffers from poor specificity especially in radiodense breasts, uses ionizing radiation, and requires painful breast compression. [Britton et al, Nass et al, Pediconi et al] Ultrasonography has a high false positive rate, a poor field of view (FOV), and its performance is strongly operator dependent. [Kopans 2006, Nass et al, Hooley et al, Drukteinis et al] MRI requires contrast agents, has suboptimal specificity, and its quality depends on the patient’s hormonal status. [Kuhl 2007, Peters et al 2008, Onesti et al 2008] It is also expensive, not universally available, and many patients must be excluded due to claustrophobia, pacemakers etc. [Essink-Bot et al] Most importantly, the interaction of the interrogating energy – whether x-rays, ultrasound or radiofrequency waves (in a magnetic field) – with the malignancy is often not sufficiently specific to allow discrimination of the malignancy from healthy tissue or a benign abnormality. This results in recourse to multiple and/or repeat imaging, and often unnecessary biopsy. The consequences of the shortcomings are often physical, psychological and economic burdens felt at individual, familial and societal levels.