Breast Cancer Detection

It is estimated that breast cancer results in 40,000 deaths (39,210 women, 410 men) annually in the USA [12]. The method by which breast cancer is detected can occur as follows:

1. Physical Examination for a palpable mass a) Patient b) Physician 2. Imaging a) Mammography b) Ultrasound 3. Biopsy a) Surgical b) Fine-needle Aspiration c) Core-needle Biopsy 4. Histologic confirmation

If a patient has a suspected tumour on a mammographic image they will undergo a surgical, fine-needle aspiration or more commonly a core-needle biopsy (CNB). This extracts a representative sample of tissue from the breast and is usually performed under ultra-sound guidance to aid with needle placement to ensure correct sampling of the target lesion. These samples

14

are then processed in the histology laboratory and examined histologically by a pathologist to confirm the presence of malignant tumour cells.

1.6.2.1 X-ray Mammography

Mammography has over time become the “gold standard” target population screening tool for early breast cancer detection. The technique uses low- levels of ionizing radiation to generate an image of the breast which aids in the detection of cancerous masses or characteristic micro-calcifications suggestive of DCIS. The introduction of mammography has been proven to detect breast cancer at an early stage and, when followed up with appropriate diagnosis and treatment, to reduce mortality from breast cancer [51]. The average size at which breast cancer tumours can be detected with mammographic screening is 7.5 mm compared to 15 mm without screening [52]. Prior to the introduction of a national breast screening programme in Ireland (1994-1999) the 5-year survival rate for women with breast cancer was 74.3%. Women who were diagnosed between 2006 and 2011 had a five-year survival rate of 84.7% [53]. This increase in patient survival cannot entirely be attributed to the introduction of the mammographic screening programme. However, the ability to detect breast cancers at an earlier stage, allows a patient to undergo treatment as soon as possible which increases the likelihood of survival.

1.6.2.2 Limitations of Mammography

Mammography does however have some significant limitations including, relatively low sensitivity and specificity (79% and 90% respectively) which are both significantly reduced in young patients (less than 40 years old) due to the increased breast density [54-56]. There are two major problems surrounding mammographic screening. The first of these is radiologically occult disease. This manifests as breast cancer tumours which cannot be detected using mammography. The second significant issue is the interpretation of mammography results which requires highly trained, specialist radiologists to systematically review each individual mammogram. Misinterpretation of mammography results can alter either the sensitivity

15

(disease is present but not detected) or the specificity (disease is absent but interpreted as being present) of the screening test.

A comprehensive review of clinical trial data relating to screening programmes for breast cancer detection determined significant increases in the rates of over-diagnosis and over-treatment of up to 30%. In reality this figure is hard to quantify and is probably much lower than 30%. A number of drawbacks are associated with breast cancer screening including an increase in psychological distress which can include anxiety, worry, despondency and sleeping problems [57-60]. The report also suggested that the number of mastectomies can increase by up to 20% as a result of screening programs [58]. A recent independent review conducted by a panel in the United Kingdom noted that there were significant methodological limitations to the Cochrane Review and that the true rate of over-diagnosis is likely to be closer to 11% for women invited to attend a screening programme and approximately 19% for those who actually attend a screening [61]. In a study by Berg et al. (2004), the team assessed the specificity and sensitivity of a number of cancer detection modalities individually and in combinations. They determined, using 258 proven lesions, that mammography on its own had a sensitivity of 67%, specificity of 75% and a positive predictive value of 85.7% [55] . They then determined the effectiveness of mammography by breast tissue composition (extremely dense, heterogeneously dense, minimal scattered fibro-glandular densities and predominantly fatty). As before 258 histologically proven lesions were used of which mammography was only able to detect 45% (21/47) in extremely dense tissue compared with 100% (8/8) in predominantly fatty breasts [55]. A limitation of this study was that only a small number of patients were analysed.

The current imaging modalities used to further evaluate mammographically suspicious lesions are magnetic resonance imaging (MRI) [56, 62], and ultrasound (US) [62]. Computed tomography (CT) and positron emission tomography (PET) [62] are not routinely used in clinical practice for evaluation of breast lumps or abnormal mammographic findings. The major limitation of these technologies is the significant cost of both the hardware

16

and the procedures. PET/CT scanning, as with mammogram, uses low doses of ionising radiation during the procedure which is a potential limiting factor for its use in cancer patients. It is primarily used in the detection of metastatic diseases [62]. MRI on the other hand does not use any radiation and instead utilises an intravascular injection of a contrast agent such as gadolinium diethylene tri-amine penta-acetic acid (GdDTPA) [63, 64] but MRI has limitations with its cost, potential adverse reactions and nephrotoxicity to contrast media and an unacceptably high false positive rate [65].