DIAGNOSTIC IMAGING IN BREAST CANCER

Prof Dr Humairah Samad Cheung[A]

INTRODUCTION

Breast cancer is a common and deadly disease that metastasises early in its natural history and may recur late[1].  It shows an incidence that increases with age.  In American women the average lifetime risk of developing breast cancer is about 1 in 8[2].  The incidence of breast cancer in developing eastern countries is lower than in the West^[1] however there is concern that it is on the increase[3].  The disease is extremely rare in males, accounting for ~0.7% of all cases[4]. Multidisciplinary teams that comprise breast surgeons, radiologists,

pathologists and oncologists, should provide appropriate breast cancer management^[1] Radiological imaging

methods available for the diagnostic work-up of breast cancer include mammography (MMG), breast ultrasound (US), and magnetic resonance imaging (MRI).

MAMMOGRAPHY

It was recognized more than 60 years ago that clinically occult breast cancer could be visualized on radiograph[5]. Technical developments in film-screen MMG coupled with evidence suggesting that MMG screening resulted in a reduction in breast cancer mortality[6] [7] led to the introduction and wide acceptance of screening MMG in several western countries by the 80s.

It is generally accepted that the benefit of screening has been documented in large randomised trials involving a total of half a million women in New York, Edinburgh, Canada and Sweden[8]. 4 A meta-analysis of the five Swedish trials showed that screening lowered mortality from breast cancer by 29% in women aged 50-69 years[6] [7] However more recent evidence from the United Kingdom showed that screening reduced mortality only by an estimated 6.4%[9].  A re-examination of data from eight trials showed that six had baseline imbalances and inadequate randomisation methods and were rejected from further analysis. A meta-analysis of the remaining two unbiased trials from Malmo and Canada found no effe6ct of screening on breast cancer mortality[8].  A subsequent Cochrane review confirmed this and suggests that breast cancer mortality is a misleading outcome measure[10].

Screening MMG aims to diagnose breast cancer early and is advocated in women above 50. The accuracy and positive predictive value of MMG are higher in older than in younger women[2]. This may be related to the higher frequency of the disease and the reduced breast density on MMG seen with increasing age.  There is no agreement on the case for breast cancer screening in women aged <50 as higher false positive rate in younger women[2]. often leads to unnecessary patient anxiety.  More cases of ductal carcinoma in-situ (DCIS) are being diagnosed with improved MMG technology especially in younger women[11], and currently there is concern that these lesions are being treated too aggressively as more than half may never become invasive or metastasise[12].

The cost of screening MMG is high as its true financial cost includes all follow-up procedures including biopsies[2]..  The “triple test” approach practiced in Europe is associated with a lower biopsy rate of ~1% compared to that in the US where it is about ten times higher, and approximately 4 out of 5 biopsies are benign[1] The triple test relies on the correlative findings at clinical examination, MMG, and fine needle aspiration cytology (FNAC) before management decisions are made in each individual patient.

The increasing use of picture archiving and communications systems (PACS) has generated great interest in whether digital MMG, with cost-saving potential in the long term, will be able to replace conventional film-screen MMG in the near future.  The Digital MMG Imaging Screening Trial (DMIST) has commenced and will include 49,500 women at 19 centres in the US and Canada.  Results, in late 2004, are expected to show whether digital MMG is as sensitive, specific and more cost effective than film MMG, and whether it will be able to obviate unnecessary biopsies[13] [14].

In symptomatic patients MMG is used primarily to screen the remainder of the ipsilateral as well as the contra-lateral breast for clinically unsuspected cancer[15].  As many as 60% of palpable breast masses are not visible on MMG[16]. Occasionally, the demonstration on MMG of a lesion with benign features is sufficiently diagnostic that biopsy can be avoided[17].

BREAST ULTRASOUND

Breast ultrasound (US) was first described by Wild and Neal in 1951[18]. The accepted role of ultrasound is as an adjunct to mammography, and it has been advocated as a tailored examination to assess an area of mammographic and/or palpable abnormality rather than as a complete survey of the breasts[19].  However whole breast US has been recently shown to be of value in the detection of multicentric and multifocal cancer when used pre-operatively in situations where breast conservation surgery is contemplated[20].  US is the initial method of choice in young women with breast symptoms because it does not involve radiation. It is 96-100% accurate in the diagnosis of cysts, which constitute some 25% of all palpable or mammographically detectable lesions[19].. The negative predictive value of a normal mammogram and normal US in women presenting with a breast lump was found to be 100%[21].

Breast US is capable of more than differentiating solid from cystic nodules as advances in ultrasound technology has made it possible to clearly characterize breast lesions with high frequency transducers.  The typical US features of benign and malignant solid lesions have been described[22]. Using these features the negative predictive value for a benign classification on US was 99.5%, and the sensitivity for cancer was 98.4%[22] Current US equipment is also able to detect malignant microcalcifications[22] and is able to show axillary nodal involvement.

The expanding role of breast US includes the use of Doppler in the assessment of vascularity of breast masses. With penetrating vessels as an indication of malignancy, power Doppler ultrasound had a specificity of 95% and a sensitivity of 68%[23].  Breast US is increasingly used in image-guided breast procedures such as FNAC, biopsies and hook-wire localization of lesions prior to surgical excision.  It offers the advantages of greater patient comfort, real-time visualization of the needle entering the targeted lesion, shorter procedure time and reduced operating cost[24].

BREAST MRI

The ability of contrast-enhanced MRI to demonstrate breast cancer was first reported by Hewang et al[25]. Most authors subsequently report high sensitivity exceeding 98% in breast cancer detection using contrast MRI, with much lower specificity because some benign lesions also enhance[26].  Morphological features on contrast MRI are also useful in differentiating benign from malignant lesions; the latter often show avid contrast enhancement, irregular or spiculated margins and peripheral enhancement due to central tumour necrosis or desmoplasia[27]. 

Breast MRI is better than mammography in cancer detection in dense or scarred post-operative breasts and in the presence of implants.  It contributes to tumour staging allowing appropriate single stage surgical resection.  It is also useful in excluding breast cancer in women presenting with axillary lymphadenopathy, and in pre-operative assessment of patients opting for breast conservation surgery, to exclude multicentric carcinoma[27][28].  Research areas in breast MRI include MR spectroscopy in the detection of choline metabolites in tumours[29] and cancer screening in high-risk women[30]. 

Despite promising results there is still a lack of firm data regarding efficacy, appropriate clinical indications and recommended techniques for MR image acquisition and interpretation.  These issues are being addressed in multi-centre efforts led by the International Working Group on Breast MRI and the International Breast MRI Consortium^[28].

CONCLUSION

This paper briefly reviews the current role of the three main diagnostic imaging modalities used in breast cancer detection.  There are controversial issues regarding the benefits derived from mammography, while exciting developments in Breast MRI promise more accurate imaging in staging breast cancer and monitoring treatment response.