Imaging is required at all three stages of this process, and mammography and ultrasound have a pivotal role to play. About 60% of breast cancer is diagnosed in symptomatic breast referral clinics. These clinics follow protocols that define the triple test, the combination of clinical assessment, imaging (mammography and ultrasound) and core biopsy or needle cytology, as the required standard.⁴ ‘One-stop’ clinics are recommended at which all the necessary tests required to make a diagnosis, including needle biopsy, are performed at one clinic visit. In order to achieve the earliest possible diagnosis of symptomatic breast cancer, women are encouraged through a variety of health promotion methods to present to these clinics as soon as they develop any change in their breasts. The clinical and imaging assessments in these clinics should be performed by appropriately trained and experienced staff. All such staff do not need to be doctors but they need to be able to give an independent opinion and be trained to an appropriate level.

Breast imaging techniques

Mammography

X-ray mammography has been the basis of breast imaging for more than 30 years. The sensitivity of mammography for breast cancer is age dependent. The denser the breast, the less effective this method is for detecting early signs of breast cancer. Breast density tends to be higher in younger women and increased density obscures early signs of breast cancer. The sensitivity of mammography for breast cancer in women over 60 years of age approaches 95%, while mammography can be expected to detect less than 50% of breast cancers in women under 40 years of age.⁵

Mammography uses ionising radiation to obtain an image and therefore should only be used where there is likely to be a clinical benefit. Consensus is that the benefits of mammography in women over the age of 40 years are likely to far outweigh any oncogenic effects of repeated exposure. Screening of women over the age of 40 by mammography is accepted practice. However, in symptomatic practice, there is rarely an indication for performing mammography in women under the age of 35 unless there is a strong clinical suspicion of malignancy. In many centres, all women over the age of 35 presenting to breast clinics undergo mammography as a routine. Practice is changing and ultrasound alone is being used increasingly for the assessment of women with focal breast symptoms in women under 40 years of age and even in some women aged 40–50. Mammography is routine in all women in the screening age group attending symptomatic clinics who have not had a screening mammogram in the past year.

Most mammography in the UK is now carried out using digital image acquisition.6–9 There are major benefits from acquiring mammograms in direct digital format.⁹ Compared with conventional film/screen mammography, the benefits of full-field digital mammography include better imaging of the dense breast, the application of computer-aided detection and a number of logistical advantages providing potential for more efficient mammography services.¹⁰^,¹¹ The much wider dynamic range of digital mammography means that visualisation of the entire breast density range on a single image is easily achievable. In the clinical setting, comparative studies have shown that digital mammography performs in general as well as film/screen mammography but is better in younger women and in women with dense breasts.⁶^,⁷

Mammography is the basis of stereotactic breast biopsy, which can be carried out using a dedicated prone biopsy table or by using an add-on device to a conventional upright mammography unit. Stereotaxis is used to biopsy impalpable lesions that are not clearly visible on ultrasound (e.g. microcalcifications).

Ultrasound

High-frequency (≥10 MHz) ultrasound is a very effective diagnostic tool for the investigation of focal breast symptoms.¹² Ultrasound does not involve ionising radiation and is a very safe imaging technique. It has a high sensitivity for breast pathology and also a very high negative predictive value.¹³

High-resolution ultrasound easily distinguishes between most solid and cystic lesions and can differentiate benign from malignant lesions with a high degree of accuracy. However, in most circumstances, solid lesions seen on ultrasound require needle sampling for accurate diagnosis.

Ultrasound is the technique of choice for the further investigation of focal symptomatic breast problems at all ages. Under 40 years of age, when the risk of breast cancer is very low, it is usually the only imaging technique required. Over 40, when the risk of breast cancer begins to increase, it is often used in conjunction with mammography. Ultrasound is less sensitive than mammography for the early signs of breast cancer and is therefore not used for population screening. However, ultrasound does increase the detection of small breast cancers in women who have a dense background pattern on mammography.⁵ In the screening setting there is clear evidence that the addition of ultrasound improves small cancer detection rates, particularly in women with dense breasts, but there is currently insufficient evidence of any mortality benefit and insufficient resources to allow for routine ultrasound screening of women with dense breasts on mammography. Adding ultrasound to mammography or magnetic resonance imaging (MRI) screening does increase cancer detection but also significantly increases the false-positive rate. Ultrasound is the technique of first choice for biopsy of both palpable and impalpable breast lesions visible on scanning.

Ultrasound is now used routinely to assess the axilla in women with breast cancer in most units. Axillary nodes that show abnormal morphology can be sampled accurately by fine-needle aspiration (FNA) or needle core biopsy.¹⁶^,¹⁷ Discussion of the role of axillary ultrasound and FNA and core biopsy can be found in Chapter 7.

Up to 50% of patients with axillary metastatic disease can be diagnosed by ultrasound combined with FNA or core biopsy, which may avoid the need for sentinel node biopsy in some women with pathologically proven nodal involvement.¹⁴^,¹⁵

Doppler ultrasound adds little to breast diagnosis and is not widely used. Three-dimensional ultrasound of the breast is said to increase the accuracy of biopsy and the detection of multifocal disease but is not widely available. Elastography is a new application of ultrasound technology that allows the accurate assessment of the stiffness of breast tissue. It is being evaluated at present and may prove to be a useful tool in excluding significant abnormalities, for instance in assessment of asymptomatic abnormalities detected by ultrasound screening.

Magnetic resonance mammography (MRM)

MRM is now widely available. In order to image the breast the patient is scanned prone and injection of intravenous contrast is required. MRM is the most sensitive technique for detection of breast cancer, approaching 100% for invasive cancer and up to 92% for ductal carcinoma in situ (DCIS), but it has a high false-positive rate.¹⁸^,¹⁹^,²⁰ Rapid acquisition of images facilitates assessment of signal enhancement curves that can be helpful in distinguishing benign from malignant disease. Significant overlap in the enhancement patterns is seen, so needle sampling of the lesions detected is often required. Magnetic resonance-guided breast biopsy is available in a few centres but most breast lesions seen on MRM that are larger than 5 mm can be seen on ultrasound if they are clinically significant.

MRM is the best method for screening younger women (under 40 years) at increased risk of breast cancer but, because of cost, it is unlikely to be used for general population screening.21–24

MRM is the best technique for imaging women with breast implants. It is also of benefit in identifying recurrent disease where conventional imaging and biopsy have failed to exclude recurrence. Provided it is carried out more than 18 months after surgery, MRI will accurately distinguish between scarring and tumour recurrence. MRI is recommended to detect multifocality prior to conservation surgery for women with lobular cancers and those with occult cancer on mammography or with a significant discrepancy of size on conventional imaging. However, it should not be used routinely and a randomised trial (COMICE) showed no benefit in reducing re-excision rates but did increase significantly the mastectomy rates for those who had MRI. Breast MRI is of value in assessing response of large or locally advanced breast cancers to neoadjuvant chemotherapy. MRI of the axilla can demonstrate axillary metastatic disease but its sensitivity is not sufficient to replace surgical staging of the axilla. For advanced breast cancer, MRI is the technique of choice for assessing spinal metastatic disease.

Computed tomography

Computed tomography (CT) has no current proven role in primary imaging of the breast. but dedicated low-dose breast CT is being introduced; its clinical efficacy has yet to be determined. CT is used to diagnose and stage systemic spread of breast cancer and to assess response of metastatic disease to treatment, particularly lung, pleural and liver metastases. Some patients with breast cancer do have their cancers diagnosed incidentally during a routine CT scan.

Isotope imaging

Breast scintigraphy is not widely used because of its lack of sensitivity compared with other techniques. It is used in a few centres to stage the breast prior to surgery and to assess response to treatment. Scintigraphy is widely used to diagnose and assess the presence of skeletal metastatic disease. It is now often combined with a low-resolution non-contrast CT scan.

Positron emission scintigraphy, particularly when combined with CT, is a technology that may have a role in future in staging breast cancer and monitoring response to treatment. It is widely used in the USA but elsewhere, at present, it continues to be regarded as a research tool and its specific uses and indications in assessing breast disease are still being defined.

Breast cancer screening

Aim

The aim of breast screening is to reduce mortality through early detection. Randomised controlled trials and case–control studies carried out between the 1960s and 1980s have demonstrated that population screening by mammography can be expected to reduce overall breast cancer mortality by around 25% and by 35–40% in those who participate.

The validity of these trials was questioned in 2000–2002 but subsequent reviews by the Swedish combined trials group and a World Health Organisation International Agency for Research on Cancer committee of experts have reaffirmed the mortality benefit of mammographic screening and determined that criticisms of the mammographic screening trials were unjustified.25–30

The mortality benefit of screening is greatest in women aged 55–70 years.²⁷^,²⁸ The mortality benefit of screening women aged between 40 and 55 is approximately 20%. Screening women under the age of 40 has not been shown to provide any mortality benefit.²⁷^,²⁸

Population screening

Breast screening has been introduced in many countries over the past 25 years. In most countries, screening is recommended in all women aged 40 and over but in countries that provide population-based screening, women of 50 and over are specifically targeted. Breast cancer screening was introduced in the UK in 1987 and provides screening by invitation, free at the point of delivery, to all women between the ages of 50 and 70.¹ Women over 70 can attend but are not invited. Over 70% of the invited population need to attend for a significant overall mortality benefit to be achieved. Women under the age of 50 are not offered screening in the UK unless they are at increased risk. A randomised trial of extending the screening invitation to the age range 47–73 years was started in 2010. The results of this trial will not be available until after 2020. From 2010 screening with annual MRI in addition to mammography has been offered to women at very high risk of breast cancer, including BRCA1 and BRCA2 gene carrriers.

Method and frequency

The optimum screening method is two-view mammography; clinical examination of the breast and breast self-examination have not been shown to contribute to mortality reduction through early detection and so are not recommended.⁹^,³¹^,³²

Women aged 50–70 in the UK are invited for mammography every 3 years. There has been some concern that this screening interval is too long. Mammography can be expected to detect breast cancer approximately 2 years before it becomes clinically apparent. The frequency of mammographic screening is determined by the lead-time of breast cancer. Based on the average growth time of breast cancer in different ages, this means that mammographic screening should ideally be carried out yearly in women aged 40–50, every 2 years in women aged 50–60 and every 3 years thereafter. However, the UK breast screening frequency trial completed in 1995 did not show any predicted benefit for women aged 50–64 screened every year compared with those screened every 3 years.³³ Screening once every 3 years can be expected to detect approximately two-thirds of all breast cancers that will arise during the 3-year screening interval.

One-third of breast cancers present in the interval between screens and are called interval cancers. Half of these present in the third year after screening.

Factors affecting the effectiveness of screening

HRT increases breast density and in a proportion of women this reduces the sensitivity of mammography for breast cancer.⁹^,^32–40 Up to 25% of women taking combined oestrogen/progestogen preparations continuously show increased density on mammography. This effect is significantly less with other HRT preparations. As well as reducing sensitivity HRT also reduces the specificity of mammographic screening. HRT also increases the risk of developing breast cancer.³⁴

Quality assurance

Breast screening programmes should have inbuilt quality assurance; the UK NHS Breast Screening Programme is subject to comprehensive quality assessment and all 100 screening units across the country have to comply with nationally defined standard guidelines. There are national targets for screening set by a central Department of Health Advisory Committee (Table 1.1).

Table 1.1

NHS Breast Screening Programme: screening targets, June 2005

The screening process

Women invited for screening attend either a static or mobile screening unit where two-view mammography is performed. The images are then double read within a few days. The vast majority of women (95%) are informed by letter within 2 weeks of attendance that their mammograms show no evidence of breast cancer. Those women in the appropriate age range will be invited for screening 3 years later. They are advised to contact their general practitioner as soon as possible if they become aware of any change in their breasts in the meantime.

The screening process includes a fully integrated multidisciplinary assessment process for all screen-detected mammographic abnormalities; screening programmes should ideally retain responsibility through to definitive diagnosis. Approximately 5% of women screened are recalled for further assessment of a problem identified at screening. Some women are recalled for further assessment of a clinical sign or symptom identified at the time of screening but the vast majority of women are recalled because of a mammographic abnormality.

The most important cancers detected at screening are high-grade DCIS, as most cases of this type will progress to grade 2 or 3 invasive breast cancer within the following 3 years, and grade 2 and 3 invasive breast cancers under 10 mm in diameter, as at this size these tumours are much less likely to have metastasised.⁴¹^,⁴²

The common types of mammographic abnormality and their positive predictive value for cancer are shown in Table 1.2. Well-defined masses are almost always benign and do not require recall, whereas ill-defined masses and spiculated lesions always require further assessment (Figs 1.1 and 1.2). Clustered microcalcifications account for a high proportion of recalls that result in needle biopsy. More than 20% of screen-detected breast cancer is DCIS, mostly high or intermediate grade, and most of this type of cancer is detected by the presence of clustered microcalcifications (Fig. 1.3). Invasive cancer is usually represented on mammography by either an ill-defined or spiculated mass. It is essential to detect these lesions at small size as they more commonly represent grade 2 or 3 invasive cancer.

Table 1.2

Positive predictive value (PPV) for malignancy of mammographic signs

Sign	PPV (%)
Well-defined mass	<1
Ill-defined mass	35–50
Spiculated mass	50–90
Architectural distortion	20–40
Asymmetric density	<2
Clustered microcalcifications	15

Figure 1.1 (a,b) Digital mammograms showing multiple well-defined masses, the typical appearance of simple breast cysts. (c) Ultrasound image showing typical features of a simple cyst, i.e. a well-circumscribed anechoic mass with distal acoustic enhancement.

Figure 1.2 (a,b) Digital mammograms showing a spiculated mass in the right breast. The appearances are typical of an invasive carcinoma. The mass contains microcalcifications and there is evidence of skin tether. (c) Doppler ultrasound image showing the typical features of an invasive carcinoma with an irregular mass containing abnormal central vessels.

Figure 1.3 Digital mammograms showing a cluster of casting microcalcifications in the left breast. The appearances are typical of high-grade ductal carcinoma in situ.

Three-quarters of women recalled undergo further imaging (mammography and/or ultrasound) and clinical assessment before being reassured and discharged. The remaining 25% proceed to needle biopsy and this results in a diagnosis of around six cancers per 1000 women screened. Interval follow-up of uncertain mammographic findings is discouraged; the emphasis is on obtaining a definitive diagnosis by the use of image-guided breast biopsy. Over 90% of breast cancers should be diagnosed prior to first surgery. Despite advances in breast needle biopsy techniques, a small proportion of women still require open surgical biopsy for diagnosis (up to 0.25% of women screened).

The performance of the NHS Breast Screening Programme in 2010 is shown in Table 1.3. The screening programme was predicted to produce a 25% reduction in mortality (1750 cancers per year) directly attributable to early detection through screening by the year 2010.

Table 1.3

NHS Breast Screening Programme: results 2010

	2008/2009	2009/2010
Total number of women invited (50–70)	2 642 511	2 662 298
Acceptance rate	73.8%	73.5%
Number of women screened (invited)	1947.424	1 954 815
Number of women screened (self-referral)	44,070	43 410
Total number of women screened	1 991 494	1 998 225
Number of women recalled for assessment	87,400	82 650
Percentage of women recalled for assessment	4.4%	4.1%
Number of benign surgical biopsies	1644	1519
Number of cancers detected	15 673	15 517
Number of in situ cancers detected	3253	3064
Number of cancers less than 15 mm	6460	6544
Standardised detection ratio (invited only)	1.45	1.44

From NHS Breast Screening Programme Annual Review 2011. Available at http://www.cancerscreening.nhs.uk.

Adverse effects

Receiving an invitation for screening and attending for mammography are not associated with any significant anxiety. However, recall for further assessment does cause measurable anxiety, although this has largely subsided by 3 months.

The numbers of women who undergo open surgical biopsy for what proves to be benign disease should be kept to a minimum. Considerable training and investment in equipment has resulted in a fourfold decline in benign surgical biopsies generated through the screening programme, although rates of benign biopsy vary from unit to unit. False-positive recall and benign surgical biopsy are both more likely in younger women.

Overdiagnosis refers to the detection by screening of breast cancers that require treatment but that would never have threatened the life of the woman. This is inevitable in screening and there continues to be considerable debate about what proportion of screen-detected breast cancers fall into this category. It is likely that most low-grade DCIS and some special low-grade invasive cancers represent overdiagnosis, and detection of these cancers results in unnecessary treatment and unnecessary morbidity associated with knowledge of the diagnosis of cancer. The consensus view is that overdiagnosis applies to no more than 10% of screen-detected breast cancer and that at this level this does not negate the overall mortality benefit of breast screening. Women attending for screening must be informed fully about both the likely positive and negative effects of screening. Efforts continue to reduce the morbidity of screening and to understand better the natural history of cancers so that potential over-treatment is minimised. Even the most ardent critics of breast screening believe screening should continue but they argue it needs to be refined. This is accepted by those who organise and run screening programmes.

Screening women at increased risk

Women at increased risk of developing breast cancer due to a proven inherited predisposing genetic mutation, family history (with no proven genetic mutation), previous radiotherapy (e.g. mantle radiotherapy for Hodgkin’s lymphoma) or benign risk lesions (atypical hyperplasia, lobular intraepithelial neoplasia) may be selected for screening at young age. Whether it is possible to identify other substantially increased risk groups by summating various other epidemiological factors (e.g. age at menarche, body mass index, age at first pregnancy, alcohol intake) continues to be debated. The cut-off point at which clinical management of a woman is altered is often referred to as moderate risk. Those individuals likely or proven to be carriers of a predisposing genetic mutation are termed high risk.

NICE guidelines have been produced (latest version 2006) to classify risk groups and guide care.⁴³ They state that women at or near population risk should be managed in primary care (defined as <3% risk for women aged 40–49). Women at moderate risk are those with a 10-year risk of 3–8% between 40 and 49 years or a lifetime risk >17%, and those at high risk are defined as those with a 10-year risk of >8% between 40 and 49 years or a lifetime risk >30%.

Such cut-offs are useful as guidelines for specialist referral, but most risk factors require clinical interpretation before risk management is discussed with the individual.

Unfortunately, the problem with screening young women at increased risk of breast cancer is that no screening test has as yet been shown to reduce mortality in such women. Screening in this group is therefore a management option for which an exact benefit cannot be quoted for an individual woman. Screening should not be offered to those who fall below the moderate-risk cut-off.

Methods of screening young women at increased risk: mammography

A national evaluation study of mammographic screening for young women with a family history of breast cancer has been conducted (FH01 study). The study compared screening in women aged 40–44 who were at moderate or high risk with the control arm of the age trial (population-based trial of screening women in their forties in which the control arm was not screened); this showed a non-significant mortality benefit for screening. It demonstrated that screening was likely to reduce deaths from breast cancer. The FH02 study is currently looking at the effectiveness of screening women aged 35–39.

Mammography has a greater positive predictive value in young women at high risk when compared with age-matched controls but lacks sensitivity. This may be a particular problem in women with BRCA1 mutations.²⁴^,^44–47

BRCA1-related breast cancer is usually high grade and often has a ‘pushing’ margin. It rarely presents with associated DCIS. The mammographic features are therefore usually of a mass lesion with no associated microcalcification and no architectural distortion (Fig. 1.4a). Such cancers often present symptomatically as interval cases. BRCA2-related cancers are more similar to sporadic cases and may be more likely to be detected by mammography. Ultrasound screening significantly improves sensitivity when there is a dense mammographic background pattern but has a lower positive predictive value and has not been shown to be a useful screening modality. Ultrasound features of BRCA1 cancers are often benign or indeterminate (Fig. 1.4b). If mammographic screening is performed, it should be repeated annually in women under age 50.

Figure 1.4 (a,b) Digital mammograms showing a small circumscribed but ill-defined mass in the upper outer right breast. (c) Ultrasound image of the same mass. Core biopsy showed grade 3 invasive ductal carcinoma.

Methods of screening young women at high risk: MRI

MRI is the most sensitive method of imaging young women but has significant resource implications.⁴⁴^,⁴⁸ The specificity of MRI has been a concern, although with second-look recall (after which many potentially abnormal findings may resolve), targeted ultrasound and the slowly increasing availability of MRI-guided biopsy, this may be less of a problem than initially thought. The MARIBS study evaluating MRI in addition to mammography and several other studies have shown that MRI is the most sensitive screening test for young high-risk women, but it is arguable whether the cancers detected are sufficient to change the outcome of these young women.⁴⁹ On the basis of its better performance compared with mammography in increasing sensitivity, NICE has recommended annual MRI surveillance for women aged 30–39 years with a 10-year risk of >8% and women aged 40–49 years with a 10-year risk >20%.⁴³ MRI is also recommended for high-risk women with a dense mammographic background pattern.

Age to start screening in young women at increased risk

The age for starting screening should be based on risk rather than the age of affected relatives. For women at moderate risk, screening should start at age 40. This can seem paradoxical if the reason moderate risk has been established is because there is one first-degree relative affected in their thirties. However, if this is the only relative affected then the individual is only at moderate risk and the emphasis of management should be on reassurance rather than screening. For women at high risk, screening may be started at age 30. Such high-risk women should ideally be managed in a specialist setting where experience with MRI screening is available. In the UK such women may be best managed within the NHS Breast Screening Programme. Women must be advised about the limitations of screening at young age. This is particularly relevant to known mutation carriers for whom there is no evidence that screening improves survival (cf. risk-reducing surgery).

Image-guided breast biopsy

Needle biopsy is highly accurate in determining the nature of most breast lesions.50–53 Patients with benign conditions avoid unnecessary surgery; carrying out open surgical biopsy for diagnosis should be regarded as a failure of the diagnostic process. For patients who are proven to have breast cancer, needle biopsy provides accurate understanding of the type and extent of disease so ensuring that patients, and the doctors treating them, are able to make informed treatment choices. Needle biopsy not only provides accurate information on the nature of malignant disease, such as histological type and grade, but also facilitates pretreatment assessment of tumour biology.

Which biopsy technique?

The current methods available for breast tissue diagnosis are FNA cytology, needle core biopsy, vacuum-assisted biopsy (VAB) and open surgical biopsy.

FNA versus needle core biopsy

There has been much debate about the comparative benefits of FNA and core biopsy,50–53 but 14 G 22-mm automated core biopsy provides significantly greater sensitivity, specificity and positive predictive value than FNA. Results with core biopsy are particularly superior to FNA in stereotactic biopsy of microcalcifications and architectural distortions.

The overall better performance achievable with core biopsy compared with FNA is illustrated in the performance of the NHS Breast Screening Programme in the UK. In 1994, using FNA as the primary diagnostic technique, fewer than 10% of 90 units were able to achieve the target of 70% preoperative diagnosis rate for cancer. By 2003, most units had converted to automated core biopsy and all units achieved the minimum standard and the majority exceeded the expected standard of 90% preoperative diagnosis rate.¹

Vacuum-assisted biopsy (VAB)

The predominant reasons for not achieving an accurate diagnosis by needle biopsy are sampling error (missing the target) and failure to retrieve sufficient representative material. These problems have been largely addressed by the development of larger directional core techniques that yield significantly greater volumes of tissue.54–56

VAB is a very successful method for improving the diagnostic accuracy of borderline breast lesions and lesions at sites in the breast difficult to biopsy using other techniques. VAB has been shown to understage both in situ and invasive cancer approximately half as often as conventional core biopsy (typically 10% vs. 20%).⁵⁷^,⁵⁸ The VAB technique has a higher sensitivity because it allows sampling of lesions at sites that are difficult to biopsy using either FNA or core biopsy and because the amount of tissue harvested is at least five times greater per core specimen.

The indications for VAB include:

• very small mass lesions;

• architectural distortions;

• failed ‘conventional’ core biopsy;

• small clusters of microcalcifications;

• papillary and mucocele-like lesions;

• diffuse non-specific abnormality;

• excision of benign lesions;

• sentinel node sampling.

Core biopsy and VAB are now the recommended techniques for sampling calcifications and mammographic architectural distortions.⁵⁹^,⁶⁰ For calcifications it is imperative that there is proof of representative sampling with specimen radiography. If calcification is not demonstrated on the specimen radiograph and the histology is benign, then management cannot be based on this result as there is a high risk of sampling error; the procedure must either be repeated or open surgical biopsy carried out.

Guidance techniques for breast needle biopsy

Ultrasound guidance is the technique of choice for biopsy of both palpable and impalpable breast lesions; it is less costly, easy to perform and more accurate than freehand or other image-guided techniques.⁵⁰

Ultrasound provides real-time visualisation of the biopsy procedure and visual confirmation of adequate sampling. Between 80% and 90% of breast abnormalities will be clearly visible on ultrasound and amenable to biopsy using this technique. For impalpable abnormalities not visible on ultrasound, stereotactic X-ray-guided biopsy is required. A few lesions are only visible on MRI and require magnetic resonance-guided biopsy.⁶¹ A number of different approaches have been developed for this procedure using both closed and open magnets. VAB is the biopsy technique recommended for magnetic resonance-guided sampling.

The negative predictive value of combined normal mammography and ultrasound is extremely high; where there is a clinically palpable abnormality and mammography and ultrasound are entirely normal, the likelihood of malignancy is low (<1%). However, in these circumstances it remains prudent in the presence of a localised clinical abnormality to carry out freehand needle biopsy to exclude the occasional diffuse malignant process, such as classical invasive lobular carcinoma or low-grade DCIS, that may be occult on both mammography and ultrasound.

For stereotactic procedures it is prudent to mark the biopsy site for future reference. Gel pellets or cellulose combined with a metallic marker are preferred and can be placed during the procedure to mark the biopsy site. These markers have the advantage of being visible on ultrasound so that repeat biopsy or localisation for surgery can be subsequently performed under ultrasound rather than X-ray guidance. These markers dissolve and are reabsorbed in a few weeks, leaving a small metal marker in case delayed X-ray identification of the biopsy site is required.

Number of samples

A simple rule for satisfactory sampling using needle techniques is to obtain sufficient material to achieve a diagnosis.⁵⁹^,⁶⁰^,⁶² For ultrasound-guided core biopsy, a diagnosis may be possible on a single core. Showing on ultrasound that the needle has passed through the centre of the abnormality and by examining the sample with the naked eye, it is usually, but not always, possible to confirm whether a satisfactory sample has been obtained. Because of this and the knowledge that some lesions are heterogeneous, more extensive sampling of a lesion increases sensitivity. The number of core specimens obtained should reflect the nature of the abnormality being sampled. For ultrasound-guided biopsy where there is a suspicion of carcinoma, it is recommended that multiple core specimens are obtained.

As stereotactic biopsy is used for abnormalities that are difficult to define on ultrasound and are therefore more difficult to sample, a minimum of five core specimens should be obtained. Ensuring that calcification is present in at least three separate cores and/or five separate flecks of calcification are retrieved from the area of suspicion is essential to ensure an accurate diagnosis. For calcifications many prefer VAB, although some units perform 14-gauge core biopsy as their initial biopsy technique.

When there is diagnostic uncertainty after core, VAB can be used to obtain larger tissue volumes (a 7-gauge VAB probe will retrieve approximately 300 mg per core). Ten- to seven-gauge mammotomy probes can be used and are preferred for therapeutic removal of breast lesions such as fibroadenomas.

Biopsy results

It is important that the results of FNA and/or core needle breast biopsy are always correlated with the clinical and imaging findings before clinical management is discussed with the patient. This is best achieved by reviewing each case prior to any surgical or other therapeutic procedure at multidisciplinary meetings.⁵⁰

Surgery for clinically occult breast lesions

Wire-guided excision

The number of impalpable, clinically occult breast lesions detected by screening is increasing. Accurate localisation techniques are required to facilitate their surgical excision. The hooked wire is the most commonly employed technique and has proved very reliable but does have inherent associated problems. There are various designs of localisation wire in common use. All have some form of anchoring device such as a hook with a splayed or barbed tip. The wire is deployed under stereotactic or ultrasound guidance within a rigid over-sheath cannula, which is then removed once positioning is satisfactory (Fig. 1.5). The patient is then transferred to the operating theatre with the wire in situ. Most wires are very flexible and when the cannula is removed the wire may assume a quite circuitous course, especially after stereotactic insertion when the breast is released from compression. In a very fatty breast in which there is no solid lesion or the wire has not transfixed the lesion, care must be taken to avoid displacing the wire. A cosmetically considered incision is placed near to the tip of the wire and an excision performed. Accurate wire placement is essential and ideally the shortest possible length of wire should be within the breast. In recent practice this has been greatly facilitated by the use of radio-opaque and ultrasound visible markers placed at the time of initial stereotactic biopsy such that wire localisation can be performed under ultrasound guidance (Fig. 1.6). In addition, for superficial lesions a skin marker may be more appropriate.

Figure 1.5 Digital mammogram showing a Reidy localisation wire placed under ultrasound guidance transfixing and marking an impalpable mass to facilitate surgical wide local excision (as shown in Fig. 1.4).

Figure 1.6 (a) Ultrasound showing a cluster of gel pellets placed at the site of a previous stereotactic biopsy. The clear visibility of the pellets facilitates ultrasound localisation for surgery of abnormalities that would normally require X-ray localisation. (b) Mammogram after ultrasound localisation in the same case showing accurate placement of the marker wire.

Although lesions may be clinically occult prior to surgery, most mass lesions will be palpable intraoperatively. Procedures that can be surgically more challenging are wide local excisions for DCIS with no mass lesion. In such cases, where the distribution of disease is often more eccentric, careful excision planning is necessary. Inserting more than one wire and bracketing the lesion with three or four wires can be useful.

If the procedure is being performed to establish a diagnosis, a representative portion of the lesion is excised through a small incision, so leaving a satisfactory cosmetic result if the lesion proves to be benign (the European surgical quality assurance guidelines require such diagnostic surgical excision specimens to weigh less than 30 g). For diagnostic excisions of very small lesions, a therapeutic wide excision may (after discussion with the patient) be considered appropriate, as the resulting cosmetic effect of removing an extra rim of normal surrounding tissue may be insignificant. Protocols vary for therapeutic excisions, but in general the lesion should be excised with a 10-mm macroscopic margin of normal tissue. Intraoperative specimen radiography is essential, both to check that the lesion has been removed and, if cancer has been diagnosed, to ensure that adequate wide local excision has been achieved.

Some surgeons experienced in this imaging technique have also used intraoperative ultrasound. Not only can excision be guided but the margins of a wide local excision specimen can also be assessed intraoperatively using ultrasound.

Radioisotope occult lesion localisation

Radioisotope occult lesion localisation (ROLL) has been advocated as an alternative to the hooked-wire technique.⁶³ ROLL was first described by the Milan group using ^99mTc-labelled human macroaggregate albumin, using scintigraphy and a hand-held gamma probe to guide surgical excision. The Nottingham method has modified the Milan technique and uses radio-opaque contrast injected with the radiolabel and immediate check mammography (Fig. 1.7). Subsequently some centres have combined ROLL with sentinel node biopsy. ROLL uses essentially the same equipment as sentinel node biopsy. It has been described using macroaggregate (which does not migrate from the injection site) or low-molecular-weight colloid (which does migrate and is normally used for sentinel node biopsy). In both situations it is radiolabelled with ^99mTc and injected directly into the lesion. The threshold of the signal processor on the gamma detector is then adjusted so that an audible signal is heard only when the probe is directly over the lesion. The probe then directs excision intraoperatively.

Figure 1.7 (a) Mammogram of the right breast showing a small impalpable cancer. (b) Mammogram after injection of radionuclide mixed with X-ray contrast confirming satisfactory localisation (ROLL).

In a randomised trial of ROLL versus wire localisation, 2% of ROLL patients had a failed technique due to intraductal injection of radiolabelled colloid and dye that gave a ductogram appearance on check mammography in both cases.⁶⁴^,⁶⁵ As the radio-opaque dye is absorbed rapidly, both cases were successfully converted to wire localisation. The main differences between ROLL and wire guidance were that both surgeons and radiologists found ROLL easier to perform overall and patients found ROLL less painful. There has been no significant difference in accuracy of marking, operating time, mean specimen weight, intraoperative re-excision or second therapeutic operation in the majority of reports, although a recent European trial reported greater volumes of tissue were excised using ROLL than standard wire localisation. Some studies have suggested that obtaining clear margins may be significantly easier with ROLL. In reality there is little to choose between ROLL and wire localisation. ROLL may be a more suitable technique in the localisation of non-mass lesions (e.g. DCIS), although even for these lesions when multiple wires are placed any advantage is small.

There are various methods described for combining ROLL with sentinel node biopsy.66–68 Low-molecular-weight colloid can be injected at a different site, at the same site with a different radiolabel, or into the tumour. With intratumoral injection of ^99mTc nanocolloid, only one injection is required and high success rates have been reported. Combined with radio-opaque contrast, this modification of the Nottingham method has proved simple and successful.