Intervention widens breast disease options

Options for image-guided procedures in the breast have expanded considerably over the past 20 years. A variety of modalities are now being used to perform diagnostic, localization, and therapeutic interventional procedures for breast disease.

Image-guided percutaneous procedures for breast diagnosis are accepted and well documented. Whereas such procedures were initially used to examine impalpable breast lesions, radiologists now recognize that image-guided biopsies of palpable lesions can improve diagnostic accuracy. Assessment of impalpable lesions for diagnosis or prior to surgery involves image-guided localization. Interest is increasing as well in image-guided therapeutic procedures such as focused ultrasound and ablation.

The aim of image-guided needle biopsy is to gain an accurate diagnosis of a breast lesion. This principle is enshrined in quality standards for breast screening in the U.K. that set a minimum target of 80%, and an expected target of 90%, for the preoperative diagnosis rate of screen-detected cancers.¹ This means that for all confirmed cancers, at least 80% should have this diagnosis confirmed pathologically prior to surgery. Widespread adoption of wide-bore core biopsy over fine-needle aspiration (FNA) in the U.K. breast screening program has helped achieve this 80% target.

EXPERTISE NEEDED

Both FNA and core biopsy are used widely in breast examinations of symptomatic patients. Up to 40% of FNA cases are not concordant, however, meaning that up to 40% of FNA results prove inaccurate when compared against final outcome.² FNA appears to depend on individual operators' technique and the quality of breast cytology reporting. Lack of suitable expertise in these areas and low diagnosis rates have prompted a shift toward 14-gauge core biopsy. The FNA arm of a study comparing image-guided FNA with core biopsy of impalpable lesions was abandoned due to high rates of insufficient sampling, particularly in the diagnosis of microcalcifications and benign masses.³

Aspirates that are inadequate or noncellular vary from 3.8% to 54%. FNA is also inferior to core biopsy in establishing a diagnosis of lobular carcinoma.⁴ A meta-analysis of 31 papers, covering 17,108 image-guided procedures, demonstrated a mean absolute sensitivity and specificity of 62.4% and 86.9%, respectively, for stereotactic FNA, compared with figures of 90.5% and 98.3% for core biopsy.⁵ Another study has shown that core biopsy can achieve a definitive diagnosis of mass lesions in more than 95% of cases.⁶ Core biopsy also offers the potential to differentiate between in situ and invasive malignancy and to obtain hormonal and human epidermal growth factor-2 receptor status.

Certain histologic results should be interpreted with caution, however, as there is a tendency to underestimate the existence of some pathology from core biopsies. More than 50% of atypical ductal hyperplasia diagnosed with core biopsy proves malignant at surgery, and invasive carcinoma is found in up to one-third of core biopsy-confirmed ductal carcinoma in situ cases. This is particularly true if the microcalcifications were radiologically malignant, more than 30 mm in extent, or high-grade DCIS on core biopsy.

Radial scars diagnosed from core biopsies should also be regarded as high-risk lesions that require excision. It is more difficult to achieve a diagnosis in cases of low-risk calcifications or underlying causes that subsequently prove to be benign. Core biopsy results should therefore be analyzed carefully to ensure that imaging and pathologic data agree.

Although core biopsy has improved the accuracy of image-guided needle biopsy in the diagnosis of impalpable lesions, problems with underestimation and the potential for sampling error have led to the introduction of percutaneous biopsy devices involving a larger volume. Vacuum-assisted biopsy devices such as the Mammotome (Ethicon Endo-Surgery) and the ATEC (Suros Surgical Systems), with needles ranging up to 8 gauge in size, can sample larger tissue volumes than core biopsy devices.

The Mammotome probe, for example, consists of an outer shell with a tissue collection aperture at its end. It is a single-insertion device that uses vacuum suction to pull target tissue into the collecting aperture. Tissue is then excised by a rotating cutter. Multiple harvests can be performed 360 degrees around the lesion, with the probe remaining in the lesion throughout.

ACCURACY RATES

Vacuum biopsy devices have been shown to be superior in the diagnosis of DCIS compared with 14-gauge core biopsy. One study found that 6% of cases diagnosed as DCIS on vacuum biopsy turned out to be invasive carcinoma at surgery. This figure rose to 21% when core biopsy had made the DCIS diagnosis.⁷ Repeat biopsy rates for inadequate sampling of microcalcifications is also significantly lower using vacuum biopsy rather than core biopsy for DCIS (11.6% vs. 23.7%), though an equal proportion of malignancy is diagnosed following rebiopsy.⁸ Vacuum biopsy appears to be nearly three times more accurate than core biopsy in the diagnosis of atypical ductal hyperplasia, but underestimation still occurs in 18% to 25% of cases of vacuum biopsy alone.^9,10 Underestimation for core biopsy occurs in 32% to 71% of cases.

Because vacuum biopsy removes more tissue during sampling than does core biopsy, it can sometimes remove the mammographic abnormality completely.^7,11 This does not always mean that the entire pathologic lesion has been excised, however.¹¹ A localizing clip can be inserted if the mammographic lesion is small and excised during the biopsy procedure. This enables the biopsy site to be readily identified if surgery is subsequently required. Some authors have also used repeat vacuum biopsy to remove such clips if a benign diagnosis is obtained.

Diagnostic biopsies have traditionally been guided by ultrasound and stereotactic methods. MR imaging is now being used as well for biopsy guidance. Use of MRI for the assessment of breast disease and asymptomatic screening in women at high risk of developing breast cancer has led to the detection of lesions that would otherwise have not been visualized. About 40% of lesions that enhance on MRI are occult on ultrasound and mammography, and 20% of incidental enhancing lesions are malignant (30% if synchronous breast cancer).¹² Thus, 20% of such ultrasound and mammographically occult lesions detected on MRI are malignant. Where MRI has been performed on patients with known breast cancer, the incidence of malignancy of such enhancing lesions increases to 30%.

MR-guided FNA and core biopsy are less accurate if the lesion is less than 10 mm in size. MR-guided vacuum biopsy techniques are now replacing MR-guided core biopsies (Figure 1). This has improved sampling accuracy of such lesions to more than 95%.^13,14

LOCALIZATION PROCEDURES

Image-guided localization¹⁵ is required in two clinical settings. Diagnostic surgery may be needed if image-guided needle biopsy has not achieved a definitive diagnosis of a breast lesion. This can occur when radiologic and pathologic findings disagree and the pathologic diagnosis on biopsy is associated with a risk of associated malignancy (e.g., papillary lesions, radial scars, atypical ductal hyperplasia). Localization may also be needed for therapeutic excision of a lesion.

Localization can be guided by ultrasound, MRI, or mammographic/stereotactic methods (Figure 2). The choice will depend on lesion type and visibility. Lesions that are visible on ultrasound and relatively superficial can be identified by simply marking the skin. The most common localization procedures employ various hooked or barbed wires. It is essential that the lesions be adequately transfixed by about 1 cm, particularly when mammographic/stereotactic procedures are used, as the thickness of the breast expands when compression is released, which leads the wire to fall short of the lesion. To ensure adequate localization, the whole width of the lesion should optimally be transfixed, with the tip of wire extending 1 cm beyond the margin of the lesion. The wire's final position is assessed with mammography performed at orthogonal planes to ensure accurate placement. The wire is then excised with the lesion at surgery.

Impalpable breast lesions may be marked with an injection of methylene blue, charcoal suspension, or radioisotopes. Colloidal albumin labeled with technetium-99m can be injected directly into the lesion under stereotactic or ultrasound guidance, in a manner similar to sentinel lymph node biopsy procedures. The accuracy of isotope placement is checked with scintigraphy. A gamma probe can guide excision biopsy. Both the excised lesion and the cavity are checked for radioactivity after excision. X-rays of the specimen ensure radiographic adequacy. This technique is accurate and at least comparable to conventional wire localization.¹⁶ Measured doses of radiation to the breast and to the surgeon's hand are also negligible.

THERAPEUTIC INTERVENTIONS

Image-guided aspiration to relieve symptomatic tense cysts is the simplest therapeutic procedure. The same technique can be extended to nonsurgical management of breast abscesses. Repeat aspirations can be made in smaller collections, and drains placed in larger abscesses (more than 3 cm in size).

Solid breast lesions can be removed by either excision or ablative procedures. Increasing use of wide-bore core biopsy has led to reports of radiologic abnormalities undergoing incidental excision. Removal of mammographic lesions under stereotactic guidance is more likely with vacuum biopsy as opposed to core biopsy. Vacuum biopsy is also associated with less radiologic-pathologic disagreement and fewer underestimates of DCIS than is core biopsy.^11,17

Complete mammographic excision does not, however, correlate with complete pathologic excision. Residual disease can still be found in up to 79% of breast cancer cases at surgery. Ultrasound-guided vacuum biopsy of masses ranging from 1.2 to 1.5 cm in diameter can achieve total excision of ultrasound-visible lesions in 88% to 89% of cases. But 38% of these patients will have a residual mass at six-month follow-up, despite the fact that palpable lesions will no longer be palpable or symptomatic in 88% of cases. Such excisions are best reserved for histologically proven benign lesions such as fibroadenomas.^18-21 Piecemeal methods of sample removal also make it difficult to assess the excision margins of malignant lesions.

Image-guided single cylinder excision alternatives, with diameters of up to 20 mm, include Advanced Breast Biopsy Instrumentation (USA Surgical) and the En-Bloc (Neothermia Corporation). Both manufacturers have exercised caution in promoting these devices for therapeutic use. The ability to remove a single cylinder of tissue makes complete excision of small malignancies technically viable. Studies have also shown that biopsies performed with the En-Bloc led to far fewer underestimations of DCIS and atypical ductal hyperplasia than those performed with the Mammotome.²²

ABLATIVE THERAPIES

The most exciting developments relate to ablative therapies. These involve image-guided percutaneous insertion of devices that will induce tumor necrosis, either by cooling (cryotherapy) or by heating. Radiofrequency waves, microwaves, lasers, or high-intensity focused ultrasound can all be used to induce hyperthermia.²³

Both cryoablation and focused ultrasound can be successful in treating symptomatic fibroadenomas.^24,25 All ablative techniques show promise in the treatment of small breast cancers.²⁶ Most techniques are limited by difficulties in judging whether tumor necrosis is complete. Focused ultrasound may be generating the most interest because it avoids the need to insert a delivery device. MRI is the preferred method of guidance owing to its high sensitivity in detecting breast malignancies.^27-29

FOLLOW-UP NEEDED

Long-term follow-up and additional research are needed to determine the efficacy of ablative techniques as the main treatment option for breast cancer. None can evaluate the status of tumor margins satisfactorily. Local recurrence rates and survival need to be assessed in properly randomized controlled trials involving sizable patient populations.

In conclusion, widening options for image-guided procedures in the breast are reducing the number of diagnostic surgical interventions in favor of minimally invasive procedures. Looking to the future, ablative techniques may eventually offer a nonsurgical option for breast cancer treatment. Long-term studies will be needed to assess disease-free survival and recurrence rates in patients who might benefit most from such procedures.

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