Preoperative breast imaging guides surgical management

Breast cancer is the most common malignancy in adult women. One woman in 11 will contract the disease during her lifetime. The primary goal of treatment is cure, through surgery either alone or in combination with radiotherapy and/or chemotherapy. Surgical management options include breast conservation, mastectomy, and palliative treatment.

The goal of breast surgery is treatment of the cancer in a single definitive procedure, leaving clear margins while also ensuring a satisfactory cosmetic outcome. Preoperative breast imaging provides vital information for the surgeon, enabling optimal procedural planning. It should also increase the likelihood that the surgeon can achieve clear margins, which is considered essential to avoid recurrent disease. An accurate preoperative radiological assessment of local disease extent is possible only if users understand the role of available imaging modalities and their pitfalls. Users should also appreciate the indications and contraindications of different surgical options and the information required by the surgeon.

Breast conservation surgery includes lumpectomy, quadrantectomy, and segmental mastectomy. Eligibility for this type of surgery depends on local disease extent relative to breast size. The total extent of disease (solitary focus or multiple foci) should, in general, measure less than 5 cm. Patients who undergo breast conservation surgery always require adjunctive radiotherapy.

Mastectomy is performed when the disease extent is greater then 5 cm or is multicentric (foci of cancer in different quadrants of the breast) is present. Other patients requiring mastectomy include those with recurrent disease or a new primary lesion in a previously irradiated breast. Some patients may opt for mastectomy out of personal preference.

MODALITY CHOICE

Mammography and breast ultrasound are both often used for the preoperative assessment of breast cancer patients. Although the value of mammography has been demonstrated repeatedly, the modality has poor sensitivity in patients with dense and heterogeneously dense breast tissue.

Reports of sensitivities ranging from 30% to 48% suggest that screening mammography is of limited value in this subgroup.^2,3 Studies are now showing, however, that digital mammography is more sensitive than screen-film mammography in this patient population.⁴

Focused breast ultrasound is extremely useful for examining areas of concern in symptomatic patients and for further evaluation of suspicious lesions identified on mammography. Ultrasound may also be used to guide biopsies in these patients, if required.

The use of breast MRI is increasing, though its availability remains limited. American College of Radiology practice guidelines suggest that breast MRI should be used to establish the extent and/or presence of disease in patients with radiologically dense breasts, infiltrating lobular carcinoma, or possible invasion of pectoralis muscle.

The diagnostic accuracy of mammography, clinical examination, ultrasound, and MRI for the preoperative assessment of patients with breast cancer has been evaluated (Tables 1 and 2).¹ Researchers studied 111 consecutive women with 258 histologically proven foci, of which 177 foci were malignant. They found that additional breast imaging identified tumor foci, altering the surgical approach, in 31% of patients. A total of 9% of the patients were found to have synchronous bilateral cancer at the time of presentation. MRI was confirmed as the most sensitive modality, though it overestimated the extent of disease in 21% of patients.

PREOPERATIVE CHECKLIST

A simple checklist helps guide surgical decisions.

• Side, site, and size of invasive cancer. Multiple studies have shown MRI to be more accurate than mammography and ultrasound in determining tumor size, particularly in patients with dense breast parenchyma. Just one tumor was underestimated for size in the above-mentioned study when using mammography, clinical examination, and MRI (1% of cases). Tumor size was overestimated in 20% of cases.¹

Adding ultrasound to this group of tests did not improve the overall diagnostic yield. The availability and lower cost of ultrasound must be taken into consideration, however. Ultrasound also provides a fast and reliable means of image-guided biopsy.

• Contralateral breast cancer. Mammography and clinical examination will reveal 2% to 3% of patients as having synchronous bilateral cancer at presentation.⁵ Additional imaging will take the rate of synchronous bilateral cancer up to 9%.¹ Incidence increases in patients younger than 55 years old and in those who have invasive lobular carcinoma.⁶

• Suspicious microcalcifications. Malignant calcifications extending over a distance greater than 5 cm are a contraindication to breast conservation surgery.

• Multifocal disease. Multifocal disease implies the presence of multiple discrete discontinuous tumor foci associated with one duct network; that is, within one quadrant of the breast. The majority of additional tumor foci will be found in the same quadrant as the index lesion. In one reported series, for 40 out of 46 breasts with additional tumor foci, these foci were found within 4 cm of the index lesion.¹ It is consequently advised that, at the very least, the quadrant in which the index lesion lies must be evaluated with ultrasound (Figure 1).

• Multicentric disease. Multicentric disease implies that multiple foci of cancer are present within separate quadrants of the breast. These foci may represent the independent transformation of two separate cell groups. Multicentric disease occurs less frequently than multifocal disease, and it is a contraindication to breast conservation surgery (Figure 2).

• Pectoralis muscle invasion. Pectoralis muscle invasion is best assessed with contrast-enhanced MRI. Find¬ings include obliteration of the fat plane and pectoralis muscle enhancement. The addition of sagittal acquisitions to a standard breast MRI protocol is helpful (Figure 3).

• Axillary lymph node status. The ipsilateral axilla should be examined in all patients presenting with malignancy. Abnormal and indeterminate nodes should be sampled using either ultrasound-guided fine-needle aspiration or core biopsy. Ultrasound-guided FNA has a reported sensitivity of 89%, specificity of 100%, and positive predictive value of 100% in axillary lymph nodes that are palpable or suspicious on ultrasound.⁷ If FNA or core biopsy yields a positive result, then the patient may proceed to axillary clearance and will not require a sentinel lymph node procedure.

USE OF MR IMAGING

A review article published in a leading journal in 2007 contained the following words of caution: "Whilst breast MRI is far superior to mammography with or without concomitant ultrasound, for the local staging of breast cancer, it may result in unnecessary mastectomy if old guidelines are simply copied onto a new situation."⁸ Patients with multicentric disease are not eligible for breast conservation surgery, as mentioned above. The relevance of this guideline to MRI-detected multicentric disease, however, is now open to question.

This particular guideline was established when preoperative local staging of breast cancer was performed exclusively with mammography. Because MRI is a more sensitive imaging modality, it will detect more small disease foci than mammography. In other words, it will detect foci that would not have been seen if only mammography had been available. Some physicians believe that surgical resection of these lesions is unnecessary and, possibly, overtreatment. They contend that radiotherapy will deal adequately with these small foci of disease.⁸ It could also be argued that MRI should not replace other breast imaging modalities because its accuracy has not been assessed in a randomized control trial. This could equally be said of diagnostic breast mammography, however.

Randomized control trials have been conducted only on screening mammography, not diagnostic mammography. Randomized control trials are not actually required to justify the use of a diagnostic test. Current guidelines from the Oxford Centre for Evidence-based Medicine in the U.K. state that a diagnostic test must be evaluated by several prospective trials and compared with a reference standard. The new diagnostic test may become the new standard once this has been done and it has consistently and concordantly proven to be superior to the previous standard.⁹

One group of researchers showed that a cohort of women who had preoperative staging with MRI had a three-year recurrence rate of 1.2%.¹⁰ The three-year recurrence rate in patients who underwent mammography and ultrasound was found to be 6.8%. Although this was a retrospective study, the results cannot be ignored. Institutions that offer MRI for the preoperative evaluation of disease extent must also be able to offer MR-guided biopsy of those additional lesions that have been identified by MRI alone.

MR-guided vacuum-assisted biopsy has been shown to be safe and accurate for this task.¹¹ MR-guided preoperative needle localization may be used as an alternative, though it carries the added risks associated with surgery and may result in a poor cosmetic outcome.

CHEMOTHERAPY AND CLIPS

Many patients with breast cancer undergo neoadjuvant chemotherapy to reduce the size of the tumor preoperatively. Some breast cancers are so chemosensitive that they shrink to such a small size that subsequent radiological detection becomes problematic. This problem can be solved by prior placement of radiopaque clips for tumor localization.

Researchers have demonstrated that clip placement is associated with better local control, independent of stage and other clinicopathologic findings. The risk ratio of local recurrence in this study was found to be 3.69 greater if clip insertion was omitted, compared with patients who did have clip placement.¹²

Clip placement is a relatively simple procedure, though early and/or late migration of clips can cause complications. Clips may move within the same quadrant or even to another quadrant of the breast, which may affect localization for surgery. A two-view mammogram should be performed following placement to check position.

In conclusion, mammography should be the initial modality used for preoperative imaging. Ultrasound should be used to evaluate the index lesion and the quadrant in which it lies. It should also be used to assess ipsilateral axilla and guide biopsies of suspicious lymph nodes. MRI may be used judiciously. It is advised for women with dense breast tissue and intralobular carcinoma and for younger patients.

References

1. Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR Imaging in pre-operative assessment of breast cancer. Radiology 2004;233(3):830-849.
2. Mandeslon MT, Oestreicher N, Porter PL, et al. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 2000;92(13):1081-1087.
3. Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluations. Radiology 2002; 225(1):165-175.
4. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast cancer screening. NEJM 2005;353(17):1773-1783.
5. Hungness ES, Safa M, Shaughnessy EA, et al. Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts. Surgery 2000;128(4):702-707.
6. Healey EA, Cook EF, Orav EJ, et al. Contralateral breast cancer clinical characteristics and impact on prognosis. J Clin Oncol 1993;11(8):1545-1552.
7. Jain A, Haisfield-Wolfe ME, Lange J, et al. The role of ultrasound-guided fine needle aspiration of axillary nodes in the staging of breast cancer. Ann Surg Oncol 2008; 15(2):462-471.
8. Kuhl C, Kuhn W, Braun M, et al. Pre-operative staging of breast cancer with breast MRI: one step forward, two steps back? Breast 2007;16(Suppl 2):S34-S44.
9. Oxford Center for Evidence-based Medicine's Levels of Evidence (2001). Available at: www.sciencedirect.com/science.
10. Fischer U. The influence of preoperative MRI of the breasts on recurrence rate in patients with breast cancer. Europ Radiol 2004;14(10):1725-1731.
11. Perlet C, Heinig A, Prat X, et al. Multicenter study for the evaluation of a dedicated biopsy device for MR-guided vacuum biopsy of the breast. Europ Radiol 2002;12(6): 1463-1470.
12. Oh JL, Nguyen G, Whitman GJ, et al. Placement of radiopaque clips for tumor localization in patients undergoing neoadjuvant chemotherapy and breast conservation therapy. Cancer 2007;110(11):2420-2427.

Dr. Thornton, Dr. Looby, and Dr. Hanlon are specialist registrars in radiology at Beaumont Hospital in Dublin, Republic of Ireland. Assisting in the preparation of this article were Dr. Deidre Duke and Prof. Michael Lee, both from the radiology department at Beaumont Hospital.