Update on detection of sentinel lymph nodes in patients with breast cancer

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Sentinel lymph node biopsy is now the practice of choice for the management of many patients with breast cancer. This was not true in the early 1990s, when the first such procedures were performed and protocols for such were refined often. This was also not true in the first years of the 21st century, when a decade of collective experience and information acquired from numerous clinical investigations dictated additional subtle and not-so-subtle refinements of the procedures. However, it is true today; reports of the latest round of clinical investigations indicate that there are several breast cancer sentinel node procedures that result in successful identification of potential sentinel nodes in nearly all patients who are eligible for such procedures. A significant component of many of these successful sentinel node procedures is a detection and localization protocol that involves radiotracer methodologies, including radiopharmaceutical administration, preoperative nuclear medicine imaging, and intraoperative gamma counting. The present state and roles of nuclear medicine protocols used in breast cancer sentinel lymph node biopsy procedures is reviewed with emphasis on discussion of recent results, unresolved issues, and future considerations. Included are brief reviews of present radiotracer and blue-dye techniques for node localization, including remarks about injection strategies, counting probe technology, and radiation safety. Included also are discussions of on-going investigations of the implications of the presence of micrometastases; of the management value of detection, localization, and excision of extra-axillary nodes such as internal mammary nodes; and of the broad range of recurrence rates presently being reported. Remarks on the present and possible near- and long-term roles for nuclear medicine in the staging of breast cancer patients including comments on positron emission tomography and intraoperative imaging conclude the article.

Section snippets

Background

The history of breast cancer management during the past few decades has been one of decreasing invasiveness, decreasing morbidity, and increasing effectiveness. Absent the latter result, the former 2 are partial successes, but it is the latter that is the most desired and most beneficial. Today, women diagnosed with breast cancer survive, on average, longer than ever before. This is, in part, a result of the broad multidisciplinary approach now used in the evaluation and treatment of

Some sentinel node history

Sentinel lymph nodes are the nodes in a tumor bed that first receive lymphatic drainage from the tumor and are, therefore, the nodes most likely to harbor tumor cells, if tumor cells have indeed entered the lymphatics. William Halsted described lymph nodes as barriers to the spread of tumor cells, as vehicles for progression of tumor spread within lymphatics, and as vehicles for progression of tumor spread from lymphatics to more remote sites.2 That description includes good precursors of the

Radiotracer versus blue dye

Overwhelmingly, there is agreement that using a combination of blue-dye and radiotracer techniques is a better approach for successful sentinel lymph node identification and excision than using either technique singularly.11 Success here is defined as accurate staging of a patient’s disease, although, as noted above, few studies are conducted with this as a measure of success. In the blue-dye technique, isosulfan blue is injected in the operating room. It is injected intradermally,

Radiotracer methodologies

Among the hundreds of articles published on breast cancer sentinel node procedures are numerous ones investigating the details of various radiotracer strategies. Such details include the choice of radiopharmaceutical, the sizes of the particles of the radiopharmaceutical, the dose per injection, the volume per injection, the site(s) of injection, the localization or not of internal mammary sentinel nodes, the time span between injection and surgery, the use or not of preoperative imaging, the

Gamma counting probes

The nuclear medicine tool used intraoperatively in sentinel lymph node protocols is the gamma counting probe. Because a probe should accurately discriminate between primary and scatter photons, good sensitivity, side shielding, and energy resolution are probe characteristics that are important to successful detection and localization of foci of radioactivity. Today, a practitioner’s choice of probe system for breast cancer sentinel node protocols is mostly a matter of personal preference as

The role of the pathologist

The thorough histopathologic examination of sentinel lymph nodes given by a pathologist includes multisectioning and multiple analyses. Given practical considerations, such thorough analysis cannot be applied to all nodes excised in a total axillary nodal dissection. The sentinel node procedure results in 1, 2, sometimes 3, and less commonly 4 or more sentinel nodes, compared with the 10 to 30 nodes that are often excised and submitted for pathological analysis in axillary dissection

Prognostic significance of micrometastases

On this topic, three important questions often are asked (1) What is the significance of micrometastases? (2) Does the presence of micrometastases have the same clinical significance as the presence of macrometastases? (3) How many tumor cells in a lymph node constitute micrometastases such that they can result in further tumor growth and spread? In an effort to evaluate the clinical significance of axillary lymph node micrometastases, Sakorafas and coworkers performed a literature review from

Internal mammary sentinel lymph nodes

This controversy centers on the utility of information obtained in lymphoscintigraphy about drainage to internal mammary sentinel nodes (see Fig. 1). Most surgeons are reluctant to excise internal mammary nodes because of the difficulty of such surgery and, thus, some question the value of obtaining information about such nodes. Other physicians have said that patients that have lymphatic drainage to internal mammary nodes and axillary sentinel node involvement should have prophylactic

Radiation safety

If all members of the multidisciplinary team practice standard biohazard safety and radiation safety procedures, breast cancer sentinel lymph node protocols are considered radiation safe for patients, nuclear medicine technologists, nuclear medicine physicians, oncology surgeons, surgical nurses, and pathologists. Standard practice should always include at minimum the use of the Universal Precautions biohazards guidelines and the As Low As Reasonably Achievable (ALARA) radiation safety

Other cancers

Patients with intermediate thickness malignant melanoma were the first to benefit significantly from sentinel lymph node excisional biopsy procedures. The sentinel node concept was popularized for the staging of cutaneous melanoma, and indeed, sentinel node biopsy using radiocolloid with imaging has become the preferred method of staging melanoma. As noted in our opening paragraphs, the success in recent years of lymphoscintigraphic imaging for sentinel lymph node localization, is, in part, the

Intraoperative gamma imaging

Various technologies for intraoperative gamma imaging are being developed and investigated. Many articles have reported on devices that are being investigated for intraoperative imaging of sentinel nodes in patients with breast cancer.81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94 The broad clinical goals of the investigations being conducted vary, with the goals of each being defined in part by the technologies involved and in part by the difficulties with existing technologies and

The future

There is no single “best” or “optimal” protocol for detection, localization, and assessment of sentinel lymph nodes of breast cancer patients. Because allocation of resources vary among institutions, it is not clear there will be. It does seem relatively clear that the use of a sentinel lymph node protocol as opposed to one for full axillary lymph node dissection is appropriate management for some breast cancer patients. We note, however, there are no study reports that provide data that can be

Acknowledgments

The authors thank Sandra F. Grant, Robert A. Mintzer, and Carmen M. Greene for assistance in the preparation of the manuscript.

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