T. Kuehn

The prognosis of mammary carcinoma depends on both local tumor control and adequate adjuvant systemic therapy. Chemo-therapy, hormone therapy, and antibody therapy are used individually and in a targeted way. Selection of the systemic treatment approach depends on the likely effectiveness of different substances (predictive factors, such as estrogen and progesterone receptor status, HER2 status) and on the urgency of therapy (prognostic factors). In clinical practice, the nodal status is the most important prognostic factor, substantially influencing the adjuvant treatment decision.

Axillary lymphadenectomy. For many decades, axillary lymph node dissection (ALND) has been an integral component of primary surgical therapy of mammary carcinoma. The objective has been to determine the pathologic nodal (pN) status for designing the adjuvant therapy plan and to secure local tumor control if lymph nodes are positive. ALND therefore represented both a diagnostic and a preventative therapeutic measure.

Numerous studies, however, have demonstrated that ALND is associated with high morbidity in the shoulder–arm region and considerably affects the patient’s quality of life (Kuehn et al, 2000; Keramopoulos et al, 1993). Research has therefore focused on how to identify patients with negative nodal status to save them from radical axillary dissection.

Imaging procedures. The imaging procedures available for evaluating the nodal status are ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography (PET). It has not been possible to obtain acceptable diagnostic accuracy for any of these procedures (Fehr et al, 2004; Rajesh et al, 2002; Rieber et al, 2002; Schirrmeister et al, 2001; Yoshimura et al, 1999).

Alternative surgical procedures. As an alternative to open axillary dissection, an endoscopic method for ALND was developed some years ago. Lymph nodes were removed through the endoscopic access following liposuction and dilatation of the axilla with CO₂ gas. Because of high equipment costs, long surgery times, and comparatively low reduction in morbidity, this procedure did not find its way into routine clinical practice (Kuehn et al, 2001).

Fig. 11.1 Axillary and mediastinal lymph nodes. Diagram of axillary and media-stinal lymph nodes showing sentinel nodes and levels I–III.

SLND is a targeted means of staging to establish the nodal status in patients with mammary carcinoma. The aim is to reduce the morbidity of the standard procedure (complete ALND), without loss of staging accuracy (Kuehn et al, 2005).

False-negative rate. Numerous validation studies have shown that SLND has a false-negative rate (FNR) of 5 to 29% (Kim et al, 2006; Kuehn et al, 2004). In a meta-analysis by Kim and coworkers covering 69 studies and involving over 8000 patients, a mean sensitivity of 92.6% was found (FNR of 7.4%). When calculating the FNR, the number of false-negative cases does not refer to the entire collective, but only to the number of patients with positive nodal status; hence, the rate of women with incorrectly classified nodal status and thus receiving systemic undertreatment is very low.

Due to considerable interinstitutional variability of the FNR (an FNR of up to 60% was found in individual studies), it is essential to pay close attention to clear and standardized procedural instructions to achieve widely reproducible results at a high level (see below).

Relapse rate. Data on the local relapse rate following SLND are now available from numerous studies on several thousand patients (Palesty et al, 2006; Smidt et al, 2005). They all show that the rate lies far below 1% in patients who develop clinically apparent axillary lymph node (ALN) metastasis after SLND.

Postoperative morbidity. Several randomized studies on postoperative morbidity are available; they clearly document the considerable advantage of SLND as compared with standard axillary dissection (Fleissig et al, 2006; Veronesi et al, 2003).

SLN biopsy has therefore become the standard of care to determine the pN-status in patients with early breast cancer.

The introduction of lymphatic mapping has led to renewed interest in the network of lymph vessels and the functional anatomy of the lymphatic drainage from various regions of the breast. An understanding of the lymphatic system is of utmost importance for choosing the tracer and the injection techniques to be used. Although not all aspects of physiology and pathophysiology of the lymphatic drainage from the breast are fully understood, the current view may be summarized as follows (Romrell and Bland, 1998):

Blind-ended lymph capillaries transport the lymph from the parenchymal tissue of the breast through a system of communicating vessels. There are three main directions of drainage:

lymph vessels draining directly through the parenchymal tissue to the lymph nodes

lymph vessels draining along the mammary ducts through the subareolar plexus to the axillary lymph nodes

lymph nodes draining a deep plexus at the base of the breast and through the transpectoral pathway into the axillary and internal lymph nodes

Mapping and imaging of the lymphatic flow by means of tracers has greatly extended our knowledge on the lymphatic drainage of the breast. Currently, the following ideas greatly influence the tracer injection techniques used for SLND.

The entire breast and the overlying skin drain into one or more axillary SLNs. Only regions near the thoracic wall may have additional drainage through the mediastinal lymph node chain. Dermal, subdermal, and periareolar injection can only map the axillary SLNs; deep injection near the tumor or into the tumor also maps the mediastinal SLNs in up to 29% of cases (Borgstein et al, 2000; Nathanson et al, 2001; Roumen et al, 1999; Tanis et al, 2001). Hence, the question of mediastinal lymph drainage depends less on the quadrant than on the proximity of a tumor to the thoracic wall.

SLNs are mapped by using either dyes or radioactive tracers. The use of radionuclides has been established in clinical practice as a standard procedure because of higher detection rates, better reproducibility, and less tissue trauma. The dye method is considered as an optional supplement to make it easier for the surgeon to find the SLN under image guidance.

Dye Method

Fig. 11.2a–c Dye method. Injection of dye in the periphery of the tumor (a). Exposed sentinel lymph node, dye-stained (b, c).

Fig. 11.3a,b Lymphoscintigraphy. Tracer injected in the periphery of the tumor, nuclear medicine imaging of axillary tumor site; (a) without lead shielding, 2.5 hours postinjection, (b) with lead shielding, 2.5 hours postinjection.

Lymphoscintigraphy