Accuracy of SLN Biopsy in Patients with Large Primaries

Up to a few years ago the question implied by this heading was not discussed at all, because in cases with large primaries the routine treatment was mastectomy with axillary revision (levels I and II).

In early pT2 cases the SLN concept can be applied in the same manner as in pT1 cases. However, in more advanced pT2 and in pT3 cases, especially when these have developed in small breasts, peritu-moral 99mTc-sulfur colloid labeling is difficult and breast-conserving surgery becomes progressively more difficult and ultimately impossible.

Now, however, with the developing tendency to perform preoperative down-staging by means of chemotherapy (CMF or anthracycline-containing regimens in c-erbB2- and/or p53-positive cases) the chance that breast-conserving surgery will become possible increases (McCready et al. 1988; Bo-nadonna et al. 1990; Schwartz et al. 1994; Botti et al. 1995; Fisher et al. 1997, 1998; Kling et al. 1997; Cunningham et al. 1998; Kuerer et al. 1998).

In this context, it must be emphasized that it is of critical importance to perform axillary lymph node staging before chemotherapy is started, for the following reasons:

• Because lymphatic spread after axillary revision before down staging - especially in cases with chemoresistant primaries - would be directed to other basins (interpectoral, infraclavicular or parasternal)

• Because noninvasive imaging techniques fail to detect incipient metastasis in the axillary lymph nodes.

Furthermore, no systematic investigations have been carried out in order to find out whether the rate of simultaneously developing axillary and para-sternal lymph node metastases (we call it "double basin sentinel node implication") increases in proportion to the size (pT-value) of the primary.

To avoid extended axilla revision before chemotherapy-induced down-staging of the primary the team working in the Mayo Clinic and the Philadelphia University Hospital has recently tried to eval

Table 13. Important histological and radiodiagnostic delineation criteria of cancer subtypes and fibroadenomas

Malignant lesions

Specific characteristics (histology/radiology)

Mucinous cancer

Mostly grade I or (II) PAS, Alcian blue, positive mucus

Medullary cancer

Mostly grade III (II) lymphocyte infiltration, high rate of mitosis

Benign lesions

Intra- and extraca-nalicular fibroadeno-mas

"Young" — strong signal in MRT

"Older types" — less intensive signal in MRT, because of fibrosis

Nodes of sclerosing adenosis

No strong signal in MRT, because of reduced vascularization

uate the accuracy of SLN biopsy in a collective of 103 patients with large primaries (>2 but <5 cm ~pTl-2). The detection and localization of SLN(s) could be confirmed in 99% of these cases. The overall rate of lymph node metastasis was 59% [95% exact confidence interval (95% CI), 49-68%], or 61 of 104 cases.

The SLN false-negative rate was 2% (95% exact CI, <1-11.5%) (2 patients).

In 56 tumor cases with primaries > 3 cm 1 false-negative result [2% (95% exact CI, <1-15%)] was identified, and the rate of lymph node metastasis was 62.5% (95% exact CI, 48.5-75%) (35 of 56 tumors).

Among 30 SLN-positive patients with tumors > 3 cm in size who underwent complete axillary lymph node dissection, 3 of 8 patients [37.5% (95 exact CI, 8.5-75.5%)] with micrometastasis (< 2 mm) to the sentinel lymph node had positive non-SLN, compared with 21 of 22 patients [95.5% (95% exact CI 77-100%)] with macrometastases (>2 mm) to the SLN (P = 0.002).

An overview of Bedrosian's data is given in Table 14 (Bedrosian et al. 2000), which documents the sentinel node detection rate, the rate of false-negative sentinel nodes, the average number of axillary lymph nodes investigated, and the rates of metastatically involved nodes in the presence of pT2-cancers (divided into > 2 cm and > 3 cm).

The comparison of a collective (n = 87) with 2% false negative sentinel nodes with a collective of cancers with diameters > 3 cm (n = 56) with approximately the same overall rate of metastases (59% vs 62%) and a 37% rate of micrometastases showed the same rate of false-negative nodes (2%) in the second collective.

The results of this group are summarized in Table 15. These results can only give a clue that might help in individual decision-making in cases with larger primaries. The most critical points, which must be very carefully calculated and discussed, are:

• Unfavorable relation of the size of the breast to tumor size plus necessary tumor free margins.

• Resistance of the cancer to the cytostatics usually used (e.g., c-erbB2-, p53-, or vimentin-posi-tive cancers resistant to CMF).

In CMF-resistant cases, when a non-anthracycline-containing combination is used, if there are no lo-coregional and hematogenous metastases at the time of primary diagnosis the cancers can spread

Table 14. Overview regarding accuracy in the Pennsylvania project (CI confidence interval)
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