Sentinel lymph node biopsy in breast cancer : aspects on indications and limitations

Sammanfattning: Axillary lymph node status is the most important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) was introduced in the late 1990s and has replaced axillary lymph node dissection (ALND) as the gold standard axillary nodal staging procedure in early breast cancer due to higher accuracy and less morbidity compared with ALND. The overall aim of this thesis was to investigate SLNB and its current role in breast cancer today with a focus on current controversies and its limitations in different clinical settings. The first paper (I) is a national registry study investigating the incidence of positive sentinel lymph nodes (SLNs) in women with a postoperative diagnosis of pure DCIS (ductal carcinoma in situ). We also investigated whether additional tumor sectioning could reveal occult tumor invasion among the patients with tumor deposits in their SLNs. SLNB was performed in 753 patients of whom 11 had tumor deposits in their SLNs. Two patients had macro- and three micrometastasis (N1). Six patients had isolated tumor cells (N0(i+)), resulting in a SLN positive rate of 0.7% (5/753). We did not find any risk factors for SLN metastasis. Occult invasion was found to the same extent among patients with SLN metastasis 9% (1/11) as in the matched control group of 10% (2/21). The aim of the second paper (II) was to evaluate lymph drainage patterns to the axillary lymph nodes with hybrid SPECT/CT imaging before, compared with six weeks after a diagnostic breast excision of an unsuspicious breast tumor. SPECT (single photon emission computed tomography) integrates nuclear medicine imaging with CT (computed tomography) which results in functional images with precise anatomical localization of radioactive SLNs. The contralateral breast served as a control. The SLN detection rate was 91.9% (34/37) on operated sides postoperatively compared with 93.7% (104/111) on non-operated sides, p=0.0771. Partial or total concordance regarding number and localization of radioactive lymph nodes was not significantly lower on operated at 85.7% (30/35) compared with 88.9% (32/36) on non-operated sides, P=0.735. In the third (III) and fourth (IV) papers SLNB in the neoadjuvant settting was evaluated in a Swedish prospective multicenter trial recruiting women with biopsy-verified breast cancer planned for neoadjuvant systemic therapy (NAST). In paper III clinically node-negative (cN0) patients were enrolled and SLNB performed prior to commencement of NAST. A completion ALND was performed in all patients in both trial arms. The identification rate (IR) was 100% (224/224). The proportion of patients with a negative SLNB but still positive lymph nodes in the axilla after NAST was 7.4% (9/121, 95%, CI: 4.0-13.5). In paper IV, SLNB was attempted after NAST in 195 patients with biopsy-proven node-positive breast cancer at stage T1-4d. The overall IR was 77.9% (152/195) and the overall FNR 14.1 % (13/92). The FNR decreased to 4.0% when two or more SLNs were retrieved. Conclusions: Positive SLNs are rare in pure DCIS. SLNB should only be performed if mastectomy is planned or in case of high risk of invasive disease if breast-conserving surgery is planned. SLNB after prior diagnostic surgery seems accurate with minor impact on lymph drainage patterns. SLNB in cN0 patients before NAST is highly reliable. SLNB after NAST in clinically node-positive patients with T1-4d stage breast cancer is feasible but associated with lower IR and higher FNR than in clinically node-negative patients. Only if two or more SLNs are retrieved can the omission of ALND be considered.