【medical-news】Lancet Oncol述评：哨兵淋巴结活检在新辅助化疗中的作用仍属未知

Sentinel node biopsy and neoadjuvant chemotherapy



Use of sentinel-lymph-node biopsy as standard care foraxillary staging in patients with clinically node negative (cN0) breast canceris supported by scientific literature covering all aspects of the procedure.Women with negative sentinel lymph nodes do not need axillary dissectionbecause axillary local recurrence after the biopsy procedure is rare (<1%).Furthermore, axillarylymph- node dissection offers no benefi t over sentinel lymph-node biopsy with respect to survival or morbidity.

The role of sentinel-lymph-node biopsy in patients receivingneoadjuvant chemotherapy remains controversial. About 40% of node-positivepatients (cN+) achieve a pathological complete response with current neoadjuvantchemotherapy protocols and might avoid axillary-lymph-node dissection. However,most studies of sentinel-lymph-node biopsy after neoadjuvant chemotherapy,validated by backup axillary-lymphnode dissection, are limited by small size,retrospective design, and wide variation in results. Nevertheless, in threemeta-analyses,1–3 sentinel-lymph-node identification(90–91%) and false-negative (8–10%)rates were only slightly inferior to those of sentinel-lymphnode biopsy ingeneral.

In The Lancet Oncology, ThorstenKuehn and colleagues report fi ndings of SENTINA, a prospective, multicentre cohortstudy of 1737 patients, all of whom received at least six cycles ofanthracycline-based neoadjuvant chemotherapy. All cN0 patients hadsentinel-lymph-node biopsy upfront; if they were node-negative, no further axillarysurgery was done (arm A, n=662), and if they were node-positive, a secondsentinel-lymph-node biopsy procedure and axillary-lymph-node dissection weredone

after neoadjuvant chemotherapy (arm B, n=360). All cN+patients had neoadjuvant chemotherapy upfront; those who converted to cN0status had sentinel-lymphnode biopsy and axillary-lymph-node dissection (arm C,n=592), and those who remained cN+ had axillary-lymphnode dissection (arm D,n=123).

In arms A and B (sentinel-lymph-node biopsy done beforeneoadjuvant chemotherapy), the detection rate was 99·1%. This fi nding validated the study’ssentinellymph-node biopsy protocol (mandatory isotope and optional blue-dyemapping) and confi rmed a high level of quality control within and betweenparticipating centres (n=103; median eight patients per centre).

Sentinel-lymph-node biopsy done after neoadjuvant chemotherapywas less successful. Detection was more frequent in arm C (80·1%) than in arm B (60·8%; second biopsyprocedure) and the false-negative rate was lower (14·2%vs 51·6%). This result accords with findingsof six studies of so-called reoperative sentinel-lymphnode biopsy,5 in whichpositive sentinel lymph nodes were identifi ed in 74% of patients who hadundergone previous sentinel-lymph-node biopsy and in 38% of individuals who hadundergone axillary-lymph-node dissection before. Although positive sentinellymph nodes are found less frequently after neoadjuvant chemotherapy than whenthe biopsy procedure is done upfront, they are found even less often whensentinel lymph-node biopsy is done twice, probably because lymphatic drainageis disrupted by the previous sentinellymph-node biopsy procedure. These findings suggest that sentinel-lymph-node biopsy should be done only once, afterneoadjuvant chemotherapy.

For sentinel-lymph-node biopsy done after neoadjuvantchemotherapy, technique matters. The detection rate was higher, and thefalse-negative rate lower, with a combined dye–isotope technique than with isotopealone, and the false-negative rate was lower with the removal of three or moresentinel lymph nodes (<10%) versus two (18·5%) andone sentinel node (24·3%). These findings accord with otherpublished work on sentinel lymph nodes and are quite similar to those of theACOSOG Z1071 study,6 a prospective trial in which patients with biopsy-proven sentinel-lymph-nodemetastases received neoadjuvant chemotherapy followed by sentinel-lymph-node biopsyand axillary-lymph-node dissection.

Where do we go from here? Many studies have addressed theresults of sentinel-lymph-node biopsy after neoadjuvant chemotherapy, andSENTINA is the

fi rst to do so by clinical node status before and after neoadjuvantchemotherapy. Good performance must now be validated by long-term follow-up,with attention to patterns of local, regional, and distant recurrence.

Kuehn and colleagues suggest that we revisit the relevanceof the false-negative rate—ie, the proportion of axillarynode-positive patients in whom the sentinel lymph node is negative. In patientsalready committed to neoadjuvant chemotherapy, axillary local recurrence is themost meaningful outcome measure, not the false-negative rate.

Growing evidence suggests that selected patients withpositive sentinel lymph nodes can avoid axillary lymph-node dissection. In theACOSOG Z0011 study,7,8 813 women with positive sentinel lymph nodes and clinicalstage T1–2N0 breast cancer were randomized toaxillary-lymph-node dissection versus no further surgery. At 6 years’ follow-up, no diff erences were noted between treatment arms inlocal, regional, or distant events. Many clinicians in the USA (and to a lesserextent in Europe and elsewhere in the world) regard these data as persuasiveand practice-changing, incorporating into their treatment guidelines a policyof no axillary-lymphnode dissection for patients with positive sentinel lymphnodes who meet selection criteria for the Z0011 study. Whether the premise ofZ0011 can be applied after neoadjuvant chemotherapy is uncertain.