Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival-a propensity score cohort study.

PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial).

Introduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. Methods and analyses: This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. Discussion: This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. Ethics and dissemination: The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results. Trial registration: ClinicalTrials.gov, identifier number NCT04889924.

Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

PURPOSE: To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis. METHODS: A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter. Axillary lymph node dissection (ALND) was indicated only in SLNB macrometastasis, although in selected elderly patients, it was omitted. Kaplan-Meier survival curves were estimated in relation to the status of the axilla, and the differences assessed using the log-rank test. RESULTS: Between December 2006 and March 2022, SLNB was performed pre-NET in 14 cases and post-NET in 77. Both groups were similar in baseline tumor and patient characteristics. SLNB positivity was similar regardless of whether SLNB was performed before (5/14, 35.7%) or after NET (27/77, 37%), with 2/14 SLN macrometastases in the pre-NET cohort and 17/77 in the post-NET cohort. Only three patients (18.7%) with SLN macrometastasis had > 3 positive nodes following ALND. The 5-year overall survival and distant disease-free survival were 92.4% and 94.8%, respectively, with no significant differences according to SLNB status (p 0.5 and 0.8, respectively). CONCLUSION: SLN positivity did not differ according to its timing (before or after NET). Therefore, NET has no effect on lymph node clearance. Furthermore, the prognosis is good regardless of the axillary involvement. Therefore, factors other than axillary involvement may affect the prognosis in these patients.

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

PURPOSE: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. METHODS: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. RESULTS: After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). CONCLUSIONS: In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Lymphoscintigraphy in oral squamous cell carcinoma sentinel node biopsy and its role in the surgical planning.

AIM: The purpose of this study was to analyze the influence of different lymphatic pathways on surgical planning and the reliability of sentinel lymph node (SLN) biopsy to predict regional recurrence in patients with clinically N0 oral squamous cell carcinoma (OSCC). METHODS: Twenty-five patients with cT1/T2 N0 OSCC underwent a lymphoscintigraphy and an SLN biopsy. Elective neck dissection was performed at the validation stage and in patients with metastatic SLN. Scintigraphic and surgical SLN detection, pathologic status of SLN and of elective neck dissection, and regional recurrence in patients with negative SLN (pN0(sn)) were all analyzed. RESULTS: Scintigraphic and surgical detection were 96% and 100%, respectively, with 68% of negative SLN. Lymphoscintigraphy modified surgery in 32% of patients. In pN0(sn) patients, the free-of-disease survival rate was 88%. CONCLUSIONS: These results support the reliability of sentinel node biopsy in OSCC. Presurgical lymphoscintigraphy is essential, because it can modify the surgical procedure.

Avoiding axillary treatment in sentinel lymph node micrometastases of breast cancer: a prospective analysis of axillary or distant recurrence.

BACKGROUND: The need for axillary lymph node dissection (ALND) in breast cancer patients with sentinel lymph node (SLN) micrometastases remains controversial. The aims of the study were to evaluate the locoregional failure and outcome of breast cancer patients with sentinel node micrometastases who did not undergo completion ALND. METHODS: Between November 2000 and December 2006, SLN biopsy was successfully performed in 1178 patients with invasive breast carcinoma. Only patients with macrometastasis (>2 mm) underwent ALND, while patients with negative SLN or micrometastases did not undergo further treatment of the axilla, by either surgery or radiotherapy. Regarding adjuvant therapy decision, patients with SLN-micrometastases (pN1(mi)) were considered as node-positive patients. RESULTS: Of 1,178 patients, 59 (5%) had micrometastases. Of those with micrometastases, 14 (24%) underwent ALND because the intraoperative study of the SLN yielded a positive result. With a median follow-up of 60 (range, 8-94) months, none of the patients with SLN micrometastases in whom ALND was omitted developed an axillary recurrence, while one patient in whom ALND was performed developed infraclavicular lymph node recurrence. One patient, who declined postoperative breast irradiation, developed breast recurrence and distant metastasis. CONCLUSIONS: Breast cancer patients with SLN micrometastases in whom ALND was omitted had a very low locoregional failure rate. This study supports the theory that ALND might be avoided in these patients, providing that adjuvant systemic treatment equal to treatment provided to treat node-positive disease is administered. However, longer follow-up and results of additional prospective studies are needed.

Patients with breast cancer and negative sentinel lymph node biopsy without additional axillary lymph node dissection: a follow-up study of up to 5 years.

OBJECTIVE: To analyze the rate of axillary recurrences and survival in patients operated on for breast cancer who had not undergone an axillary lymph node dissection (ALND) because of a negative sentinel node biopsy. METHODS: The study includes 97 patients operated on for breast cancer and selective node biopsy from June 2000 to December 2001 who had a negative sentinel node biopsy and did not undergo ALND. Mean age was 58.2 years (55.9-60.5). Follow-up was done up to 5 years. After surgery all patients underwent clinical examination. Complementary treatment depended on the hospital protocol. Rate of axillary recurrences, presence of distant metastases and survival (Kaplan-Meier method) were studied. RESULTS: After a median follow-up of 4.1 years (2.18-5.25), only 2/95 patients (2.1%) developed distant metastases. Four patients died but only the death of the patient who presented multiple metastases was related to the primary breast cancer (1%). The 5-year overall survival rate was 96%. CONCLUSIONS: (1) Only 1/95 patients studied developed nodal extra-axillary recurrence together with distant metastases. (2) The results obtained support the selective sentinel node biopsy as an accurate technique in the axillary stratification of patients with breast cancer, offering in the cases of negative sentinel node biopsy a safe axillary control after a 5-year follow-up.