Breast Cancer Recurrence in Initially Clinically Node-Positive Patients Undergoing Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in the NEOSENTITURK-Trials MF18-02/18-03.

This study aims to identify factors predicting recurrence and unfavorable prognosis in cN+ patients who have undergone sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC). The retrospective multi-centre "MF18-02" and the prospective multi-centre cohort registry trial "MF18-03" (NCT04250129) included patients with cT1-4N1-3M0 with SLNB+/- axillary lymph node dissection (ALND) post-NAC. A total of 2407 cN+ patients, who later achieved cN0 status after NAC and subsequently underwent SLNB, were studied. The majority had cT1-2 (79.1%) and N1 (80.7%). After a median follow-up time of 41 months, the rates of locoregional recurrence and axillary recurrence (AR) were 1.83% and 0.37%, respectively. No significant difference in locoregional recurrence or AR rates was observed between the SLNB/targeted axillary dissection-only (n = 1470) and ALND (n = 937) groups. Factors significantly linked with AR included age younger than 45 years, nonpathological complete response (non-pCR) in the breast, and nonluminal pathology. Locoregional recurrences were associated with nonluminal or HER2(+) pathology, non-pCR in the breast, and ALND. Poor prognostic factors for disease-free survival (DFS) included having cT3-T4, no breast pCR (non-pCR), ypN(+), and nonluminal pathology. No significant difference was found in DFS or disease-specific survival (DSS) rates among ypN0, ypN-isolated tumour cells, ypNmic, and ypN1. However, significant decreases in DFS and DSS rates were observed when comparing ypN2 or ypN3 disease with ypN0. The present large registry data indicate that younger patients (<45), those with nonluminal pathology, and those who only partially respond in the breast are more susceptible to axillary and locoregional recurrences.

Cabioglu N ，Karanlik H ，Igci A ，Muslumanoglu M ，Gulcelik MA ，Uras C ，Kocer HB ，Trabulus DC ，Ozkurt E ，Cakmak GK ，Tukenmez M ，Bademler S ，Yildirim N ，Akgul GG ，Sen E ，Senol K ，Emiroglu S ，Citgez B ，Ersoy YE ，Dag A ，Zengel B ，Basaran G ，Kara H ，Dilege E ，Ugurlu MU ，Celik A ，Ilgun S ，Bolukbasi Y ，Karaman N ，Sakman G ，Ozbas S ，Kilic HG ，Polat AK ，Ozemir IA ，Kilic B ，Altınok A ，Varol E ，Dogan L ，Akcan A ，Ozcinar B ，Zer L ，Soyder A ，Velidedeoglu M ，Erozgen F ，Goktepe B ，Dogan M ，Kebudi A ，Yigit B ，Celik B ，Yormaz S ，Arici C ，Agcaoglu O ，Sevinc AI ，Atahan MK ，Valiyeva V ，Baran E ，Aljorani I ，Utkan Z ，Yeniay L ，Kivilcim T ，Soran A ，Aydiner A ，Ibis K ，Ozmen V ... -  《-》

Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.

The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC. A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation. Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n = 353) or TAD alone (n = 148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n = 2) and 0.8% (n = 4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LN of one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence. The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Muslumanoglu M ，Cabioglu N ，Igci A ，Karanlık H ，Kocer HB ，Senol K ，Mantoglu B ，Tukenmez M ，Çakmak GK ，Ozkurt E ，Gulcelik MA ，Emiroglu S ，Mollavelioglu B ，Yildirim N ，Bademler S ，Zengel B ，Trabulus DC ，Ugurlu MU ，Uras C ，Ilgun S ，Akgul GG ，Akcan A ，Yormaz S ，Ersoy YE ，Ozbas S ，Dilege E ，Citgez B ，Bolukbasi Y ，Altınok A ，Dag A ，Basaran G ，Utkan NZ ，Ozcinar B ，Arici C ，AlJorani I ，Kara H ，Yigit B ，Sen E ，Erozgen F ，Soyder A ，Celik B ，Kilic HG ，Zer L ，Sakman G ，Yeniay L ，Atahan K ，Varol E ，Veliyeva V ，Goktepe B ，Velidedeoglu M ，Karaman N ，Soran A ，Aydiner A ，Yılmaz R ，Ibis K ，Ozmen V ... -  《-》

ASO Author Reflections: Nodal Recurrence Is Rare in Patients with cN+/ycN0 Breast Cancer after Neoadjuvant Chemotherapy Regardless of the Extent of Axillary Surgery or Nodal Pathology in the NEOSENTITURK-Trials MF18-02/18-03 Provided Regional Nodal Irradi

The combined analysis of the retrospective multicentre and prospective multicenter cohort registry trial NEOSENTITURK MF18-02/18-03 (NCT04250129) investigated the outcomes and factors associated with recurrence in patients with cT1-4N1-3M0 who underwent a succesful sentinel lymph node biopsy or targeted axillary dissection (n = 1470), with or without axillary lymph node dissection (n = 937) after neoadjuvant chemotherapy. The present large registry data suggest that axillary recurrences (AR) can be detected at exceedingly low rates (< 0.5%) within 3 years after surgery. This is regardless of the extent of axillary surgery or nodal pathology, provided that regional nodal irradiation is administered. Factors associated with increased risk for AR included age under 45 years, nonpathologic complete response (non-pCR) in the breast, and nonluminal pathology. Similarly, having cT3-4, a non-pCR in the breast or axilla, and nonluminal pathology were identified as poor prognostic factors.

Cabioglu N ，Karanlik H ，Igci A ，Muslumanoglu M ，Gulcelik MA ，Uras C ，Kocer HB ，Soran A ，Ibis K ，Ozmen V ... -  《-》

De-Escalation of Nodal Surgery in Clinically Node-Positive Breast Cancer.

Cabioglu N ，Koçer HB ，Karanlik H ，Gülçelik MA ，Igci A ，Müslümanoglu M ，Uras C ，Mantoglu B ，Trabulus DC ，Akgül G ，Tükenmez M ，Senol K ，Özkurt E ，Sen E ，Karadeniz Çakmak G ，Bademler S ，Emiroglu S ，Yildirim N ，Kara H ，Dag A ，Dilege E ，Altinok A ，Basaran G ，Varol E ，Ugurlu Ü ，Bölükbasi Y ，Ersoy YE ，Zengel B ，Karaman N ，Özbas S ，Zer L ，Gül Kiliç H ，Agcaoglu O ，Sakman G ，Utkan Z ，Soyder A ，Akcan A ，Ergün S ，Yilmaz R ，Aydiner A ，Soran A ，Ibis K ，Özmen V ... -  《-》

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy.

Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) have excluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) status (odds ratio [OR] 2.5; p < 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and two of the three underwent ALND at the initial surgery with no additional positive nodes. In cT1-2N0 breast cancer, HR+/HER2- status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.

So A ，Yi M ，Simons JM ，Kuerer HM ，Caudle A ，DeSnyder SM ，Bedrosian I ，Nead KT ，Chavez-MacGregor M ，Teshome M ，Hunt KK ... -  《-》