Sentinel Lymph Node Macrometastases Research Articles

Abstract PO1-19-03: The T-REX trial: a randomized international non-inferiority trial on Tailored Regional EXternal beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases

Abstract Background: Modern systemic treatment has reduced the incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still indicated in patients with sentinel lymph node (SLN) macrometastases. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease, and secondary cancer. Therefore, there is a need to individualize the indication for regional RT in relation to risk of recurrence. Trial design: In this multicenter, prospective randomized phase 3 trial, eligible patients have a clinically node-negative, estrogen receptor-positive, HER2-negative BC with 1-2 SLN macrometastases, and have not undergone completion axillary lymph node dissection. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axillary levels I-III and the supraclavicular fossa. Internal mammary nodes are targeted in selected patients. After breast-conserving surgery (BCS), RT to the remaining breast is given in both groups while after mastectomy, chest-wall RT is only given in the standard arm. In the intervention arm, chest wall RT may be indicated in selected cases with extensive multifocality, according to national guidelines. RT quality assurance is an integral part of the trial. In addition, material from the primary tumor, SLN metastases and any recurrences is subjected to gene expression analysis to identify both prognostic markers for locoregional recurrence and predictive markers for the benefit of regional RT. After confirmation of eligibility and written informed consent, patients are randomized 1:1 between the treatment arms. Allocation is stratified by trial site and breast surgery (BCS vs. mastectomy). Participation in T-REX should not affect decisions on systemic adjuvant treatment. Eligibility criteria: Trial inclusion and exclusion criteria are given in Table 1. Specific aims: The main aim of the trial is to investigate if the omission of regional RT is non-inferior to routine regional RT in clinically node-negative BC patients with estrogen receptor-positive, HER2-negative T1-2 tumors with 1-2 SLN macrometastases not receiving axillary lymph node dissection. Secondary aims are to investigate whether refraining from regional RT reduces arm morbidity and late RT side effects, and improves short- and long-term health-related quality of life. In addition, the use of genomic classifiers for the prognostication of locoregional recurrences and the prediction of a benefit from regional RT will be investigated. Statistical methods: Primary outcome is recurrence free survival (RFS) at five years. Non-inferiority will be declared if the outcome in the intervention arm is not more than 4.5 percentage units below the standard arm, corresponding to a hazard ratio of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity, and health-related quality of life. Accrual: The trial will include 1350 patients in Sweden, Norway and Finland from April 2023 to December 2028. First sites have been opened in April 2023. Contact information: Primary Investigator: Sara Alkner, Skåne University Hospital, Lund University, sara.alkner@med.lu.se. Responsible for the biobank: Per Karlsson, Sahlgrenska University Hospital, Gothenburg University, per.karlsson@oncology.gu.se. Inclusion and exclusion criteria Citation Format: Sara Alkner, Jana de Boniface, Dan Lundstedt, Ingvil Mjaaland, Lisa Rydén, Johan vikström, Pär-Ola Bendahl, Erik Holmberg, Helena Sackey, Elinore Wieslander, Per Karlsson. The T-REX trial: a randomized international non-inferiority trial on Tailored Regional EXternal beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-03.

Abstract PO3-17-09: Outcome after the introduction of personalized treatment for axilla in patients with clinically node-negative early breast cancer

Abstract Background : After the results of ACOSOG Z0011 and AMAROS trials were reported, axillary treatment has been promoted to de-escalation. For clinically negative cases of axillary lymph node metastasis (cN0), axillary dissection (Ax) has been the standard treatment when sentinel lymph node (SN) metastasis is positive. In our hospital, for patients with cN0, if SN macro metastasis is positive, Ax or irradiation (RT) is selected after sufficient explanation to the patients. Five years have passed since the introduction of treatment selection for the axilla, we examined treatment outcomes retrospectively. Methods : The subjects were 1376 patients who underwent SN biopsy for primary breast cancer with cN0 at our hospital from October 2004 to December 2018 (median observation period 79 months). Cases who underwent preoperative chemotherapy were excluded. We have introduced the treatment choice system since December 2015, and compared prognosis (local recurrence, distant recurrence and breast cancer specific death) before and after introduction using the log-rank test. Results : There were 947 cases before introduction of treatment choice system (pre group) and 429 cases after introduction (post group). The median observation period for each group was 91 months and 41 months. The maximum observation period post group was 67 months, then we compared the number of events in patients with observation period less than 67 months in pre group. There was no significant difference between two groups (Pre/Post) in terms of age (p=0.52), menopausal status (p=0.90), invasion of primary lesion (p=0.19), biology and SN metastasis status (p=0.41). There were 54 patients (12.6%) in pre group and 135 (14.3%) patients in post group had positive sentinel lymph nodes. In post group, 33 patient (61.1%) were macrometastasis of SN, 28 of whom underwent Ax and 5 underwent RT. Local recurrence was 4 cases (1.7%) in pre group, 9 cases (2.1%) in post group (p=0.84), distant recurrence was 13 cases (5.6%) and 5 cases (1.2%) (p=0.0002), and breast cancer specific death was 8 cases (0.8%) and 1 case (0.2%) (p=0.0003), respectively. Discussion : There was no significant difference in local recurrence rate within 67 months, but were poor prognosis in pre introduction group for distant metastasis and breast cancer specific survival. In the results of this study, there was no significant difference in local recurrence, but the prognosis for distant recurrence and breast cancer-specific death was poor in the before introduction group. The median observation period in the post introduction group was 47 months, and late recurrence of ER-positive breast cancer occurs later. It is necessary to continue the study by extending period and accumulation cases. Conclusion : For cN0 cases, if the case is suitable, we introduced the treatment choice system that allows omitting Ax by performing radiotherapy in SN macrometastasis positive patients. After introduction, there was no increase in the relapse rate after introduction in the short term. Appropriate case selection allowed the safety introduction of individualizes treatment for axilla. Citation Format: Mai Tomiguchi, Kaori Hidaka, Lisa Goto-Yamaguchi, Ayako Kajiwara, Kanako Nishikido, Toko Inao, Yutaka Yamamoto. Outcome after the introduction of personalized treatment for axilla in patients with clinically node-negative early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-09.

Abstract GS02-06: Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial

Abstract Background The omission of a completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy in patients with clinically node-negative breast cancer has been demonstrated to yield survival outcomes non-inferior to routine cALND in breast-conserving surgery followed by whole-breast irradiation (ACOSOG Z0011 and IBCSG 23-01 trials), and to axillary radiotherapy (RT) regardless of breast surgery (EORTC AMAROS trial). Mainly due to the under-representation of mastectomy patients, and a limited number of observed events compromising statistical power, the international randomized SENOMAC trial was initiated in 2015. The main aim of this non-inferiority trial was to address knowledge gaps relating to individuals treated by mastectomy, those with larger tumors and those with SLN extracapsular extension. Method The SENOMAC trial (NCT 02240472) enrolled patients with cT1-3cN0 primary breast cancer and 1-2 SLN macrometastases at 67 sites in five countries between January 27, 2015, and December 31, 2021. Participants were randomized 1:1 between cALND (standard) and omission of cALND (intervention). Stratification was per country. Breast-conserving surgery and mastectomy were eligible surgical interventions. Preoperative axillary ultrasound was mandatory; patients with non-palpable suspicious axillary lymph nodes, even if proven metastatic by biopsy, were eligible. SLN extracapsular extension was allowed. Adjuvant radiotherapy was dictated by national guidelines and not by the trial protocol. Statistical sample size calculation was based on the primary outcome overall survival. Non-inferiority was defined as a 5-year overall survival not worsened by more than 2.5% when refraining from cALND after the observation of 190 all-cause deaths in a target sample size of 3000 included patients. In the present analysis, the pre-specified secondary outcome of recurrence-free survival is reported. Results Out of 2766 randomized individuals, 2539 comprised the per-protocol population: 1204 in the standard and 1335 in the intervention group. Median follow-up was 37.1 months (1.5-75.0) and median age at inclusion 61 years (range 20-94). Most tumors belonged to the luminal subtype (93.6%); tumor stage was T1 in 1358 (53.5%), T2 in 1034 (40.7%) and T3 in 146 participants (5.8%). Out of 347 participants with suspicious lymph nodes on ultrasound, 36 had confirmed non-palpable metastasis. SLN extracapsular extension was reported in 866 (34.1%). The breast was conserved in 1621 (63.8%) and a mastectomy performed in 918 (36.2%) patients. Most patients (2127, 83.8%) received radiotherapy including nodal target volumes. In 34.1% of the standard group, additional non-SLN metastases were identified on cALND. Overall, 104 recurrences were reported, 54 (4.5%) in the standard and 50 (3.7%) in the intervention group. Of these, 11 recurrences were found in the ipsilateral axilla: 5 (0.4%) and 6 (0.5%), respectively. Recurrence-free survival did not differ between groups (country-adjusted HR 0.89, 95% CI 0.65-1.20). Conclusion Despite extended inclusion criteria, there was no difference in recurrence-free survival whether cALND was omitted (intervention) or not (standard). Patients undergoing mastectomy will specifically be addressed in subgroup analyses. Long-term follow-up is crucial considering the high proportion of luminal cancers. Citation Format: Jana de Boniface, Tove Tvedskov, Bergkvist Leif, Jan Frisell, Yvette Andersson, Sara Alkner, Malin Sund, Roger Olofsson Bagge, Dan Lundstedt, Oreste Davide Gentilini, Michalis Kontos, Toralf Reimer, Birgitte Offersen, Thorsten Kühn, Lisa Rydén, Peer Christiansen. Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-06.

Size of extranodal extension in the sentinel lymph node as a predictor of prognosis in early-stage breast cancer

IntroductionThe presence of extranodal extension (ENE) in sentinel lymph nodes (SLNs) can predict non-SLN metastases in breast cancer (BC) patients; however, the prognostic relevance of its extent remains controversial. The purpose of this study was to examine the predictive role of ENE in SLNs measured by its widest dimension (WD), highest dimension (HD), and the WD/HD ratio for non-SLN involvement, overall, and disease-free survival (OS, DFS) in cT1-2N0 BC patients with positive SLNs. Materials and MethodsA total of 511 women with cT1-2N0 BC and positive SLNs undergoing axillary lymph node dissection were retrospectively enrolled. The associations of ENE's WD, HD, and WD/HD ratio with non-SLN metastases, five-year OS, and DFS were established through a multivariable modeling approach. ResultsSLNs were ENE-positive in 149 (29.16%) participants, and 133 (26.03%) had non-SLN metastases. During the median 60 (16-60)-month follow-up, 69 (13.50%) patients experienced recurrences, and 62 (12.13%) died. The numbers of SLNs, non-SLNs, and total axillary LNs involved differed between the ENE-negative and ENE-positive groups, as well as between the WD/HD ≤1.2 and WD/HD >1.2 subgroups (all p-values were <0.001). Multivariable analyses showed significant associations of the WD/HD ratio >1.2 with non-SLN involvement, OS, and DFS (p-values were 0.003, <0.001, and 0.005, respectively). DiscussionDespite no predictive value of ENE's WD and HD, the WD/HD ratio >1.2 was an independent predictor of non-SLN involvement, mortality, and recurrence.ENE's WD/HD ratio could be a valuable indicator for cT1-2N0 BC individuals with positive SLNs for whom further axillary treatment may be beneficial. Micro abstractIn breast cancer (BC), the prognostic relevance of extranodal extension (ENE) size in sentinel nodes (SLNs) is controversial. All cT1-2N0 BC participants had SLN macrometastases; 29.16% had ENE-positive SLNs. As an independent predictor of non-SLN metastases and survival, ENE's widest dimension (WD) to highest dimension (HD) ratio >1.2 could indicate Z011-eligible BC patients who may benefit from further axillary treatment.

Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases

BackgroundTrials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.MethodsWe conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.ResultsBetween January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy–only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.ConclusionsThe omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.)

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

313 (PB-129) Poster - Predictive factors of micro and macrometastasis in sentinel lymph node in invasive lobular carcinoma

313 (PB-129) Poster - Predictive factors of micro and macrometastasis in sentinel lymph node in invasive lobular carcinoma

Non-sentinel lymph node metastases risk factors in patients with breast cancer with one or two sentinel lymph node macro-metastases

Approximately 59 % of patients with breast cancer with one or two sentinel lymph nodes (1–2 SLN) macrometastases do not benefit from axillary lymph node dissection (ALND), which may also incur morbidities. It is necessary to evaluate the association between various clinicopathological characteristics and non-sentinel lymph node metastases (non-SLNM) in patients with breast cancer with 1–2 SLN macrometastases, and determine whether they 1–2 should avoid ALND. Eight electronic literature databases (PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal, Wanfang, and Chinese Biomedical Literature) were searched from their inception to June 30, 2023, and two reviewers independently extracted the data and assessed the risk of bias. Association strength was summarized using odds ratios (OR) and 95 % confidence intervals (CI). Heterogeneity was accounted for using a subgroup analysis. Publication bias was evaluated using funnel plots and Egger's test. There were 25 studies with 8021 participants, and 27 potential risk factors were evaluated. The risk factors for non-SLNM in patients with 1–2 SLN macrometastatic breast cancer include the following: factors of primary tumor: multifocality (OR (95 % CI (2.63 (1.96, 3.54))), tumor size ≥ T2 (2.64 (2.22, 3.14)), tumor localization (upper outer quad) (2.06 (1.23, 3.43)), histopathological grade (G3) (2.45 (1.70, 3.52)), vascular invasion (VI) (2.60 (1.35, 4.98)), lymphovascular invasion (LVI) (2.87 (1.80, 4.56)), perineural invasion (PNI) (3.16 (1.18,8.43)). Factors of lymph nodes: method of SLNs detected (blue dye) (3.85 (1.54, 9.60)), SLN metastasis ratio ≥0.5 (2.79 (2.24, 3.48)), two positive SLNs (3.55, (2.08, 6.07)), zero negative SLN (3.72 (CI 2.50, 4.29)), extranodal extension (ENE) (4.69 (2.16, 10.18)). Molecular typing: Her-2 positive (2.08 (1.26, 3.43)), Her-2 over-expressing subtype (1.83 (1.22, 2.73)). Factors of examination/inspection: axillary lymph nodes (ALNs) positive on imaging (3.18 (1.68, 6.00)), cancer antigen 15-3 (CA15-3) (4.01 (2.33,6.89)), carcinoembryonic antigen (CEA) (2.13 (1.32–3.43)). This review identified the risk factors for non-SLNM in patients with 1–2 SLN macrometastatic breast cancer. However, additional studies are needed to confirm the above findings owing to the limited number and types of studies included.

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial

IntroductionModern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with...

A hybrid approach: a safe option for surgical treatment of early-stage cervical cancer.

The aim of the study was to describe the surgical treatment of early-stage cervical cancer (CC) via minimally invasive surgery (MIS) and a sequential hybrid approach combining MIS and mini-Pfannenstiel. Evaluate sentinel lymph node (SLN) detection using a hybrid tracer (ICG-99m Tc nanocolloid). Prospective, observational, descriptive, single-center study conducted at Son Espases University Hospital between January 2019 and September 2021. Patients with early-stage CC (FIGO 2018 IA1 with ILV-IIA1) who underwent surgical treatment with a follow-up of at least one year were included. Thirty early-stage CC patients were included, of whom four (13.3%) were upstaged due to positive SLNs. In these cases, laparotomy was avoided, and paraaortic lymphadenectomy was performed via MIS approach. Twenty-six patients had a radical hysterectomy: 15 underwent a hybrid approach, 10 laparoscopy, and one laparotomy. Patients undergoing laparoscopic surgery had a smaller estimated tumor size than those undergoing the hybrid approach. The overall SLN detection rate was 96.1%, with 88.5% of cases occurring bilaterally. Five out of 26 patients (19.2%) presented SLN macrometastases, and five (19.2%) had atypical drainage. Surgery refined staging in 33.3% (10/30) of cases. No recurrences were reported after an average follow-up of 32 months. MIS for SLN avoids laparotomy leading to rapid recovery and early adjuvant treatment initiation in nodal metastasis. In our study, tumor size is an important clinical implication in the surgical approach to be used. The hybrid tracer provided a high detection rate and combined the advantages of the two tracers. The hybrid approach has a quick recovery and optimal results.

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1–2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study

BackgroundThe randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1–2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1–2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1–2 SLN macrometastases undergoing TM.MethodsThe clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis.ResultsA total of 273 patients with 1–2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019–1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302–36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1–2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%.ConclusionsThe breast cancer patients with cT1/2N0 stage, undergoing TM and 1–2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

56 (PB-056) Poster - Predictive factors of macrometastasis in sentinel lymph node in invasive lobular carcinoma

Background: The axillary impact of invasive ductal carcinoma (IDC) has been extensively studied. But, invasive lobular carcinoma’s (ILC) lower prevalence, its tumor biology and its poor axillary disease translation in imaging tests, results in a greater lack of knowledge about its influence at the axillary level.

Risk factors of non-sentinel lymph node metastasis in 443 breast cancer patients with sentinel lymph node-positive.

Axillary lymph node dissection is the standard surgical procedure for breast cancer patients with sentinel lymph node (SLN) positive. In clinical practice, axillary lymph node dissection may be an unnecessary treatment for some breast cancer patients with non-sentinel lymph node (NSLN) negative. The aim of this study was to analyze the risk factors of NSLN metastasis in breast cancer patients with SLN positive. Four hundred fifty-six clinical early stage breast cancer patients with SLN positive were collected and analyzed in the oncological surgery department of Fujian Provincial Hospital during 2013 to 2018. All these patients underwent surgical treatment. The average age and tumor size of 443 patients with SLN positive breast cancer were (49.8 ± 10.8) years and (2.42 ± 0.94) cm. Univariate analysis showed that the size of primary tumor, the number of positive SLN, the number of negative SLN, the ratio of positive SLNs, and the type of metastases in SLN were the influencing factors of NSLN metastasis. Multivariate regression analysis showed that primary tumor size T > 2 cm (P < .001, OR = 2.609), the positive number of SLNs ≥3 (P = .002, OR = 5.435), the ratio of positive SLNs ≥ 50% (P = .017, OR = 1.770), and SLN macrometastases (P < 0.001, OR = 16.099) were independent risk factors for NSLN metastasis. Combined with the 4 independent risk factors, the area under the curve to predict NSLN metastasis was 0.747 > 0.7. For clinical early breast cancer with positive SLN, primary tumor size T > 2 cm,the positive number of SLNs ≥ 3, the ratio of positive SLNs ≥ 50%, and SLN macrometastases could predict NSLN metastasis well, and guide surgery to avoid overtreatment.

Factors Influencing Non-sentinel Lymph Node Involvement in Patients with Positive Sentinel Lymph Node(s) After Neoadjuvant Chemotherapy for Breast Cancer.

When a positive sentinel lymph node (SLN) is identified after neoadjuvant chemotherapy (NAC), completion axillary lymph node dissection (cALND) is generally recommended. We sought to evaluate the rate of non-SLN positivity and factors influencing this in patients with a positive SLN following NAC. We identified all patients at our hospital between 2006 and 2021 with a positive SLN (> 0.2mm) following NAC who underwent cALND. Rates of positive non-SLN (NSLN) on cALND were compared by nodal status. Chi-square tests and multivariable logistic regression were used to assess factors predictive of positive NSLN and overall nodal burden. Overall, 229 cases (177 cN+, 52 cN0 prior to NAC) with positive SLN(s) after NAC underwent cALND. Additional NSLN involvement was found in 129/229 (56.3%) patients, including 24/52 (46.2%) cN0 and 105/177 (59.3%) cN+ patients (p = 0.09). There was a trend for patients with SLN micrometastases to be less likely to have positive NSLN(s) than those with SLN macrometastases (38.5% vs. 58.6%; p = 0.05). Subgroup analyses showed no clinicopathologic factors significantly associated with additional axillary involvement for initially cN0 patients. Factors found to significantly influence NSLN positivity in the initially cN+ subgroup were HER2 status, multicentricity/multifocality, number of positive SLNs, and size of SLN metastasis. SLN metastasis size > 5mm and three or more positive SLNs exerted the greatest influence on NSLN positivity. Rates of nodal positivity on cALND in the setting of positive SLN after NAC are high, supporting the current standard of routine cALND. In cN+ disease, NSLN positivity varies by tumor biology, multicentricity/multifocality, number of positive SLNs, and SLN metastasis size.

Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes.

e12576 Background: From the results of ACOSOG Z0011, IBCSG23-01 and AMAROS trials, axilla surgery in node-positive breast cancer (BC) tends to be less invasive with sentinel node biopsy (SNB) followed by adjuvant therapy and regional node irradiation (RNI). However, optimized axilla treatment including SNB without RNI is still debated. The Japanese Society for Sentinel Node Navigation Surgery conducted a multi-institutional prospective cohort study to compare SNB with SNB followed by axillary lymph node dissection (ALND) in cases with positive-sentinel lymph nodes (SLN)(UMIN No. 000011782, Jpn J Clin Oncol, p.876-9, 2014). Methods: Female BC patients with cT1-3N0-1M0 were eligible. When 1 to 3 positive micrometastases or macrometastases in SLN were confirmed by histological or molecular diagnosis, SNB alone or additional ALND had been decided by physician’s discretion. Primary chemotherapy before or after SNB was acceptable for registration. Lymph node sampling was also allowed in the SNB group. Cases with bilateral BC, isolated tumor cells only in SLN, past history of invasive cancer within 5 years at the registration were ineligible. The primary endpoint was the 5-year recurrence rate of regional node (RN) in the SNB group. The secondary endpoint was overall survival (OS). We planned to collect 240 patients to reject that the 5-year recurrence rate of RN was more than 10% assuming the rate 5%. To compare the SNB group and ALND group, the propensity score matching (PSM) was performed. Matching variables were initial treatment, metastatic size and numbers of SLN, clinical stage, age, body mass index, menopausal status, family history, past history of invasive cancer, breast surgery. Results: Eight-hundred eighty cases had been registered between 2013 and 2016. In the 871 eligible cases, 308 cases were the SNB group. At the median follow-up of 6.3 years, 5-year recurrence rate of RN was 2.7% [95% confidence interval, 1.4% to 5.4%] and 5-year OS was 97.6% [94.9% to 98.8%]. After PSM, 209 cases were matched in the SNB and ALND group. Among them, 343 cases (82%) received operation at initial treatment. Partial and total mastectomy was performed in 225 (54%) and 193 cases (46%), respectively. One-positive SLN was recorded in 366 cases (88%), 2 in 48 (11%) and 3 in 4 (1%). Macrometastases and micrometastases in SLN were diagnosed in 271 (65%) and 147 cases (35%), respectively. Three-hundred seventy-six cases (90%) belonged to luminal-like subtype. RNI was underwent in 42 cases (20%) of the SNB group and 13 cases (6%) of the ALND group. Five-year recurrence rate of RN was 2.1% [0.8% to 5.5%] and 2.0% [0.8% to 5.3%] for the SNB and ALND group, respectively. Conclusions: Our series suggests that RNI is not necessary for regional control in cases with 1 to 3 positive SLN. In conclusion, SNB alone is acceptable in cases with fewer metastatic SLN. Clinical trial information: UMIN No. 000011782.

The effect of omitting axillary dissection and the impact of radiotherapy on patients with breast cancer sentinel node macrometastases: a cohort study following the ACOSOG Z0011 and AMAROS trials.

To report the outcomes of implementing the ACOSOG Z0011 and AMAROS trials relevant to clinical practice, and to define target groups in whom to avoid or recommend axillary radiotherapy (ART). We also aimed to analyse the reduction in morbidity when axillary lymph node dissection (ALND) was omitted. A retrospective cohort study of T1-T2 patients with macrometastases at sentinel lymph node (SLN) who were treated between 2011 and 2020. Breast surgery included either lumpectomy or mastectomy. Patients with ≤ 2 positive SLN were divided into two cohorts by whether they received ART or not. Survival outcomes and morbidity were analysed by Kaplan-Meyer curves and Cox-regression, respectively. 260 pN1a patients were included and ALND was avoided in 167 (64.2%). According the Z0011 results, 72 (43.1%) received no further ART; and based on AMAROS criteria 95 (56.9%) received ART. Median follow-up was 54months. The 5-year overall survival was 96.8% in the non-RT cohort and 93.4% in the RT cohort (p = 0.19), while the respective 5-year disease-free survivals were 100% and 92.3% (p = 1.06). Lymphedema developed in 3.6% of patients after SLNB versus 43% after ALND (OR 20.25; 95%CI 8.13-50.43). Decreased upper-extremity range of motion appeared in 8.4% of patients after SLNB versus 31.2% after ALND (OR 4.95; 95%CI 2.45-9.98%). Our study confirms that omitting ALND is safe and has high survival rates in patients with T1-T2 tumours and ≤ 2 positive SLNs. Adding ART could be a treatment option for patients who present other risk factors. Avoiding ALND with or without ART was associated with significantly less arm morbidity.

Development and validation of nomograms for predicting axillary non-SLN metastases in breast cancer patients with 1\u20132 positive sentinel lymph node macro-metastases: a retrospective analysis of two independent cohorts

BackgroundIt is reported that appropriately 50% of early breast cancer patients with 1–2 positive sentinel lymph node (SLN) micro-metastases could not benefit from axillary lymph node dissection (ALND) or breast-conserving surgery with whole breast irradiation. However, whether patients with 1–2 positive SLN macro-metastases could benefit from ALND remains unknown. The aim of our study was to develop and validate nomograms for assessing axillary non-SLN metastases in patients with 1–2 positive SLN macro-metastases, using their pathological features alone or in combination with STMs.MethodsWe retrospectively reviewed pathological features and STMs of 1150 early breast cancer patients from two independent cohorts. Best subset regression was used for feature selection and signature building. The risk score of axillary non-SLN metastases was calculated for each patient as a linear combination of selected predictors that were weighted by their respective coefficients.ResultsThe pathology-based nomogram possessed a strong discrimination ability for axillary non-SLN metastases, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.727 (95% CI: 0.682–0.771) in the primary cohort and 0.722 (95% CI: 0.653–0.792) in the validation cohort. The addition of CA 15–3 and CEA can significantly improve the performance of pathology-based nomogram in the primary cohort (AUC: 0.773 (0.732–0.815) vs. 0.727 (0.682–0.771), P < 0.001) and validation cohort (AUC: (0.777 (0.713–0.840) vs. 0.722 (0.653–0.792), P < 0.001). Decision curve analysis demonstrated that the nomograms were clinically useful.ConclusionThe nomograms based on pathological features can be used to identify axillary non-SLN metastases in breast cancer patients with 1–2 positive SLN. In addition, the combination of STMs and pathological features can identify patients with patients with axillary non-SLN metastases more accurately than pathological characteristics alone.

Abstract PS1-53: Does the axilla surgical management for limited sentinel lymph nodes involvement vary between total mastectomy and breast-conserving surgery

Abstract Purpose: The ACOSOG Z0011 study demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with one to two positive sentinel lymph node (SLN) who underwent breast-conserving surgery (BCS) with planned whole-breast irradiation. This study aimed to analysis the surgical management in patients with one to two positive SLNs, and further evaluate the rates of non-sentinel lymph node (non-SLN) metastasis between patients receiving BCS or total mastectomy (TM). Methods: We performed a retrospective analysis of patients with early breast carcinoma from the Shanghai Jiao Tong University-Breast Cancer Database (SJTU-BCDB) between 2011 to 2018. The inclusion criteria were (1) cT1-2N0M0 invasive breast cancer, (2) aged ≥18 years at diagnosis, (3) received surgical treatment for the primary tumor and the axilla, (4) had one to two positive SLNs, (5) no history of previous or concurrent malignant disease, and (6) no neoadjuvant therapy. Patients were classified into the BCS and TM groups. Time trends of ALND rates were analyzed with Chi-square tests. And the rates of non-SLN metastasis between BCS and TM groups were also analyzed with Chi-square tests. Multivariable logistic regression was used to determine factors influencing the completion of ALND and non-SLN metastasis. And Kaplan-Meier estimator and log-rank tests were used to analysis the recurrence-free survival (RFS) between SLNB alone and SLNB+ALND arms. Results: Of the 891 patients enrolled, 586 (65.8%) received TM and 305 (34.2%) received BCS. Between 2011 and 2018, the completion of ALND for 1-2 positive SLN decreased from 100% to 72.7% (P &amp;lt;0.001). And the rate of ALND was significantly higher in the TM group compared with the BCS group (n = 541, 92.3% vs n = 195, 63.9%; P &amp;lt;0.001).Earlier year of diagnosis (P &amp;lt;0.001), primary mastectomy (P &amp;lt;0.001), SLN positive-total ratio &amp;gt;50% (P =0.001), and SLN macro-metastasis (P &amp;lt;0.001) were all independently associated with a higher probability of completing ALND. Among the 736 patients undergone ALND, the rates of non-SLN metastasis were significantly higher in the TM group, compared to the BCS groups (TM: n = 170, 31.4% vs BCS: n = 46, 23.6%; P =0.044). The multivariable regression analysis indicated that non-SLN metastasis was significantly associated with SLN positive-total ratio &amp;gt;50% (OR=3.43, 95%CI 2.28-5.17; P &amp;lt;0.001), Her-2 positive disease (OR=1.63, 95%CI 1.09-2.46; P =0.019), and pT2-3 disease (OR=1.46, 95%CI 1.01-2.09; P =0.042). However, surgery of the breast was not independently associated with the rate of non-SLN metastasis (P =0.090). After a median follow-up time of 31.9 months (range, 1.0-96.5 months), there were no significant difference in RFS between the SLNB alone and SLNB+ALND arms, regardless of the surgery of the breast (TM group: Log-rank P = 0.910; BCS group: Log-rank P =0.840). Conclusion: There is an increasing trend toward omitting ALND in patients with one to two positive SLNs. Compared with the patients undergone BCS, the rate of non-SLN metastasis was significantly higher in patients undergone TM. However, the omission of ALND had limited influence on disease outcome among those patients received TM. Citation Format: Weiqi Gao, Xiaosong Chen, Kunwei Shen. Does the axilla surgical management for limited sentinel lymph nodes involvement vary between total mastectomy and breast-conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-53.

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer.

BackgroundMethylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.MethodsWe retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.ResultsBetween January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224−0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).ConclusionOur single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

Application of OSNA Nomogram in Patients With Macrometastatic Sentinel Lymph Node: A Retrospective Assessment of Accuracy

Introduction:Almost 50% to 70% of patients who undergo axillary lymph node dissection (ALND) because of a single metastatic sentinel lymph node (SLN) have no further metastatic nodes at the axillary histology. On these grounds, the one-step nucleic acid amplification (OSNA) nomogram was designed and validated. As a mathematical model, calculated through tumor size (expressed in millimeters) and CK19 mRNA copy number, it is thought to predict nonsentinel lymph node (NSLN) status. The aim of the study is to verify the diagnostic accuracy of the OSNA nomogram in a group of patients with macrometastatic SLN, with a retrospective analysis.Methods:The OSNA nomogram was retrospectively applied to a group of 66 patients with macrometastatic SLN who underwent ALND. The result of the final histology of the axillary cavity was compared to the nomogram prediction. We calculated the prevalence of NSLN metastasis in patients who underwent ALND, sensitivity and specificity, negative and positive predictive value of the nomogram.Results:In patients with macrometastasis in SLN, the prevalence of patients with metastatic NSLN was 45%. The sensitivity of the nomogram was excellent (90%). The specificity was low (36%). Positive predictive value amounted to 54%, while negative predictive value was good (81%).Conclusions:These results suggest that the OSNA nomogram is a valid instrument that can help choose the best surgical strategy for the treatment of axillary cavity. The mathematical model is useful to avoid surgery in a selected group of patients because it accurately predicts NSLN status.