Sentinel Node Positive Breast Cancer Research Articles

Prediction of non-sentinel lymph node metastases in T1–2 sentinel lymph node-positive breast cancer patients undergoing mastectomy following neoadjuvant therapy

BackgroundAxillary lymph node dissection (ALND) is the standard axillary management for breast cancer patients with positive sentinel lymph node biopsy (SLNB) after neoadjuvant therapy. Nevertheless, when that happens, the frequency of additional positive nodes is not properly evaluated. We aim to develop a prediction model to assess the frequency of additional nodal disease after a positive sentinel lymph node following neoadjuvant therapy.MethodsWe retrospectively analyzed the ultrasound and clinicopathological characteristics of breast cancer patients with 1–3 positive sentinel lymph nodes (SLN) undergoing mastectomy after neoadjuvant therapy (NAT) at our institution, and performed univariate and multivariate logistic analyses to confirm the factors affecting non-SLN metastasis. These factors were included to establish a nomogram, and the area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were utilized to assess the validity of this model.ResultsA total of 126 breast cancer patients were ultimately included in our study, 38 (53.5%) patients were diagnosed with non-SLN metastases of all 71 patients in training set. The results of multifactorial logistic analysis suggested that lymph node metastasis ratio (LNR), short axis of lymph node and progesterone receptor (PR) were strongly associated with non-SLN metastasis. We established a nomogram using the above three variables as predictors, which yielded an area under the curve of 0.795, and validated with a favorable AUC of 0.876.ConclusionThe nomogram we constructed can accurately predict the likelihood of non-SLN metastasis in our patients with 1–3 positive SLN after NAT, which may help guide decision making regarding axillary management.

Long-Term Survival Outcomes and Risk Factors for Axillary and Locoregional Recurrence in Japanese Patients with Sentinel Node-Positive Breast Cancer Treated in Accordance with the ACOSOG Z0011 Strategy.

In 2018, we reported the results of a study to assess the feasibility of applying the ACOSOG Z0011 criteria to Japanese patients with early-stage breast cancer (median follow-up, 3 years). Their results over the longer term can now be presented. Risk factors for axillary and locoregional recurrence in Z0011-eligible patients are unknown. Long-term survival outcomes were investigated by analyzing data from patients enrolled in the feasibility study. Data from the feasibility study patients, and from patients eligible for the Z0011 strategy after its introduction into clinical practice, were subjected to multivariate logistic regression analysis to identify risk factors for axillary and locoregional recurrence. Regarding long-term outcomes for the feasibility study patients (n = 189), distant disease-free survival rates at 5 and 7 years were 90.4 ± 2.1% and 85.9 ± 2.6%, respectively, and overall survival rates at 5 and 7 years were 97.3 ± 1.2% and 95.3 ± 1.7%, respectively. Analysis of data from these patients plus the 93 who received Z0011 in clinical practice (total, n = 282) identified the following independent risk factors for axillary recurrence: absence of high axillary tangential irradiation (OR, 5.87 [95% CI, 1.09-31.35], p = 0.04) and number of positive sentinel lymph nodes (OR, 4.65 [95% CI, 1.11-19.48], p = 0.04). Only high Ki67 labeling index (OR, 5.92 [95% CI, 1.31-26.70], p = 0.02) was identified as an independent risk factor for locoregional recurrence. Long-term survival outcome results of the feasibility study show that the Z0011 strategy can be used to treat Japanese patients with early-stage breast cancer. Our findings regarding risk factors suggest that high axillary tangent irradiation is necessary for the prevention of axillary recurrence and that irradiation, including of the regional lymph nodes, should be considered, especially in patients with high Ki67 index values.

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.

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.

Oncological Safety of Skipping Axillary Lymph Node Dissection in Patients with Clinical N0, Sentinel Node-Positive Breast Cancer Undergoing Total Mastectomy

ObjectiveThis study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive.MethodsThis study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group.ResultsMean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70–2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69–5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02).ConclusionCollectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.

Association between postoperative pathological results and non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node-positive breast cancer

ObjectiveFor patients with 1–2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer.MethodsThis research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis.ResultsAmong the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10–4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31–11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35–7.42, P < 0.0001) were positively correlated with NSLNM.ConclusionIn our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence.MethodsThe Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication’s bias assessment.ResultsIn total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76–1.20), DFS (HR = 1.02, 95% CI: 0.89–1.16), and OS (HR = 0.97, 95% CI: 0.92–1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59–0.97) compared with ALND.ConclusionFor patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting.Trial registrationCRD 42023397963

ASO Visual Abstract: Trends of Axillary Treatment in SentinelNode-Positive Breast Cancer Patients Undergoing Mastectomy.

ASO Visual Abstract: Trends of Axillary Treatment in SentinelNode-Positive Breast Cancer Patients Undergoing Mastectomy.

Trends of Axillary Treatment in Sentinel Node-Positive Breast Cancer Patients Undergoing Mastectomy

BackgroundThe ACOSOG-Z0011- and the AMAROS-trial obviated the need for axillary surgery in most sentinel node-positive (SLN+) breast cancer patients undergoing breast-conserving surgery (BCS). Data for patients who undergo mastectomy is scarce. The purpose of this study was to investigate patterns of axillary treatment in SLN+ patients treated by mastectomy in the years after the publication of landmark studies regarding axillary treatment in SLN+ breast cancer patients undergoing BCS.MethodsThis was a population-based study in cT1-3N0M0 breast cancer patients treated by mastectomy and staged as SLN+ between 2009 and 2018. The performance of an axillary lymph node dissection (ALND) and/or administration of postmastectomy radiotherapy (PMRT) were primary outcomes and were studied over time.ResultsThe study included 10,633 patients. The frequency of ALND performance decreased from 78% in 2009 to 10% in 2018, whereas PMRT increased from 4 to 49% (P < 0.001). In ≥N1a patients, ALND performance decreased from 93 to 20%, whereas PMRT increased to 70% (P < 0.001). In N1mi and N0itc patients, ALND was abandoned during the study period, whereas PMRT increased to 38% and 13% respectively (P < 0.001), respectively. Age, tumor subtype, N-stage, and hospital type affected the likelihood that patients underwent ALND.ConclusionsIn this study in SLN+ breast cancer patients undergoing mastectomy, use of ALND decreased drastically over time. By the end of 2018 most ≥N1a patients received PMRT as the only adjuvant axillary treatment, whereas the majority of N1mi and N0itc patients received no additional treatment.

ASO Author Reflections: A Perspective on Nonsentinel Axillary Lymph Node Status in Sentinel Lymph Node-Positive Early Breast Cancer After Primary Systemic Therapy and ALND-Predict.

ASO Author Reflections: A Perspective on Nonsentinel Axillary Lymph Node Status in Sentinel Lymph Node-Positive Early Breast Cancer After Primary Systemic Therapy and ALND-Predict.

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.

Abstract P3-20-05: Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation

Abstract Objectives: To evaluate patterns of care in axillary treatment of Dutch patients - who were diagnosed with stage I-IV primary invasive breast cancer, underwent amputation and were found positive by sentinel lymph node biopsy (SLNB) - in the years following the publication of the American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trials. Methods: Data from females diagnosed between January 1st 2009 and December 31st 2018 were obtained from the Netherlands Cancer Registry (NKR). Trends in completion axillary lymph node dissection (cALND), administration of adjunctive radiotherapy and, inversely, of omission of any kind of axillary treatment, were revealed by descriptive analyses on SNL positive patients. Results: Of 28,070 cT1-4 breast cancer patients undergoing amputation with SLNB from 2009 up until 2018, 10,706 were diagnosed as SLN positive. In the latter, the frequency of subsequent cALND went down significantly from 78% in 2009 to 10% in 2018 (P &amp;lt; 0.001), while adjunctive radiotherapy increased from 4% to 49% (P &amp;lt; 0.001). Omission of any additional local treatment increased from 18% to 41% (P &amp;lt; 0.001). In N1 patients cALND decreased from 57% to 13% (P &amp;lt; 0.001) and was mostly replaced by radiotherapy, increasing from 2% to 70% (P &amp;lt; 0.001). In N1mi and N0i+ patients, cALND decreased to less than 1% of cases in 2018, while radiotherapy increased from 4% to 40% and 8% to 13% (P &amp;lt; 0.001), respectively. Conclusion: In SLN positive breast cancer patients undergoing breast amputation, cALND had become rare 10 years following the AMAROS and Z0011 trial results. While radiotherapy mostly replaced cALND in the vast majority of N1 patients, less than half of N1mi and only a tenth of N0i+ patients received radiotherapy as the only adjunctive axillary treatment by the end of 2018. Citation Format: Eline EF Verreck, Julia van Steenhoven, Anne Kuijer, Marissa van Maaren, Sabine Siesling, Thijs van Dalen. Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-05.

Axillary surgery in node-positive breast cancer

Long-term follow-up data from multicenter phase III non-inferiority trials confirmed the safety of omission of axillary dissection in selected patients with clinically node-negative, sentinel node-positive breast cancer. Several ongoing trials investigate extended eligibility of the Z0011 protocol in the adjuvant setting. De-escalation of axillary surgery in patients with clinically node-positive breast cancer is currently limited to the neoadjuvant setting, where the sentinel procedure is used to determine nodal pathological complete response. Targeted axillary dissection lowers the false-negative rate of the sentinel procedure, which, however, is consistently associated with a very low risk of axillary recurrence in several recent single-center series. Axillary dissection remains standard care in patients with residual disease after neoadjuvant chemotherapy while the results of Alliance A011202 are pending. The TAXIS trial investigates the role of tailored axillary surgery in patients with clinically node-positive breast cancer, a novel concept designed to selectively remove positive nodes in the adjuvant and neoadjuvant setting.

Comparison of survival outcomes for axillary surgery extent based on intraoperative sentinel lymph node biopsy result after neoadjuvant chemotherapy for breast cancer.

To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups. At a median follow-up of 59.4months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43-2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58-4.65, p = 0.347) between the two groups. Our analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

1A Oral - The generalisability of randomised clinical trials: An interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

Background: None of the key randomized trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph node (SLN)-positive breast cancer have reported external validity, though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC).

The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer

PurposeNone of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC).MethodsIn the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years.ResultsOverall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time.ConclusionsThis interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials.Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015

Prediction score model for non-sentinel and four or more nodal metastases using a combined method of one-step nucleic acid amplification and histology in sentinel node-positive breast cancer patients

BackgroundALN dissection (ALND) is the only way to obtain information on ALN metastasis status accurately when sentinel lymph node (SLN) metastasis is present. In this study, we established a model for intraoperatively predicting non-SLN metastasis and the presence of four or more ALNs (pN2), based on the combined use of one-step nucleic acid amplification (OSNA) and histological examination following SLN biopsy. Materials and methodsSubjects comprised 318 consecutive breast cancer patients (cTis-3, N0) who underwent SLN biopsy with a combination of OSNA and histological examination, and who were found to have SLN metastasis and were treated by ALND. We allotted points to each patient according to their SLN metastasis status as defined by both OSNA and histology, then defined the “National Cancer Center sentinel lymph node metastatic score” (NCS score) based on the total points. Correlations between the NCS score and both non-SLN metastasis and pN2 status were analyzed by logistic regression analysis. The accuracy of this score was evaluated using receiver operating characteristic (ROC) analysis. ResultsThe NCS score was significantly correlated with both non-SLN metastasis and pN2 status (adjusted odds ratio: 1.26 for non-SLN metastasis, 1.56 for pN2 status). The area under the ROC curve (AUC) of the NCS score demonstrated 0.74 for non-SLN metastasis, 0.91 for pN2 status. ConclusionsThe NCS score was a strong independent predictor of non-SLN metastasis and pN2 status. Use of this score will facilitate the selection of optimal adjuvant therapies without requiring unnecessary ALND.

A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer

BackgroundAxillary lymph node dissection (ALND) in breast cancer patients is infamous for its accompanying morbidity. Selective preservation of upper extremity lymphatic drainage and accompanying lymph nodes crossing the axillary basin - currently resected during a standard ALND - has been proposed as a valuable surgical refinement. MethodsPeroperative Axillary Reversed Mapping (ARM) was used for selective preservation of upper extremity lymphatic drainage. A multicentre patient- and assessor-blinded randomized study was performed in clinical node negative, sentinel node positive early breast cancer patients. Patients were randomized to undergo either standard-ALND or ARM-ALND. Primary outcome was the presence of surgery-related lymphedema at six, 12 and 24 months post-operatively. Secondary outcomes included patient reported and objective signs and symptoms of lymphedema, pain, paraesthesia, numbness, loss of shoulder mobility, quality of life and axillary recurrence risk. ResultsNo significant differences were found between both groups using the water displacement method with respect to measured lymphedema. ARM-ALND resulted in less reported complaints of lymphedema at six, 12 and 24 months postoperatively (p < 0.05). No axillary recurrence was found in both groups. ConclusionsIn contrast to results of volumetric measurement, patient reported outcomes support selective sparing of the upper extremity lymphatic drainage using ARM as valuable surgical refinement in case of ALND in clinically node negative, sentinel node positive early breast cancer. If completion ALND in clinically node negative, sentinel node positive early breast cancer is considered, selective sparing of upper extremity axillary lymphatics by implementing ARM should be carried out in order to reduce morbidity.

Predicting the extent of nodal involvement for node positive breast cancer patients: Development and validation of a novel tool.

BackgroundThis study aimed to develop an easy to use prediction model to predict the risk of having a total of 1 to 2, ≥3, or ≥4 positive axillary lymph nodes (LNs), for patients with sentinel lymph node (SLN) positive breast cancer.MethodsData of 911 SLN positive breast cancer patients were used for model development. The model was validated externally in an independent population of 180 patients with SLN positive breast cancer.ResultsFinal pathology after ALND showed additional positive LN for 259 (28%) of the patients. A total of 726 (81%) out of 911 patients had a total of 1 to 2 positive nodes, whereas 175 (19%) had ≥3 positive LNs. The model included three predictors: the tumor size (in mm), the presence of a negative SLN, and the size of the SLN metastases (in mm). At external validation, the model showed a good discriminative ability (area under the curve = 0.82; 95% confidence interval = 0.74‐0.90) and good calibration over the full range of predicted probabilities.ConclusionThis new and validated model predicts the extent of nodal involvement in node‐positive breast cancer and will be useful for counseling patients regarding their personalized axillary treatment.