Node-negative Early Breast Cancer Research Articles

Abstract PO1-02-02: Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence

Abstract Background: RSClin® (Sparano et al J Clin Oncol 2020, PMID 33306425) is an educational tool that estimates the 10-year risk of distant recurrence (DR) and the absolute benefit of chemotherapy in HR-positive, HER2-negative, node-negative early breast cancer. The RSClin tool integrates the Recurrence Score® (RS) result with the clinical-pathological features tumor grade, tumor size and patient age using patient-specific meta-analysis (PSMA) applied to the NSABP B-14, TAILORx and NSABP B-20 studies. Approximately 3 years of additional follow-up data have accumulated in the TAILORx study since the RSClin tool was developed, including 50% more DR events in the RS 11-25 group (375 vs. 250), and 46% more DR events in the overall population (561 vs. 384). Methods: The RSClin tool estimates were updated to include the extended follow-up data from TAILORx. As before, the PSMA included 10,004 women with hormone-receptor positive, HER2-negative, node-negative breast cancer from the NSABP B-14 (n=577) trial receiving endocrine therapy (ET) alone and the TAILORx trial receiving ET alone (n=4854) or chemotherapy (CT) plus ET (n=4573). The baseline risk estimate used TAILORx event rates with ET alone. Since there was evidence of differing hazard ratios in years 0-5 versus 5+, models using time-varying effects were used. A patient-specific estimator of absolute CT benefit was computed by combining a PSMA estimate of the individualized relative CT effect from the TAILORx and NSABP B-20 (n=550 HER2-negative) trials with risk estimates for ET alone. Similar methods were used to develop and validate a new tool for assessing the risk of late DR (from year 5 to 10) in patients who survive DR-free for 5 years on ET alone after surgery. External validation of DR risk estimation was performed in an independent cohort of 1098 women enrolled in the Clalit Health Service registry. Results: With the updated data, the model integrating RS result with clinical-pathological features was more informative for DR risk than either RS result alone or the clinical-pathological features alone, both for 10-year DR risk and for late DR risk (likelihood ratio tests, each p≤.001). The updated 10-year RSClin risk estimates are similar to the existing RSClin tool risk estimates with slightly lower risk estimates for very high RS results and more precise estimates for mid-range RS results. The updated chemotherapy effect estimates are slightly lower than for the existing RSClin. The updated RSClin tool 10-year risk estimates were strongly associated with DR risk in the independent Clalit registry (Cox regression p< .001) and closely approximated the observed DR risk (Lin concordance 0.87). The new tool’s late DR risk estimates beyond 5 years were strongly associated with late DR risk in the Clalit registry (Cox regression p=.002) and closely approximated the observed late DR risk (Lin concordance 0.92). Conclusions: The RSClin tool 10-year DR risk estimates have been updated to incorporate extended follow-up data from the TAILORx study. A new tool for assessing late DR risk has been developed and validated that provides more prognostic information than either clinical-pathological features or genomic risk used individually. Citation Format: Joseph Sparano, Michael Crager, Robert Gray, Gong Tang, Jess Hoag, Frederick Baehner, Charles Geyer, Steven Shak, Norman Wolmark, Salomon Stemmer. Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence [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 PO1-02-02.

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.

Efficacy of frozen section in sentinel lymph node biopsy in early breast cancer – An Australian single-centre experience

IntroductionSentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in patients with clinically lymph node negative early breast cancer, reducing the need for axillary lymph node dissection (ALND) and its associated risks. Intra-operative frozen section is a method of rapid pathological assessment of the sentinel node to identify the presence of metastatic disease and potentially avoid the need for a second operation in patient who will require an axillary lymph node dissection. MethodsA retrospective review of a prospectively collected breast cancer database was performed. All patients with breast cancer who underwent SLNB and/or ALND at our institution, between May 1st 2017 to June 1st 2022 were identified. There were 565 patients who were included in the study. ResultsIntra-operative frozen section was able to accurately identify 71% of patients who had macrometastasis in their sentinel lymph node, thus allowing them to immediately proceed to ALND and avoid a second operation. In patient who had a false negative frozen section result, only 6.5% required ALND. The majority of false negative results were due to isolated tumour cells or micrometastasis, and therefore would not have required further intervention. ConclusionIntra-operative frozen section of sentinel lymph node biopsy in breast cancer is useful in reducing the need for a second operation, allowing staging of the axilla to occur more efficiently and with high diagnostic accuracy.

Concordance between Axillary Ultrasound and Sentinel Biopsy in Clinically Node-Negative Early Breast Cancer

Objective: To determine the sensitivity of axillary ultrasound in detecting axillary nodal metastasis in clinically and radiologically uninvolved axillary nodes in early carcinoma breast by comparing with sentinel node biopsy histopathology on frozen section. Study Design: Comparative cross-sectional study Place and Duration of Study: Breast Clinic, CMH, Rawalpindi Pakistan, from Aug 2020 to May 2021. Methodology: Patients included in the study presented with breast cancer lesions with clinically impalpable axillary lymph nodes aged 18-75. Patients with clinically impalpable nodes underwent an ultrasound of the axilla; if suspicious nodes were found, the patient had subsequent axillary node dissection. Sentinel node biopsy (SLNB) was performed on axillary ultrasound in all patients with no suspicious or benign-looking nodes. Histopathological reporting was taken as standard. Lymph nodal status on axillary ultrasound, SLN biopsy and axillary lymph node clearance were documented and analyzed. Results: Twenty-nine patients were included who had benign-looking lymph nodes on axillary ultrasound and underwent sentinel lymph node biopsy. The mean age of the patients was 54.03 ± 7.94. Out of 29 patients, 24(82.8%) patients had negative Sentinel lymph node biopsy, and 5(17.2%) had positive Sentinel lymph node biopsy, who then underwent axillary lymph node dissection. Conclusion: Sentinel lymph node biopsy is the gold standard to determine axillary lymph nodes involved in early carcinoma breast, which seem benign on pre-operative axillary ultrasound.

The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients.

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66-0.85) and 0.99 (95% CI 0.97-1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16-198.84) and 0.23 (95% CI 0.15-0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76-804.56) and the area under the sROC curve was 0.97 (95% CI 0.95-0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate – The ICE randomized clinical trial

Aim of the studyEvaluation of the impact of a de-escaleted chemotherapy regimen consisting of capecitabine (Cap) on invasive disease-free survival (iDFS) in patients ≥65 years with node-positive/high-risk node-negative early breast cancer (BC) receiving ibandronate (Ib). MethodsICE (Ib with or without Cap in Elderly patients with early breast cancer) was a multicentre phase 3 clinical trial with a 2020 update of long-term follow-up for overall survival enroling node-positive/high-risk node-negative patients ≥65 years with early BC. Patients were randomised to Cap 2000 mg/m² day 1–14 q3w for 6 cycles plus Ib (50 mg p.o. daily or alternatively 6 mg intravenous q4w) or Ib alone for 2 years. Endocrine therapy was recommended for hormone receptor (HR)-positive patients. The primary endpoint was iDFS analysed using Cox proportional hazards regression and log-rank analysis. Results1358 (96.4%) of 1409 randomised patients started treatment. 564 (83.4%) completed 6 cycles of Cap. 513 (77.7%) and 516 (78.8%) completed Ib in the Cap+Ib and Ib alone arm, respectively. Median age was 71 (range 64–88) years, 1099 (81%) were HR-positive, 705 (51.9%) node-negative. At a median follow-up of 61.3 months, 5-year iDFS was 78.8% for Cap+Ib versus 75.0% for Ib alone (p = 0.80). Effects were independent of age, nodal, and HR status. The addition of Cap caused significantly higher skin and gastrointestinal toxicity. ConclusionsThe adjuvant combination of Cap+Ib did not show significantly better iDFS than Ib alone in node-positive/high-risk node-negative older BC patients, of whom HR-positive patients were also treated with endocrine therapy. Trial registrationStudy in elderly patients with early breast cancer (ICE), NCT 00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Impact of cost of Oncotype DX versus CanAssist Breast, an Indian prognostic test, in the management of node-negative early breast cancer in a single centre in India.

14 Background: It is well known that prognostication is important as not all women benefit equally from adjuvant chemotherapy, especially in HR+/HER2- early breast cancer (BC). Multiple publications have showcased the cost-effectiveness of Oncotype DX (ODX) in various countries. However, ODX remains out of reach for many patients in under-resourced geographies like Asia, Africa etc where healthcare insurance is not a norm. CanAssist Breast (CAB) is an affordable prognostic test developed on Indian patients. CAB couples the immunohistochemistry technique with an AI/ML-based prediction model to segregate patients as either low-risk or high-risk for distant breast cancer recurrence. CAB has been validated in the USA, Spain, Germany, Austria, Italy, and The Netherlands for predicting 5–10-year distant recurrences and has comparable low-risk accuracy with that of ODX/MammaPrint. In this abstract, we present real-world data about cost-analysis of the use of CanAssist Breast versus ODX in a single cancer care centre in Rajasthan, a state in Western India that has a per capita income of $ 1504 as against $ 68,400 in the USA. Methods: 124 patients with node-negative early BC were treated at a trust hospital in Jaipur, Rajasthan from 2020-2022. All the high-risk patients received chemotherapy at the treating clinician’s discretion. For the cost analysis model, the cost of chemotherapy drugs, hospitalization charges, and costs involved in managing short-term adverse events was compared for CAB and ODX. Treatment is provided at subsidized costs to the patients in this trust hospital. Results: The median age of this cohort was 55 years (35-78), with primarily T2 and G2 diseases. High-risk proportions were 27% and 17% (as per TAILORx) and by CAB and ODX respectively. The cost of ODX is 5.8 times higher than the cost of CAB. The cost savings per patient with CAB over ODX were US $ 3477 (Rs. 278161) in this trust hospital. Conclusions: This economic model shows that the use of ODX could impose an economic burden due to its cost. Use of CAB would lead to savings without comprising the patient’s health, as both tests have comparable performance.

ASO Visual Abstract: Nonsentinel Axillary Lymph-Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph-Node-A Predictive Model Proposal.

ASO Visual Abstract: Nonsentinel Axillary Lymph-Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph-Node-A Predictive Model Proposal.

Treatment outcomes in patients with discordant recurrence score and RSClin risk predictions.

574 Background: Guidelines recommend the use of genomic assays to aid decision making regarding the use of adjuvant chemotherapy (CT) for hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). Recently, the RSClin tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was developed to better estimate CT benefit. Here, we studied patients with RSClin/RS discordance to determine if patients (pts) should be treated according to RS or RSClin. Methods: This was a retrospective cohort study of pts from the National Cancer Database who were diagnosed with HR+/HER2- node negative EBC from 2010-2020 who underwent RS testing and received adjuvant endocrine therapy with or without CT. Pts were classified as low RS ( < 26) or high RS (≥ 26) and low ( < 3%) versus high (≥ 3%) predicted CT benefit per RSClin. The primary outcome was overall survival (OS) benefit associated with CT administration for pts with discordant RS/RSClin, measured as hazard ratio [HR] for receipt of CT. Hazard ratios were adjusted for age and comorbidity index, and inverse probability of treatment weighting was performed for age, comorbidity index, race, ethnicity, and insurance status. Results: 262,748 pts with EBC were included, with a median follow-up of 58 months. Median age was 60 years; 82% were White, 7% Black, 5% Hispanic, and 4% Asian/Pacific Islander. Median tumor size was 1.5 cm, and median RS was 15. The 31,955 cases with concordant high RS/RSClin had an OS benefit with CT (HR: 0.71, 95% CI: 0.67 - 0.75, p < 0.001), while the 206,631 cases with concordant low RS/RSClin did not have a survival benefit (HR: 1.00, 95% CI: 0.95 - 1.04, p = 0.85, Table). High RS with low RSClin was seen in 435 cases – all with grade 1 tumors, with RS no greater than 28, and tumor size under 1.3cm. No significant CT benefit was seen in this small subset of pts (HR 1.57, 95% CI 0.75 – 3.26, p = 0.23). In 23,727 pts with low RS but high RSClin, a CT benefit was seen (HR 0.73, 95% CI 0.67 – 0.78, p < 0.001). These pts had high-intermediate RS (median 23, interquartile range 20 – 24) with other higher risk features. Similar results were seen in older (age > 50) and younger (age ≤ 50) subgroups – although no pts ≤ 50 were in the low RS/high RSClin group. Conclusions: RSClin may identify a small number of grade 1 tumors with high RS for which CT is not needed, and may help guide appropriate use of CT for EBC in the sizeable group with intermediate RS. [Table: see text]

Evaluation of Dual Dye Technique for Sentinel Lymph Node Biopsy in Breast Cancer: Two-Arm Open-Label Parallel Design Non-Inferiority Randomized Controlled Trial.

Radioisotope and blue dye are standard agents for performing sentinel lymph node (SLN) biopsy in breast cancer. The paucity of nuclear medicine facility poses logistic challenge. This study evaluated performance of radioisotope & methylene blue (MB) with indocyanine green (ICG) and MB for SLNB. This randomized controlled trial was conducted from December 2019 to July 2022 comparing SLN identification proportions of radioisotope-blue dye [Group A] with dual dye (MB + ICG; Group B]. Secondary objective included time required and cost effectiveness of performing SLNB. Sample size of 70 (35 in each arm) was calculated. Upfront operable node negative early breast cancer was included in the study. Clinico-demographic data, number & type of SLN, time taken were noted. Cost analysis was done including the equipment, manpower & consumables. Chi-square/Fisher exact test was used to compare proportion between two groups. p value of less than 0.05 was considered to represent statistical significance. Seventy patients randomized to either group were similar in clinico-demographic and tumor characteristics. SLN identification rate (IR) was 91.43% in group A and 100% in group B. Overall IR of MB, radioisotope and ICG were 91.43%, 91.43% and 100%, respectively. Mean number of SLNs identified were 3 in group A and 4 in group B. Median time required for SLNB was 12min and 14min in either group, respectively. Cost of performing SLNB was higher in Group B. SLNB using dual dye is non-inferior to radioisotope-blue dye in upfront operable early breast cancer. Trial registration number Clinical Trial registry India CTRI/2020/02/023503.

103P Impact of Prosigna test on treatment decision in lymph node-negative early breast cancer: A prospective multicenter study (EMIT1)

103P Impact of Prosigna test on treatment decision in lymph node-negative early breast cancer: A prospective multicenter study (EMIT1)

Abstract GS1-05: Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates

Abstract Background: Late recurrence of breast cancer after 5 years accounts for about 50% of recurrences in hormone receptor (HR)-positive early breast cancer (EBC). TAILORx established non-inferiority of adjuvant endocrine therapy (ET) given for at least 5 years to chemotherapy plus ET (CET) in EBC and a 21-gene recurrence score (RS) of 11-25, although there was some chemotherapy benefit in women Methods: Eligibility criteria included women 18-75 years with HR-positive, HER2-negative, T1b-T2N0 EBC who agreed to have CT assigned or randomized based on the RS assay. The primary endpoint was invasive disease-free survival (iDFS) in the RS 11-25 group. The “primary analysis” refers to the original prespecified analysis for the primary IDFS endpoint (836 IDFS events at full information in the RS 11-25 group) after a median of 7.5 years. The “updated analysis” was performed after a median followup of 11.0 and 10.4 years in the randomized and overall populations, respectively. Results:10,253 eligible women enrolled between 4/7/06-10/6/10.The updated analysis includes substantially more events that the primary analysis, including IDFS events (1819 vs. 1210), distant recurrences (561 vs. 384), locoregional +/- distant recurrences (764 vs. 543), and deaths (910 vs. 499). The table provides 5 and 12-year event rates (and standard errors) for all arms, and comparisons of the randomized arms. The primary trial conclusions remain unchanged: ET was non-inferior to CET in the randomized group with a RS 11-25. Although recurrence occurred in < 10% by 12 years for a RS 0-25, late recurrence events beyond 5 years exceeded earlier recurrence. Non-recurrence events occurred in about 13% at 12 years (~1%/year), contributing substantially to the IDFS rates. For women Conclusions: The current updated analysis confirms findings from the original primary analysis that ET is non-inferior to CET in HR-positive, HER2-negative, node-negative EBC and a RS 11-25. As in the original primary analysis, the subgroup of women Citation Format: Joseph Sparano, Robert J. Gray, Della Makower, Kathy S. Albain, Daniel F. Hayes, Charles Geyer, Elizabeth Dees, Matthew P. Goetz, John A. Olson Jr, Tracy G. Lively, Sunil Badve, Thomas Saphner, Lynne I. Wagner, Timothy Whelan, Virginia Kaklamani, George Sledge. Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-05.

Nonsentinel Axillary Lymph Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph Node: A Predictive Model Proposal

BackgroundIn clinically node-negative (cN0) early stage breast cancer (EBC) undergoing primary systemic treatment (PST), post-treatment positive sentinel lymph node (SLN+) directs axillary lymph node dissection (ALND), with uncertain impacts on outcomes and increased morbidities.Patients and MethodsWe conducted an observational study on imaging-confirmed cN0 EBC, who underwent PST and breast surgery that resulted in SLN+ and underwent ALND. The association among baseline/postsurgical clinic–pathological factors and positive nonsentinel additional axillary lymph nodes (non-SLN+) was analyzed with logistic regression. LASSO regression (LR) identified variables to include in a predictive score of non-SLN+ (ALND-predict). The accuracy and calibration were assessed, an optimal cut-point was then identified, and in silico validation with bootstrap was undertaken.ResultsNon-SLN+ were detected in 22.2% cases after ALND. Only progesterone receptor (PR) levels and macrometastatic SLN+ were independently associated to non-SLN+. LR identified PR, Ki67, and type and number of SLN+ as the most efficient covariates. The ALND-predict score was built based on their LR coefficients, showing an area under the curve (AUC) of 0.83 and an optimal cut-off of 63, with a negative predictive value (NPV) of 0.925. Continuous and dichotomic scores had a good fit (p = 0.876 and p = 1.00, respectively) and were independently associated to non-SLN+ [adjusted odds ratio (aOR): 1.06, p = 0.002 and aOR: 23.77, p < 0.001, respectively]. After 5000 bootstrap-adjusted retesting, the estimated bias-corrected and accelerated 95%CI included the aOR.ConclusionsIn cN0 EBC with post-PST SLN+, non-SLN+ at ALND are infrequent (~22%) and independently associated to PR levels and macrometastatic SLN. ALND-predict multiparametric score accurately predicted absence of non-SLN involvement, identifying most patients who could be safely spared unnecessary ALND. Prospective validation is required.

Omission of axillary sentinel lymph node biopsy in early invasive breast cancer

Local treatment of the axilla in clinically node-negative (cN0) early breast cancer patients with routine sentinel lymph node biopsy (SLNB) is debated after publication of ACOSOG Z0011 data in 2010. Currently, prospective randomized surgical trials investigating the omission of SLNB in upfront breast-conserving surgery (BCS) and in the neoadjuvant setting, respectively. Several prospective randomized trials (SOUND, INSEMA, BOOG 2013–08, and NAUTILUS) with axillary observation alone versus SLNB in cN0 patients and primary BCS have primary objectives to evaluate oncologic safety when omitting SLNB. The Italian SOUND trial was the earliest to open in 2012 and has completed accrual in 2017. First oncologic outcome data are expected soon for SOUND and at the end of 2024 for INSEMA. Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to de-escalate surgery in patients who have a pCR. Two prospective single-arm trials (EUBREAST-01, ASICS) include only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) and type of surgery will be defined according to the response to NAST rather than on the classical T and N status. The ongoing trials will hopefully help us to understand whether we might take the best therapeutic decisions without the pathologic evaluation of nodal status.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

59 (PB-059) Poster - Validation Sentinel Lymph Node Biopsy Study in post NACT cN0 Axilla using low-cost dual dye technique: Potential Solution for Resource Poor Settings

Background: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer and increasingly being used for post NACT cN0 axilla as well. High costs and limited availability of radio-pharmaceutical and/or gamma probe are major deterrents in performing SLNB in developing countries. In this study, we evaluated feasibility of SLN identification (SLN-IR) of fluorescein-guided (FG) SLNB in combination with methylene blue dye (MBD). Methods: This was a prospective cross-sectional non-randomized validation study in patients with post NACT clinically node negative axilla. Patients underwent validation SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and False Negative Rate (FNR) were assessed. Results: The SLNs were identified in 51 out of 56 (91%) post Neoadjuvant Chemotherapy (NACT) patients. The median number of sentinel lymph nodes identified 1 (range 1–3) in post NACT patients. The SLN-IR using MBD was 91%, FD was 85%, and combined MBD FD was 89%. The false negative rate (FNR) was 7.8% (MBD), 8.3% (FD) and 7.8% (MBD+FD) Conclusions: This prospective validation study showed adequate SLN-IR and FNR using low cost dual dyes in post NACT cN0 patients and can be used in low resource settings. No conflict of interest.

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

ObjectivesTo evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer.Materials and methodsWe prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves.ResultsA total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001).ConclusionsCEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer.Key Points• The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis.• The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV).• Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

Cost-Effectiveness Analysis of the Oncotype DX Breast Recurrence Score® Test in Node-Negative Early Breast Cancer.

BackgroundThe 21-gene assay (the Oncotype DX Breast Recurrence Score® test) is a validated multigene assay which produces the Recurrence Score® result (RS) to inform decisions on the use of adjuvant chemotherapy in human epidermal growth factor receptor 2-negative (HER2-), hormone receptor positive (HR+) early invasive breast cancer. A model-based economic evaluation estimated the cost-effectiveness of the 21-gene assay against the use of clinical risk tools alone based on the latest evidence from prospective studies.MethodsThe proportion of patients assigned to chemotherapy conditional on their RS result was obtained from retrospective data from the Clalit registry. The probability of distant recurrence with endocrine and chemo-endocrine therapy conditional on RS result was obtained from TAILORx and NSABP B-20 trials. The cost-effectiveness of the 21-gene assay compared to using clinical risk tools alone was estimated in terms of cost per quality-adjusted life-year (QALY) over a lifetime horizon.ResultsThe 21-gene assay was more effective (0.17 more quality-adjusted life years) at a lower cost (-£519) over a lifetime compared to clinical risk alone. The model results were sensitive to assumptions around the magnitude of benefit of chemotherapy in the high RS result subgroup. Other assumptions underpinning the model, such as the proportion of patients assigned to chemotherapy in the low and mid-range RS result subgroups and long-term distant recurrence probabilities, had a smaller impact on the results.ConclusionThe analysis showed that the cost-effectiveness of the 21-gene assay is sensitive to assumptions for chemotherapy sparing for patients with RS 0–25 whose outcomes with endocrine therapy are no worse compared to chemotherapy-assigned patients, and a chemotherapy benefit in the RS 26–100 group. Future studies need to incorporate a wider set of tumour profiling tests other than the 21-gene assay to allow a direct comparison of their cost-effectiveness.

Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

BackgroundThe 21-gene Breast Recurrence Score (RS) assay, “the assay”, has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada.Patients and MethodsWe conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results.ResultsFor the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up.ConclusionAltogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.