Node-negative Early Breast Cancer Research Articles

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.

DECRESCENDO: De-escalation of adjuvant chemotherapy in patients with HER2+/HR-/node-negative early breast cancer who achieve pCR after neoadjuvant taxane and subcutaneous dual anti-HER2 blockade.

TPS621 Background: Human Epidermal growth factor Receptor-2 positive (HER2+) breast cancer (BC) heterogeneity can be captured at the mRNA level by the PAM50 classification. The HER2 “Enriched” (HER2-E) intrinsic subtype is encountered more often in HER2+ Hormone Receptor negative (HR-) tumors compared to HER2+ HR+ tumors and is particularly sensitive to HER2 blockade. HER2+ HR- and HER2-E achieve high pathological complete response (pCR) rates with neoadjuvant chemotherapy (CT) and dual anti-HER2 blockade with trastuzumab and pertuzumab. Additionally, the patients with pCR have improved outcomes. However, standard CT with common drugs such as anthracyclines has significant short and long-term toxicities, including cardiac events and secondary leukemias. Thus, tailoring the neoadjuvant treatment among carefully selected patients in order to reduce toxicity while preserving efficacy is a priority in early HER2-positive BC. Methods: DECRESCENDO is a large, multicentric, single-arm, phase 2 de-escalation study evaluating the efficacy of neoadjuvant CT with paclitaxel 80mg/m2 weekly or docetaxel 75mg/m2 every 3 weeks (Q3W) with pertuzumab and trastuzumab (P+T) 600/600mg fixed-dose combination (FDC) for subcutaneous (SC) injection Q3W for patients with early HER2+, HR- (ER&lt;1% and PR&lt;1%) BC. After surgery, the patients with pCR (defined as Residual Cancer Burden (RCB)=0, per local assessment) will receive 14 additional cycles of P+T FDC SC. Patients with RCB≥1 will receive adjuvant T-DM1 (preceded by anthracycline-based CT if RCB≥2). Eligible patients must be candidates for neoadjuvant treatment, with a tumor between 15 and 50mm, N0, ECOG PS 0-1, with LVEF ≥55%. 1,065 patients will be enrolled in 12 countries. A baseline tumor sample is required to retrospectively assess the intrinsic tumor subtype. The primary objective is to evaluate 3-year recurrence-free survival (RFS) in patients with HER2-E tumors who achieve pCR after neoadjuvant treatment. The key secondary objective is to evaluate 3-year RFS in all patients with pCR. If a 3-year RFS ≥94% with the lower boundary of a 1-sided 95% CI ≥92% is observed in the target group, the study treatment will be considered an acceptable alternative to strategies that include the addition of other chemotherapies such as anthracyclines, alkylating agents and platinum salts. A flexible care sub-study will enroll 121 patients with pCR in Belgium, France, Ireland, Israel and Italy to receive adjuvant P+T FDC SC in a location outside the hospital, such as at home or workplace. The aim is to compare patient preference for administration of P+T FDC SC outside the hospital vs in the hospital. The first patient was enrolled in January 2022. The trial is co-led by the Breast International Group (BIG) and Institut Jules Bordet. Clinical trial information: NCT04675827.

Diagnostic performance and survival outcome following sentinel lymph node biopsy in breast cancer patients from a tertiary cancer centre in India.

BackgroundSentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in early node-negative breast cancer (BC) patients in developed countries. However, in resource-constrained developing countries, adoption of SLNB is slow due to logistic issues and lack of outcome data from non-screened BC cohort. Therefore, we aim to report diagnostic performance, surgical morbidity and survival outcome of SLNB in BC patients from a tertiary care cancer centre in India.Methodology1,521 consecutive early node-negative T1-3N0 BC patients having SLNB from 2011 to 2020 were included in the study. Data were retrieved from the institutional Redcap database and electronic medical records. Analysis was done using Stata14.ResultsSLNB was done by dual dye (methylene blue (MB) + radioisotope (RI)/indo cyanine green (ICG)) in 57.7%, MB only in 39.3%, and RI alone in 3% of patients. The identification rate (IR) and SLNB positivity rate were 96% and 27.7%, respectively. IR was highest (98%) with MB + ICG and lowest (94%) with MB alone SLNB. UltraSonoGraphy guided fine needle aspiration cytology of radiological suspicious nodes has significantly reduced the SLNB positivity rate from 34.6% to 26.4% (p < 0.01). One patient had skin necrosis, and 16 had persistent blue staining of the skin in the MB injection site. All were managed conservatively. The lymphedema rate was significantly higher (5.2%) in the ALND versus 0.5% in the SLNB alone patients (p < 0.05). In a median follow up of 27 months, the axillary recurrence rate was 0.04% (4/1,023), and false-negative rate was 0.9% in SLNB negative patients. There were 35 recurrences and 25 deaths in SLNB negative patients, with 10 years predicted disease-free survival of 81% (95% CI 66% to 89%) and overall survival of 79% (95% CI 59% to 90%).ConclusionsSLNB should be offered as an axillary staging procedure to all eligible BC patients from developing countries to avoid the morbidity associated with ALND. Fluorescent dye can be used as an alternative for RI in a resource-constrained setup.

Sentinel lymph node biopsy using methylene blue dye and intraoperative palpation method in node-negative early breast cancer

Background: Early breast cancer with clinical or radiological node-negative axilla is treated with breast conservation surgery where lumpectomy with axillary dissection is done. Sentinel lymph node biopsy (SLNB) is an acceptable alternative to axillary clearance and has relatively lesser morbidity. SLNB methods include radioisotope (RI)-guided, blue dye-guided, or a combination of both. However, access to RI can be limited in certain geographic locations. Objective: This study aimed to determine the effectivity of methylene blue (MB) dye-guided SLNB as an alternative to RI. Methods: In this investigation, 43 clinically nodenegative early breast cancer patients were prospectively enrolled. SLNB was performed using MB dye (1%) administered to the peritumoral or periareolar region. The histopathology reports of the harvested nodes were studied, and the results were computed using SPSS and 2×2 contingency table. Results: The sensitivity, specificity, false-negative rate (FNR), and accuracy of MB-guided SLNB in our study were 92.8%, 100%, 7.14%, and 97.7%, respectively. Conclusion: The use of MB dye along with intraoperative palpation after meticulous lymph node dissection in each level is more effective and has lower FNR than RI.

Evaluating Delays in Commencing Adjuvant Treatment for Early Breast Cancer Following Oncotype Dx Testing

Purpose: The Oncotype DX assay predicts the risk of 10-year distant recurrence in hormone receptor-positive, HER2-negative, node-negative early breast cancer [1]. Its use is recommended by NICE in patients with an intermediate risk of recurrence, to inform treatment decisions on adjuvant chemotherapy [2].

Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial.

Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor-negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Efficacy of the Management of Node Negative Early Stage Breast Cancer Using 1% Methylene Blue in Sentinel Lymph Node Biopsy:prospective study, kasrAlaini University Hospital

Background:Accurate staging and proper management of axillary lymph nodes are important for the treatment of breast cancer. Sentinel lymph node biopsy (SLNB) provides accurate assessment of nodal status.Aimof work:Evaluation the safety, the accuracy and the cost of the application of SLNB using methylene blue 1% (MB 1%) in cases of node negative early stage breast cancer.Patients and methods:This study was conducted at Kasr Al-Ainy university Hospitals, Faculty of Medicine, Cairo University. Fifty-two female patients with node negative early stage breast cancer who agreed on undergoing breast conservative surgery( BCS), SLNB using 1% methylene blue and frozen section examination then managed according to ACOSOG Z0011 criteria .Results:Identification in 50 surgical specimens (identification rate 96.15%). By evaluating frozen section examination of the lymph nodes in relation to paraffin section examination we found that the sensitivity of the frozen section examination was 100% and specificity was 97.5% with positive predictive value 90.9%, negative predictive value 100% and overall accuracy was 98%.Conclusion:One % MB dye is very effective as a single agent in SLNB in node negative early stage breast cancer with very high identification rate compared to patent blue and radiocolloids. Implementation of ACOSOG Z0011 criteria proved its validity throughout our study as average 12 months follow up showed no locoregional recurrence

The Oncotype DX recurrence score impact on the management of ER-positive, HER2-negative, node-negative breast cancer

Introduction: Oncotype DX recurrence score is used to categorize estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer in high- or low-recurrence risk groups. It has a guiding significance for whether post-operative chemotherapy or only hormonal manipulation is selected as an adjuvant treatment. Aims: Assess the impact of the Oncotype DX recurrence score on adjuvant chemotherapy-related management decision-making in the cases of ER+ve, HER2–ve, LN–ve early breast cancer in our local unit. Material and methods: A cohort of 76 patients with early breast cancer were included, two had bilateral disease. All were operated for estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer. Tumor grade, Ki67 proliferative index, PREDICT and Oncotype DX recurrence score results were obtained in addition to the offered treatment information for each case. Results: After the primary tumor surgery and an Oncotype DX recurrence score assessment, 18 patients (24%) were eligible for adjuvant chemotherapy; out of them, 10 patients (56%) had a chemotherapy absolute survival benefit of &gt; 15% at 10 years, where 5 patients (30%) had a chemotherapy relative survival benefit of ~ 6.5%, 3 patients (17%) had a chemotherapy relative survival benefit of ~1.6%. In this cohort, 10 patients (13%) had a low Oncotype DX recurrence score; however, they received adjuvant chemotherapy based on other clinico-biological parameters. The other 48 patients (63%) with a low recurrence risk were spared potential adverse events related to the systemic therapy. Based on the menopausal status, every patient had received suitable hormonal manipulation therapy. The data also revealed the absence of a relationship between the Ki67 proliferative index and the Oncotype DX recurrence score (p = 0.06); moreover, the size of the tumor did not correlate with the Oncotype DX recurrence score (p = 0.5). Conclusion: The Oncotype DX recurrence score provides a credible prediction of distant disease recurrence risk in early breast cancer; however, it does not correlate with other prognostic markers, such as the Ki67 proliferative index as well as the tumor size. In this cohort, the use of the Oncotype DX recurrence score led to a 24% rate of treatment recommendations in the direction of adjuvant chemotherapy in addition to anti-hormonal therapy for estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer.

Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study.

Sentinel lymph node biopsy (SLNB) is a well-established procedure for staging clinically node-negative early breast cancer (BC). Superparamagnetic iron oxide (SPIO) demonstrated efficacy for nodal identification using a magnetic probe after local retroaeroal interstitial injection. Its benefits lie in its flexibility, which is an essential property in the global setting, where access to the isotope is difficult. To the best of our knowledge, this is the first study to evaluate the feasibility and safety of the SPIO for SLNB in BC patients treated with neoadjuvant chemotherapy (NAC). Seventy-four female patients were included. The median time of lymph node retrieval was 20 min. The median number of resected sentinel nodes (SNs) was 4. SN was detected in all patients. No serious adverse event was observed. SPIO in identifying SN in BC patients after NAC is feasible and oncologically safe.

PCN42 Budget Impact Analysis of the Oncotype DX Breast Cancer Recurrence Score Test to Guide Chemotherapy Use in ER+/HER2- Node-Negative Early Invasive Breast Cancer

The budget impact of the Oncotype DX® test in the UK was estimated compared to clinical risk tools only and other commercially available multigene assays (MGAs) used to guide adjuvant chemotherapy in ER+/HER2- node-negative early breast cancer. The model was informed by a systematic literature review of clinical studies of MGAs, including TAILORx and MINDACT randomised controlled studies.

Axillary Reverse Mapping—Factors Affecting ARM Node Detection and Its Role in Preventing Lymphedema in Node Negative Early Breast Cancer Patients

Axillary Reverse Mapping—Factors Affecting ARM Node Detection and Its Role in Preventing Lymphedema in Node Negative Early Breast Cancer Patients

PCN2 Recurrences Avoided and Life Years Saved Attributable to Trastuzumab Use in HER2+ Early and Metastatic Breast Cancer in the United States

We estimated the cumulative life years saved and recurrences avoided after incorporating trastuzumab as therapy for metastatic breast cancer (MBC) in 1999 and early breast cancer (EBC) in 2006 in the United States. We constructed a model to estimate population survival and recurrence among patients who received trastuzumab each year, and compared it to a counterfactual model in which trastuzumab treatment was not available. We incorporated US population counts, the age-, year-, and nodal status-specific incidence rates of HER2+ EBC, the age- and year-specific rates of de novo MBC, recurrence rates in HER2+ EBC, and year-specific trastuzumab utilization rates in EBC and MBC. Women with low-risk, node-negative EBC were excluded. The risk of recurrence with and without trastuzumab were based on 10-year trial data. Recurrences were estimated for 15 years after diagnosis by carrying the year 10 rate forward. Survival after local and regional recurrences was estimated using the 5-year relative survival for HER2+ EBC. In MBC, the survival estimates with and without trastuzumab were pooled across seven studies. Uncertainty intervals (UI) were estimated using Monte Carlo simulation with 500 replicates. We estimate that between 2006-2019, trastuzumab use in HER2+ EBC led to the avoidance of 4,500 (95% UI 2,900-6,200) loco-regional and 10,100 (95% UI 6,400-13,800) distant recurrences. This in turn resulted in an incremental 407,900 (95% UI 291,800-528,500) life years saved compared to projected survival with chemotherapy alone. In HER2+ MBC from 1999-2019, there were 72,300 (95% UI 68,300-76,900) women with de novo or recurrent metastatic cancer treated with trastuzumab, leading to an additional 155,200 (95% UI 144,900-166,100) life years relative to projected survival with chemotherapy alone. Trastuzumab has substantially increased the years lived, and reduced recurrences for women with HER2+ MBC and EBC in the United States.

Can preoperative axillary ultrasound and biopsy of suspicious lymph nodes be an alternative to sentinel lymph node biopsy in clinical node negative early breast cancer?

The aim of this study was to assess the efficacy of preoperative axillary ultrasonography (AUS) and preoperative axillary fine-needle aspiration biopsy (FNAB) from suspicious lymph nodes in clinically node-negative breast cancer to compare with radiologically positive and sentinel lymph node biopsy (SLNB) positive involvement. Clinically node-negative early-stage breast cancer patients were included in the study. These patients underwent preoperative AUS examination, suspicious lymph nodes were evaluated with FNAB. AUS-FNAB results were compared with those of SLNB or axillary dissection. Of 181 patients undergoing AUS, 32 were reported to have axillary metastasis, 25 suspicious, and 124 benign nodes. The suspicious group underwent FNAB examination and metastasis was found in 9 of them. The sensitivity of AUS-FNAB was found to be 64.06%, specificity 100%, positive predictive value 100%, and negative predictive value (NPV) 83.5%. The false negativity rate (FN) of this method was 16,4%. Lymphovascular invasion and tumour size were found statistically significant factors for false negativity. It was concluded that axillary AUS-FNAB with its high NPV, low FN rate, may be a clinical alternative to SLNB for early-stage breast cancer patients.

Abstract PS1-30: A prospective phase II trial to evaluate the feasibility of omit sentinel lymph node biopsy after integrate18F-FDG dedicated axillary PET in early breast cancer: SOAPET trial

Abstract Purpose: Sentinel Lymph Node Biopsy (SLNB) is currently the standard of care in clinical node negative (cN0) early breast cancer. The aim of this study is to evaluate the negative predictive value of 18F-FDG dedicated axillary PET (DA-PET) and to verify whether SLNB can be omitted in patients with negative preoperative axillary assessment. Patients and Methods: SOAPET is a prospective phase II trial consisted of 2 stages (NCT04072653). In the first stage, cN0 patients detected by clinical examination, received routinely axillary imaging evaluation (ultrasound and CT etc) and DA-PET, then received SLNB. In the second stage, SLNB will be omitted in the patients with negative preoperative axillary assessment after integrate DA-PET. Now we report the results of the first stage, the primary outcome is negative predictive value (NPV) of DA-PET to detect non-macrometastases of lymph nodes. Results: From Sep 9, 2019 to May 30, 2020, 224 patients were screened, and 189 patients with invasive breast cancer (180 invasive ductal carcinoma, 9 invasive lobular carcinoma) received DA-PET followed by surgical operations with definitive pathological reports. Media tumour size was 2.2cm, 120 HR+HER2-, 23 HR+HER2+, 27 HR-HER2+, 19 HR-HER2-. 40 patients had at least 1 macrometastases lymph nodes (8 patients had over 3 nodes involved), and 16 patients had only micrometastasis nodes. Among 131 patients with DA-PET negative (maxSUV&amp;lt;0.27), 16 patients had macrometastases lymph nodes and 11 patients had micrometastasis diseases. For 58 patients with DA-PET positive (maxSUV&amp;gt;=0.27), 24 patients had macrometastases and 5 patients had micrometastasis nodes. The NPV of DA-PET was 87.8%. The NPV of ultrasound was 86.3%. When combine axillary imaging evaluation with ultrasound and DA-PET, 100 patients were screened out with both DA-PET and ultrasound negative, among which 9 patients had macrometastases and 9 patients had micrometastasis nodes, the NPV was 91%. Conclusions: DA-PET can be used to identify cN0 patients, reducing the false negative rate &amp;lt; 10%. The second stage of SOAPET trial is ongoing to validate the safety of omitting SLNB according to preoperational axillary evaluation when integrating DA-PET. Key words: Breast cancer, Sentinel lymph node biopsy; Dedicated PET;18F-FDG; Table 1: Axillary lymph node detection efficiency of ultrasound and DA-PETAxillary imaging assessmentPatients nmacrometastasesmicrometastasis onlyultrasound*4016US-neg1241712US-det46144US-met1990DA-PET**negative1311611positive58245*:US-neg: no lymph nodes detected by ultrasound;US-det: lymph nodes detected by ultrasound;US-met: suspected metastatic lymph nodes detected by ultrasound**:Maximum single-voxel Standard Uptake Value (maxSUV) cutoff value of DA-PET was set at 0.27 (&amp;lt;0.27 is negative) Table 2: Intergrate axillary imaging assessment with ultrasound and DA-PETmacrometastases+-axillary imaging assessment+315889-*99110040149189*:no lymph nodes detected by ultrasound and maxSUV in DA-PET &amp;lt; 0.27 Citation Format: Junjie Li, Jingyi Cheng, Guangyu Liu, Yifeng Hou, Genghong Di, Benlong Yang, Yizhou Jiang, Liang Huang, Sheng Chen, Yan Wang, Keda Yu, Zhimin Shao. A prospective phase II trial to evaluate the feasibility of omit sentinel lymph node biopsy after integrate18F-FDG dedicated axillary PET in early breast cancer: SOAPET trial [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 PS1-30.

Abstract PS8-38: Development of random forest classifier method to predict breast cancer mortality among early stage breast cancer patients

Abstract Background: Among women diagnosed with early stage breast cancer, breast cancer mortality was conditional on the onset of distant recurrence. Gene expression profiling (GEP) tests (e.g., Oncotype Dx) have been commonly used to determine the risk level of distant recurrence, but its predictive ability is often questioned. The objective of this study aims to explore the potential of random forest machine learning to predict the risk of breast cancer mortality.Method: 63,104 patients with node-negative early stage breast cancer in the SEER-GHI dataset were randomly sampled into two groups, for the purpose of training and testing the model where each group consisted of 67% and 33% of all patients, respectively. The patient characteristics and tumor features in the study included age, tumor size, grade, chemotherapy use, Oncotype DX test recurrence score, and more. Further feature selection in the construction of the predictive model was conducted via the Boruta algorithm. As the dataset is highly imbalanced with only a very small percentage of samples being fatal, Synthetic Minority Over-Sampling Technique (SMOTE) was employed to address this issue. A cross-validated grid search finds the best combination of hyper-parameters to improve the model’s performance.Results: The mean and standard deviation of follow-up duration in the cohort of patients were 32.4 and 14.3 months, respectively. Of 37,043 patients, there were 158 breast cancer deaths. Within up to a 59-month follow-up period, the breast cancer specific mortality rate was 0.43%. Based on the limited available data, the outcome of the random forest classifier method in predicting breast cancer mortality shows sensitivity 0.712, specificity 0.773, overall accuracy 0.773, and AUC (area under ROC curve) 0.742. Conclusion: The use of the random forest ML algorithm to predict breast cancer mortality is promising when the hyper-parameters are fine-tuned. However, the model's positive predictive value is highly associated with sufficient data sources. Citation Format: Arwen Chandler. Development of random forest classifier method to predict breast cancer mortality among early stage breast cancer patients [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 PS8-38.

An assessment of axillary lymph node positivity in clinically node-negative early breast cancer

An assessment of axillary lymph node positivity in clinically node-negative early breast cancer

Improved detection of sentinel lymph node metastases allows reliable intraoperative identification of patients with extended axillary lymph node involvement in early breast cancer

BackgroundAn improved procedure that allows accurate detection of negative sentinel lymph node (SLN) and of SLN macrometastases during surgery would be highly desirable in order to protect patients from further surgery and to avoid unnecessary costs. We evaluated the accuracy of an intraoperative procedure that combines touch imprint cytology (TIC) and subsequent frozen section (FS) analysis. 2276 SLNs from 1072 patients with clinical node-negative early breast cancer were evaluated during surgery using TIC. Only cytologically-positive SLN were subsequently analysed with a single FS, preserving cytologically-negative SLN for the final postoperative histological diagnosis. Sensitivity, specificity and the accuracy of this approach were analysed by comparing the results from intra- and postoperative SLN and axillary node evaluation. This intraoperative method displayed 100% specificity for SLN metastases and was significantly more sensitive for prognostically relevant macrometastases (85%) than for micrometastases (10%). Sensitivity was highest for patients with two or more positive LNs (96%) than for those with only one (72%). 98% of the patients with final pN2a-pN3a were already identified during surgery. Patients who received primary axillary lymph node dissection had significantly more frequent metastases in further LNs (44.6%). Sensitivity was highest for patients with luminal-B, HER2+ and triple negative breast cancer and for any subtype if Ki-67 > 40%. TIC and subsequent FS of cytologically-positive SLNs is highly reliable for detection of SLN macrometastases, and allows accurate identification of patients with a high risk of extended axillary involvement during surgery, as well as accurate histological diagnosis of negative SLN.

Primary 21-Gene Recurrence Score and Disease Outcome in Loco-Regional and Distant Recurrent Breast Cancer Patients.

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown.Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups.Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS.Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation.