Number Of Positive Nodes Research Articles

Clinical study of bilateral axillo-breast approach robot in obese women with thyroid cancer

Objective:To explore the safety and feasibility of bilateral axillo-breast approach （BABA） robot in the operation of thyroid cancer in obese women. Methods:The clinical data of 81 obese female patients who underwent da Vinci robotic thyroid cancer surgery（robotic group） at the Department of Thyroid and Breast Surgery, PLA 960 Hospital from May 2018 to December 2021 were retrospectively analyzed and compared with the clinical data of 106 obese female thyroid cancer patients who underwent open surgery（open group） during the same period. The age, body mass index（BMI）, mean time of surgery, mean postoperative drainage, tumor diameter, postoperative tumor stage, number of lymph node dissection in the central and lateral cervical regions, number of positive lymph nodes in the central and lateral cervical regions, postoperative cosmetic outcome satisfaction score, mean postoperative hospital stay and postoperative complications of all patients were counted. The results were analyzed using SPSS 26.0 statistical software, and the count data were compared using the χ² test, and the measurement data were compared using the t test. Results:All patients completed the operation successfully, and there was no conversion in the robot group, postoperative pathological results were all composed of papillary thyroid carcinoma. The operation time in the robot group was（144.62±36.38） min, which was longer than that in the open group（117.06±18.72） min（P<0.05）. The average age of the robot group was（40.25±9.27） years, which was lower than that of the open group（49.59±8.70） years（P<0.05）. The satisfactory score of cosmetic effect in the robot group（9.44±0.65） was higher than that in the open group（5.23±1.07）（P<0.05）. There was no significant difference in tumor diameter, BMI, average postoperative drainage, temporary hypoparathyroidism and recurrent laryngeal nerve injury, number of central and lateral cervical lymph node dissection, number of positive lymph nodes in the central and lateral cervical regions, and average postoperative hospital stay between the two groups. There was no permanent hypoparathyroidism and recurrent laryngeal nerve injury in both groups. Conclusion:The application of BABA pathway robot in thyroid cancer surgery in obese women is safe and feasible, and the cosmetic effect is better after operation.

Rational Extent of Regional Lymphadenectomy and the Prognostic Impact of the Number of Positive Lymph Nodes for Perihilar Cholangiocarcinoma.

The definition and classification of regional nodes are not standardized for perihilar cholangiocarcinoma. This study aimed to clarify the rational extent of regional lymphadenectomy and to elucidate the impact of number-based regionalnodal classification on survival of patients with this disease. Data of 136 patients with perihilar cholangiocarcinoma who underwent surgery were reviewed. The incidence of metastasis and the survival of patients with metastasis were calculated for each node group. The incidence of metastasis for the node groups in the hepatoduodenal ligament (denoted as no. 12) ranged from 3.7% to 25.4%, with 5-year disease-specific survival of 12.9% to 33.3% for patients with metastasis. The incidences of metastasis in the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups were 14.4% and 11.2%,respectively, with 5-year disease-specific survival rates of 16.7% and 20.0% for the patients with metastasis. When these node groups were defined as regional nodes, the 5-year disease-specific survival rates for the patients with pN0 (n = 80), pN1 (1-3 positive nodes, n = 38), and pN2 (≥4 positive nodes, n = 18) were 61.4%, 22.9%, and 17.6%, respectively (p < 0.001). The pN classification was independently associated with disease-specificsurvival (p < 0.001). When only the no. 12 node groups were regarded as regional nodes, pN classification failed to stratify the patients prognostically. No. 8 and no. 13a node groupsshould be considered regional nodes in addition to no. 12 node groupsand should be dissected. The number-based regionalnodal classification allows patients with this disease to be stratified prognostically.

Prognostic Significance of the Proximal Margin for Esophagogastric Junction Adenocarcinoma with Type II and III Tumors after Surgery

Background: The incidence of Esophagogastric Junction Adenocarcinoma (EJA) has increased in recent years, with surgical resection the main choice of treatment. The optimal length of the proximal margin for EJA is still under debate, and the impact of EJA survival and recurrence remains unclear. The aim of the present study was to investigate the influence of the optimal length of the proximal margin on EJA. Methods: From January 2011 to December 2015, 131 patients who had EJA with type II tumors were included and retrospectively analyzed. All patients underwent radical R0 resection. The proximal margin was measured promptly after resection, and the frozen-section pathological examination was negative for the margin. Results: There were 3 cases of Siewert type I EJA (2.9%), 75 cases of Siewert type II EJA (57.9%), and 53 cases (40.1%) of Siewert type III EJA. The median number of lymph nodes examined was 19 (range: 1-41), and the median number of positive lymph nodes was 2 (range: 0–18). Sixty-three patients underwent total gastrectomy (48.1%), and 68 underwent proximal gastrectomy (51.9%). The median follow-up time was 57.3 months: (range 1.9–174.1); 34 patients (26%) relapsed and 74 (56.5%) died. The 5-year overall survival rate of type II tumor patients was 68.2%, and that of type III tumor patients was 38.5% (P=0.02). For patients with a proximal margin &lt;2cm, the median recurrence time was 41.6 months, whereas it was for 42.8 months for patients with proximal margin &gt;2cm (log–rank: 0.496). Our data analysis found that a proximal margin length of 2cm was a prognostic variable for type II and type III tumors. Conclusions: There are a number of factors associated with recurrence and overall survival at 5 years for patients who have EJA with type II and type III tumors, and a proximal margin &gt;2cm may indicate better prognosis.

Clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy: A prospective randomized study

ObjectivesThis prospective study aimed to explore the clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy. MethodsWe prospectively recruited 45 patients (total 90 patients) who met the eligibility criteria to undergo conventional open thyroidectomy or submental endoscopic thyroidectomy from January 2021 to July 2022 in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. These patients were evaluated using the following indices: number of lymph nodes dissected, complications, pain severity, inflammatory indicators, cosmetic satisfaction, and economic cost. All data were analyzed by the t-test or chi-squared test. ResultsNinety patients were enrolled. The two groups did not significantly differ regarding baseline characteristics. All patients who underwent thyroidectomy had a similar trauma index and increased level of inflammation. There were no significant differences between the open thyroidectomy and submental endoscopic thyroidectomy groups in the total number of lymph nodes dissected, number of positive lymph nodes, drainage volume, and complications. The Vancouver scar score and cosmetic satisfaction score were significantly better in the submental endoscopic thyroidectomy group than the open thyroidectomy group. The submental endoscopic thyroidectomy group had a significantly lower pain scores on postoperative days 1 and 2, less downtime, and cheaper medical and esthetic costs than the open thyroidectomy group. ConclusionCompared with conventional open thyroidectomy, submental endoscopic thyroidectomy did not increase the degree of trauma, had superior clinical efficacy, caused less pain, required a shorter downtime, achieved a better cosmetic effect, and was associated with lower healthcare costs.

Number of positive lymph nodes affects outcomes in parotid adenoid cystic carcinoma.

Survival significance of the number of positive lymph nodes (LNs) in parotid adenoid cystic carcinoma (ACC) remains unknown; thus, this study aimed to determine the impact of the number of positive LNs on the prognosis of parotid ACC. Patients with surgically treated parotid ACC were enrolled from the SEER database. The number of positive LNs was analyzed using three models (0 vs 1+, 0 vs 1 vs 2 vs 3 vs 4 vs 4 vs 5 vs 6+, 0/1 vs 2-4 vs 5+), its hazard ratios on disease specific survival (DSS) and overall survival (OS) were assessed using univariate and multivariate Cox analyses. A total of 1,689 patients were included. In all models, the number of positive LNs was independently related to DSS and OS, model 3 had the highest C-index for DSS [0.83 (95% CI: 0.81-0.85)] and OS [0.82 (95% CI: 0.80-0.84)]. Compared with the 0/1 positive LN group, the 2-4 positive LN group had an HR of 2.81 (95% CI: 1.73-4.56) for DSS and 2.36 (95% CI: 1.58-3.54) for OS. The 5+ LN group had an HR of 20.15 (95% CI: 7.50-54.18) for DSS and 14.20 (95% CI: 5.45-36.97) for OS. No overlap existed in the 95% CI of the HR. The three prognostic categories based on the number of positive LNs (0/1 vs 2-4 vs 5+) could stratify the DSS and OS in parotid ACC without overlap.

Determining the survival benefit of postoperative radiotherapy in patients with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a retrospective analysis

BackgroundThe National Comprehensive Cancer Network guidelines recommend routine postoperative adjuvant radiotherapy and chemotherapy for patients with stage III rectal cancer who do not receive neoadjuvant therapy before surgery. The present study aimed to evaluate the value of postoperative radiotherapy in patients with low-risk disease (pT1-3N1M0) who did not receive neoadjuvant therapy prior to total mesorectal excision.MethodsWe used the Surveillance, Epidemiology, and End Results database (2004–2016) to retrospectively recruit patients with pT1-3N1M0 rectal cancer whose initial treatment was radical surgery with postoperative adjuvant chemotherapy. A propensity score model was used to balance the baseline covariates.ResultsOf the 2012 patients included in the present study, 1384 received adjuvant chemoradiotherapy (radio group), whereas the remaining 718 received chemotherapy alone (no-radio group). There was no significant difference in cancer-specific survival rate between the two groups (log-rank test χ2 = 2.372, P = 0.124) in the overall sample. Additionally, in the propensity score−matched cohort, adjuvant radiotherapy did not improve cancer-specific survival. Subgroup analysis showed that having three positive lymph nodes and a tumor > 50 mm, combined with postoperative adjuvant chemotherapy, could lead to an improved tumor-specific survival rate, while other cases did not benefit from postoperative radiotherapy.ConclusionsFor patients with pT1-3N1M0 rectal cancer who did not receive neoadjuvant therapy before surgery, postoperative radiotherapy in addition to adjuvant chemotherapy did not significantly improve survival rates. The number of positive nodes (n = 3) and tumor size (> 50 mm) were found to be potential screening indicators for postoperative adjuvant radiotherapy.

Early Disturbance of Lymphatic Transport as a Risk Factor for the Development of Breast-Cancer-Related Lymphedema

Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., dermal backflow) before the lymphedema is clinically visible. The main objective of this study is to investigate whether this early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of BCRL. All patients scheduled for unilateral breast cancer surgery with axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the volume difference between both arms and hands (through circumference measurements and water displacement). Clinical BCRL was defined as a ≥5% increase in relative arm volume difference compared to the baseline value. Variables related to (1) the disturbance of lymphatic transport (through lymphofluoroscopy), (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were collected. We included data of 118 patients in the present study. Thirty-eight patients (39.8%) developed BCRL. Early disturbance of lymphatic transport was identified as a risk factor for the development of clinical BCRL (HR 2.808). Breast-cancer- and treatment-related variables such as axillary lymph node dissection (ALND) (HR 15.127), tumor stage (HR 1.745), mastectomy (HR 0.186), number of positive lymph nodes (HR 1.121), number of removed lymph nodes (HR 1.055), radiotherapy of the axilla (HR 2.715), adjuvant taxanes (HR 3.220) and postsurgical complications (HR 2.590) were identified as significant risk factors for the development of BCRL. In the multivariate analysis, age and ALND were withheld as independent risk factors for the development of BCRL. Lymphofluoroscopy can identify an early disturbance of lymphatic transport after breast cancer treatment. Patients with an early disturbance of lymphatic transport are considered to be a high-risk group for the development of BCRL. This study also confirms that age and ALND are predictors for the development of BCRL. Therefore, a surveillance program of these patients with lymphofluoroscopy could be useful to identify lymphedema in subclinical stages.

Improving the Assessment and Diagnosis of Breast Lymphedema after Treatment for Breast Cancer.

Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast cancer treatment were recruited with and without breast lymphedema. Blinded clinical assessment determined the presence or absence of breast lymphedema. Measurement of skin thickness by ultrasound scanning, local tissue water by tissue dielectric constant (TDC) and tissue indentation by tonometry was recorded. Breast cancer treatment and demographic details were documented. Descriptive statistics were undertaken to compare sample characteristics, including the Chi-squared test, Odds Ratio (OR) and Relative Risks (RR) calculated. Increased body mass index (BMI), larger bra size, increased number of positive lymph nodes, axillary surgery, chemotherapy and increased Nottingham Prognostic Index (NPI) were all associated with breast lymphedema (p < 0.05). Ultrasound and TDC measurements were significantly higher in the lymphedema group (p < 0.05). Receiver Operator Characteristic (ROC) curves demonstrated that ultrasound and TDC measurements could distinguish between edematous and non-edematous breasts. Threshold levels were produced, which demonstrated good levels of sensitivity and specificity. These findings have the potential to improve the diagnosis of breast lymphedema.

Predictors of Recurrence After Metastasis-directed Therapy in Oligorecurrent Prostate Cancer Following Radical Prostatectomy

BackgroundMetastasis-directed therapy (MDT) is performed to delay systemic treatments for oligorecurrent disease after primary prostate cancer (PCa) treatment. ObjectiveThe aim of this study was to identify the predictors of therapeutic response of MDT for oligorecurrent PCa. Design, setting, and participantsbicentric, retrospective study, including consecutive patients who underwent MDT for oligorecurrent PCa after radical prostatectomy (RP; 2006–2020) was conducted. MDT encompassed stereotactic body radiation therapy (SBRT), salvage lymph node dissection (sLND), whole-pelvis/retroperitoneal radiation therapy (WP[R]RT), or metastasectomy. Outcome measurements and statistical analysisndpoints were 5-yr radiographic progression-free survival (rPFS), metastasis-free survival (MFS), palliative androgen deprivation treatment (pADT)-free survival, and overall survival (OS) together with prognostic factors for MFS following primary MDT. Survival outcomes were studied by Kaplan-Meier survival and univariable Cox regression (UVA). Results and limitationsA total of 211 MDT patients were included; 122 (58%) developed a secondary recurrence. Salvage lymph node dissection was performed in 119 (56%), SBRT in 48 (23%), and WP(R)RT in 31 (15%) of the cases. Two patients received sLND + SBRT and one received sLND + WPRT. Eleven (5%) patients received metastasectomies. The median follow-up since RP was 100 mo, while follow-up after MDT was 42 mo. The 5-yr rPFS, MFS, androgen deprivation treatment(–free survival, castration-resistant prostate cancer–free survival, CSS, and OS after MDT were 23%, 68%, 58%, 82%, 93%, and 87% respectively. There was a statistically significant difference between cN1 (n = 114) and cM+ (n = 97) for 5-yr MFS (83% vs 51%, p < 0.001), pADT-free survival (70% vs 49%, p = 0.014), and CSS (100% vs 86%, p = 0.019). UVA was performed to assess the risk factors (RFs) for MFS in cN1 and cM+. Alpha was set at 10%. RFs for MFS in cN1 were lower initial prostate-specific antigen (PSA) at the time of RP (hazard ratio [95% confidence interval] 0.15 [0.02–1.02], p = 0.053], pN stage at RP (2.91 [0.83–10.24], p = 0.096), nonpersisting PSA after RP (0.47 [0.19–1.12], p = 0.089), higher PSA at primary MDT (2.38 [1.07–5.24], p = 0.032), and number of positive nodes on imaging (1.65 [1.14–2.40], p < 0.01). RFs for MFS in cM+ were higher pathological Gleason score (1.86 [0.93–3.73], p = 0.078), number of lesions on imaging (0.77 [0.57–1.04], p = 0.083), and cM1b/cM1c (non-nodal metastatic recurrence; 2.62 [1.58–4.34], p < 0.001). ConclusionsFollowing MDT, 23% of patients were free of a second recurrence at 5-yr follow-up. Moreover, cM+ patients had significantly worse outcomes in terms of MFS, pADT-free survival, and CSS. The RFs for a metastatic recurrence can be used for counseling patients, to inform prognosis, and potentially select candidates for MDT. Patient summaryIn this paper, we looked at the outcomes of using localized, patient-tailored treatment for imaging-detected recurrent prostate cancer in lymph nodes, bone, or viscera (maximum five recurrences on imaging). Our results showed that targeted treatment of the metastatic lesions could delay the premature use of hormone therapy.

Abstract P3-05-39: Expert consensus on the definition of high risk of recurrence in HER2-negative early breast cancer: a modified Delphi panel

Abstract PURPOSE: There is currently no standardised definition for patients at high risk of recurrence of HER2-negative early breast cancer (eBC, stages 1–3) after surgery. Recognising that the assessment of high risk is often multifactorial, the aim of this modified Delphi panel was to establish expert UK consensus on this definition, separately considering HR-positive and triple-negative (TN) patients. METHODS: A total of 45 UK-based clinicians, including breast cancer oncologists and surgeons, were invited to participate. The number of respondents in each of three rounds was 29, 24 and 22 respectively. Statements were developed using the results from a targeted literature review and the guidance of a lead clinician, and comprised free-text, single-choice or numerical formats. The first round aimed to determine which factors are currently used in clinical practice to assess risk of recurrence in the populations of interest. In the subsequent rounds, the objective was to establish thresholds indicative of high risk in a 10-year timeframe for each of the factors retained in Round 1. Between each round, statements were refined, considering the distribution of responses and free-text notes provided by participants. Consensus for single-choice questions was set at a pre-defined threshold of ≥70% of respondents. RESULTS: Consensus was achieved on the need to assess age, tumour size, tumour grade, number of positive nodes, presence of inflammatory breast cancer and one or more risk prediction tools to define high risk of recurrence in all HER2-negative patients. In HR-positive patients, there was agreement on the use of one or more tumour profiling tests and biomarkers to define high risk of recurrence. However, there was no consensus on biomarker use in TN patients, and support for specific biomarkers (such as Ki-67) was conflicting for both sub-populations based on the analysis of free-text notes. Similarly, while there was consensus on the use of pCR status/residual disease to indicate high risk in TN patients, this factor failed to reach consensus for the HR-positive sub-population. Germline BRCA status and menopausal status were not considered to be key factors for risk of recurrence in either biological subtype. In the second and third rounds, thresholds indicative of high recurrence risk were agreed; it should be noted that the free-text responses provided by the participants frequently highlighted that many of the factors should be considered along a continuous scale when assessing the risk of individual patients. In HR-positive patients, these thresholds included: age &amp;lt; 35 years, tumour size &amp;gt;5 cm (each when considered independently from other risk factors); tumour grade 3 (independently or in combination with other factors); number of positive lymph nodes ≥4 when considered independently or ≥1 in combination with other factors. For patients with TN tumours, the following thresholds reached consensus, whether considered independently or in combination with other factors: tumour size &amp;gt;2 cm, tumour grade 3, number of positive lymph nodes ≥1. In several cases, however, no consensus could be reached on the appropriate threshold indicating high risk of recurrence. In the HR-positive sub-population, these included thresholds for age and tumour size, when considered in combination with other factors. In the TN sub-population, this included age, whether independently or in combination with other factors. CONCLUSIONS: The expert consensus reached in this panel highlights that an integrated model is important in assessing recurrence risk in eBC and that definitions of high risk differ according to biological subtype. The results may serve as a valuable reference point for clinicians to use in assessing risk of disease recurrence and in making treatment decisions after surgery in the HER2-negative eBC population. FUNDING: AstraZeneca UK Ltd. Writing support: Costello Medical. Citation Format: Ellen R. Copson, Jean E. Abraham, Jeremy P. Braybrooke, Stuart A. McIntosh, Caroline O. Michie, Carlo Palmieri, Rebecca Roylance, Saiqa Spensley. Expert consensus on the definition of high risk of recurrence in HER2-negative early breast cancer: a modified Delphi panel [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 P3-05-39.

Abstract P1-06-03: Differences in Breast Cancers among American-Indians and Whites in the United States

Abstract Differences in Breast Cancers among American-Indians and Whites in the United States Background - The United States has made substantial progress in improving breast cancer (BC) outcomes over the years, but unfortunately, this improvement has not impacted all races equally. BC death rates have not improved significantly for American Indian (AI) women, whereas, it significantly decreased for White women. In addition, AI women were more likely to be diagnosed at a younger age with a late-stage disease. We sought to determine the reasons for these disparities. Methods - This is a retrospective cohort study using a hospital registry database (the National Cancer Data Base) (NCDB). We identified female AIs and non-Hispanic Whites in the US diagnosed with BC between the years 2004 and 2016. We compared patient and tumor characteristics between the 2 groups and its effect on age and stage at diagnosis. We also determined hazard ratios (HRs) for overall survival using Cox regression models, both before and after adjustment for covariates. Results – Data on 6,866 AIs and 1,987,324 White women diagnosed with BC were analyzed. The mean (SD) age at diagnosis was significantly younger for AI than for White women (57.72 ± 12.23 vs. 61.87 ± 13.21). AI women traveled double the distance to their treatment facilities, lived in lower median income zip codes, reported a higher percentage of no insurance, and higher comorbidities than Whites. Furthermore, AIs were less likely to be diagnosed with Stage 0 and I BCs, had a larger tumor size, greater number of positive lymph nodes at diagnosis, and higher proportion of triple negative and HER2-positive BCs than Whites. Whites were more likely to have other cancers diagnosed prior to or after their BC diagnosis. All the above tests for comparisons were significant (p-value &amp;lt; 0.001). Correlation between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AIs and Whites. Unadjusted overall survival (OS) was significantly worse for AIs as compared to Whites (HR=1.07; 95% CI: 1.01-1.14, p-value = 0.025). After adjustment of all covariates including age, travel distance, median income of residential zip code, insurance status, cancer sequence, comorbidities, stage, tumor size, number of positive lymph nodes, grade, histology, and hormonal/HER2 status, OS was not significantly different between AIs and Whites (HR=1.04; 95% CI: 0.90-1.20, p-value = 0.601). Conclusion - Our study showed significant differences in patient and tumor characteristics among AI and White BC patients which adversely impacted BC outcomes in AIs. Survival was lower in AIs, but when adjusted for various covariates, the survival difference disappeared. Improvement in BC outcomes in AIs will involve not only improved and early access to screening to identify patients at younger ages and earlier stages at diagnosis, but also long term plans to provide affordable and the full spectrum of cancer care closer to home. Citation Format: Anu Gaba, Li Cao, Rebecca Renfrew, Janet Wernisch, Abe Sahmoun, Sanjay Goel, Ross Crosby. Differences in Breast Cancers among American-Indians and Whites in the United States [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 P1-06-03.

Abstract PD15-11: PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101)

Abstract Introduction: Chemotherapy is recommended for patients with luminal breast cancer and more than three positive nodes. In addition, recent landmark trials raised the question if the exact number of positive nodes is required to indicate genomic testing. In the neoadjuvant setting, response-driven therapy is increasingly used and may be influenced by surgical staging of the axilla. The present study addressed the role of axillary lymph node dissection (ALND) as decision aid for systemic therapy in a contemporary cohort of patients with clinically node-positive breast cancer in the adjuvant and neoadjuvant setting. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614). The first 500 patients with clinically node-positive breast cancer who were randomized after tailored axillary surgery (TAS) to undergo ALND or axillary radiotherapy (ART) without ALND in the context of extended regional irradiation were included from August 2018 to June 2022. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, the finding of residual nodal disease was mandatory for randomization. TAS consisted of removal of palpably suspicious findings and the sentinel nodes with the option of image guidance. In the ART arm, the total number of positive nodes was not known. We analyzed the impact of ALND on rate and type of systemic therapy. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers from six European countries. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. Of 343 patients (68.6%) who were treated in the adjuvant setting, 297 had HR+/HER2- disease. Of these 297 patients, 145 (48.8%) underwent ART without ALND and 152 (51.2%) underwent ALND after TAS. In the ART arm, the median number of lymph nodes removed was five (IQR 4-8), three (IQR 1-4) of which were positive and in the ALND arm, the number was 19 (IQR 14-26), four (IQR 2-9) of which were positive (p &amp;lt; 0.001). The use of ALND had no significant impact on the rate of patients with HR+/HER2- disease undergoing adjuvant chemotherapy (51.0% in the ART and 57.9% in the ALND arm, p=0.2), and there were no significant differences in type of systemic therapy with the exception of tamoxifen, which was 18.4% with ALND versus 9.0% without (p=0.018). A total of 143 patients (28.6%) underwent neoadjuvant chemotherapy, 13 had neoadjuvant antihormonal treatment and one had neoadjuvant double HER2-blockade without chemotherapy. Of the 143 patients who received neoadjuvant chemotherapy, 71 (49.7%) underwent ART without ALND and 72 (50.3%) underwent ALND. In the ART arm, the median number of lymph nodes removed was four (IQR 3-6), one (IQR 1-3) of which was positive and in the ALND arm, the number was 16 (IQR 12-19), two (IQR 1-5) of which were positive (p &amp;lt; 0.001). The use of ALND in patients after neoadjuvant treatment had no significant impact on the rate of adjuvant systemic therapy (71.8% in the ART and 65.3% in the ALND arm, p=0.4), with no significant differences in type of chemotherapy (e.g., capecitabine: 11.3% vs 12.5%, p=0.8; T-DM1: 11.3% vs. 11.1%, p&amp;gt;0.9) or antihormonal therapy (e.g., aromatase inhibitors: 49.3% vs. 41.7%, p=0.4; tamoxifen: 11.3% vs. 5.6%, p=0.2). Discussion: This study showed that although ALND significantly increased the number of positive nodes removed in the adjuvant and neoadjuvant setting, it had no relevant impact on rate and type of adjuvant systemic therapy. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christian Kurzeder. PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [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 PD15-11.

Abstract PD15-02: PD15-02 Long Term Outcome in Patients with Nodal-Positive Breast Cancer Treated with Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy

Abstract Importance: The use of neoadjuvant chemotherapy (NAC) in the clinical care of breast cancer patients has increased considerably over recent years especially in node positive cases. For patients who have axillary nodal metastases prior to NAC, the prevailing standard of care is to undergo an axillary lymph node dissection (ALND), regardless of response to therapy. Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in patients who had clinical complete response in the axilla following NAC. This is due to the presumed high false negative rate associated with SLNB in such scenario. But there are limited data on the long term outcome of these patients who are only treated with SLNB alone. Aim: A retrospective cohort study comparing the long term outcome of breast cancer patients with clinically node positive disease (N1) but turned clinically node negative (N0) following NAC, receiving SLNB alone versus ALND. Methods: Patients who had pathologic proven N1 breast cancer (before NAC) treated with NAC and turned clinically N0 from January 2009 to December 2014 were identified from Asan Medical Center breast cancer database in South Korea. Primary endpoint was axillary recurrence rate (ARR) and secondary endpoints were disease-free survival (DFS) and overall survival (OS). These outcomes were reported for patients who had SLNB alone versus ALND. Results: 561 patients with clinically stage N1 (cN1) cancer treated with NAC and turned clinically stage N0 (cN0) were identified. 253 (45.1%) patients received SLNB only while 308 (54.9%) patients had ALND. The clinicopathological features of these patients were illustrated in Table 1. Majority of these patients received adjuvant radiotherapy, 81.2% in the SLNB group and 76.5% in the ALND group. In the pathologically stage N0 (ypN0) group, at a median follow up of 69 months, ARR was 3.0% in the SLNB only group and 1.7% in the ALND group (p=0.704). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p= 0.561 and 0.810 respectively). Median number of SLN harvested in the SLNB only group is 5 (range 1 -17). In the pathologically stage N1 (ypN1) group with only 1-2 lymph node positive for metastasis, at a median follow up of 66 months, ARR was 5.8% in the SLNB group and 4.7% in the ALND group (p=0.768). There was no significant difference in DFS and OS between the SLNB and ALND group (p=0.537 and 0.645). In the SLNB only group, the median number of positive lymph node was 1 (range 1-2), the median number of sentinel lymph node was 6 (range 2-18). Conclusion: In cN1 breast cancer patients who were converted to cN0 following NAC, axillary recurrences were rare. No statistically significant differences were noted in DFS and OS between patients with SLNB or ALND. Our findings suggest that these patients may be safely treated with SLNB only, even when there are up to 2 positive SLNs. Table 1 Clinicopathological features of breast cancer patients with nodal disease and NAC Citation Format: Sue Zann Lim, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Hee Jeong Kim. PD15-02 Long Term Outcome in Patients with Nodal-Positive Breast Cancer Treated with Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy [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 PD15-02.

Abstract P2-26-21: The Principal Factors Associated with Engraftment Success of Patient-Derived Xenograft of Breast Cancer

Abstract Background: Patient-derived xenografts (PDXs) are increasingly used in cancer research as tools for studying cancer biology and personalized immunotherapy response. However, a comprehensive evaluation of patient-derived breast cancer xenograft generation rates in various settings is understudied. Methods: We conducted a prospective study of breast cancer patients treated with surgery to generate PDXs. PDXs were characterized by molecular subtypes, specific diagnostic entities, modified Bloom-Richardson system nuclear and histologic grades, treatment with neoadjuvant chemotherapy (NAC), Miller Payne grade, residual caner burden class, invasive tumor size, lymphovascular invasion status, number of positive lymph nodes, and the percentage of tumor infiltrating lymphocytes in the implanted tumors. Results: Three hundred and seventy-two (157 post-chemotherapy, 215 chemo-naïve) patient-derived tumors were implanted and 63 PDXs were established (17.0%). PDX engraftment was higher in the patients with higher nuclear and histologic grades using the modified Bloom-Richardson system (27.6% vs. 3.2%, p = 0.003) and triple negative breast cancer (TNBC) than in those with hormone receptor-positive cancer (36.4% vs. 3.2%, p = 0.02). Tumors from patients who received NAC (30.0% vs. 7.4%, p = 0.05) were also close to being statistically significant for successful PDX generation. Conclusions: PDXs can be established from clinically aggressive breast cancers, especially in patients with high nuclear and histologic grade TNBC treated with NAC. The prediction of engraftment success using these factors would establish cost-effective immunotherapy trials employing PDXs. Citation Format: Jongwon Lee, Uk Lee, Hee Jin Lee, Gyungyub Gong. The Principal Factors Associated with Engraftment Success of Patient-Derived Xenograft of Breast Cancer [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 P2-26-21.

Abstract P1-07-08: Prediction of breast cancer late recurrence according to Clinical Treatment Score post-five years (CTS5) and progesterone receptor in a wider patient population

Abstract Background The duration of adjuvant endocrine therapy remains a continuous challenge in hormone-receptor positive (HR+) early breast cancer. The Clinical Treatment Score post-five years (CTS5) is an online model used to predict late distant metastasis for women with HR+ breast cancer who are recurrence-free 5 years after endocrine therapy (ET). It incorporates patients age, tumor size, grade, and number of positive lymph nodes, and is an important tool to help in this treatment decision. There is a paucity of data in premenopausal women and whether other variables could add additional information. Methods A single-center retrospective analysis of patients that have received adjuvant ET for 5 years, between January 2007 and December 2008 at the Instituto Nacional de Cancer (INCA), Brazil. Disease-Free Survival (DFS) was compared between the low, intermediate, and high-risk subgroups. Data analysis was descriptive and exploratory. Kaplan-Meier estimates and Cox regression models were used. Results A total of 183 patients were enrolled, 26.5% being premenopausal. Median age at diagnosis was 66 years. Tumor stage: I (44%) and II (56%). ET consisted of tamoxifen (88%), anastrozol (6%), and a switch (6%). There were 39.5%, 39.5% and 21% of patients in the low, intermediate, and high-risk (L/I/H) subgroups, respectively. Progesterone-receptor was ≥ 20% in 71% of tumors and in 55%, 49% and 34% in the L/I/H subgroups, respectively. Median follow up was 88.9 months. After 5 years, the median DFS was 100%, 96.3% and 68.2% in L/I/H subgroups (p &amp;lt; 0,001). Progesterone-receptor was also an independent prognostic factor for late recurrence (p &amp;lt; 0,05). Conclusion CTS5 performed well in a wider patient population including premenopausal women. Progesterone-receptor was an independent prognostic factor for DFS and should be further considered into the model. Citation Format: Giselle S. Carvalho, GUSTAVO O. BRETAS, Daniel Musse, Victor Gondim, José Bines. Prediction of breast cancer late recurrence according to Clinical Treatment Score post-five years (CTS5) and progesterone receptor in a wider patient population [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 P1-07-08.

Abstract P2-11-11: Computer analysis of nuclear morphology with Multiple Instance Learning Predicts Overall Survival for Node Positive Breast Cancer Patients from SWOG S8814: A Blinded Validation Study

Abstract Background: Adjuvant chemotherapy is a common treatment for breast cancer patients with aggressive tumors, but imposes severe side effects. Although lymph node involvement is associated with higher likelihood of mortality, a subset of LN+ patients can survive without relapse, even without adjuvant chemotherapy. SWOG-8814 (S8814) was a randomized clinical trial of hormone receptor positive, LN+ post-menopausal women (pathologic stage T1-3N1-2) to compare patient outcome between endocrine therapy alone (tamoxifen), chemotherapy (cyclophosphamide, doxorubicin, and 5-fluorouracil) followed by 5 years of tamoxifen, and chemotherapy with concurrent tamoxifen. In this work, we evaluated the ability of a machine learning approach called multiple instance learning (MIL) to predict long-term overall (OS) and disease-free survival (DFS) in patients from the S8814 clinical trial via analysis of digitized H&amp;E tissue slides. Methods: The training set (St, n=121) consisted of digitized H&amp;E Whole Slide Images (WSIs) of ER+ LN+ patients from ECOG-2197 - a clinical trial to compare patient outcome under chemotherapy with doxorubicin/docetaxel vs. doxorubicin/cyclophosphamide. For each WSI, the nuclei of ten tumor patches (2000 × 2000 pixels) were automatically segmented by a pretrained machine learning algorithm called Convolutional Neural Networks (CNN). The results of the CNN’s segmentations were used to obtain ten corresponding feature vectors of 3963 features relating to nuclear morphology and spatial arrangement. Five top discriminative features (Haralick texture, Delaunay triangulation, orientation entropy, perimeter kurtosis, architecture) were identified by reliefF-MI feature filtering and forward selection on St. A Normalized Set Kernel Support Vector Machine classifier was trained on St to construct a MIL binary classifier (M+), which generates a continuous survival score to predict which patients would have &amp;gt;10-years of DFS and OS. The score cutoff thatmaximized F1 score on St was used to generate binary predictions of patient outcome. Blinded validation of the risk scores on S8814 was performed by SWOG. Results: M+ was significantly prognostic of OS in univariate analysis (HR=0.72, p=0.020, 95% CI= 0.55 – 0.95) on S8814. M+ stratifications remained statistically significant after multivariable analysis controlling for treatment, number of positive lymph nodes, and tumor size (HR = 0.71, p=0.017, 95% CI=0.54-0.94). M+ predictions did not achieve statistical significance for DFS in univariate analysis (HR=0.81, p=0.081, 95% CI 0.64-1.03) nor multivariable analysis (HR=0.81, p=0.080, 95% CI 0.63-1.03). M+ was not predictive of chemotherapy benefit for OS (p=0.88) and DFS (p=0.65). There was no correlation of the generated continuous score with Recurrence Score (r=-0.05), previously shown to be a predictive factor for chemotherapy benefit. Conclusion: Our findings demonstrate that nuclear morphology provides insight into overall survival in ER+ LN+ breast cancer patients. Future work will involve combining the MIL based morphologic predictor with other clinicopathologic factors to improve DFS risk stratification. Funding: Funding NIH/NCI grants U10CA180888, U10CA180819, U24CA196175; and in part by Genomic Health, INC. (now Exact Sciences Corp.) Citation Format: Daniel Shao, William E. Barlow, Haojia Li, Cheng Lu, Kathy S. Albain, James Rae, Daniel F. Hayes, Andrew K. Godwin, Alastair M. Thompson, Anant Madabhushi, Lajos Pusztai. Computer analysis of nuclear morphology with Multiple Instance Learning Predicts Overall Survival for Node Positive Breast Cancer Patients from SWOG S8814: A Blinded Validation Study [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 P2-11-11.

Abstract GS1-01: Race and clinical outcomes in the RxPONDER Trial (SWOG S1007)

Abstract Introduction: Racial disparities in breast cancer (BC) outcomes continues to be a major health care challenge. The 21-gene recurrence score (RS) is an important tool to guide treatment (tx) decisions among women with early-stage BC. We report an analysis of clinical characteristics, survival outcomes and race in association with RS in participants (pts) in the RxPONDER trial. Methods: We analyzed clinical outcomes with respect to race and ethnicity. Unreported race excluded 18.7% of the pts, with most due to privacy rules. The primary outcome was invasive disease-free survival (IDFS). Distant relapse-free survival (DRFS) was also evaluated. Analyses adjusted for assigned tx arm, RS, and grade were performed. There were too few events to include Native American/Pacific Islander (NAPI) women in the survival analyses. Results: A total of 4,048 trial women with Hormone Receptor positive, HER2 negative (HR+/HER2-) BC, 1-3 involved axillary lymph nodes (LNs), RS ≤ 25 and known race/ethnicity were included in this analysis including the following: 2,833 non-Hispanic (NH) White pts (70%), 248 NH Black pts (6.1%), 610 Hispanic pts (15.1%), 324 Asian pts (8.0%), and 33 NAPI pts (0.8%). Asian and Hispanic women were younger than NH Whites (by 7.1 and 2.4 years, respectively) but NH Blacks did not differ in age. RS distribution did not differ among all racial subgroups (p=0.49). There were also no significant differences in tumor size (p=0.10) or number of positive LNs (p=0.26) across all racial groups. However, tumor grade was found to be significantly different with grade 3 tumors higher for NH Blacks (18.0%), NH NAPI (21.1%), and Hispanics (14.5%) vs. NH Whites (10.4%) and Asians (6.5%) (p&amp;lt; 0.001). Overall five-year IDFS was lower for NH Blacks (87.0%) compared to that for Asians (93.9%), NH Whites (91.5%), and Hispanics (91.4%) (Table 1). A multivariable Cox model adjusting for RS and tx arm showed worse IDFS for NH Blacks compared to NH Whites (HR=1.38; 95% CI 1.00-1.90; p=0.048), although Asian pts had better IDFS than NH Whites (HR=0.65; 95% CI 0.44-0.97; p=0.034). In a separate analysis by menopausal status the magnitude of the IDFS hazard ratios (HRs) for NH Blacks was similar, although no longer statistically significant (premenopausal HR=1.37; 95% CI 0.69-2.72; postmenopausal HR=1.38; 95% CI 0.96-1.98). While there was no statistically significant interaction between NH Blacks vs. NH Whites and tx arm for either premenopausal (p=0.99) or postmenopausal women (p=0.44), adjusting for RS, the small number of events in the NH Black cohort, particularly in premenopausal women (n = 9 IDFS events), limit power and inference about differences in chemotherapy benefit. Among postmenopausal women, NH Blacks had worse DRFS compared to NH Whites (HR=1.69; 95% CI 1.12-2.53; p=0.01), adjusting for tx and RS. A similar trend was seen among premenopausal women (HR=1.74; 95% CI 0.79-3.82; p=0.17), although not statistically significant. Data on tx adherence over 5 years was not mature, although NH Blacks were more likely to accept tx assignment compared to NH Whites at randomization (93% vs. 86%, p=0.004). Conclusion: Black women with HR+/HER2- BC, 1-3 involved LNs and RS ≤ 25 have worse outcomes compared to White women despite similar RS results. There was no significant interaction between NH Blacks vs. NH Whites and tx arm, although this analysis was limited due to sample size. There remains an important need for novel approaches to improve clinical outcomes particularly for NH Black Women. Table 1. IDFS by Race and Ethnicity. Citation Format: Yara Abdou, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Stephen K. Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F. Schott, Steven Shak, Priyanka Sharma, Danika L. Lew, Jieling Miao, Joseph M. Unger, Debu Tripathy, Lajos Pusztai, Gabriel N. Hortobagyi, Kevin Kalinsky. Race and clinical outcomes in the RxPONDER Trial (SWOG S1007) [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 GS1-01.

Abstract HER2-14: HER2-14 HER-2 low status in early stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series

Abstract Objectives: The concept of human epidermal growth factor receptor 2 (HER2)-low status has been proposed as a potential treatment target for breast cancers previously considered to be HER2-negative. Defined by an immunohistochemistry (IHC) score of 1+ or 2+ and negative fluorescent in situ hybridization (FISH) for HER2, HER2-low status predicts significant clinical benefit from novel therapeutic compounds in recent clinical trials. The prevalence and clinical implications of HER2-low status in patients with early stage invasive lobular carcinoma (ILC) has not been described. We aimed to describe the clinicopathologic features and prevalence of HER2-low status in ILC, and identify any potential differences in clinical outcome. Methods: We evaluated stage I-III ILC tumors from a prospectively maintained institutional database of patients where both IHC and FISH testing for HER2 status was performed as standard clinical care. Tumors were classified as HER2 negative (IHC=0), HER2-low (IHC=1+ or 2+ and negative FISH), or HER2 positive (IHC=3+ or FISH ratio ⇒2). Data were analyzed in Stata 16.1 using chi-squared tests, t-tests, and Cox proportional hazards models for disease free survival (DFS). Results: 666 ILC tumors with available HER2 status were available for analysis. The mean age at diagnosis was 59.8 years (range 21-91). The majority of patients had stage I disease (63.1%) with an average follow up time of 6.7 years (standard deviation [5.4]). Overall, 184 (27.6%) tumors were HER2 negative, 434 (65.1%) were HER2-low, and 48 (7.2%) were HER2 positive. There were no associations between HER2 status and age, menopausal status, body mass index, tumor stage, grade, presence of lymphovascular invasion, or molecular assay results. Hormone receptor status was significantly associated with HER2 status, with HER2 positive tumors significantly less likely to be estrogen receptor (ER) positive than both HER2 negative and HER2-low tumors (89.6% versus 97.3% and 96.8% respectively, p=0.03). HER2-low tumors were also significantly more likely to have progesterone receptor (PR) positivity (86.6% compared to 79.9% of HER2 negative and 72.9% of HER2 positive tumors, p = 0.01). This difference remained significant when comparing just HER2-low to HER2 negative cases (p=0.034). While there were no differences in use of neoadjuvant or adjuvant chemotherapy by HER2 status, HER2-low patients were significantly more likely to undergo mastectomy versus lumpectomy when compared to HER2 negative and HER2 positive patients (53.7% versus 38.0% and 43.8% respectively, p= 0.001). In a multivariable Cox proportional hazards model adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse DFS than those with HER2 negative tumors (hazard ratio 2.0, 95% confidence interval 1.0 - 4.1, p=0.05). Conclusions: In this analysis of 666 early stage ILC cases, we found that most tumors were HER2-low, and that those with HER2-low disease were significantly more likely to have PR positive tumors and to undergo mastectomy. When adjusting for these variables, we identified a difference in DFS between HER2 negative and HER2-low early stage ILC. These findings support the contention that HER2-low and HER2 negative disease represent two different clinical entities. Further investigation of the potential benefit of HER2 targeted therapy in ILC, which predominately lacks HER2-amplified disease, is needed to ensure optimal outcomes in this understudied tumor type. Citation Format: Harriet T. Rothschild, Elle Clelland, Anne Patterson, Julissa Molina-Vega, Mandeep Kaur, Mary Kathryn Abel, W. Fraser Symmans, Christopher J. Schwartz, Rita Mukhtar. HER2-14 HER-2 low status in early stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series [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 HER2-14.

Abstract P2-11-16: Computerized Measurements of Nuclear Morphology Features, Mitosis Rate, and Tubule Formation from H&amp;E Images Predicts Disease-Free Survival in Patients with HR+ &amp; LN+ Invasive Breast Cancer from SWOG S8814

Abstract Background: Lymph node (LN) involvement is a strong indicator of poor prognosis for breast cancer (BC), with adjuvant chemotherapy remaining fundamental to management of these patients. SWOG S8814 was a Phase III randomized trial of postmenopausal patients with pathologic LN-positive BC who were hormone receptor positive (HR+). The objectives of the clinical trial were to compare disease free survival (DFS) and overall survival (OS) of 1) these postoperative patients treated with a combination of cyclophosphamide, doxorubicin, fluorouracil (CAF) plus tamoxifen versus tamoxifen alone; and 2) patients treated with CAF followed by tamoxifen versus CAF plus concurrent tamoxifen. In this study we sought to evaluate the potential of applying computational image analysis on whole slide images (WSI) for predicting DFS and OS in SWOG S8814. Methods: A cohort of 135 patients (N=53 DFS event) diagnosed with HR+ &amp; LN+ BC from clinical trial ECOG 2197 was utilized as training set D1. Validation set D2 comprised 630 patients (N=260 DFS event, N=195 death) with HR+&amp; LN+ BC from SWOG S8814. Three deep learning models were employed to respectively detect nuclei, mitosis, and tubules in WSIs. Subsequently, a total of 1,810 features relating to nuclear morphology (e.g., spatial distribution, shape, texture, orientation), mitotic activity (e.g., mitosis hotspot, mitotic rates) and tubule formation (e.g., tubular nuclei distribution, ratio of tubule to non-tubule area) were extracted from each WSI. A lasso regularized Cox regression model (IbRiS) was trained on D1 to respectively identify four features from each of the feature categories (nuclei morphology, mitotic activity, and tubule formation) most strongly associated with DFS, a continuous risk score based on the selected features was then constructed. An optimal risk threshold was identified on D1 to dichotomize the risk scores into high vs. low risk of recurrence categories. Blinded validation of the machine learning model on SWOG S8814 using Cox regression was performed by SWOG to evaluate its performance in terms of DFS and OS. Results: In D2, patients identified as high risk of recurrence by IbRiS had a significantly worse prognosis in terms of DFS with hazard ratio=1.30 (p=0.039, 95% CI=1.01-1.66). IbRiS was also found to be significantly prognostic of OS with hazard ratio=1.38 (p=0.026, 95% CI=1.04-1.83). IbRiS was however, neither prognostic of DFS (HR = 1.20; 95% CI 0.93-1.54) nor OS (HR = 1.28; 95% CI 0.96-1.71) in multivariable analysis adjusting for treatment, tumor size, and number of positive nodes. IbRiS was also not a significant predictor of chemotherapy benefit (DFS p=0.45; OS p=0.25). Conclusion: We developed a prognostic model (IbRiS) based on the combined features of nuclear morphology, mitosis count, and tubule formation that can help further risk stratify HR+ &amp; LN+ BC patients by only using H&amp;E slides. Citation Format: Yuli Chen, William E. Barlow, Haojia Li, Cheng Lu, Andrew Janowczyk, German Corredor, Shridar Ganesan, Michael Feldman, Pingfu Fu, Hannah Gilmore, Kathy S. Albain, Lajos Pusztai, James Rae, Daniel Hayes, Andrew K. Godwin, Alastair M. Thompson, Anant Madabhushi. Computerized Measurements of Nuclear Morphology Features, Mitosis Rate, and Tubule Formation from H&amp;E Images Predicts Disease-Free Survival in Patients with HR+ &amp; LN+ Invasive Breast Cancer from SWOG S8814 [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 P2-11-16.

Abstract P4-02-06: Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization

Abstract Background: Over the last years, the management of patients with node positive early breast cancer has gone through important innovations. On the medical side, new targeted therapies such as olaparib and abemaciclib have been introduced, with promising results on the invasive disease-free survival. Moreover, sparing axillary lymph node dissection has proven to be noninferior in terms of overall survival. However, no tools are currently available to predict lymph node involvement before definitive surgical evaluation. The aim of the study was to analyze clinical and pathological characteristics of patients with node positive early breast cancer to explore potential risk profiles associated with a ≥3 nodal involvement. Methods: The study retrospectively analyzed 335 node-positive breast cancer patients treated at the Breast Unit of the CRO Aviano National Cancer Institute, between 2017 and 2021. Data regarding primary tumor biological features, lymph node involvement and surgical approach were collected. Associations between clinico-pathological characteristics and ≥3 lymph node involvement were tested through stepwise logistic regression and the gradient boosting machine learning algorithm (GBM). Results: Among the 335 analyzed patients, 87.0% had a primary tumor &amp;lt; 5 cm, with a single positive lymph node in 73.3% of cases. Hormone receptors were mainly positive (respectively 93.5% and 83.4% for estrogen and progesterone receptors). Tumor grade was most frequently well differentiated (Grade 1 in 60.7%), with a Ki67 &amp;lt; 20% (59.5%). After multivariable logistic regression, a tumor size ≥ 3 cm (OR 3.24, CI95% 1.47-7.17, p = 0.004), the presence of massive lymphovascular stromal invasion (OR 2.50, CI95% 1.02-6.14, p = 0.045) and 2 or more positive sentinel lymph nodes at surgical evaluation (OR 6.08, CI95% 3.34-11.05, p &amp;lt; 0.001) were associated with a higher risk of identifying ≥ 3 positive lymph nodes after subsequent axillary dissection. Similar results were observed in the luminal-like cohort. A GBM machine learning model was then developed with a 0.77 Area Under the Curve. Features with the highest relative importance (RI) were single sentinel node involvement (RI 16.1873), followed by tumor size ≥ 3 cm (RI 10.2024), ≥2 positive sentinel lymph nodes (RI 8.5050) and lymphovascular stromal invasion (4.0217). Consistently, number of positive sentinel lymph nodes and tumor size were the predominant features in all top 20 GBM models. Conclusions: The present study explored the definition of risk profiles linked to 3 or more positive lymph nodes based on clinical and pathological features. It, moreover, tested the feasibility of developing machine learning classifiers to support future clinical decision-making. Due to the growing complexity of the adjuvant setting, finding a balance between minimally invasive surgical and staging approaches and risk definition for treatment personalization will become increasingly critical. Citation Format: Tania Pivetta, Brenno Pastò, Martina Urbani, Elisabetta Benozzi, Nicola De Pascalis, Tiziana Perin, Mario Mileto, Bruno Pasquotti, Erica Piccoli, Lorenzo Vinante, Chiara Bampo, Silvia Bolzonello, Mattia Garutti, Milena Nicoloso, Serena Corsetti, Simona Scalone, Lucia da Ros, Paola di Nardo, Camilla Lisanti, Simon Spazzapan, Barbara Belletti, Michele Bartoletti, Lorenzo Gerratana, Samuele Massarut, Fabio Puglisi. Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization [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 P4-02-06.