High Risk Of Distant Recurrence Research Articles

Distinct transcriptional and prognostic impacts of TERT promoter mutations C228T and C250T in papillary thyroid carcinoma.

TERT promoter mutations C228T and C250T are associated with disease aggressiveness and poor clinical outcomes in patients with papillary thyroid carcinomas. However, very little is known about the transcriptional consequences of these mutations and whether they both carry similar oncogenic potential. Here we characterized the transcriptional disturbances and clinical outcomes associated with the presence of each of these two mutations using data derived from The Cancer Genome Atlas. We observed that tumors harboring the C228T mutation (n = 27) exhibited a 16-fold increase in TERT mRNA levels (P = 5.3 × 10-42), whereas C250T tumors (n = 8) showed only a two-fold increase in expression (P = 0.034). The C228T mutation was associated with the activation of signaling pathways controlling the cell cycle, cellular division, and extracellular matrix degradation. Univariate analysis demonstrated that the C228T mutation was associated with older age at diagnosis, large tumor size, lymph node invasion, and distant metastases at diagnosis. The C228T mutation was also associated with worse progression-free interval (PFI) in comparison to WT tumors (HR = 5,04; P < 0.001). This association remained significant in a multivariate analysis (HR = 3.74, P = 0.003) adjusting for BRAF-V600E status and ATA risk group. Our data indicate that TERT promoter mutations C228T and C250T have distinct transcriptional consequences in papillary thyroid carcinoma (PTC), suggesting a greater oncogenic potential for the C228T mutation. TERT promoter mutation C228T may be a useful prognostic marker to identify patients at high risk of distant recurrence. Clinical data for the C250T mutation is still limited, with no evidence up to date to confirm its prognostic significance.

Examining a genomic test in predicting extended endocrine benefit and recurrence risk in a diverse breast cancer population.

e12526 Background: Extending adjuvant endocrine therapy (EET) beyond five years for early-stage hormone receptor-positive (HR+) breast cancer reduces late distant recurrence risk. The genomic test, Breast Cancer Index (BCI), has prognostic value and predicts the benefits of prolonged therapy, yet no studies have explored this testing in a diverse population. This study assesses late distant recurrence risk and predictive benefits of EET to better understand its relevance in a diverse early-stage HR+ breast cancer population. Methods: We analyzed patient demographics, clinical and pathologic characteristics, and BCI scores of 150 women in Hawaii with early-stage HR+ breast cancer, self-identifying as White, Filipino, Japanese, Native Hawaiian, or other. Tumor characteristics examined include size, grade, histology, lymph node, and ER/PR/HER2 receptor status. Logistic regression analyses used race, distant recurrence risk, and tumor features as predictor variables. BCI prediction of benefit and distant recurrence risk served as outcome variables. Results: Japanese patients had significantly lower odds of having a high risk for distant recurrence (OR = 0.02, p &lt; 0.0001) compared to White. Other Asian PIs also showed reduced odds of high distant recurrence risk (OR = 0.07, p = 0.02), albeit to a lesser extent than Japanese. Patients with high distant recurrence risk had significantly greater odds of a score predicting benefit than those with low risk (OR = 5.03, p = 0.009). Racial or ethnic differences in predicting benefit with EET were not statistically significant. Conclusions: Results show no racial or ethnic differences in predicting the benefit of EET, strengthening BCI’s universal applicability in diverse women with early-stage HR+ breast cancer. Patients with higher distant recurrence risk were predicted to benefit from EET. This suggests potential variations in tumor features or other factors affecting distant recurrence risk among racial groups. Limitations include a relatively small sample size and lack of data from patients representing other racial groups. Future studies should expand the sample size and adjust for known breast cancer risk factors to better understand the racial and ethnic implications of BCI.

Abstract PO1-28-01: MammaPrint and BluePrint identify racial disparities among women with HR+HER2- early-stage breast cancer

Abstract INTRODUCTION: Black women are 41% more likely to die from breast cancer compared to White women yet remain underrepresented in clinical trials and population studies. We have previously shown a higher proportion of Black women with HR+HER2- tumors further classify as Basal-Type compared with White women, using BluePrint molecular subtyping. Other studies have demonstrated higher 3-year recurrence rates in patients with BluePrint Basal-Type tumors compared to Luminal-Type. To determine whether the increased frequency of HR+/Basal-Type tumors impacts long-term outcomes in this cohort, we compared 3-year outcomes with BluePrint and the risk of distant recurrence signature, MammaPrint (MP), between Black and White women with HR+HER2- breast cancer. We also evaluated the association of MP and BluePrint with 10-year outcomes in a subset of Black women. METHODS: This study included 635 women with stage I-III, HR+HER2- breast cancer, of whom, 135 Black women were enrolled in the BEST study between 2005-2015 (R01-CA204819), and 120 Black women and 380 White women are enrolled in the ongoing FLEX study (NCT03053193). Each patient had MP and BluePrint testing. MP classifies tumors as having a Low Risk or High Risk of distant recurrence. BluePrint categorizes tumors as Luminal-Type, HER2-Type, or Basal-Type. Together, MP and BluePrint further stratify Luminal tumors into Luminal A-Type (MP Low Risk) and Luminal B-Type (MP High Risk). Recurrence-free survival (RFS) was the primary endpoint. Overall survival (OS) at 10 years was the secondary endpoint for those with long-term follow up. RFS and OS are defined per STEEP criteria. Survival curves were estimated using Kaplan-Meier analyses, and significance between groups was determined using log-rank test. RESULTS: Among all patients, 14.5% of Black women had BluePrint Basal-Type tumors compared to 5.8% of White women (p &amp;lt; 0.001). Median follow up was 3.0 years for patients in FLEX, and 10.1 years for patients in BEST. The unstratified 3-year RFS was 93.6% (95% CI 90.7 – 96.7) for Black patients and 93.6% (95% CI 91.1 – 96.3) for White patients. When further stratified by MP and BluePrint, 3-year RFS for patients with HR+HER2- tumors significantly differed (p=0.002). Patients with HR+/Luminal A tumors exhibited the best 3-year RFS (96.9%; 95% CI 95.0 – 98.9), followed by HR+/Luminal B tumors (91.6%; 95% CI 88.2 – 95.1), and HR+/Basal tumors (85.8%; 95% CI 77.2 – 95.5). For a subset of patients with 10-year follow up, we evaluated the association of MP and BluePrint with RFS (n=135) and OS (n=134). The unstratified 10-year RFS and OS rates for Black women were 88.4% (95% CI 82.9 – 94.2) and 89.0% (95% CI 83.7 – 94.7), respectively. When stratified by MP and BluePrint, Black patients with HR+/Luminal A tumors had a 10-year RFS of 97.7% (95% CI 93.4 – 100), versus 83.5% (95% CI 74.8 – 93.1) for patients with HR+/Luminal B, and 85.0% (95% CI 70.7 – 100) for patients with HR+/Basal tumors (p=0.080). Similarly, Black patients with HR+/Luminal A tumors exhibited excellent 10-year OS (100%), whereas OS for patients with HR+/Luminal B (83.5%; 95% CI 74.8 – 93.1) and HR+/Basal tumors (85.0%; 95% CI 70.7 – 100) were significantly lower (p=0.026). CONCLUSION: Survival outcomes at 3 years were comparable between Black and White patients. MP and BluePrint more precisely stratified tumors resulting in distinct 3- and 10-year outcomes, independent of race, beyond clinical subtype alone. Additionally, the subset of Black patients with Low Risk, Luminal A-Type tumors had excellent 10-year survival outcomes. Patients with HR+ tumors that further classify as Basal-Type, which occur more frequently in Black patients, have worse outcomes compared to Luminal A-Type tumors, and may warrant more aggressive treatment. These data highlight the importance of genomic testing to help optimize treatments and reduce outcome disparities in Black women. Citation Format: Sonya Reid, Xiao-Ou Shu, Lindsay Venton, Josien Haan, Andrea Menicucci, Patricia Dauer, William Audeh, Tuya Pal. MammaPrint and BluePrint identify racial disparities among women with HR+HER2- early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-01.

Abstract PO4-02-03: Distribution of MammaPrint, BluePrint, and Response Predictive Subtypes based on ImPrint and Reprint in ER+/HER2- Invasive Lobular Carcinoma – A FLEX sub study

Abstract Background: Invasive lobular carcinoma (ILC), the second most common histologic subtype of breast cancer, is increasingly recognized as a distinct tumor type compared to the more common invasive ductal carcinoma (IDC). While ILC is known to have lower rates of pathologic complete response to neoadjuvant chemotherapy, ILC tumors are biologically heterogenous. As such, genomic signatures might identify patients with ILC who might benefit from tailored treatment options. The gene expression signature MammaPrint (MP) classifies tumors as having a Low Risk or High Risk of distant recurrence. MP combined with BluePrint (BP), a molecular subtyping signature, categorizes tumors as Luminal A (MP Low Risk), Luminal B (MP High Risk), Basal or HER-2 type. ImPrint is a 53-gene signature that identifies HR+HER2- patients predicted to benefit from immune checkpoint inhibitors. RePrint is a 60-gene DNA repair deficiency (DRD) signature that identifies HR+HER2- patients who may benefit from PARP inhibitors with platinum agents. Response Predictive Subtypes (RPS), used in the I-SPY2 trial, combine clinical subtype and these genomic signatures to personalize treatment planning and improve outcomes. In this study, we determined the distribution of 3 RPS in HR+HER2-: (1) ImPrint-/RePrint-, (2) ImPrint-/RePrint+ (3) ImPrint+, in patients ILC compared to IDC enrolled in the FLEX trial. Methods: This study includes 1078 HR+HER2-women with ILC and 6078 with IDC enrolled in FLEX registry. FLEX (NCT03053193) is a prospective, observational trial that includes stage I-III breast cancer patients who undergo MammaPrint testing (with or without BluePrint) as standard of care, and consent to full transcriptome and clinical data collection. MP High Risk tumors were further stratified into High 1 and High 2. ImPrint and Reprint results were used to determine RPS. A two-tailed proportional z-test was used to assess differences between ILC and IDC as well as between RPS. Results: ILC patients had a significantly lower percentage of MP High Risk tumors in comparison to IDC. Among MP High Risk tumors, those with ILC had significantly more MP High 1 than patients with IDC. BP subtyping in ILC tumors showed significantly lower percentage of Basal, and Luminal B, and higher percentage of Luminal A compared to IDC tumors. For RPS, a higher percentage of ILC tumors were ImPrint-/RePrint- compared to IDC, whereas lower frequencies of ImPrint-/RePrint+ and ImPrint+ were found. Within the ILC ImPrint+ subgroup (n=14), 1 (7.1%) was classified as High 2 and 10 (71.4%) as High 1 and 3 (21.4%) as Low Risk. All 14 (100%) ImPrint+ patients were BP Luminal. In contrast, within the IDC MP High Risk ImPrint+ subgroup (n=328), 233 (71.0%) were High 2, 88 (26.8%) High 1 and 7 Low Risk (2.1%). Furthermore 193 (60.7%) were classified as BP Basal, 2 HER2 (0.6%) and 123 (38.7%) Luminal within this IDC RPS. Conclusions: This is the first study to investigate the distribution of Response Predictive Subtypes in ILC, which will be beneficial to optimize the treatment selection for patients with early-stage HR+/HER2- ILC. Though the percentage of ImPrint+ is lower in ILC, this study revealed a small subset of patients in ILC with potential response to Immunotherapy. Furthermore, these results underscore the heterogeneity of ILC tumors and generate further hypotheses to investigate the immune cell abundance in ILC compared to IDC and correlate immune cell abundance to ImPrint status. Table: Genomic and Tumor Characteristics of HR+HER2- ILC and IDC tumors Citation Format: Rita Mukhtar, Christina Yau, Denise Wolf, Adam Brufsky, Hannah Linden, Natasha Hunter, Reshma Mahtani, Abirami Sivapiragasam, Trevor Feinstein, Fengting Yan, Ian Grady, Priscilla McAuliffe, Michaela Tsai, Joyce O'Shaughnessy, Blanche Mavromatis, Sasha Davis, Josien Haan, William Audeh, Lavanya Samraj, FLEX Investigators' Group. Distribution of MammaPrint, BluePrint, and Response Predictive Subtypes based on ImPrint and Reprint in ER+/HER2- Invasive Lobular Carcinoma – A FLEX sub study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-03.

Abstract PO1-02-11: Characterization of MammaPrint UltraLow Risk tumors in more than 1400 patients from the real-world evidence FLEX study

Abstract BACKGROUND: MammaPrint is a gene expression signature used to determine the risk of distant recurrence for patients with early-stage breast cancer. Previous studies from MINDACT, FOCUS, IKA, and STO-3 trials have demonstrated that postmenopausal node-negative patients with MammaPrint UltraLow Risk tumors are considered indolent and patients have excellent long-term survival outcomes up to 20 years with little to no endocrine treatment. These studies suggest that patients with UltraLow Risk tumors are ideal candidates for treatment optimization which has resulted in the inclusion of the UltraLow Risk result in the NCCN guidelines. Here, we characterized patients with UltraLow Risk tumors from the real-world evidence FLEX study. METHODS: FLEX (NCT03053193) is a prospective, observational registry study with 99 sites open in the United States, Canada, Greece, and Israel. Patients enrolled in FLEX have early-stage breast cancer and receive MammaPrint testing as standard of care (with or without BluePrint molecular subtyping), and consent to full transcriptome analysis and clinical data collection. MammaPrint is a gene expression signature of 70 genes that classifies tumors as having a Low Risk or High Risk of distant recurrence. Within Low Risk tumors, a subcategory of UltraLow Risk (MammaPrint Index &amp;gt; 0.355) has been defined in previous studies. Clinical data for this analysis was locked February 2023. Clinical risk was defined as low risk or high risk based on Adjuvant Online criteria. RESULTS: Among the 12,328 patients enrolled in FLEX, 1465 (11.9%) have UltraLow Risk tumors. All tumors with available BluePrint molecular subtyping were classified as Luminal-Type. Of the patients with detailed clinical data, the majority had clinically low risk tumors (78.8%; Table 1). Notably, 34.6% of patients with UltraLow Risk tumors had Ki67 tumor staining of greater than 10%, 16.7% were pre- or peri-menopausal, 43.6% had grade 2-3 tumors, and 20.1% had tumors &amp;gt; 2 cm (Table 1). Among patients with treatment information, 6.5% received a combination of chemotherapy with or without endocrine and HER2-targeted therapy, 82.4% received endocrine therapy, 4.8% received other treatment (endocrine with targeted therapy (CDK4/6), radiation alone, novel treatment regimen, or supporting agents), and 6.3% did not receive treatment (Table 1). CONCLUSIONS: Previous trials have demonstrated the utility of MammaPrint UltraLow Risk in patients with clinically low risk features. In this large real-world evidence study of patients with early-stage breast cancer, UltraLow Risk tumors can be identified across all clinical categories. Overall, we report a substantial number of premenopausal patients with UltraLow Risk tumors, and these young women would be good candidates for treatment optimization. Future studies will assess long-term outcomes in this cohort further stratified by treatment. Table 1. Clinical and genomic characteristics of UltraLow Risk tumors Data are presented as n (%). Patients with unknown or missing data for each category have not been included. Citation Format: Cathy Graham, Kent Hoskins, Vijayakrishna K. Gadi, Suzanne Hoekstra, Gordon Srkalovic, Douglas Marks, Beth Sieling, Patricia Dauer, Andrea Menicucci, William Audeh, Joyce O'Shaughnessy, FLEX Investigators' Group. Characterization of MammaPrint UltraLow Risk tumors in more than 1400 patients from the real-world evidence FLEX study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-11.

EMP2 Serves as a Functional Biomarker for Chemotherapy-Resistant Triple-Negative Breast Cancer.

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

Prognostic Factors Associated with Tumor Recurrence and Overall Survival in Soft Tissue Sarcomas of the Extremities in a Colombian Reference Cancer Center.

Introduction: Soft tissue sarcomas (STS) are low-incidence tumors whose clinical and histopathological factors are associated with adverse oncological outcomes. This study evaluated prognostic factors (PF) associated with tumor recurrence and overall survival (OS) in patients diagnosed with STS of the extremities, treated at the Instituto Nacional de Cancerología (INC), Bogotá, Colombia. Materials and Methods: An analytical observational study of a historical cohort was carried out, including patients diagnosed with STS and managed surgically in the Functional Unit for Breast and Soft Tissue Tumors of the INC from January 2008 to December 2018. Results: A total of 227 patients were included; 74.5% had tumors greater than 5 cm. Most patients (29.1%) were in stage IIIB at diagnosis. Age was associated with higher mortality (HR = 1.01; CI95%: 1-1.02; p = 0.048). Tumor persistence at admission to the INC (HR = 2.34; CI95%: 1.25-4.35; p = 0.007) and histologic grade III (HR = 5.36; CI95%: 2.29-12.56; p = <0.001) showed statistical significance in the multivariate analysis for recurrence of any type, as did the PFs associated with a higher risk of local recurrence (HR = 2.85; CI95%: 1.23-6.57; p = 0.014 and HR = 6.09; CI95%: 2.03-18.2; p = 0.001), respectively. Tumor size (HR = 1.03; CI95%: 1-1.06; p = 0.015) and histologic grade III (HR = 4.53; CI95%: 1.42-14.49; p = 0.011) were associated with a higher risk of distant recurrence. Conclusions: This cohort showed that in addition to histologic grade and tumor size, tumor persistence at the time of admission has an impact on disease recurrence, so STS should be managed by a multidisciplinary team with experience in this pathology in high-volume reference centers.

A Podcast on Pre- or Perioperative Chemoimmunotherapy for Stage III Non-Small Cell Lung Cancer: Shared Agreement from the Thoracic Surgeon and Oncologist Perspectives.

Management of stage II-III non-small cell lung cancer (NSCLC) has been dramatically revolutionized by studies testing the addition of immunotherapy (IO) to chemotherapy in the pre- or perioperative setting. That is because the integration of chemoimmunotherapy (chemo-IO) with surgery has consistently shown a significant improvement in pathological complete response (path CR) rate, event-free survival, and, more recently, overall survival, versus preoperative chemotherapy alone. Particularly, resectable stage III NSCLCs represent a disease entity with a high risk of distant recurrence after radical surgery, for whom pre- or perioperative chemo-IO should be considered as the preferential treatment option. However, owing to the heterogeneity of stage III NSCLC, a standard definition of resectability is not established yet, being often subjective according to the expertise and clinical background of the thoracic surgeon. In addition, careful patient selection on the basis of tumor biomarkers, meticulous staging of the disease, and accurate monitoring of treatment-related adverse events are critical factors that could prevent the ineligibility for surgery of patients treated with pre- or perioperative chemo-IO. Finally, the impact of downstaging for initially borderline resectable tumors, as well as the exact number of preoperative chemo-IO cycles needed and the indications for adjuvant IO, still need to be fully elucidated. In this podcast, we will touch upon the above-mentioned topics from the perspectives of the thoracic surgeon and the oncologist, and suggest a shared agreement between two of the main actors involved in the treatment of resectable stage III NSCLCs.Podcast audio available for this publication.

Abstract PD11-06: PD11-06 Circulating tumor DNA association with residual cancer burden after neoadjuvant therapy in triple negative breast cancer in TBCRC 030

Abstract Background. Patients (pts) with early triple negative breast cancer (eTNBC) are at increased risk of breast cancer recurrence and death. Recent studies have focused on escalation of therapy, with current treatment standard of at least five drugs – and associated toxicities - for eTNBC. Though presence of residual disease after neoadjuvant therapy (NAT) as measured by residual cancer burden (RCB) helps guide addition of adjuvant treatment, more effective tools to tailor therapy are limited. Persistence of circulating tumor DNA (ctDNA) in the setting of residual disease is associated with high risk of distant recurrence. However, more sensitive minimal residual disease (MRD) assays are needed to potentially guide optimization of systemic therapy. Methods. TBCRC 030 is a phase II randomized study of 12 weeks of NAT single agent cisplatin or paclitaxel for stage II-III TNBC, followed by surgery. The primary objective of the parent study was to correlate baseline biomarker for homologous recombination deficiency and RCB by study arm. From this group, responders (RCB 0/1) and non-responders (RCB 2/3) from both study arms who did not receive additional NAT prior to surgery were selected for analysis from the study cohort, matched on baseline nodal status and tumor size. As a post hoc study amendment, available pts were followed for event free survival (EFS). Plasma samples were collected prior to treatment initiation (W0), at three weeks (W3), and at twelve weeks, prior to surgery (W12). Whole genome sequencing (WGS) was performed on primary tumor tissue to identify somatic mutations and design for each pt a tumor-informed, ctDNA assay tracking up to 1000 mutations to detect MRD. Detection limit was computed for each tested sample as previously described. For each sample assayed, we report tumor fraction (TFx) when MRD was detected and the detection limit at 90% power when MRD was not detected. Results. Of 139 study pts, 68 had complete tissue and plasma samples and no receipt of additional NAT. Of these, 22 were responders. These responders, and 22 matched non-responders were identified for analysis. Data from 22 pts – 11 responders, 11 non-responders - are described here; full analysis on all 44 pts will be presented at the meeting. Personalized ctDNA assays were designed targeting 434 to 1000 variants (median 1000) and applied to 66 plasma samples. At W0, 100% (22/22) were positive for ctDNA; 73% (16/22) and 55% (12/22) were positive at W3, and W12, respectively. In pts with T1-T2 tumors median TFx was 4.1e-3(7.8e-6, 3.4e-2) and 4.7e-1(4.3e-2, 9.0e-1) in pts with T3-T4 tumors. TFx decreased from W0 to W3 and from W0 to W12 in responders (Table 1). By W12, ctDNA had cleared in 7/8 pts with RCB 0, 1/3 with RCB 1, 2/8 with RCB 2, and 0/3 with RCB 3. Overall, ctDNA levels were broad with median TFx of 1.5e-3 (range 2.9e-6 to 0.90). Detection limit at 90% power for all tested samples was a median of 8.8e-6 (range 9.9e-7 to 6.8e-3). To investigate whether ctDNA persistence after NAT was associated with BC recurrence, we analyzed a separate group of all 8 pts with known recurrence and with complete data and samples. All pts had persistent ctDNA at W12 (median TFx 6.8e-3, [2.9e-6 to 6.6e-2]). Conclusions. After 3 weeks of NAT for eTNBC, ctDNA TFx decreased, with a 3900-fold change in responders and 18-fold change in non-responders. By W3, TFx for most pts with RCB 0/1 were below the 1 in 10,000 limit of detection for many currently available assays, emphasizing the need for sensitive tests to potentially guide therapy. Additional studies will determine if ctDNA-guided approaches in eTNBC can improve pt outcomes. Table 1: Tumer Fraction and Tumer Fraction Fold Change by Response to Neoadjuvant Therapy Citation Format: Heather A. Parsons, Timothy Blewett, Xiangying Chu, Sainetra Sridhar, Katheryn Santos, Kan Xiong, Vandana Abramson, Ashka Patel, Ju Cheng, Adam M. Brufsky, Justin Rhoades, Jeremy Force, Ruolin Liu, Tiffany A. Traina, Lisa Carey, Mothaffar Rimawi, Ahmed Elkhanany, Vered Stearns, Jennifer M. Specht, Harold Burstein, Antonio C. Wolff, Eric Winer, Nabihah Tayob, Ian Krop, Todd Golub, Erica L. Mayer, Viktor Adalsteinsson. PD11-06 Circulating tumor DNA association with residual cancer burden after neoadjuvant therapy in triple negative breast cancer in TBCRC 030 [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 PD11-06.

Preoperative controlling nutritional status score predicts systemic disease recurrence in patients with resectable biliary tract cancer.

This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC). A total of 224 BTC patients (gallbladder, n=69; intrahepatic bile ducts, n=26; perihilar bile ducts, n=72; distal bile duct, n=57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ2 scores. The sites of recurrence were subclassified as locoregional or distant. Patients were subdivided into the CONUT-low (score ≤ 3, n=156) and the CONUT-high (score > 3; n=68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p=0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p=0.001), worse disease-specific survival (HR 1.840, p=0.006), and worse recurrence-free survival (HR 1.680, p=0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p=0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p=0.001). The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC.

Precision Breast Cancer Medicine: Early Stage Triple Negative Breast Cancer-A Review of Molecular Characterisation, Therapeutic Targets and Future Trends.

Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.

Invasive lobular carcinoma: an understudied emergent subtype of breast cancer.

Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer after invasive ductal carcinoma (IDC), accounting for 10-15% of all breast cancer cases. Although most ILCs are of the luminal A intrinsic subtype, with favorable prognostic features, conflicting literature data are available on their outcomes compared to IDC with reports suggesting a higher risk of distant recurrence after 10years. Historically, studies have combined ILC and IDC, with outcomes largely driven by the behavior of IDC given that it represents 90% of breast cancers. However, over the past 5years, reports of several studies aimed at understanding ILC at the clinical, cellular, and molecular levels have been published, showing that IDC and ILC are distinct entities. In this review, we highlight the unique characteristics of ILC and describe the need for dedicated ILC clinical trials.

Elective Neck Treatment for Clinically Node-Negative Salivary Gland Cancer: Observation, Neck Dissection, or Neck Irradiation?

<h3>Purpose/Objective(s)</h3> Malignancies of salivary glands are rare and heterogeneous making large comparative studies challenging. Management of the clinically node-negative neck (cN0) varies and the optimal approach is undefined. We present a single institution experience of cN0 salivary gland cancer cases with primary endpoints of local and regional recurrence. We compared four management approaches; observation (None), elective neck dissection (END), elective neck irradiation (ENI), and combined elective neck dissection and neck irradiation (END+ENI). <h3>Materials/Methods</h3> An IRB approved registry of head and neck cancer patients treated at a tertiary care center was queried for diagnoses of cN0 salivary gland cancer. Cases were categorized into observation only, END, ENI, and END+ENI. Tumor and treatment characteristics were compared with Chi-square or Kruskal-Wallis tests. <h3>Results</h3> 445 cases were included in this analysis with median follow up of 60.8 months. The median age of the cohort was 59 years (13-93). The END+ENI group had older patients, the highest proportion of T3 and T4 cases, borderline nodal features, poorly differentiated tumors, perineural invasion (PNI), and lymphovascular space invasion (LVSI) (all p≤0.01). The ENI group had the highest ratio of positive margins (p<0.001). Local and regional recurrence among the 4 groups were not statistically significant. The END+ENI group had the highest incidence of distant metastasis and lowest survival. Univariate analysis revealed a significant effect of clinical T stage (cT), pathological T stage (pT), positive margins, and PNI on local recurrence (all p<0.05). Poor differentiation status, pT, positive margin, PNI, extranodal extension (ENE), and LVSI had significant impact on regional recurrence (all p<0.05). <h3>Conclusion</h3> In this cohort of patients with cN0 neck, local and regional recurrence was similar for END versus ENI. For patients with high-risk factors such as positive margins, poor differentiation, PNI and LVSI, END+ENI results in low local and regional recurrence despite higher risk pathologic features; however, the higher risk of distant recurrence limits survival.

Abstract P2-10-01: Estimating risk of breast cancer-specific mortality (BCSM) and non-BCSM in patients with triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is associated with high risk of distant recurrence and death. At present, our ability to estimate risk of death from causes other than breast cancer is limited. Particularly among elderly patients (pts), who have been historically underrepresented in clinical trials. In pts with TNBC, assessing both risks is important for our treatment recommendations. The aim of this study was to evaluate risk of BCSM and non-BCSM in TNBC by patient (pt) and tumor characteristics. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified women diagnosed with non-metastatic invasive TNBC between 2010-2016. Fine and Gray regression was used to evaluate the association of BCSM with pre-specified variables including pt age, tumor size (T), nodal status (N), and tumor grade, while considering deaths from other causes as competing events. We then estimated cumulative risk of BCSM, non-BCSM and all-cause mortality within subgroups defined by baseline clinical and pathologic variables. We conducted a subset analysis of N0 pts older than 50 years, given that we anticipated this subgroup would have the most clinically useful balance between BCSM and non-BCSM. Results: We included 37,293 pts. Age distribution was: 27.1% &amp;lt;50 years, 51.3% 50-69 years, 15.0% 70-79 years, and 6.6% ≥80 years. Among all pts, 42.4% presented with T2 tumors and 69.5% had N0 disease. In adjusted Fine and Gray regression, risks of BCSM were higher for pts aged &amp;gt;80 years vs 50-69 years (Hazard ratio [HR] 1.62; 95% CI, [1.45 - 1.80]), T4 vs T1a (HR 8.51; 95% CI, [6.20 - 11.68]), N3 vs N0 (HR 6.31; 95% CI, [5.70 - 7.00]) and grade III/IV vs grade I (HR 2.10; 95% CI, [1.44 - 3.07]). The cumulative risk of BCSM in year 0-7 was 10.7% for N0, 27.9% for N1, 46.4% for N2 and 64.0% for N3. In contrast, the cumulative risk of non-BCSM over the same period ranged from 7.5% in N1 to 8.7% in N2. The table shows risks of BCSM, non-BCSM and all-cause mortality among pts with N0 disease by age at diagnosis and tumor size. Pts 50-69 years had an increasing cumulative risk of BCSM by tumor size up to 13.0% in those with T2 tumors, while the risk of non-BCSM ranged from 4.8% to 5.9%. Pts aged 70-79 years with T1a/b, N0 tumors had risks of BCSM that were approximately 60% lower than the risks of non-BCSM. In pts aged ≥80 years, the risk of non-BCSM increased and is significantly higher than BCSM in patients with T1b-T2 disease. Conclusions: The risk of BCSM in TNBC depends on traditional clinicopathologic factors and is in general, much higher than the risk of non-BCSM. However, the high risk of non-BCSM among older pts is substantial which needs to be taken into consideration when making treatment recommendations. An interactive tool to estimate risks of BCSM, non-BCSM and all-cause mortality for TNBC will be presented at the meeting. BCSMnon-BCSMAll-cause mortalityCumulative risk (%) and 95% CICumulative risk (%) and 95% CICumulative risk (%) and 95% CIyears 0-7years 0-7years 0-7Tumor size among age 50-69, N0 onlyT1a2.6 (1.0 - 4.3)5.9 (3.2 - 8.6)8.5 (5.3 - 11.6)T1b3.9 (2.8 - 5.0)4.8 (3.3 - 6.3)8.7 (6.9 - 10.5)T1c8.1 (6.9 - 9.4)4.8 (3.9 - 5.8)13.0 (11.4 - 14.5)T213.0 (11.6 - 14.4)5.5 (4.4 - 6.5)18.5 (16.8 - 20.2)Tumor size among age 70-79, N0 onlyT1a6.1 (0 - 12.7)13.9 (7.0 - 20.9)20.0 (10.2 - 28.7)T1b5.3 (3.0 - 7.7)13.3 (9.0 - 17.7)18.6 (13.7 - 23.3)T1c11.0 (8.7 - 13.4)14.3 (11.4 - 17.2)25.3 (21.7 - 28.8)T221.0 (17.4 - 24.6)17.4 (13.4 - 21.5)38.5 (33.3 - 43.2)Tumor size among age ≥80, N0 onlyT1a6.6 (0 - 19.7)27.0 (11.0 - 43.1)33.7 (11.8 - 50.1)T1b7.1 (2.1 - 12.2)33.2 (23.2 - 43.2)40.3 (28.9 - 49.9)T1c8.4 (5.2 - 11.6)32.7 (26.4 - 39.0)41.1 (34.1 - 47.3)T222.7 (18.1 - 27.3)41.6 (34.2 - 49.1)64.3 (56.0 - 71.1) Citation Format: Jose P Leone, Noah Graham, Julieta Leone, Sara M Tolaney, Bernardo A Leone, Rachel A Freedman, Michael J Hassett, Carlos T Vallejo, Eric P Winer, Nancy U Lin, Nabihah Tayob. Estimating risk of breast cancer-specific mortality (BCSM) and non-BCSM in patients with triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-01.

Abstract PD9-04: Tumor-released circulating orphan non-coding RNAs reflect treatment response and survival in breast cancer

Abstract Background: Liquid biopsies have emerged as effective diagnostic tools in disease monitoring and minimal residual disease detection. Circulating tumor DNA (ctDNA) was recently shown to be a predictor of poor response and recurrence in breast cancer. However, ctDNA shedding from breast tumors can rapidly decrease during treatment, resulting in reduced sensitivity in measuring early changes in tumor response or residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC). We recently reported the discovery of orphan non-coding RNAs (oncRNAs), a class of small RNAs that are not present in healthy cells, but emerge from cancer cells. Similar to ctDNA, tumor-released oncRNAs can be used to detect the presence of an underlying tumor; however, since they are actively released by cancer cells, their abundance in the cell-free compartment is substantially higher than ctDNA. Therefore, we hypothesized that monitoring circulating oncRNAs in blood permits a more sensitive approach to measuring treatment response (i.e., pathologic complete response, or pCR) and estimating RCB. Patients and Methods: Cell-free RNA (cfRNA) was extracted from ~1 ml sera of 72 breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with NAC alone or combined with MK-2206 (AKT inhibitor) treatment. For each patient, treatment-naïve samples (T0) were compared with samples from post-treatment and prior to surgery (T3) time-point. RNA samples were subjected to small RNA sequencing (SMARTer), and the presence and abundance of cell-free oncRNA species were then determined by identifying and counting the reads that map to oncRNA loci across samples. Notably, oncRNAs species were pre-annotated from the Cancer Genome Atlas (TCGA), and our approach does not require bespoke personalized assays. We used a machine-learning model to compare abundance of cfRNA species before and after treatment (i.e., T3-T0) to predict pCR and RCB. For this, we split our cohort into a training and a testing set (48 and 24) and trained a model to simultaneously learn the presence of residual disease (pCR vs. no pCR) and its extent (RCB). We then measured the performance of our model on the held-out test data and the entire dataset. To confirm the robustness of our model, we also employed a leave-one-out strategy, whereby pCR and RCBIndex of each patient was predicted using a model that was trained on the other patients in the cohort. Finally, to assess the ability of our oncRNA-based model to risk-stratify patients who fail to achieve pCR (without having been explicitly trained on relapse data), we used the model’s oncRNA score to predict patients at the highest risk of distant recurrence (n=8 out of 36) and performed a multivariate Cox analysis, controlling for HR/Her2 status (median follow-up time was 4.8 years). Results: The model’s accuracy for predicting pCR—based on changes in circulating oncRNA species between T3 and T0—was 85% for the training data and 79% for the held-out test data (positive predictive value of 75% and negative predictive value of 83%) with combined accuracy of 83%; precision 86% and recall 83%; Pearson R=0.5 for RCB. A leave-one-out strategy showed similar performance (area under ROC of 0.77 versus 0.81 in train-test split). Finally, among the patients who failed to achieve pCR, we observed a significantly higher risk of distant recurrence in those with the highest scores (DRFS: hazard-ratio = 8.4, ANOVA P&amp;lt;0.05). Conclusion: In this study, we have shown that the changes in tumor-released oncRNA content of the blood are a significant predictor of clinical outcomes. Our results demonstrate that oncRNA fingerprints are blood-accessible, and allow us to build predictive models of tumor response. We are currently expanding this study to additional cohorts, and we expect to report the results for a longitudinal analysis that includes ~200 patients from I-SPY2. Citation Format: Hani Goodarzi, Albertas Navickas, Jefferey Wang, Kristle Garcia, Mark J Magbanua, Lisa Fish, Lamorna Brown Swigart, Gillian Hirst, Denise Wolf, Christina Yau, Jo Chien, Carol Simmons, Amy Delson, Laura Esserman, Laura van 't Veer. Tumor-released circulating orphan non-coding RNAs reflect treatment response and survival in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-04.

The Impact of Surveillance Imaging Frequency on the Detection of Distant Disease for Patients with Resected Stage III Melanoma

BackgroundIt is not known whether there is a survival benefit associated with more frequent surveillance imaging in patients with resected American Joint Committee on Cancer stage III melanoma.ObjectiveThe aim of this study was to investigate distant disease-free survival (DDFS), melanoma-specific survival (MSS), post distant recurrence MSS (dMSS), and overall survival for patients with resected stage III melanoma undergoing regular computed tomography (CT) or positron emission tomography (PET)/CT surveillance imaging at different intervals.Patients and MethodsA closely followed longitudinal cohort of patients with resected stage IIIA–D disease treated at a tertiary referral center underwent 3- to 4-monthly, 6-monthly, or 12-monthly surveillance imaging between 2000 and 2017. Survival outcomes were estimated using the Kaplan–Meier method, and log-rank tests assessed the significance of survival differences between imaging frequency groups.ResultsOf 473 patients (IIIA, 19%; IIIB, 31%; IIIC, 49%; IIID, 1%) 30% underwent 3- to 4-monthly imaging, 10% underwent 6-monthly imaging, and 60% underwent 12-monthly imaging. After a median follow-up of 6.2 years, distant recurrence was recorded in 252 patients (53%), with 40% detected by surveillance CT or PET/CT, 43% detected clinically, and 17% with another imaging modality. Median DDFS was 5.1 years (95% confidence interval 3.9–6.6). Among 139 IIIC patients who developed distant disease, the median dMSS was 4.4 months shorter in those who underwent 3- to 4-monthly imaging than those who underwent 12-monthly imaging.ConclusionSelecting patients at higher risk of distant recurrence for more frequent surveillance imaging yields a higher proportion of imaging-detected distant recurrences but is not associated with improved survival. A randomized comparison of low versus high frequency imaging is needed.

Prognostic value of SMAD4 in resectable pancreatic cancer

Abstract Introduction The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC. Materials and Methods A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients. Results Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008). Conclusions After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.

356 Polypoid melanoma is associated with aggressive histopathological characteristics and poor clinical prognosis

Polypoid melanoma is a rare subtype of melanoma characterized by pedunculated exophytic growth. These tumors tend to have a thick Breslow depth, but it is unknown if the prognosis of this subtype is worse compared to other variants of melanoma. A retrospective review was performed of 37 polypoid melanomas and compared to 264 non-polypoid nodular melanomas. Each case was independently re-evaluated by board-certified dermatopathologists for the following histopathologic parameters including Breslow depth, mitotic rate, ulceration, and angiolymphatic invasion. Basic demographic data and clinical characteristics were collected from electronic medical record data and compared, including clinical stage at diagnosis, rates of recurrence, and survival, between polypoid and nodular melanoma subtypes. Patients with polypoid melanoma had a younger average age than patients with nodular melanoma. Histopathologic review revealed that polypoid tumors had a significantly higher average Breslow depth, and had a higher frequency of ulceration and angiolymphatic invasion than nodular melanomas. Analysis of clinical outcomes by log-rank test showed a higher risk of distant recurrence and worse overall survival in polypoid tumors compared to nodular melanomas. Multivariate analysis showed an association of polypoid subtype with higher distant recurrence and worse survival. This association was independent of other prognostic factors including Breslow depth and ulceration. This study shows that polypoid melanoma is associated with a higher frequency of aggressive histopathological characteristics and poor clinical prognosis compared to non-polypoid nodular melanoma.

Clinical Impact of Presurgery Circulating Tumor DNA after Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Biomarker Study from the GEMCAD 1402 Trial

Abstract Purpose: Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed to determine the value of circulating tumor DNA (ctDNA) to predict tumor response, recurrence, and survival in patients with LARC treated with TNT. Experimental Design: The GEMCAD 1402 was a phase II randomized, multicentric clinical trial that randomized 180 patients with LARC to modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) +/− aflibercept, followed by chemoradiation and surgery. Plasma samples were collected at baseline and after TNT within 48 hours before surgery (presurgery). An ultrasensitive assay that integrates genomic and epigenomic cancer signatures was used to assess ctDNA status. ctDNA results were correlated with variables of local tumor response in the surgery sample, local/systemic recurrence, and survival. Results: A total of 144 paired plasma samples from 72 patients were included. ctDNA was detectable in 83% of patients at baseline and in 15% following TNT (presurgery). No association was found between ctDNA status and pathologic response. Detectable presurgery ctDNA was significantly associated with systemic recurrence, shorter disease-free survival (HR, 4; P = 0.033), and shorter overall survival (HR, 23; P &amp;lt; 0.0001). Conclusions: In patients with LARC treated with TNT, presurgery ctDNA detected minimal metastatic disease identifying patients at high risk of distant recurrence and death. This study sets the basis for prospective clinical trials that use liquid biopsy to personalize the therapeutic approach following TNT.

Abstract PS14-23: Reconsidering the management of palpable DCIS - A single institution audit

Abstract Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. The role of screening mammography is now being questioned across the world and in the developing world with no national screening programs, women with DCIS present with a palpable lump in the breast. We conducted a retrospective audit of women with DCIS treated at our institution to classify palpable DCIS and DCIS-M as distinct clinical stages and emphasize the need for a change in management of ‘palpable DCIS’ Methods: Annually we register approximately 1700 new cases of early breast cancer of which DCIS and DCIS-M constitutes less than 1%. Between 2005-2016 we registered 784 cases of with DCIS, DCIS-M and early invasive cancer with extensive intraductal component (EIC) at our centre. A retrospective analysis of these cases was performed. Results: Of the 784 patients case records reviewed, 113 (14.4%) had Tis, 87 (11.1% of all early cases and 43.5% of DCIS) had T1mic, the rest had invasive cancer with EIC, of which 46 (5.9%) wereT1a, 28(3.6%) were T1b, 146 (18.6%) were T1c and 364 (46.4%) wereT2. The median age at presentation was 48 years, median clinical tumour size was 3cm; 740 (94.4%) presented with palpable breast lumps.At a median follow up of 86 months , the disease free survival was 95.6% for Tis, 96.6% T1mic, 90.5% T1 and 82.7% T2 (p=0.00). On follow up distant recurrences were noted in 5(4.4%) patients with Tis, 3(3.4%) with T1mic, 21(9.5%) with T1 and 63(17.3%) with T2, (p=0.00). Limited use of adjuvant chemotherapy in Tis and T1mic may have contributed to the high distant recurrences in that group. Also palpable Tis,T1mic and T1a had higher percentage of HR negative compared to those with larger invasive tumours. Conclusions: DCIS presenting in palpable lesions poses a clinical dilemma for the use of adjuvant therapy. In our cohort 43.5% of the palpable DCIS showed evidence of microinvasion with high risk of distant recurrence compared to screen detected DCIS. We thus need to reconsider grossing techniques to accurately identify foci of invasion, redefine DCIS-M based on number and size of foci of invasion and explore the possible role of adjuvant chemotherapy in treating large palpable DCIS. ResultsTis (N%)T1mic (N%)T1a (N%)T1b (N%)T1c (N%)T2 (N%)cT &amp;gt;2 cm63 (55.8)68 (78.2)28 (60.9)6 (21.4)1 (0.7)363 (99.7)Palpable lump85 (75.2)81 (93.1)39 (83)28 (100)144 (98.6)363 (99.7)Nipple discharge26 (23)6 (6.8)7 (14.9)0 (0)2 (1.3)1 (0.3)Hormone receptor positive (HR+ve)60 (53.1)18 (20.7)18 (38.3)15 (53.6)92 (63)218 (60.6)HER2neu +ve31 (27.4)41 (47.1)13 (27.7)8 (28.6)27 (18.5)93 (25)Axilla +ve6 (5.3)9 (10.3)9 (19.1)9 (32.1)50 (34.2)184 (50.7) Citation Format: Karishma Kirti, Nita Nair, Tanuja Shet, Rohini Hawaldar, Vani Parmar, Seema Gulia, Shalaka Joshi, Sridevi Murali, Vaibhav Vanmali, Bipin Bandre, Sudeep Gupta, Rajendra Badwe. Reconsidering the management of palpable DCIS - A single institution audit [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 PS14-23.