Recurrence Score Research Articles

Comparison between the Nottingham Prognostic Index and Oncotype Dx Recurrence Score in Predicting Outcome in Estrogen Receptor Positive Breast Cancer

Kerin, Eoin Patrick; Davey, Matthew G Dr, MCh, MRCSI; Malone, Carmel Prof, MD, FRCSI; Barry, Michael K Prof, FRCS, FACS, MD Author Information

Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2− early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2− trial

In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin+ cyclophosphamide (90 mg+ 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n= 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P= 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P= 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P= 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P= 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P= 0.010). In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

Abstract LB119: Recurrence score for recurrence over survival outcome in the landmark TAILORx trial

Abstract Overall survival is the most relevant endpoint in clinical research and patient care. Nonetheless, cancer recurrence has been frequently utilized as a surrogate endpoint, particularly in the context of multi-gene assays and molecular signatures. The 21-gene recurrence score (RS) was originally established against distant recurrence for prognosis in breast cancer. However, it is unclear whether RS has a weight for the recurrence over survival prognosis. We investigated RS on the choice of clinical endpoints in the Trial Assigning Individualized Options for Treatment (TAILORx), which had OS, invasive disease-free survival (DFS), and recurrence-free interval (RFI) in addition to distant recurrence-free interval as the clinical endpoints. Both midrange (11-25) and high-range (26-100) scores were associated with RFI, high-range only with DFS, but not significantly associated with OS in the multivariable Cox proportional-hazards regression models. Of 462 death events, 33.1% (153 events) were ascribed to breast cancer and 91.8% (424) were due to DFS-related events that included 24.5% other cancers, 34.2% unknown and 33.1% breast cancer. It is DFS that was wound up as the most representative surrogate endpoint for survival. The lack of survival significance was probably due to the nature of 21-gene assay weighted for recurrence rather than not having enough event numbers in the TAILORx clinical trial. The data call for establishing biomarkers directly towards OS or DFS to increase survival with more precision. Citation Format: Sherry X. Yang, John Yu, Molin Wang. Recurrence score for recurrence over survival outcome in the landmark TAILORx trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB119.

Racial and Ethnic Disparities in Locoregional Recurrence Among Patients With Hormone Receptor–Positive, Node-Negative Breast Cancer

Whether racial and ethnic disparities in locoregional recurrence (LRR) exist among patients with similar access to care treated in randomized clinical trials is unknown. To examine racial and ethnic differences in LRR among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-negative, node-negative breast cancer enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx). This unplanned retrospective post hoc analysis examined a prospective multicenter clinical trial population of women with breast cancer enrolled between 2006 and 2010, with 9 years of follow-up. The TAILORx investigators randomized patients to treatment based on their Oncotype DX recurrence score, including endocrine therapy alone (recurrence score <11), endocrine therapy alone vs chemotherapy followed by endocrine therapy (recurrence score 11-25), or chemotherapy followed by endocrine therapy (recurrence score >25). Patients with unknown race and ethnicity or lack of follow-up were excluded from this analysis. Data analysis was performed between December 2021 and March 2022. Locoregional recurrence was defined as ipsilateral in breast, skin, chest wall, or regional nodal recurrence without concurrent distant recurrence, and was stratified by racial and ethnic group. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards regression models were used for survival analyses. Of the 10 273 women enrolled in TAILORx, this analysis included 9369 with T1-2N0 HR-positive, ERBB2-negative breast cancer. Of these patients, 428 (4.6%) were Asian, 886 (9.4%) were Hispanic, 676 (7.2%) were non-Hispanic Black (hereinafter Black), and 7406 (78.8%) were non-Hispanic White (hereinafter White). Assigned treatment receipt was high, with a 9.3% (n = 870) crossover of treatment groups and a median endocrine therapy duration of longer than 60 months, ranging from 61.1 to 65.9 months, across racial and ethnic groups. A total of 6818 patients (72.6%) received radiation (6474 [96.1%] after breast-conserving surgery and 344 [13.0%] after mastectomy). At a median follow-up of 94.8 months (range, 1-138 months), 8-year LRR rates were 3.6% (95% CI, 1.6%-5.6%) in Asian patients, 3.9% (95% CI, 2.2%-5.4%) in Black patients, 3.1% in Hispanic patients (95% CI, 1.7%-4.5%), and 1.8% (95% CI, 1.5%-2.3%) in White patients (P < .001). In survival analyses adjusted for patient, tumor, and treatment factors, Asian race (hazard ratio, 1.91 [95% CI, 1.12-3.29]) and Black race (1.78 [1.15-2.77]) were independently associated with LRR. In adjusted survival analyses for breast cancer mortality, LRR was independently associated with increased breast cancer mortality (hazard ratio, 5.71 [95% CI, 3.50-9.31]). In this post hoc analysis, racial and ethnic differences in LRR were observed among patients with T1-2N0 HR-positive, ERBB2-negative breast cancer despite high rates of treatment receipt in this clinical trial population, with the highest LRR rates in Asian and Black patients. Further study is needed to understand whether failure to rescue after LRR may contribute to racial disparities in breast cancer mortality. ClinicalTrials.gov Identifier: NCT00310180.

Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer

BackgroundProgesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear.MethodsThe National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively.ResultsAmong 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23–17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10–1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47–0.67; PR-negative: aHR 0.31, 95% CI 0.20–0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66–0.82; PR-negative: aHR 0.63, 95% CI 0.51–0.77).ConclusionPR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

Abstract 5354: Prediction of OncotypeDX high risk group for chemotherapy benefit in breast cancer by deep learning analysis of hematoxylin and eosin-stained whole slide images

Abstract Introduction: Breast cancer is the most common cancer in women, with most patients diagnosed with early-stage disease. While adjuvant therapy should be considered in all fit patients, in many low-risk patients drug toxicity may out-weigh the potential benefit, therefore, identifying these patients is desired. Hematoxylin and eosin (H&amp;E) is the basic staining routinely performed for biopsies. It allows visual examination of the tissue and cells. Such manual examination, however, does not provide information about the molecular profile of the cancer, which is essential for diagnosis and guidance of treatment. The OncotypeDX assay is recommended for patients with node-negative, estrogen receptor-positive invasive breast cancer for determining chemotherapy benefit. It is based on RT-PCR gene expression profiling and provides a recurrence score (RS) that enables patient stratification to non-high risk (RS &amp;lt; 26) and high risk (RS ≥ 26). It was shown that high risk patients are likely to benefit from chemotherapy, while non-high risk are not. Unlike H&amp;E staining, the OncotypeDX assay is costly, time consuming, and inaccessible in low-income countries. Here, we sought to evaluate whether analysis of scanned H&amp;E-stained slides by convolutional neural networks (CNNs) could predict the RS risk group (high versus non-high), which determines eligibility for chemotherapy. Methods: 684 H&amp;E-stained slides were collected from 430 invasive breast cancer patients who were assayed for OncotypeDX between 2014 and 2020 at Sheba medical center, Israel. The slides were scanned at 0.25 micron/pixel, and automatically segmented and split to 256 × 256 non-overlapping tiles, resulting in overall 339,986 tile images containing tissue. The patients were randomly split into training (75%) and test (25%) sets, and a CNN model was trained and validated on the training set to classify each tile to non-high risk (RS &amp;lt; 26) versus high risk (RS ≥ 26), in 5-fold cross-validation. The final model was then applied to the held-out test set, and tile scores were aggregated to produce per-patient prediction scores. The final CNN prediction scores on the test set were compared to the ground truth risk group and the AUC performance was calculated. Results: The AUC performance of the model on the held out test set for high-risk versus non-high-risk classification based on the H&amp;E images alone was high (0.798, 95% CI: 0.689 - 0.875, P value &amp;lt; 0.001), showing that the H&amp;E image analysis could predict the high risk group. Conclusions: These results show, for the first time, that CNN-based analysis of H&amp;E images could predict benefit from chemotherapy, thus implying distinct tumor morphologies differing between RS groups. Utilizing such a system may enable physicians in countries that lack genetic profiling capabilities to refine chemotherapy stratification based on H&amp;E images alone. Citation Format: Gil Shamai, Ran Schley, Ron Kimmel, Nora Balint-Lahat, Iris Barshack, Chen Mayer. Prediction of OncotypeDX high risk group for chemotherapy benefit in breast cancer by deep learning analysis of hematoxylin and eosin-stained whole slide images. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5354.

Abstract 1412: Co-existence of TP53 mutation confers endocrine resistance in PIK3CA-mutated ER+HER2- breast cancer

Abstract Background: PIK3CA mutation is commonly found in estrogen receptor (ER)+ human epidermal growth factor receptor-2 (HER2)- breast cancer (BC) and can be therapeutically targeted by alpelisib, an alpha-specific PIK3CA inhibitor. While previous studies presented conflicting results on the prognostic influence of PIK3CA mutation among ER+HER2- breast cancer, few have been able to address causes of the prognostic discrepancy on a clinical level. In this study, we investigated clinical and genomic features according to a coexistence of TP53 mutation in PIK3CA mutated ER+HER2- breast cancer. Methods: Tumor tissue based next generation sequencing (NGS) was analyzed for 224 HR+ HER2- BC patients from April 2017 to August 2021 in Gangnam Severance Hospital, Seoul, South Korea. Matching clinical records with patient information were reviewed retrospectively. Clinicopathologic features including age, tumor size, histologic grade (HG), TNM stage, estrogen receptor (ER) expression, progesterone (PgR) expression, Ki-67, and Oncotype Dx Recurrence Score (RS) were analyzed. Further analysis was carried out using The Cancer Genome Atlas (TCGA) to explore the relationship of mutation status with intrinsic subtype and risk of recurrence (ROR) score. Results: We identified PIK3CA mutation (PIK3CA m) in 105 (46.9%) of 224 patients, and of these, TP53 co-mutation was found in 25 (23.8%). None of clinicopathologic features were different according to PIK3CA mutation. When PIK3CA m cohort was analyzed according to TP53 mutation (TP53 m) status, tumors with TP53 m presented unfavorable features such as higher HG (p&amp;lt;0.001), lower PgR expression (TP53 wt: Median 7 versus TP53 m: Median 5, p=0.027), and higher N stage (p=0.008). It also displayed a significantly higher proliferative profiles with Ki-67 (TP53 wt: Median 15 versus TP53 m: Median 20, p&amp;lt;0.001) and Oncotype Dx RS (TP53 wt: Median 15 versus TP53 m: Median 26.5, p=0.002). In the 539 ER+HER2- breast cancer from the TCGA database, PIK3CA and TP53 co-mutation was found in 33 (6.1%). Distribution of intrinsic subtypes revealed a higher rate of Luminal B in PIK3CA and TP53 co-mutant tumors (51.5%) than in PIK3CA m and TP53 wt tumors (14.3%, p&amp;lt;0.001). The ROR score was found to be higher in the PIK3CA-TP53 co-mutation compared to PIK3CA m alone (p&amp;lt;0.001). Conclusion: Unlike PIK3CA mutation, PIK3CA and TP53 co-mutation clearly divided multiple clinicopathologic features of HR+ HER2- BC including with. Poorer prognosis of co-mutation was also corroborated by TCGA analysis of intrinsic subtype and ROR score. These findings indirectly suggest that co-mutation of TP53 gene may be associated with less sensitivity to PIK3CA targeted therapy in PIK3CA m ER+HER2- breast cancers. Further research is warranted to improve an efficacy of PIK3CA targeted therapy for PIK3CA m ER+ breast cancer with endocrine-resistant factors. Citation Format: Yoonwon Kook, Kyungsoo Kim, Ji Soo Jang, Seung Ho Baek, Soong June BAe, Joon Jeong, Sung Gwe Ahn. Co-existence of TP53 mutation confers endocrine resistance in PIK3CA-mutated ER+HER2- breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1412.

BCR-Net: A deep learning framework to predict breast cancer recurrence from histopathology images.

Breast cancer is the most common malignancy in women, with over 40,000 deaths annually in the United States alone. Clinicians often rely on the breast cancer recurrence score, Oncotype DX (ODX), for risk stratification of breast cancer patients, by using ODX as a guide for personalized therapy. However, ODX and similar gene assays are expensive, time-consuming, and tissue destructive. Therefore, developing an AI-based ODX prediction model that identifies patients who will benefit from chemotherapy in the same way that ODX does would give a low-cost alternative to the genomic test. To overcome this problem, we developed a deep learning framework, Breast Cancer Recurrence Network (BCR-Net), which automatically predicts ODX recurrence risk from histopathology slides. Our proposed framework has two steps. First, it intelligently samples discriminative features from whole-slide histopathology images of breast cancer patients. Then, it automatically weights all features through a multiple instance learning model to predict the recurrence score at the slide level. On a dataset of H&E and Ki67 breast cancer resection whole slides images (WSIs) from 99 anonymized patients, the proposed framework achieved an overall AUC of 0.775 (68.9% and 71.1% accuracies for low and high risk) on H&E WSIs and overall AUC of 0.811 (80.8% and 79.2% accuracies for low and high risk) on Ki67 WSIs of breast cancer patients. Our findings provide strong evidence for automatically risk-stratify patients with a high degree of confidence. Our experiments reveal that the BCR-Net outperforms the state-of-the-art WSI classification models. Moreover, BCR-Net is highly efficient with low computational needs, making it practical to deploy in limited computational settings.

Abstract 90: Exploring the role of common circulating tumor cell-associated genes in estrogen receptor-positive breast cancer recurrence

Abstract Despite having the best survival among the molecular subtypes, estrogen receptor-positive (ER+) breast cancer has a tendency for late recurrence. Circulating tumor cells (CTCs) are responsible for disease recurrence by seeding tumors at secondary sites. We have previously developed a CTC signature of 90 common regions of gene copy number gain and demonstrated that this signature is significantly more widespread among cells in metastases than primary tumors.1,2 The objective of our current work is to establish whether the expression data from a 133 gene panel largely derived from the CTC signature can be used to assess the risk of recurrence (ROR) in early ER+ breast cancer patients to help guide treatment decisions following surgery. Formalin-fixed, paraffin-embedded (FFPE) ER+ breast tumor biopsies and linked normal (control) tissues from 192 patients are being analyzed with a custom NanoString nCounter probe set of our 133 CTC genes. From data gathered to date, several genes were shown to be significantly overexpressed in tumors compared to reference normal tissues. This includes MMP11, MKI67, LILRB4, UBE2T, BIRC5, CDC6, MYBL2, and NUF2, which had a log2 fold-change of at least 3.5 (n = 34, p &amp;lt; 0.01). The correlation of our CTC genes to ROR is being evaluated by comparison to the results of the Oncotype DX Breast Recurrence Score Test, a well-established clinical test for ROR in ER+ breast cancer, for each patient. So far, it has been shown that the intratumor heterogeneity (ITH) of CTC genes as established by DEPTH2, an ITH algorithm which evaluates mRNA levels, is significantly positively corelated to Oncotype DX score (n = 23, r = 0.41, p = 0.0495). Moving forward, we will create our own ROR scoring system based on gene expression and copy number data from the CTC gene panel and validate it by comparison to Oncotype DX score and other available clinical data for each of the 192 patient samples. The goal of our work is to gain a deeper understanding of the molecular mechanisms that drive metastasis and recurrence in ER+ breast cancer by focusing on CTCs which play a pivotal role in driving these events. 1. Kanwar N, Hu P, Bedard P, Clemons M, McCready D, Done SJ. Identification of genomic signatures in circulating tumor cells from breast cancer. International Journal of Cancer. 2015;137(2):332-344. doi:10.1002/ijc.29399 2. Kanwar N, Balde Z, Nair R, et al. Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response. Cancer Research. 2021;81(24):6196-6206. doi:10.1158/0008-5472.can-21-1079‌ Citation Format: Martin Rotbauer, Melanie Dawe, Philippe Bedard, David Cescon, Susan Done. Exploring the role of common circulating tumor cell-associated genes in estrogen receptor-positive breast cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 90.

Abstract 5787: Modelling the spatial heterogeneity of CD45-positive tumor infiltrating lymphocytes in early-stage, estrogen receptor-positive breast cancer

Abstract The frequency of lymphocytes infiltrating tumors is a known prognostic in estrogen receptor (ER) negative cancers. ER+ disease is putatively believed to be immune cold, however, there exists a subset of ER+ tumors with high immune infiltrate and with a significant spatial heterogeneity. The clinic impact of such infiltrate - especially between the Oncotype Dx Recurrence Score risk categories - remains unclear. Moreover, the distribution of tumor and stromal tissues, while noted as significantly heterogenous, is still ill-defined and not yet clinically used prognostically, despite evidence to support its utility. Using a cohort (n=450) of serial sections taken from early-stage, ER+/HER2- breast tumors of the Irish arm of the TAILORx clinical trial, we aimed to investigate the tumor architecture and spatial distribution of tumor immune infiltrate and proliferating tumor cells using digital image analysis. Antibodies against Ki67 (proliferation marker) and CD45 (leukocyte common antigen), and a routine Haematoxylin and Eosin stain were applied to serial sections of 450 full-face tumors via chromogenic immunohistochemistry, as outlined previously [1]. Digital image analysis was performed using open-source software, QuPath [2]. Pixel classifiers were trained and validated against an expert pathologist in order to define observed lymphocytes as tumor or stromal-infiltrating, and to establish a classifier to quantify the tumor-stroma ratio (TSR) and infiltrating tumor area. Distances of CD45-positive cells from tumor were computed, along with autocorrelation statistics [3,4] of CD45 and Ki67 hotspots; firstly in order to quantify spatial heterogeneity, and secondly to examine whether Ki67 as a component gene in the Oncotype Dx assay has a foundation in tumor biology or is being confounded by potentially Ki67-positive lymphocytes. Subdividing by Oncotype Dx risk categories, no significant difference in TSR was observed (p=0.09799), neither for intermediary risk patients receiving hormone therapy alone or in combination with chemotherapy (p=0.3873). While there was an observed trend overall (p=0.092), no significance was found for recurrence between intermediary risk subcategories (HT alone: p=0.393, HT+CT: p=0.288). However, in the cohort as a whole, median TSR was 0.3215 (range 0 - 5.023), with statistically significant differences in recurrence risk observed (cohort high v low by median TSR. HR: 6.356, 95CI: 2.263-17.84, p&amp;lt;0.0001). Citation Format: Zak Kinsella, Anna Blümel, Mairi Lucas, Andreas Lindner, Claudia A. Gonzalez, Arman Rahman, Joanna Fay, Tony O'Grady, Verena Murphy, John Crown, Cathy Kelly, William Gallagher, Darran O'Connor. Modelling the spatial heterogeneity of CD45-positive tumor infiltrating lymphocytes in early-stage, estrogen receptor-positive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5787.

P169 Clinical outcomes in patients (pts) with estrogen receptor (ER)+ stage I breast cancer (BC) and Recurrence Score (RS) 26–30: Real-world data

P169 Clinical outcomes in patients (pts) with estrogen receptor (ER)+ stage I breast cancer (BC) and Recurrence Score (RS) 26–30: Real-world data

MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37)

You have accessJournal of UrologyCME1 Apr 2023MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37) Cosimo DE Nunzio, Costantino Leonardo, Antonio Carbone, Antonio Luigi Pastore, Riccardo Lombardo, Antonio Nacchia, Antonio Cicione, Beatrice Turchi, Giorgia Tema, and Andrea Tubaro Cosimo DE NunzioCosimo DE Nunzio More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Antonio CicioneAntonio Cicione More articles by this author , Beatrice TurchiBeatrice Turchi More articles by this author , Giorgia TemaGiorgia Tema More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Aim of our study was to evaluate recurrence free survival of sequential Mitomycin and Bacillus Calmette-Guérin (BCG) treatment versus BCG monotherapy in patients with High risk Non-Muscle Invasive Bladder Cancer. METHODS: MITO-BCG is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria: males with a diagnosis of High risk NMIBC (T1 tumor, G3, CIS, or multiple and recurrent and large (>3 cm) Ta, G1G2 tumors or patients in the last EAU recurrence category EAU/EORTC recurrence score ≥10), age >40 years and <75 years, ability of consent. Patients are randomized in two groups: first with BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with 81 mg Connaught strain BCG and second receiving BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before. Response will be assessed using cystoscopy and urine citology every 12 weeks for 2 years. Primary end points are recurrence rate; secondary end points are overall toxicity. RESULTS: The protocol study started on March 2019. Nowadays we enrolled 72 patients with a median age of 67 (IQR 59/73). Overall, 41 (57%) patients were randomized in the group of sequential combination therapy and 31 (43%) in the group of monotherapy with BCG. Mean Follow-up was 71±50 months. In BCG group 6/31 (19%) presented a recurrence while 10/41 (24 %) presented a recurrence in the combination group (p=0,611). On Cox regression analysis no differences were recorded in terms of recurrence when comparing both groups (HR: 1,23 95% CI: 0,46-3,50; p=0,640) (Figure). During follow-up only one patient experienced progression. Only 9 patients experienced adverse events with 8/9 grade I and one grade 4 (orchiectomy). No statistically significant differences were recorded in terms of complications between groups. CONCLUSIONS: The interim analysis of the Mito-BCG study suggests no differences in terms of recurrence free survival when comparing BCG alone vs sequential Mitomicin and BCG treatment. Both treatments present good and comparable tollerability. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cosimo DE Nunzio More articles by this author Costantino Leonardo More articles by this author Antonio Carbone More articles by this author Antonio Luigi Pastore More articles by this author Riccardo Lombardo More articles by this author Antonio Nacchia More articles by this author Antonio Cicione More articles by this author Beatrice Turchi More articles by this author Giorgia Tema More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement PDF downloadLoading ...

121 Development and Validation of a Predictive Score for Lumbar Synovial Cyst Recurrence

INTRODUCTION: Lumbar Synovial Cysts represent a relatively rare clinical pathology that may result in radiculopathy or neurogenic claudication. Due to their potential for recurrence, some authors advocate for segmental fusion, as opposed to decompression alone, as a way to eliminate the risk for recurrence. METHODS: A retrospective review was conducted of all patients evaluated at a single center over 20 years who were found to have symptomatic lumbar synovial cysts requiring intervention. Only patients undergoing decompression without fusion were included in the analysis. Following this, baseline characteristics were obtained as well as radiographic information. A machine learning method (RiskSLIM) was then utilized to create a risk stratification score to identify patients at high risk for symptomatic cyst recurrence requiring repeat surgical intervention. Following this a 5-fold cross validation was completed. RESULTS: In total 89 patients were identified to have complete radiographic information. Of these, 11 patients developed cyst recurrence requiring reoperation. The Lumber Synovial Cyst Score (LSCS) was then created with an area under the curve of 0.83 with CAL error of 11.0%. Predicative factors were found to include facet inclination angle greater than 45 degrees, canal stenosis greater than 50%, T2 joint space hyperintensity, and presence of grade I spondylolisthesis. The probability of cyst recurrence ranged from &lt; 5% for a score of 2 or less and &gt; 88% for a score of 7. CONCLUSIONS: The LSCS model is a quick and accurate tool to assist in clinical decision making in treatment of lumbar synovial cysts.

Anticoagulation therapy during pulmonary embolism follow-up in clinical practice

Patients with pulmonary embolism are a heterogeneous population and, after the acute phase and the first 3-6 months, the main issue is whether to continue, and hence how long and at what dose, or to stop anticoagulation therapy. In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are the recommended treatment (class I, level of evidence B in the latest European guidelines), and in most cases, an "extended" or "long-term" low-dose therapy is warranted. This paper aims to provide a practical management tool to the clinician dealing with pulmonary embolism follow-up: from the evidence behind the most used exams (D-dimer, ultrasound Doppler of the lower limbs, imaging tests, recurrence and bleeding risk scores), and the use of DOACs in the extended phase, to six real clinical scenarios with the relative management in the acute phase and at follow-up. Lastly, a practical algorithm is shown to deal with anticoagulation therapy in the follow-up of VTE patients in a simple, schematic, and pragmatic way.

P119 Recurrence Score® result by the 21-gene assay before and after systemic neoadjuvant chemotherapy in patients with HR+ HER2-breast cancer.

P119 Recurrence Score® result by the 21-gene assay before and after systemic neoadjuvant chemotherapy in patients with HR+ HER2-breast cancer.

The Predictive Value of the APPLE Score for the Atrial Fibrillation Recurrence Post the First-time Radiofrequency Ablation in Chinese Populations

The Predictive Value of the APPLE Score for the Atrial Fibrillation Recurrence Post the First-time Radiofrequency Ablation in Chinese Populations

Possible correlation of apical localization of MUC1 glycoprotein with luminal A-like status of breast cancer

Adjuvant chemotherapy has played a major role in the treatment of hormone receptor-positive breast cancer for many years. To better determine which patient subsets need adjuvant chemotherapy, various gene expression analyses have been developed, but cost-effective tools to identify such patients remain elusive. In the present report, we retrospectively investigated immunohistochemical expression and subcellular localization of MUC1 in primary tumors and examined their relationship to tumor malignancy, chemotherapy effect and patient outcomes. We retrospectively examined three patient cohorts with hormone receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: 51 patients who underwent 21-gene expression analysis (multi-gene assay-cohort), 96 patients who received neoadjuvant chemotherapy (neoadjuvant chemotherapy-cohort), and 609 patients whose tumor tissue was used in tissue-microarrays (tissue-microarray-cohort). The immunohistochemical staining pattern of the anti-MUC1 monoclonal antibody, Ma695, was examined in cancer tissues, and subcellular localization was determined as apical, cytoplasmic or negative. In the multi-gene assay-cohort, tumors with apical patterns had the lowest recurrence scores, reflecting lower tumor malignancy, and were significantly lower than MUC1-negative tumors (P = 0.038). In the neoadjuvant chemotherapy-cohort, there was no correlation between MUC1 staining patterns and effects of chemotherapy. Finally, in the tissue-microarray-cohort, we found that patients with apical MUC1 staining patterns had significantly longer disease-free-survival and overall survival than other patterns (P = 0.020 and 0.039, respectively). Our data suggest that an apical MUC1 staining pattern indicates luminal A-likeness. Assessment of the subcellular localization of MUC1 glycoprotein may be useful for identifying patients who can avoid adjuvant chemotherapy.

Evaluating the Necessity for Routine Sentinel Lymph Node Biopsy in Postmenopausal Patients Being Treated for Clinically Node Negative Breast Cancer the Era of RxPONDER

IntroductionTraditionally, sentinel lymph node biopsy (SLNB) was performed to inform adjuvant chemotherapy prescription and prognosis in breast cancer. Following RxPONDER, the OncotypeDX Recurrence Score (RS) guides adjuvant chemotherapy prescription for all postmenopausal patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2−) breast cancer with 0 to 3 positive lymph nodes (0-3 + LN). AimsTo establish the oncological safety of omitting SLNB in postmenopausal patients with ER+/HER2− breast cancer indicated to undergo SLNB and to evaluate the primary determinants of chemotherapy prescription for these patients. Patients and MethodsA retrospective cohort study was undertaken. Cox regression and Kaplan-Meier analyses were performed. Data analytics was performed using SPSS v26.0. ResultsFive hundred and seventy five consecutive patients were included (mean age: 66.5 years, range: 45-96). The median follow-up was 97.2 months (range: 3.0-181.6). Of the 575 patients, just 12 patients had positive SLNB (SLNB+) (2.1%). Using Kaplan-Meier analyses, SLNB+ failed to impact recurrence (P = .766) or mortality (P = .310). However, using Cox regression analyses, SLNB+ independently predicted poorer disease-free survival (hazard ratio: 1.001, 95% confidence interval (95% CI): 1.000-1.001, P = .029). Logistic regression analysis identified RS as the sole predictor of chemotherapy prescription (odds ratio: 1.171, 95% CI: 1.097-1.250, P < .001). ConclusionOmitting SLNB may be safe and justifiable in postmenopausal patients with ER+/HER2− breast cancer with clinically negative axillae. Following RxPONDER, RS is the most important guide of chemotherapy use in these patients and SLNB may be less important than previously perceived. Prospective, randomized clinical trials are required to fully establish the oncological safety of omitting SLNB in this setting.

Patient-Initiated Follow-Up in Ovarian Cancer

This study aimed to assess the feasibility of patient-initiated follow-up (PIFU) in combination with regular tumour marker monitoring as an alternative to conventional hospital follow-up for ovarian cancer survivors. Women who had recently completed treatment for ovarian cancer and had a raised pre-treatment tumour marker were recruited. Participants were allocated to PIFU (intervention group) or conventional hospital follow-up (control group) according to their own preference. Both groups had regular tumour marker monitoring. The change in fear of cancer recurrence (FCR) score as measured by the FCR inventory, and the supportive care need (SCN) scores as measured by the SCN survey at baseline and at 6 months between PIFU and hospital follow-up were compared. Out of 64 participants, 37 (58%) opted for hospital follow-up and 27 (42%) opted for PIFU. During the 6-month study period, there was no significant difference in the change of FCR between the two groups (p = 0.35). There was a significant decrease in the sexuality unmet needs score in the intervention group from baseline to 6-month FU (mean difference -8.7, 95% confidence interval -16.1 to -1.4, p = 0.02). PIFU with tumour marker monitoring is a feasible follow-up approach in ovarian cancer survivorship care. FCR and SCN were comparable between PIFU and conventional hospital follow-up.

Incidence, Clinicopathologic Features, HER2 Fluorescence In Situ Hybridization Profile, and Oncotype DX Results of Human Epidermal Growth Factor Receptor 2-Low Breast Cancers: Experience From a Single Academic Center

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016. Based on the cohort from 2018 to 2021, the incidence of HER2-low breast cancers was approximately 54%. HER2-low cases had less frequent grade 3 morphology, less frequent triple-negative results, ER and progesterone receptor negativity, and a higher mean HER2 copy number and HER2/CEP17 ratio than HER2-zero cases (P < .0001). Among ER+ cases, HER2-low cases showed significantly less frequent Nottingham grade 3 tumors. In the cohort from 2014 to 2016, HER2-low cases showed significantly higher ER+ percentages, fewer progesterone receptor-negative cases, lower Oncotype DX recurrence scores, and higher HER2 mRNA expression scores than HER2-zero cases. In summary, this is the first study, to our knowledge, using a large cohort of continuous cases evaluated by the Food and Drug Administration-approved HER2 IHC companion diagnostic test for HER2-low expression and HER2 fluorescence in situ hybridization profile in a real-world setting. Although HER2-low cases showed a higher HER2 copy number, ratio, and mRNA level than HER2-zero cases statistically, such small differences are unlikely to be biologically or clinically meaningful. However, our study suggests that HER2-low/ER+ early-stage breast carcinoma may represent a less aggressive group of breast carcinoma, given its association with a lower Nottingham grade and Oncotype DX recurrence score.