tbuckley/cabot-search huggingface dataset:
A nomogram to predict the risk of axillary upstaging in patients with Z0011-eligible breast cancer.
Authors: Xinyu Li, Qiang Liu, Yudong Li
Journal: Journal of Clinical Oncology (2024)

e12606 Background: ACOSOG Z0011 trial showed that in early cT1-2N0 breast cancer patients with 1-2 positive lymph nodes in sentinel lymph node biopsy (SLNB) can safely omit axillary lymph node dissection (ALND) without compromising local control and long-term survival. Although it is widely accepted worldwide, controversy and concerns remain that the incidence of non-sentinel lymph node metastasis may lead to pathological lymph node (pN) upstaging and insufficient systemic treatment. This study aims to identify risk factors for having ≥4 metastatic lymph node (pN2-3) in patients who met Z0011 criteria and received SLNB. Methods: This is a retrospective study enrolled 733 cT1-2N0 breast cancer patients with 1-2 positive SLNs treated between 2011-2022 at Sun Yat-sen Memorial Hospital. All patients had received SLNB followed by ALND. Patients included were divided into the training and validation sets at a 7:3 ratio. Differences were compared between pN1(1-3 LN+) and pN2-3(≥4 LN+) in training set using either t test or chi-squared test. Multivariate logistic regression was conducted to identify risk factors for pN upstaging and to form the basis of a predictive nomogram. The validation was processed in the other validation set and nomogram performance was evaluated using the area under ROC curve (AUC). Results: Among the 733 patients enrolled, 127 (17.3%) patients had pN upstaging (pN2-3) after ALND. There was a big difference of pN upstaging between the patients with 1 (47/511, 9.2%) and 2 (80/222, 36%) positive SLNs. 488 patients were allocated to the training set, among which 18.2% had pN upstaging. In univariate analysis, pN were differed by cT stage, axillary ultrasound appearance, histological grade, molecular subtype, Ki67, lymph vascular invasion, pathological tumor size, SLN metastasis type (micrometastasis or macrometastasis), positive SLN numbers and negative SLN numbers. Multivariate logistic analysis resulted six independent risk factors associated to pN upstaging: ultrasound suspicious node (OR=1.93; 95% CI: 1.08-3.47), positive lympho-vascular invasion (OR=2.27; 95% CI: 1.25-4.13), larger tumor size (OR=2.07; 95% CI: 1.15-3.73), SLN macro-metastasis (OR= 9.15; 95% CI: 1.07-78.13), two positive SLNs (OR= 6.59; 95% CI:3.70-11.76) and less negative SLN number (OR=1.54; 95% CI: 1.22-1.89). These factors were used to construct a predictive nomogram, exhibiting excellent performance with AUC values of 0.819 and 0.827 in the training and validation cohorts respectively. Conclusions: The Z0011-eligible patients with two positive SLNs may have a high risk of pN upstaging and need to be cautious to spare ALND. A practical nomogram is helpful to identify patients at high risk of pN upstaging and avoid insufficient systemic treatment.
Reconstructive plastic surgery in combined treatment of breast cancer: Predictive risk factors of complications and reconstruction failure.
Authors: Daria Ulrikh, Petr Krivorotko, Bryantseva Zhanna, Sergey Novikov, Viktoriia Mortada, Roman Pesotskiy, Yana Bondarchuk, Nikolay Amirov, Alexander Emelyanov, Diana Enaldieva, Valerii Levchenko, Elena Zhiltsova, Tengiz Tabagua, Konstantin Zernov, Vladimir Semiglazov
Journal: Journal of Clinical Oncology (2024)

e12594 Background: Breast reconstruction after mastectomy must consider potential complications from surgical techniques as well as additional complications of oncologic treatment such as radiation or systemic therapy. But the consensus is lacking regarding the optimal reconstruction plan for patients requiring adjuvant radiation therapy. Objective: To determine the impact of risk factors on the development complications of breast reconstruction for postmastectomy radiotherapy. Methods: This study included patients diagnosed with breast cancer who received combination treatment from 2016 to 2021 at the FSBI “N.N. Petrov National Medical Research Center of Oncology” of the Russian Ministry of Health. The patients were divided into 3 groups: immediate reconstruction (158 people), immediate-delayed (210 people) and delayed (98 people). Results: Every fourth patient (24.0%, 112/466) may encounter a complication after mastectomy with reconstruction and adjuvant radiation therapy. According to the analyzed data, there was no correlation between potential risk factors depending on the general status of patients (age, obesity, diabetes mellitus, hypertension, history of smoking) and the occurrence of complications after combination treatment. Conclusions: The analysis of complications and reconstructive failures showed that immediate breast reconstruction at the FSBI "N.N. Petrov National Medical Research Center of Oncology" of the Ministry of Health of Russia is the safest method of reconstruction in the combined treatment of breast cancer with the lowest incidence of severe complications (9.5%, 15/158, z&gt;1.96), which plays a key role in the development of reconstructive failures (Pearson Correlation=0.861, p&lt;0.001). However, these surgeries are associated with a significant number of capsular contractures (15.2%, 24/158, z&gt;1.96, Pearson Correlation=0.230, p&lt;0.001), which requires finding ways to minimize these risks to optimize treatment in each individual case in short and long term results.
Optimization of surgical management of the axilla since MonarchE trial.
Authors: Clémentine Jankowski, Sylvain Ladoire, Charles Coutant
Journal: Journal of Clinical Oncology (2024)

e12604 Background: Results of monarchE trial (1) have changed adjuvant therapy recommendations for estrogen-receptor-positive (ER+), HER-2 non amplified early breast cancer. Abemaciclib when combined with endocrine therapy has demonstrated a significant improvement in interval disease free survival for patients at high risk of recurrence defined by 4 or more positive nodes or 1 to 3 nodes and either tumor size ≥ 5cm or histologic grade 3. Given the importance of the extent of nodal disease in this study, surgical management of the axilla has resurfaced as a question asked at multidisciplinary tumor boards. Methods: Using data from a prospective historical cohort (2) in which patients underwent both sentinel node (SN) dissection and axillary node dissection (ALND), we assessed the proportion of patients in whom the absence of ALND indication would have led to a lack of awareness of "high-risk" status, and therefore of the indication for adjuvant Abemaciclib. In addition, we evaluated the contribution of the Katz nomogram (that predict pN2/N3 stage) (3) to guide possible indications for complementary ALND in patients with no indication for ALND according to current guidelines. Results: Among the 536 patients, 88 were excluded (54 were ER- and 34 had isolated cells in SLN). Among the remaining 448, 19.2% (86) already had an indication for abemaciclib (78 grade 3 and 8 with size ≥5cm). Ten patients with 3 SLN+ had an indication for ALND. Overall, among patients with 1 or 2 SLN+, only 8% (28/352) were pN2/N3 (14/279 with 1SLN+ and 14/73 with 2SLN+). When the ratio (number of SLN+/total number of SLN sampled) was less than 1, only 3.9% (9/231) were pN2/N3. The pN2/N3 rate was 16% (19/121) when the ratio was greater than 1. Patients with 1 or 2 SLN + met the ACOSOG Z0011 criteria so none would benefit from an ALND, but 8% (28/352) of patients at high risk will not receive Abemaciclib. When using the Katz nomogram with a threshold ≤5%, this rate decreases to 3.3% (7/352) but 116 patients will have an ALND with no benefit. With a threshold ≤20%, 5% (16/352) patients at high risk will not receive Abemaciclib but 21 patients will have an ALND with no benefit. Conclusions: The indications for adjuvant abemaciclib should not lead to surgical escalation in the surgical management of the axilla. 1.Johnston SRD et al. Lancet Oncology. 2023. 2. Katz A et al. J Clin Oncol. 2008 3. Werkoff G et al. J Clin Oncol. 2009.
A proof-of-concept study of LXP5268 as an add-on neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer.
Authors: Liang Chih Liu, Tzong-Der Way, Chin-Hua Lin, Ya-Hui Chen, Pin-Hung Kuo, Chung-Hsin Tseng, Chiu-Heng Chen
Journal: Journal of Clinical Oncology (2024)

e12607 Background: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype characterized by a high risk of mortality and a poor prognosis. The 2019 ASCO and St. Gallen International Consensus Guidelines strongly recommend neoadjuvant chemotherapy (NACT) for early-stage TNBC. Previous studies indicated that NACT improved overall and disease-free survival in early-stage TNBC. LXP5268, a drug in the 505(b)(2) category, has demonstrated efficacy in reducing tumor size in animal models. Our study aims to assess whether combining LXP5268 with NACT enhances anti-tumor efficacy and tumor shrinkage rates in early-stage TNBC patients. Methods: Enrolled patients had untreated stage II-III TNBC. NACT consisted of docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every 3 weeks for an additional four cycles (24 weeks total). In the LXP5268 add-on NACT (LXP5268+NACT) group, patients took LXP5268 orally once daily with NACT. After treatment, we analyzed tumor objective response rate (ORR), shrinkage rate by CT images, and adverse events (AEs) diagnosed by the principal investigator. Whole-exome sequencing (WES) was performed on 6 subjects in the LXP5268+NACT group, identifying potential germline variants and biomarkers, clinically interpreted following ACMG/AMP 2015 guidelines. Results: Both groups had similar baseline characteristics. LXP5268+NACT subjects (54.8 ± 7.2 years) and NACT subjects (59.3 ± 9.8 years) showed significant age differences ( p&lt;0.001). The ORR was 100% in both the LXP5268+NACT group (3 pathological complete response, pCR and 4 pathological partial response, pPR) and NACT group (6 pPR). The tumor shrinkage rate was significantly higher in the LXP5268+NACT group at 77.3% ± 21.8 compared to 43.4% ± 12.8 in the NACT group ( p&lt; 0.001). Moreover, subjects in the LXP5268+NACT group with a tumor reduction exceeding 50% surpassed those in the NACT group. AEs included neutropenia (85.7%), constipation (66.7%), and insomnia (66.7%), all grade 1. Interestingly, mutation in XIRP2 correlated with higher tumor shrinkage rate. Conclusions: LXP5268 combined with NACT was more effective than NACT alone for early-stage TNBC, without increasing AEs. These results highlight LXP5268's potential in TNBC therapy. Previous studies indicated XIRP2 mutations in metastatic breast cancer. LXP5268+NACT achieved pCR in XIRP2-mutated patients. Future clinical trials will expand to enhance result verification accuracy. Clinical trial information: CMUH106-REC3-145.
Clinical outcomes and prognostic factors in epithelial-myoepithelial carcinoma (EMC) of the breast.
Authors: Utsav Joshi, Pravash Budhathoki, Suman Gaire, Chengu Niu, Niraj Neupane, Vishakha Agrawal, Hatem Hussein Soliman
Journal: Journal of Clinical Oncology (2024)

e12529 Background: EMC is a biphasic neoplasm of the breast and comprises of malignant components derived from both luminal epithelium and myoepithelium. Most of the published data on EMC consists of individual case reports, and hence survival outcomes and prognosis are not clearly defined to guide evidence‐based management. We aimed to evaluate the clinical characteristics, survival outcomes, and prognostic factors in patients with EMC. Methods: All women with a histologic diagnosis of EMC irrespective of age and stage at diagnosis till 2018 in the National Cancer Database (NCDB) were included (N=111). Overall survival (OS) was assessed utilizing the Kaplan–Meier method and compared among groups using the log-rank test. Results: The median age at diagnosis was 67 years, and 101 (88.6%) were greater than 50 years of age. Most women were white (84.7%), non-Hispanic (91.9%), had a Charleston-Deyo score of 0-1 (95.5%), and treated at an academic or comprehensive community cancer programs (70.2%). Ten percent of patients were ER+/Her2-, 29.7% were ER-/Her2-, 0.9% were Her2+, 5.4% were ER+/Her2 unknown, 24% were ER-/Her2 unknown, and 29.7% had no data on ER status. Almost one-third of the women had poorly differentiated or undifferentiated tumors. Of the patients with available data, 46.7% had tumor ≤2 cm and more than 97% had no lymph node involvement or metastases. Most underwent surgical resection- radical mastectomy (16.2%), total mastectomy (18.9%), and partial mastectomy (56.8%). Chemotherapy and radiation were utilized in 35.2% and 40.6% of the women, respectively. At a median follow up of 67.6 months, the 3-year and 5-year OS was 81.6% and 74.3% respectively. The 5-year OS was 82.7%, 76.5%, and 50% for tumor ≤2 cm, 2-5 cm, and &gt;5 cm respectively (p=0.009). Details on 5-year OS based on chemotherapy, radiation, and tumor size are shown in the table below. Among women who underwent lumpectomy (N=35), the 5-year OS for those who received adjuvant radiation vs surgery alone was 81.9% vs 76% (p=0.4). Conclusions: EMC demonstrates distinctive clinicopathologic features and receptor status. Administration of chemotherapy or radiation was associated with improved OS in tumors &gt;5 cm, although small sample size and lack of recurrence data may limit this conclusion. Further studies using larger cohorts are needed to demonstrate objective efficacy of systemic treatment in lymph node positive and metastatic EMC. [Table: see text]
Malignant gastric outlet obstruction: direct biopsy in the submucosal tunnel to obtain the diagnosis
Authors: Liansong Ye, Nuoya Zhou, Yi Mou, Chao Zhang, Lihong Wei, Xinhua Zhang, Bing Hu
Journal: Endoscopy (2024)

A 59-year-old man presented with recurring early satiety for 1 year and postprandial vomiting for 2 months; he had also experienced weight loss of approximately 12 kg over the previous year. Gastroscopy showed food retention in the gastric cavity and an endoscope with a diameter of 8.9 mm could not be passed through the pylorus ([Fig. 1]). The mucosa of the pylorus appeared normal. A barium swallow showed delayed emptying of the stomach, with no filling defects or niches ([Fig. 2]). Abdominal computed tomography showed localized thickening of the gastric antrum, without enlargement of the lymph nodes ([Fig. 3]). Endoscopic ultrasonography (EUS) showed thickened muscularis propria at the pylorus ([Fig. 4]). Given the presumed diagnosis of hypertrophic pyloric stenosis, and after the patient had given informed consent, we performed peroral endoscopic myotomy (POEM) ([Video 1]).
Effects of a pilot 12-week exercise program on breast cancer survivors’ quality of life.
Authors: Lauren Imai, Kirsten Baron, Matthew Toyama, Ian Pagano, Paulette Yamada, Cheri Teranishi-Hashimoto, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2024)

e12525 Background: Previous studies have demonstrated that breast cancer survivors commonly experience a decrease in quality of life including an increased risk of depression, insomnia, cancer-related fatigue, and negative body image. Several studies have shown that exercise interventions, such as yoga, Pilates, water aerobics, and strengthening exercises can improve survivors’ quality of life. We implemented a 12-week exercise program in breast cancer survivors and evaluated quality of life changes. Here we discuss our findings evaluating 13 quality of life questionnaires. Methods: We evaluated 46 participants who completed a baseline and post 12-week questionnaire assessment. All participants underwent an exercise program 3 times/week for 90 minutes/session. We calculated differences in baseline and post 12-week quality of life through 13 questionnaires: Functional Assessment of Cancer Therapy - General (FACT-G) Physical, Social/Family, Emotional, and Functional, Social Support, Insomnia Severity Index, Brief Fatigue Inventory, Patient Health Questionnaire, and Body Image after Breast Cancer (BIBCQ) Vulnerability Scale (VS), Body Stigma Scale (BSS), Limitations Scale (LS), Body Concerns Scale (BCS), Transparency Scale (TS), and Arm Concerns Scale (ACS) and assessed the intervention's efficacy by comparing the baseline and post 12-week scores using paired t-tests. Results: The difference between baseline and post 12-week quality of life are presented in the Table. 7/13 questionnaires showed statistical significance: FACT-G Physical and Functional, Insomnia Severity Index, Brief Fatigue Inventory, Patient Health Questionnaire, and BIBCQ LS and BCS. Conclusions: Our study showed improvement in metrics evaluated in breast cancer survivors who underwent the personalized exercise program. Specifically, body image was improved with exercise which further exemplifies the impact of lifestyle changes on quality of life measures and is an important adjunct to future cancer survivorship studies. Clinical trial information: NCT04013568 . [Table: see text]
Association between PIK3CA mutations and disease-free survival in patients with HR+, HER2- tumors treated with adjuvant hormonal therapy: A real-world study in Croatia.
Authors: Dora Čerina, Natalija Dedic Plavetic, Ingrid Belac Lovasić, Robert Separovic, Josipa Flam, Marija Pancirov, Žarko Bajić, Snjezana Tomic, Eduard Vrdoljak
Journal: Journal of Clinical Oncology (2024)

e12512 Background: Disease recurrence of early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one-quarter of patients with early disease will present with the disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene have a high prevalence of 30% to 40% in HR+/HER2- advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine this association and impact of PIK3CA mutation status on disease free survival (DFS) in HR+/ HER2- early breast cancer patients. Methods: We conducted a multicentric, retrospective cohort study in five Croatian institutions from July 2020 to December 2021. Study included initially early HR+/HER2- breast cancer patients who have been diagnosed with disease recurrence during adjuvant hormonal treatment or within first six years of follow up. The Cobas PIK3CA Mutation Testing Kit was used for real-time PCR-based amplification and mutation detection on the Cobas z 480 analyzer. We have analyzed differences in DFS from initiation of adjuvant endocrine therapy, using Cox, proportional hazard regression. Results: There was total of 186 patients, out of which 40.9% tested positive for the PIK3CA mutation. Primary and adjuvant treatment and in particular adjuvant endocrine treatment was similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with positive PIK3CA status and with H1047 PIK3CA mutation had significantly lower hazard for disease recurrence in comparison to patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; HR 6.52; 95% CI 1.15; 36.95; p = 0.034 respectively; false discovery rate, FDR &lt; 10%) and higher odds for late recurrence (p = 0.001, FDR &lt; 5%). Conclusions: This study highlights the potential impact of PIK3CA mutations on disease recurrence during/following adjuvant endocrine treatment and by that potentially opens the door for further investigation of possibly more personalized treatment strategies.
Prediction of CCL2 in breast cancer based on enhanced MRI radiomics model with integrated bioinformatics analysis and machine learning.
Authors: Chen Fu, Qiuchen Chen
Journal: Journal of Clinical Oncology (2024)

e12509 Background: Breast cancer is the most common malignant tumor in women. According to the 2023 Cancer Statistics Report, breast cancer has surpassed lung cancer to become the most common malignant tumor. Its incidence and mortality both rank first among female malignant tumors. This study proposes non-invasive prediction of CCL2 mRNA expression in breast cancer tissue through enhanced MRI radiomics, while integrating bioinformatics analysis to explore the underlying molecular mechanisms and their association with the immune microenvironment. Methods: Excluding criteria were applied to select primary solid tumor samples with RNA-seq data (n = 840) from the TCGA-BRCA database. Enhanced MRI imaging data (n = 98) intersecting with the TCGA-BRCA data were obtained from TCIA-BRCA. The imaging data were randomly divided into training (n = 70) and testing sets (n = 28) in a 7:3 ratio. A feature subset was selected, and a model was constructed using the support vector machine (SVM) algorithm in the training set. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow goodness-of-fit test. The calibration of the radiomics prediction model was assessed using the Brier score, and the clinical utility of the radiomics prediction model was demonstrated by drawing decision curves (DCA). External validation of the model was performed using a validation set. The radiomics score (RS) was calculated using the LR radiomics model and categorized as a binary variable (Low/High RS). Subsequently, KEGG pathway, immune-related genes, and gene mutation analysis were conducted based on the CCL2 high and low expression levels. Results: A total of 1810 radiomic features were obtained with ICC values ≥ 0.75. Subsequently, the mRMR (Maximum relevance, minimum redundancy) method, and the optimal 7 feature subsets were further identified using the RFE (Recursive feature elimination) algorithm. The SVM model demonstrated favorable predictive performance, with an AUC value of 0.822 for the training set and 0.779 for the validation set, as indicated by the ROC curve. Calibration curve and Hosmer-Lemeshow goodness-of-fit test revealed good consistency between the radiomic predictive model for the probability of high gene expression and the actual values (P &gt; 0.05). Additionally, the decision curve analysis (DCA) demonstrated high clinical utility of the model. The TNF-α signaling pathway was found to influence the occurrence and development of breast cancer. Furthermore, the degree of Plasma Cell infiltration was observed to be highest in breast cancer. Conclusions: The CCL2 model constructed using a combination of machine learning and radiomic features, can non-invasively predict the prognosis of breast cancer treatment and exhibits good generalizability.