High Risk Of Recurrence Research Articles

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Meningioma recurrence: Time for an online prediction tool?

Background: Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient’s lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson’s and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care. Methods: A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population. Results: Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, CDKN2A deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas. Conclusion: Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas.

DGPRI, a new liver fibrosis assessment index, predicts recurrence of AFP-negative hepatocellular carcinoma after hepatic resection: a single-center retrospective study

Although patients with alpha-fetoprotein-negative hepatocellular carcinoma (AFPNHCC) have a favorable prognosis, a high risk of postoperative recurrence remains. We developed and validated a novel liver fibrosis assessment index, the direct bilirubin-gamma-glutamyl transpeptidase-to-platelet ratio (DGPRI). DGPRI was calculated for each of the 378 patients with AFPNHCC who underwent hepatic resection. The patients were divided into high- and low-score groups using the optimal cutoff value. The Lasso-Cox method was used to identify the characteristics of postoperative recurrence, followed by multivariate Cox regression analysis to determine the independent risk factors associated with recurrence. A nomogram model incorporating the DGPRI was developed and validated. High DGPRI was identified as an independent risk factor (hazard ratio = 2.086) for postoperative recurrence in patients with AFPNHCC. DGPRI exhibited better predictive ability for recurrence 1–5 years after surgery than direct bilirubin and the gamma-glutamyl transpeptidase-to-platelet ratio. The DGPRI-nomogram model demonstrated good predictive ability, with a C-index of 0.674 (95% CI 0.621–0.727). The calibration curves and clinical decision analysis demonstrated its clinical utility. The DGPRI nomogram model performed better than the TNM and BCLC staging systems for predicting recurrence-free survival. DGPRI is a novel and effective predictor of postoperative recurrence in patients with AFPNHCC and provides a superior assessment of preoperative liver fibrosis.

Nomogram built based on machine learning to predict recurrence in early-stage hepatocellular carcinoma patients treated with ablation

IntroductionTo analyze the risk factors affecting recurrence in early-stage hepatocellular carcinoma (HCC) patients treated with ablation and then establish a nomogram to provide a clear and accessible representation of the patients’ recurrence risk.MethodsCollect demographic and clinical data of 898 early-stage HCC patients who underwent ablation treatment at Beijing You’an Hospital, affiliated with Capital Medical University from January 2014 to December 2022. Patients admitted from 2014 to 2018 were included in the training cohort, while 2019 to 2022 were in the validation cohort. Lasso and Cox regression was used to screen independent risk factors for HCC patients recurrence, and a nomogram was then constructed based on the screened factors.ResultsAge, gender, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, globulin (Glob) and γ-glutamyl transpeptidase (γ-GT) were finally incorporated in the nomogram for predicting the recurrence-free survival (RFS) of patients. We further confirmed that the nomogram has optimal discrimination, consistency and clinical utility by the C-index, Receiver Operating Characteristic Curve (ROC), calibration curve and Decision Curve Analysis (DCA). Moreover, we divided the patients into different risk groups and found that the nomogram can effectively identify the high recurrence risk patients by the Kaplan-Meier curves.ConclusionThis study developed a nomogram using Lasso-Cox regression to predict RFS in early-stage HCC patients following ablation, aiding clinicians in identifying high-risk groups for personalized follow-up treatments.

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and stroke risk

Abstract Funding Acknowledgements None. Background Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. Methods We performed a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of two tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). Results After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia (12.8% vs. 4.7%; p=0.003), advanced atrioventricular block (13.2% vs. 6.0%; p=0.012), heart failure (28.5% vs. 18.7%; p=0.017), and cardiogenic shock (17.4% vs. 8.5%; p=0.006). In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p&amp;lt;0.001), without differences in stroke incidence (10.1% vs. 9.3%). Conclusion Patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-years follow up, they exhibit a high risk of AF recurrence, with no significant differences in stroke incidence.Kaplan Meier curves

The CONUT score is associated with the pathologic grade in non-small cell lung cancer.

Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

CyberKnife stereotactic radiosurgery for extramedullary plasmacytoma in the external auditory canal: illustrative case.

Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple myeloma. Extramedullary plasmacytomas (EMPs), particularly those located in the external auditory canal (EAC), are exceedingly rare and pose significant treatment challenges given their location, anatomical complexity, and high risk of recurrence. The authors report the case of a 72-year-old male with a history of multiple myeloma, presenting with recurrent left EAC plasmacytoma. After initial conventional radiotherapy for the lesion, a recurrence was documented in 7 years. The patient subsequently underwent stereotactic radiosurgery, which proved successful, leading to complete resolution of the lesion without any long-term adverse effects or radiation-related complications over a 45-month period. This case is a unique instance of utilizing stereotactic radiosurgery for recurrent EMP in the EAC, highlighting its potential as an effective approach in managing complex plasmacytomas.

Prognostic outcome of cervical laser ablation using a holmium yttrium-aluminum-garnet (Ho:YAG) laser for the treatment of cervical intraepithelial neoplasia: A single-center retrospective study

ObjectiveAlthough cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. MethodsWe evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. ResultsWe performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. ConclusionsLaser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

Abstract PS04-06: Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort

Abstract Background: Our prior study observed a 34% higher risk of breast cancer (BC) recurrence among women with major depressive disorder (MDD) at the time of their BC diagnosis compared to women without MDD after adjusting for sociodemographic, clinical, and prognostic factors. Given the high prevalence of substance abuse disorders among individuals with MDD and the positive association between alcohol use and mortality among BC survivors, we were interested to examine whether the risk of BC recurrence was compounded for women with both conditions. Objective: To investigate whether pre-diagnostic substance abuse disorders modify the association between MDD and BC recurrence. Methods: We established a retrospective cohort of women (age ≥ 18 years) with incident, early-stage BC diagnosed from 2010 through 2019 using the VHA’s electronic medical record database. A two-year window was used to identify women with MDD and co-existing substance abuse disorders prior to their BC diagnosis. We examined potential interactions between MDD and alcohol abuse and MDD and other substance abuse using multivariable proportional hazards regression, accounting for competing risk of death. Our outcome of interest was BC recurrence. The reference group for all analyses was women with BC alone. The models were adjusted for patient characteristics including age, race, ethnicity, marital status, rurality of primary residence, priority group rating (proxy for socioeconomic status), any homelessness or economic problems, comorbidity burden, body mass index, smoking status, receipt of a screening mammography, year of BC diagnosis, cancer stage, cancer subtype, and cancer treatment. Subgroup analyses were conducted by cancer subtype. Results: Our cohort comprised 6,045 women with BC, of whom 1,754 (29%) had a pre-diagnostic MDD diagnosis and 1,509 (25%) had a substance abuse disorder. Among women with MDD, 386 (22%) abused alcohol and 336 (19%) abused other substances. The median length of follow-up from BC diagnosis was 4.5 years (IQR=4.8 years). The average age at BC diagnosis was 57 years (SD=11 years) overall, 56 years (SD=10 years) among women with MDD, and 57 years (SD=9 years) among women with substance abuse disorders. On multivariable analysis, MDD (HR=1.33; 95% CI: 1.14, 1.53), alcohol abuse disorder (HR=1.37; 95% CI: 1.12, 1.68), and other substance abuse disorders (HR=1.33; 95% CI: 1.13, 1.56) were independent risk factors for BC recurrence. Further, there was a statistically significant interaction between pre-diagnostic MDD and alcohol abuse disorder (p-interaction=0.003). Women with BC who had both pre-diagnostic MDD and alcohol abuse disorder were at a 65% (HR=1.65; 95% CI: 1.29, 2.11) higher risk of BC recurrence compared to women with BC alone. A statistically significant interaction was also observed between pre-diagnostic MDD and other substance abuse disorders (p-interaction &amp;lt; 0.001). Women with BC who had both pre-diagnostic MDD and other substance abuse disorders were at a 90% (HR=1.90; 95% CI: 1.50, 2.42) higher risk of BC recurrence compared to women with BC alone. In subgroup analyses, the interaction between MDD and alcohol abuse disorders (p-interaction=0.001) and MDD and other substance abuse disorders (p-interaction &amp;lt; 0.001) was limited to women with estrogen receptor positive cancer but not estrogen receptor negative cancer. Conclusion: Women with incident BC who have prior diagnoses of both MDD and substance abuse disorder are at higher risk of recurrence than women with either exposure independently. Further research is needed to examine the etiology of our findings and to evaluate whether this newly defined risk group would benefit from closer monitoring and more tailored treatment options. Citation Format: Maya Aboumrad, Kala Visvanathan. Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort [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 PS04-06.

Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p &amp;lt; 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p&amp;lt; 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p &amp;lt; 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [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 PO2-01-13.

Abstract PO2-02-01: Online Virtual Patient Simulation CME Improves Clinical Decision-Making In The Management Of Patients With HR+/HER2- Early Breast Cancer

Abstract Background: The goal of this study is to assess whether an online, virtual patient simulation (VPS) continuing medical educational (CME) activity, improved the performance of oncologists in ordering appropriate diagnostic tests and managing and counselling patients with HR+/HER2- early breast cancer (EBC) at high risk of recurrence. Methods: Two VPS educational activities were developed, the first VPS consisted of one patient case, focused on diagnosing patients with high risk of recurrence, while the other VPS consisted of 2 patient cases focused on the management and counselling of patients with HR+/HER2- EBC with high risk of recurrence. Physicians could make clinical decisions using complete open-field entries, based on the 3 performance based learning objectives. After each decision, learners received clinical guidance (CG) based on current evidence and expert recommendations. Pre- and post-CG clinical decisions were compared using a a McNemar's test to determine P values (P &amp;lt; .05 is significant). Rationales for clinical decisions were collected in real time. Data were collected between November 2021 and August 2022 and are reported here as % point change per performance learning objective, P value. Results: A total of 922 oncologists were included in the analysis. There was a significant improvement across the 3 performance learning objectives analysed. Please see table below for the results. Conclusions: This analysis demonstrated the educational impact of an immersive, online VPS education which allowed physicians to improve evidence-based clinical decisions regarding diagnosing patients with HR+/HER2- early breast cancer at high risk of recurrence and managing and counselling them regarding their treatment. Results Citation Format: Nabil Dorkhom, Urvi Patel, Stephanie Baumhover, Jacob Cohen. Online Virtual Patient Simulation CME Improves Clinical Decision-Making In The Management Of Patients With HR+/HER2- Early 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 PO2-02-01.

Abstract PO4-27-07: A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2)

Abstract Background: Camizestrant is a next-generation oral selective estrogen receptor (ER) degrader and pure ER antagonist being investigated in early and advanced breast cancer (BC). In postmenopausal women with advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative BC and disease recurrence or progression on or after ≤1 endocrine therapy (ET) in the advanced setting, camizestrant significantly prolonged progression-free survival compared with fulvestrant in the Phase 2 SERENA-2 trial. Camizestrant may also provide benefit in the early BC setting. Following locoregional therapy (surgery ± radiotherapy), standard adjuvant treatment of ET with or without chemotherapy and/or a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has shown significant benefit in decreasing the risk of recurrence of stage I–III ER-positive/HER2-negative BC. However, BC recurrence as incurable metastatic disease is still common. Thus, adjuvant therapeutic options with improved clinical outcomes are needed. The CAMBRIA-2 study (NCT05952557) aims to assess whether upfront camizestrant can improve outcomes compared with standard ET as adjuvant treatment in patients with ER-positive/HER2-negative early BC with an intermediate-high or high risk of recurrence after definitive locoregional therapy. Trial design: This ongoing Phase 3, randomized, open-label study is enrolling women (pre-, peri-, or postmenopausal) and men with ER-positive/HER2-negative (HER2-negative status defined as immunohistochemistry 0, or 1+, or in situ hybridization-negative) early BC who are at intermediate-high or high risk of recurrence (as defined in the protocol) after having completed definitive locoregional therapy (surgery ± radiotherapy) ± (neo)adjuvant systemic chemotherapy, and who have no evidence of disease. Patients may have received up to 12 weeks of (neo)adjuvant ET prior to randomization. Patients are randomized (1:1) to receive camizestrant 75 mg ± abemaciclib ± luteinizing hormone-releasing hormone (LHRH) agonist or standard ET of the investigator’s choice (any aromatase inhibitor or tamoxifen) ± abemaciclib ± LHRH agonist for up to 7 years. The primary endpoint is invasive BC-free survival (IBCFS) (Standardized Definitions for Efficacy End Points [STEEP] 2.0 criteria). Secondary endpoints include invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Primary endpoint analysis will use a stratified log-rank test adjusting for stratification factors, assuming a two-sided significance level of 5%. Approximately 5500 patients will be randomized. Clinical trial identification: NCT05952557 Editorial acknowledgment: Writing assistance was provided by Clare Davis of BOLDSCIENCE Inc., funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca Funding: This study was supported by AstraZeneca. Citation Format: Sibylle Loibl, Yeon Park, Sara Tolaney, Ioanna Gioni, Simon Johnston, Teresa Klinowska, Ingrid A. Mayer, Raquel Nunes, Barbara Pistilli, Mary Stuart, Angela Quintana, Andrew Walding, Michael Gnant. A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2) [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 PO4-27-07.

Abstract PO2-18-09: A phase 3 randomized open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy in patients with ER+/HER2– early breast cancer and an intermediate or high risk of recurrence (CAMBRIA 1)

Abstract Background: Definitive locoregional (surgery ± radiotherapy) and standard adjuvant endocrine therapy (ET) (± chemotherapy or cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) can achieve cure in many patients (pts) with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2–) early breast cancer (BC). Nevertheless, a significant proportion of pts with stage I–III disease will experience recurrence to metastatic, incurable disease (5- and 10-year cumulative incidences of recurrence of 8.3% and 14.0%, respectively). There is evidence that incorporating a more effective endocrine therapy after 2 years of standard adjuvant ET can result in clinical benefit for high-risk individuals. Camizestrant is a next-generation oral selective ER degrader and pure ER antagonist. In SERENA-2, camizestrant 75 mg and 150 mg significantly prolonged progression-free survival vs fulvestrant in postmenopausal women with ER+/HER2– advanced BC with disease recurrence or progression after ET. The CAMBRIA-1 study (NCT05774951) is evaluating the potential of extended adjuvant therapy with camizestrant to improve outcomes in pts with ER+/HER2– early BC with an intermediate or high risk of recurrence after definitive locoregional therapy and standard adjuvant ET. Trial design: This phase 3 randomized, open-label study is enrolling women (pre- or postmenopausal) and men with ER+/HER2– (immunohistochemistry 0/1+/2+/in situ hybridization-negative) early BC who have completed definitive locoregional therapy and standard adjuvant ET (± CDK4/6i) for ≥2 and ≤5 years (+ 3 months) without disease recurrence. Pts must be considered at intermediate or high risk of recurrence based on clinical, biological, and genomic factors. Pts are randomized (1:1) to continue standard ET of the investigator’s choice (tamoxifen or aromatase inhibitor ± luteinizing hormone-releasing hormone [LHRH] agonist) or camizestrant ± LHRH agonist for up to 60 months. The primary endpoint is invasive BC-free survival (STEEP 2.0 criteria). Secondary endpoints include invasive disease-free survival and distant relapse-free survival (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Primary endpoint analysis will use a stratified log-rank test adjusting for stratification factors, assuming a two-sided significance level of 5%. Approximately 4300 pts will be randomized; enrollment is ongoing. Clinical trial identification: NCT05774951 Editorial acknowledgment: Writing assistance was provided by Alison Lovibond, PhD, of BOLDSCIENCE Inc., funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca Funding: This study was supported by AstraZeneca. Citation Format: Erika Hamilton, Sibylle Loibl, Naoki Niikura, Priya Rastogi, Kamal S. Saini, Ioanna Gioni, Teresa Klinowska, Ingrid A. Mayer, Mary Stuart, Emilia Syta, Andrew Walding, Thomas Bachelot. A phase 3 randomized open-label study of extended adjuvant therapy with camizestrant vs standard endocrine therapy in patients with ER+/HER2– early breast cancer and an intermediate or high risk of recurrence (CAMBRIA 1) [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 PO2-18-09.

Abstract PO4-02-04: Overall survival and disease recurrence rates in patients with invasive lobular breast cancer of the PenelopeB cohort

Abstract Background: In the PENELOPEB trial, the addition of 1-year of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib to standard endocrine therapy (ET) for women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer at high risk of recurrence after neoadjuvant chemotherapy (NACT) did not improve invasive disease-free survival (iDFS) or overall survival (OS) in the main study analysis. Invasive lobular breast cancer (ILC) accounts for ~15% of all breast cancers (BC) and represents an underinvestigated subtype of BC with typically less sensitivity to (neo)adjuvant chemotherapy, and poor distant disease-free survival (DDFS) irrespective of response to NACT. Here, we report the post-hoc analysis results of iDFS, DDFS and OS in pre- and postmenopausal women enrolled on PENELOPEB and with ILC. Methods: Patients with HR+/HER2-negative BC without pathological complete response (pCR) after taxane-containing NACT and at high risk of relapse (CPS-EG score ≥3, or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 of a 28-day cycle in addition to standard ET with tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age at first diagnosis (&amp;lt; 50 vs. ≥50 years), Ki-67, region, and CPS-EG score. ILC diagnosis was locally assessed and reported by the investigators on the pathology case report form. The primary objective of this post-hoc analysis was to evaluate iDFS, DDFS and OS by treatment arm in patients with high risk ILC. Results: A total of 1,250 patients were randomized, of whom 110 had ILC and were nearly uniformly distributed between both treatment arms (palbociclib n=58 vs. placebo n=52), with a higher proportion of postmenopausal women (58.6% in the palbociclib arm vs. 53.8% in the placebo arm) compared to premenopausal women (41.4% in the palbociclib arm vs. 46.2% in placebo arm). There was no difference in the distribution of AI/TAM use between the treatment arms. An estimated absolute 3-year-iDFS difference of 18.3% with palbociclib compared to placebo (iDFS 88.4% [95% CI 76.0-94.6] vs. 70.1% [95% CI 55.3-80.7]) with a HR of 0.66 [95% CI 0.27 – 1.61, log-rank p=0.354]) was observed. A comparable 3-year-DDFS difference of 16.3% was observed. An estimated 3-year-OS difference of 16.4% (98.0% [95% CI 86.6 – 99.7] vs. 81.6% [95% CI 67.5 – 90.0]) with a hazard ratio (HR) of 0.27 (95% CI 0.05 – 1.43, log-rank p=0.108) was observed. Out of 12 observed deaths (n=2 palbociclib vs. n=10 placebo), 11 (in placebo arm) were related to metastasic BC. Conclusions: In this post-hoc analysis, a trend towards improvement in OS and a trend in favor of iDFS and DDFS for the addition of palbociclib to ET was observed among women with HR+/HER2- ILC at high risk of recurrence after NACT, but these differences were not statistically significant. This could represent a valuable treatment option for patients with high risk ILC. Due to the small sample size of the ILC subgroup, further follow-up evaluation is necessary. Moreover, analyses in the ILC subgroup from other adjuvant CDK4/6 inhibitor trials could substantiate these findings. Table. Overall survival and disease recurrence rates in patients with invasive lobular breast cancer of the PenelopeB cohort Results of iDFS, DDFS and OS. Citation Format: Hervé Bonnefoi, Frederik Marmé, Miguel Martín, Michael Untch, Sung-Bae Kim, Harry Bear, Nicole McCarthy, Karen Gelmon, José Ángel García-Sáenz, Catherine M. Kelly, Toralf Reimer, Zhe Zhang, Masakazu Toi, Hope Rugo, Michael Gnant, Andreas Makris, Nader Hirmas, Valentina Nekljudova, Johannes Holtschmidt, Sibylle Loibl. Overall survival and disease recurrence rates in patients with invasive lobular breast cancer of the PenelopeB cohort [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 PO4-02-04.

Abstract PO4-26-02: Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast

Abstract Introduction: Ductal carcinoma in situ (DCIS) represents around 20% of early breast cancer diagnoses globally. Some studies evaluated risk factors associated with DCIS recurrence. Among these, age, surgical margins, comedonecrosis (CN), high nuclear grade, negative hormone receptors and HER2 expression stand out. Recent approaches have been evaluating the role of the immune microenvironment and its association with recurrence and progression of DCIS. Objective: To evaluate the association between Tumor Infiltrating Lymphocytes (TILs) in DCIS samples and disease recurrence. To characterize the immunological microenvironment of DCIS, analyzing the presence of TILs, “touching TILs” and desmoplastic reaction and their association with recurrence. Epidemiological, clinical, histological and immunohistochemical (IHC) characteristics were also evaluated. Methods: This is a retrospective cohort study with patients diagnosed with DCIS and treated at Sao Paulo State Cancer Institute and Hospital das Clinicas of University of Sao Paulo. We included women over 18 years old with a diagnosis of DCIS who underwent treatment from Jan/2007 to Dec/2020. Male patients, patients with a diagnosis of invasive or microinvasive disease in the anatomopathological examination of the surgical specimen or patients with history of any neoplasm were excluded. The main outcome was survival analysis according to the quantification of TILs, adjusted for potential confounders. For that, we collected data on age, presence of palpable mass, imaging findings, histological and IHC characteristics, such as expression of estrogen receptor (ER), progesterone receptor (PR) and hyperexpression of HER2, type of surgical approach, type of radiation therapy, use of endocrine therapy, length of follow-up, recurrence, and its type. Two pathologists evaluated TILS in the sample with the highest tumor representation and numerically quantified it as percentage. They also evaluated the presence of “touching tils” (lymphocytes in contact with the basement membrane) and desmoplastic reaction in the tumor stroma. Kaplan-Meier curves, log-rank tests and Cox regression models were used to evaluate survival. Chi-square tests were used to evaluate the association between categorical variables. Results: 283 patients met the eligibility criteria. Mean age of patients was 55 years. 15% had a palpable nodule at physical examination. Clustered amorphous microcalcifications were the most prevalent mammographic presentation, found in 41% of the patients. The most frequent histological and IHC features were cribriform presentation (73%) and ER positivity (86%), respectively. Desmoplastic reaction was absent in 10.5%, discreet in 51.9%, moderate in 24% and intense in 13.6% of the patients. Breast conserving surgery was performed in 189 patients, and 100 of them received adjuvant radiation therapy. Mean follow-up was 77.2 months, with a recurrence rate of 9.2%. We observed that tumors with focal necrosis (HR 6.4 [1.39-34.71] p 0.018) or CN (HR 4.53 [1.34 – 15.28] p 0.015) had higher risks of recurrence. Patients with a percentage value of TILs greater than or equal to 17% also had a higher risks of recurrence (HR 2.97 (1.17-7.51) p 0.02). These patients were mostly under 65 years of age (OR 0.45 [0.21 - 0.97] p 0.049). In a multivariate model, CN and TILs&amp;gt;17% remained significantly associated with recurrence (p=0.034 and p=0.035 respectively). There was a trend for invasive recurrence in 76.9% of the patients that relapsed when TILS were greater than or equal to 17% (p 0.062). “Touching TILs” were present in 12.9% of the patients but were not associated with recurrence (p=0.575). Conclusion: In our cohort, high value of TILs (&amp;gt;= 17%) and presence of CN were independently associated with DCIS recurrence. Our findings suggest that TILS are a prognostic immunological biomarker in DCIS and warrant further investigation in prospective trials to determine the most adequate cut-point. Citation Format: Camila Pasetto, Fernando Aguiar, Marcella Peixoto, Maira Doria, Bruna Mota, Jonathan Maesaka, Jose Roberto Filassi, Edmund Baracat, Rodrigo Gonçalves. Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast [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 PO4-26-02.

Abstract PO2-19-07: PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET

Abstract Background During the past years, clinical routine has shifted away from relying solely on clinicopathologic factors toward increasing use of multigene expression assays in guiding treatment decisions regarding adjuvant chemotherapy (CT) for hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (EBC) with 0 to 3 positive lymph nodes. In case of a low genomic risk, there is strong consensus in favor of endocrine treatment (ET) alone for postmenopausal patients, regardless of clinical risk (supported by data from planB, ADAPT, RxPonder, TailorX, MINDACT). However, there is still uncertainty regarding optimal therapy for pre- and perimenopausal patients with a similar clinical/genomic risk profile. Since the observed benefit of CT in this patient group may be partly attributable to CT-induced ovarian function suppression (OFS), some of these patients could be spared CT by adding OFS to endocrine therapy. The West German Study Group (WSG) initiated the PROOFS-registry to create a real-world database on how to optimally treat these patients. Eligibility Criteria PROOFS (NCT05792150) aims at the long-term follow up of pre- or perimenopausal patients with HR+/HER2- EBC with an intermediate to high clinical risk of recurrence and low genomic risk measured by MammaPrint(R). Additional endocrine response assessment (Ki67) after a short preoperative endocrine therapy is encouraged. Up to 25% of the study population may have node-positive disease. Participants undergo standard-of-care treatment at physician´s discretion and according to clinical routine, which may include CT neoadjuvant or adjuvant + ET, ET + OFS in premenopausal, or ET +/- OFS in perimenopausal women. Specific Aims PROOFS aims to give insights in the real-world use of OFS and to confirm an excellent outcome in pre-/perimenopausal women with HR+/HER2- early BC with an intermediate to high clinical risk of recurrence and low genomic risk treated by ET +/- OFS alone (without CT). In addition, quality of life is captured. Statistical Methods The primary objective is to demonstrate the 5-year distant recurrence-free interval (dRFI) in patients treated by ET +/- OFS alone. The null hypothesis H(0) is: 5-year dRFI &amp;lt; 92%. Secondary endpoints for all patients are 5- and 10-year dRFI, distant disease-free survival (dDFS), overall survival (OS), breast cancer-free interval (BCFI), quality of life (QLQ BR23 and QLQ-C30) and therapy adherence. Cox regression models, Kaplan-Meier method and log-rank tests will be applied for survival analysis. Linear mixed models will be utilized to quantitatively describe the course of quality of life-scores as well as therapy adherence, and to conduct group comparisons. Present and Target Accrual The study is open for recruitment of 1500 patients (approximately 20% receiving CT and 80% receiving ET +/- OFS) at up to 100 centers in Germany (June 2023: 24 open for recruitment). Funding AGENDIA N.V., Amsterdam Contact Information rachel.wuerstlein@med.uni-muenchen.de Citation Format: Rachel Wuerstlein, Lotta Ada Fischer, Nadia Harbeck, Monika Graeser, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Christine zu Eulenburg, Matthias Warm, Oleg Gluz. PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET [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 PO2-19-07.

Abstract PO3-13-09: Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes

Abstract Background: Molecular residual disease (MRD) describes detectable circulating tumor DNA (ctDNA) after definitive surgery and is an expanding field in breast oncology. Multiple studies have demonstrated detectable MRD to be poorly prognostic, and clinical trials are now underway assessing the efficacy of therapeutic interception. However, most retrospective studies did not obtain baseline imaging at the time of MRD detection, such that the proportion of patients with detectable ctDNA and concurrent radiographically evident recurrent disease is not known. Furthermore, the role of serial ctDNA testing in the adjuvant setting remains unclear. Meanwhile, tumor-informed assays such as the SignateraTM platform are now covered by Medicare. To address these outstanding clinical questions, we aimed to determine the temporal dynamics of MRD detection in HR+/HER2- breast cancer, association with radiographic recurrence, and impact on clinical outcomes. Methods: Patients with HR+/HER2- breast cancer who underwent MRD testing either as part of a clinical trial or via an expanded access program were reviewed for MRD positivity and assessed alongside clinically annotated data. All patients completed surgical resection prior to MRD testing. Whole exome sequencing of primary tumor tissue and personalized ctDNA primers were designed for multiplex PCR targeting up to 16 single nucleotide variants for MRD testing via the SignateraTM platform. Clinical data was determined through focused chart review. Results: Among 185 patients with HR+/HER2- breast cancer who underwent MRD testing, 37 patients (20%) did not complete testing due to factors including tumor tissue not meeting pathology parameters, insufficient quantity of primary tissue, or tumor/normal discordance. 14 patients (8%) had detectable ctDNA (1, 5, and 8 patients had stage I, II, and III breast cancer, respectively). Among the 6 patients who did not have stage III disease, 3 had other high-risk features (Oncotype 40; grade 3 disease x2). Overall, 71% (n=10) of the +MRD population tested positive at the first test, while 29% (n=4) tested positive only on serial sampling. Median time from surgery to positive test was 3.5 years (range: 1 month – 10.2 years). Twelve patients (86%) were on adjuvant endocrine therapy at the time of detectable MRD. Among the 14 +MRD patients, 9 underwent staging scans shortly after positive MRD testing, and among these patients, 3 (33%) had radiographic evidence of asymptomatic metastatic recurrence (2 bone-only; 1 visceral); two of these pts had 1 MRD test, while the other had a negative test followed by a positive test 11 months later. The other 3 patients with radiographic recurrences had scans prompted only by clinical symptoms &amp;gt;6 months after +MRD. Among the 4 patients with serial data after first +MRD testing, none experienced subsequent ctDNA clearance. Serial testing occurred over a median of 11.5 months (range 1.1-21.7 months). With median follow up of 8.6 months, 43% (n=6) of patients with +MRD had distant disease recurrence. Conclusions: Personalized tumor-informed ctDNA testing identified patients with high risk of recurrence, including patients without classic high-risk clinical, pathologic, or genomic features, suggesting a complementary role of MRD testing for risk assessment. Serial monitoring was necessary to identify MRD in more than a quarter of patients. Furthermore, one-third of patients with +MRD disease had asymptomatic metastatic recurrence, highlighting the importance of staging scans in studies and clinical trials assessing therapeutic interception in the adjuvant setting. Citation Format: Arielle Medford, Elyssa Denault, Zanta Ephrem, Douglas Micalizzi, Yael Bar, Rachel Abelman, Amy Comander, Justine Knape, Minetta Liu, Angel Rodriguez, Steven Isakoff, Beverly Moy, Laura Spring, Aditya Bardia. Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes [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 PO3-13-09.

Abstract PO1-01-12: A retrospective cohort study on the effect of adding adjuvant ovarian function suppression to endocrine therapy in premenopausal women with T1-T2 tumor hormone-positive breast cancer on survival and disease recurrence

Abstract Background: Breast cancer is the most common diagnosed cancer in women and is the leading cause of cancer death. Young women diagnosed with breast cancer are at higher rates of adverse outcomes in terms of survival and recurrence. Hormone sensitive breast cancer is the commonest subtype of breast cancer in this group. To date, the standard adjuvant treatment is endocrine therapy for both pre and post-menopausal women. Recent published studies have recommended adding ovarian function therapy to premenopausal women who are at high risk of recurrence. In this study we evaluated the impact of adding adjuvant ovarian function suppression for premenopausal women with small (T1 and T2) hormone receptor positive node negative breast cancer who did not receive any form of chemotherapy on overall survival and disease-free recurrence. Methods: We performed a retrospective study where we evaluated the electronic medical records of 4431 premenopausal women diagnosed with breast cancer in Asan Medical Center in Seoul, South Korea. All the analyzed patients were operated from the period of January 2006 till December 2019. The inclusion criteria were age of 55 and below, T1 and T2 tumors with N0 disease who received selective estrogen receptor modulators (SERM - Tamoxifen) and didn’t receive neo or adjuvant chemotherapy. We compared patients who received SERM (Tam Only) only to patients who received SERM and ovarian function suppression (Tam + OFS) medications. The primary endpoint was overall survival (OS), and the secondary endpoint was mortality and disease-free survival (DFS). We used chi-square test for categorical variables and t-test for continuous variables. The p-value was set as p&amp;lt; 0.05 as statistically significant. Kaplan Meier curve and log rank test were used to analyze the data for overall survival, disease-free survival and mortality. We performed an additional subgroup analysis adjusted to age, tumor size, Ki67%, progesterone receptor, HER2 status and type of operation. Results: There was equal distribution of cases between tamoxifen only group and tamoxifen + OFS group (2121 versus 2310 respectively). The median age in each group was 45 years of age. Tumor size of ≤0.5cm was the commonest in the tamoxifen only group whereas tamoxifen + OFS group had majority of cases with tumor size of 1 - 2cm. Both groups had a Ki-67% of 10-20%. Histologic grade of 2 and nuclear grade of 2 were most commonly representative in the comparing groups. Invasive ductal carcinoma was the most common histological subtype (93-94%) and invasive lobular carcinoma accounted for 5-6% of cases. Regarding immunohistochemistry results, 91-93% of patients were progesterone receptor positive and 68-73% were HER2 negative. The majority underwent breast conserving surgery compared to mastectomy. We have also looked at the pattern of prescribing OFS treatment in the Tamoxifen + OFS group regarding the length of treatment. Nearly 80% of patients received OFS treatment for a period of 1-2 years whereas only 5.2% received &amp;lt; 1 year and 1.8% &amp;gt;2years. After adjusting to age, tumor size, Ki67%, PR receptor and HER2 status, the result was only significant for higher risk of DFS in the TAM + OFS group in Ki67 &amp;lt; 20%. The OFS+TAM had more DFS and mortality events compared to TAM only group. However, the only significant result was the overall survival favoring tamoxifen only group with a p-value of 0.039 and HR of 1.05-7.99. Conclusion: Adding ovarian function suppression to tamoxifen in premenopausal hormone positive node negative T1-T2 tumors didn’t show any benefit in terms of disease-free interval and overall survival. Further studies are advised to assess the benefit of adding ovarian function suppression to this group of patients Table 1: baseline characteristics of Table 2: Disease Free Survival Subgroup Analysis Citation Format: Sarah Al Safi, Hee Jeong Kim, Seonok Kim, Sae Byul Lee, Jisun Kim, Tae-Kyung Yoo, Il-Yong Chung, Beom Seok Ko, Byung Ho Son. A retrospective cohort study on the effect of adding adjuvant ovarian function suppression to endocrine therapy in premenopausal women with T1-T2 tumor hormone-positive breast cancer on survival and disease recurrence [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 PO1-01-12.

Abstract PO4-16-08: Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City

Abstract Background: Breast cancer is the most common malignancy in the world, reporting more than 2 million new cases in 2020. In early stages, patients undergo primary surgery. Breast-conserving surgery (BCS) has generally been accepted as a treatment for invasive breast cancer, findings at 20 years still show that lumpectomy and breast irradiation, as compared with mastectomy, have no significant difference in overall survival among the treatment groups. Approximately 10-15% of patients will develop local or systemic recurrence in 5 to 10 years. Factors such as young age (&amp;lt; 45 years), close/positive margins, no breast radiation, are associated with ipsilateral breast tumor recurrence. High grade has been related to distant metastasis. The mortality trend is upward due to a higher incidence of the disease and earlier detection. Methods: This is an observational and retrospective cohort study, which included patients with early breast cancer, who were treated with conserving surgery and received radiotherapy, at the Breast Oncology Service at the UMAE Gineco 4 "Luis Castelazo Ayala" during the period from January 2012 to December 2022. The aim of our study was to describe the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with localized breast cancer treated with BCS. DFS was defined as time from surgery to recurrence event (local recurrence, distant recurrence, contralateral breast cancer, second primary cancer, or death from any cause) whichever occurred first. For statistical analysis, Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: We included 399 patients, the median follow-up was 88 months (95%CI 86-91). Median age was 59 years. The most common pathological stage was IA in 44.9%, the predominant immunophenotype was luminal A in 56.1% of patients, follow by luminal B in 19.3% and 13% were triple negative. Management of axilla with sentinel node biopsy occurred in 50.1% and 49.9% underwent to lymph node dissection. Regarding surgery outcomes 40.4% of the patients required widening of the margins, 5% of the patients remained with close surgical margins ≤2 mm, 7.5% had complications associated with the surgery, and none related death ocurred. All patients received adjuvant radiotherapy, the median time to initiation was 32 weeks (range 3-70) and 65.4% received adjuvant chemotherapy. Recurrence events occurred in 15.5% of patients, local 2.8%, systemic 8.8%, contralateral breast cancer 1.7%, and second primary 2.2%. Estimated disease-free survival at 5 and 10 years were 86.6% and 74.2%, respectively. In the multivariate analysis independent prognostic factors for DFS were: lobular histology HR 2.95 (95%IC 1.5-5.7), tumor size ≥ 2cm HR 1.95 (95%IC 1.1-3.6), close surgical margins HR 2.62 (95%IC 1-6.6), and ER low expression (1-10%) HR 4.39 (95%CI: 1.6-12.4). Estimated OS at 5 and 10 years for patients who experienced recurrence were 78.4% and 47.4% and for patients without recurrence were 96.8% and 93.5%, respectively (adjusted HR: 10.4, 95%CI: 5.2-20.6). Conclusion: These results suggest that patients with early breast cancer treated with conserving surgery and radiotherapy with risk factors such as lobular carcinoma, tumor size ≥2cm, close margins, and low expression of estrogen receptors have a high risk of recurrence and significantly decreased overall survival at 5 and 10 years. Citation Format: Nayeli Ortega-Avila, Yuly A. Remolina-Bonilla, Janett Caballero-Jasso. Prognostic factors for tumor recurrence after breast-conserving and radiotherapy treatment for early invasive breast cancer: ten years of results in a referral center in Mexico City [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 PO4-16-08.

Abstract PO4-01-01: Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience

Abstract Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer – Single Tertiary Center Experience Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada The HER2 oncoprotein is an established therapeutic target, and the combination of adjuvant chemotherapy and targeted anti-HER2 therapy substantially reduces the risk of recurrence and death over chemotherapy alone in high-risk operable breast cancers that overexpress HER2. However, most studies demonstrating the benefits of anti-HER2 treatments have focused on cohorts at high risk of recurrence. Limited data exists for low-risk cancers to justify this treatment. We performed a retrospective study from 263 patients treated at our oncology center at the Centre hospitalier de l’Université de Montréal between 2006 and 2019 for HER2-positive, N0 or N0(i+) and T1mic to T1c breast cancers. A total of 227 patients were included, 149 (57%) with anti-HER2 treatment and 78 (30%) without. Patients had a single site of HER2-overexpressing invasive breast neoplasia with a follow-up of at least 6 months. Primary outcome was overall survival. Secondary outcomes were disease-free survival and the impact of tumoral and demographic factors. Median follow-up period was 6.7 years. Overall survival at 5 years was 97% (CI 94, 100) for the group with anti-HER2 treatment versus 92% (CI 85, 98) for the group without anti-HER2 treatment. The difference in overall survival between the two treatment groups increased with tumor size. Disease-free survival at 5 years was 93% (CI 88, 87) for the group with anti-HER2 treatment versus 82% (CI 74, 92) for the group without anti-HER2 treatment. In subgroup analysis, age and tumor size had a significant impact on the difference in disease-free survival between groups. Our study demonstrates the significant impact of anti-HER2 targeted therapies on overall survival and disease-free survival for patients with small, HER2 positive localized breast cancers. Further benefit is seen in certain subgroups, such as older patients and those with tumors larger than 1.0 cm, and this should be considered when determining appropriate treatment. Citation Format: Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub. Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience [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 PO4-01-01.