Stage IIIA Research Articles

Incidence and prevalence of light chain amyloidosis in the United States in 2019–2021 using Optum EHR data

Immunoglobulin light chain amyloidosis (AL amyloidosis) is among the most common forms of systemic amyloidosis. Using electronic health records (EHR) data from the United States, we aimed to estimate the incidence and prevalence of AL amyloidosis over time, to evaluate the distribution of different disease stages, and to assess patients’ demographic characteristics. We conducted a retrospective cohort study using Optum EHR data from 2016 to 2022. AL amyloidosis was defined by ≥ 2 ICD-10-CM codes or positive mentions in the EHR that were ≥ 30 days apart. Incident and prevalent patients were included. Staging was assessed using cardiac biomarkers (whenever available) according to the European modification of the 2004 Mayo staging system. A total of 1976 AL amyloidosis patients were identified. In 2021, the estimated AL amyloidosis incidence was 16.7 per million person-years in adults, and the prevalence was 69.0 per million adult population. Among patients with staging available near the time of diagnosis (41.7% of incident patients), the following distribution was observed: 16.1% Stage I, 44.5% Stage II, 20.6% Stage IIIa, and 18.8% Stage IIIb. At the most recently available staging assessment, combined Stage IIIa and IIIb was more common among males (38.6% vs. 27.1%) and was more common with increasing age (25.7% for 40–49 years vs. 38.5% for 80+ years). We observed the highest prevalence of AL amyloidosis published to date. This may be due to true increased prevalence, consistent with reports of improved survival in AL amyloidosis.

Long-term outcomes of S-1 monotherapy in stage IIIA gastric cancer with small tumors and low nodal involvement

BackgroundIn Japan, adjuvant chemotherapy with docetaxel/S-1 is recommended for stage III gastric cancer. However, this regimen may not be suitable for all patients due to toxicity and tolerability issues, particularly in older individuals or those with comorbidities. This study aimed to explore prognostic factors in stage IIIA gastric cancer and assess long-term outcomes in patients treated with S-1 monotherapy after curative gastrectomy.MethodsWe retrospectively analyzed 73 patients with stage IIIA gastric cancer (UICC 7th edition) who underwent curative gastrectomy and received postoperative adjuvant S-1 monotherapy between 2005 and 2018.Various prognostic factors, including preoperative (age, sex, BMI, tumor markers), perioperative (surgical approach, operative duration, blood loss, complications), and tumor-related variables (tumor size, lymph node status, histological features), were analyzed. Recurrence-free survival (RFS) was the primary endpoint, and cut-off values were determined using ROC analysis. Cox proportional hazards models were used for univariate and multivariate analyses.ResultsThe 3- and 5-year RFS rates were 71.7% and 64.3%, respectively. Multivariate analysis identified smaller tumor size (≤ 55.0 mm, P = 0.006) and lower lymph node positivity rate (≤ 0.079, P = 0.008) as independent favorable prognostic factors.ConclusionS-1 monotherapy may be associated with favorable long-term outcomes in selected patients with stage IIIA gastric cancer who have small tumors and low lymph node positivity rates. While these results are encouraging, they should not be interpreted as a rationale for broadly recommending S-1 monotherapy. Further studies are needed to define its role in individualized treatment strategies.

Rationality of FIGO 2018 IIIC cervical cancer according to local tumor and pelvic lymph node metastatic extent–a cohort study

PurposeThere is still controversy for FIGO 2018 stage IIIC. In order to better manage patients with stage IIIC. This study explored the prognostic performance of Stage IIIC patients according to the 2018 FIGO staging system.MethodsCervical cancer patients who underwent radical surgery or chemo-radiotherapy at our institute between June 2011 and June 2021 were retrospectively enrolled. Patients before year 2018 were re-staged according to the 2018 FIGO staging principle. Survival outcome was analyzed by Kaplan-Meier curves and compared using Log-rank method. The best cut-off values for the number of positive lymph nodes and the positive lymph node ratio (LNR) were obtained using X-tile software V3.6.1. The Cox proportional hazard regression model was used for multi-variable analysis.ResultsA total of 2553 cervical cancer patients were enrolled initially. Finally, 443 patients classified as 2018 FIGO stage III were included in the survival analysis.The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of patients with stage IIIC2 were significantly poor than stage IIIA, IIIB and IIIC1, while IIIC1 patients had similar prognosis to IIIA/IIIB. For stage IIIC1 patients (n = 233), multivariate analysis showed that tumor size > 4 cm (DFS: HR 2.472, P < 0.001; OS: HR 2.368, P = 0.002) and poorly-differentiated histology (DFS: HR 2.158, P = 0.002; OS: HR 2.410, P = 0.002) were independent prognostic factors for reduced DFS and OS. In a subgroup analysis of IIIC1p women, tumor size > 4 cm (DFS: HR 2.658, P = 0.023; OS: HR 2.785, P = 0.039) and the number of positive pelvic lymph nodes(pLN) > 3 (DFS: HR 4.829, P < 0.001; OS: HR 5.614, P < 0.001) were found to be independent risk factors for reduced DFS and OS. Combining the local tumor size (TS) and pLN, patients with TS ≤ 4 cm + pLN ≤ 3 revealed significantly better 5-year DFS (89.2%) and 5-year OS (94.9%) than those with TS ≤ 4 cm + pLN > 3 and TS > 4 cm (P < 0.001). Moreover, stage IIIC1p patients with TS ≤ 4 cm + pLN ≤ 3 showed better DFS (P = 0.002) and OS (P = 0.001) than women with stage IIIA and IIIB.ConclusionThe survival outcomes for stage IIIC1 had similar prognosis for stage IIIA or IIIB in the current study. Patients with stage IIIC1p showed variable prognoses dependent on local tumor size and the extent of pelvic lymph node metastases. Therefore, the existing staging criteria might be further improved to provide better guidance for individualized treatment.

Adjuvant Radiotherapy in Incidental Positive Nodal Disease in Rectal Cancer-A Systemic Review.

The optimal adjuvant treatment strategy for incidentally detected node-positive rectal cancer following curative surgery remains uncertain. While preoperative chemoradiotherapy (CRT) is the standard for locally advanced rectal cancer, the role of adjuvant radiotherapy (RT) in early stage node-positive disease (stage IIIA) remains debated. This systematic review evaluates survival outcomes associated with different adjuvant modalities and identifies key prognostic factors influencing disease progression. A systematic search of PubMed, EMBASE, MEDLINE and the Cochrane Library was conducted up to August 2024, following PRISMA guidelines. Retrospective studies assessing oncological outcomes in patients with incidental nodal disease rectal cancer who underwent curative surgery without prior neoadjuvant therapy were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to heterogeneity of studies, a meta-analysis was not performed. This review is registered with PROSPERO (CRD42024596805). No funding was received. Nine studies comprising 5989 patients were analysed. Adjuvant therapy was associated with improved outcomes compared to observation alone. Overall survival (OS) ranged from 61.3% to 92% for adjuvant chemotherapy (CT), 63% to 93% for CRT, and 42% to 82.1% for no adjuvant therapy. Disease-free survival (DFS) ranged from 43% to 90%. Local recurrence (LR) was lowest with CRT (2%-9.1%), while metastatic disease (MD) ranged from 20% to 50%. Poorer outcomes were linked to pN2 disease, positive margins, perineural invasion, high lymph node ratio and low tumour location. Adjuvant CT improves survival in incidental node-positive rectal cancer; RT may benefit high-risk subgroups. Further prospective studies are warranted.

Surgery in the treatment of small cell lung cancer

Background. Small cell lung cancer (SCLC) is one of the most aggressive forms of lung tumors. Currently, there are ongoing discussions about the role of surgery in the treatment of patients with SCLC.The purpose of the study: does surgery improve prognosis in patients with small-cell lung cancer (SCLC)?Methods. The material for the study was 7549 patients with lung cancer diagnosed in Ugra from 2002 to 2022. 71 SCLC with stage I to III undergoing surgical resection were enrolled. Lobectomy was performed in 49 patients, pneumonectomy in 22. Systematic nodal dissection (SND) was performed in 59 patients (83.1 %).Results. In stage I, the ten-year overall survival rate was 65.8 %, in stage II – 33.2 %, in stage III – 14.4 % (p=0,001). Remote results of surgical treatment of SCLC had a significant dependence on the state of regional lymph nodes: with N 0, the 10-year OS was 53.1 %, with N 1 the 10-year OS was 30.6 %, with N 2–15.1 % (p=0,003). Ten-year OS with SND was significantly exceeded other dissections on the lymphatic collector to 42.0 %, while with sampling nodal dissection the 10-year OS was only 20.0 % (p=0,028).Conclusion. Good remote results in patients with stage I and II SCLC indicate the need to include surgery in the complex treatment of patients with SCLC. The optimal volume of surgery is lobectomy with systematic nodal dissection. Surgery can be performed in patients with stage IIIA and IIIB SCLC in case of tumor regression after induction chemoor chemoradiotherapy, as well as in case of life-threatening complications. Prospective studies are required to determine the indications for surgery in this cohort of patients.

Developmental and quantitative expression profile of the six pollen allergens of mugwort (Artemisia vulgaris L.)

BackgroundArtemisia vulgaris L. (Asteraceae family), a wind-pollinated perennial weed, is a significant source of allergenic pollen, responsible for respiratory allergies in late summer. Six allergenic proteins—Art v 1, Art v 2, Art v 3, Art v 4, Art v 5, and Art v 6—have been identified in A. vulgaris pollen. However, knowledge regarding significant scientific questions, such as where, when, and in what quantities these proteins are expressed, remains limited.ResultsThis study fills these gaps by determining the expression profiles of all six genes encoding allergenic proteins in mugwort pollen. The real-time PCR method was used to analyze the level of allergen expression at three stages of pollen development: microsporocytes before meiosis (stage I), tetrads after meiosis (stage II), and enclosed mature pollen (stage IIIa), as well as isolated mature pollen grains (stage IIIb). The results showed that the expression levels of the most immunogenic allergens, Art v 1 and Art v 3, are extremely high at stage IIIa but very low at stage IIIb, suggesting their production occurs in mature inflorescence tissues. The expression levels of these two major allergens are significantly higher than those of other minor allergens in Artemisia pollen. Art v 2 is expressed in both pollen grains and anther tissues, whereas Art v 5 and Art v 6 are transcribed only in mature pollen, with no noticeable expression in earlier stages of pollen development. Art v 4 expression begins at the tetrad stage and reaches its highest levels in mature pollen grains, where it surpasses the expression level of all other allergens.ConclusionsOur study provides new insights into allergen expression in A. vulgaris pollen, highlighting significant quantitative and developmental differences. These findings may help explain why some proteins are more likely to cause pollen allergies than others.

Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.

Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.

Incidence of regional lymph node metastases in patients with early prognostically unfavorable molecular biological breast cancer

To study the incidence and risk factors of regional lymph node metastases in patients with early primary operable prognostically unfavorable breast cancer. The study included 200 patients with early (stage I and IIA) prognostically unfavorable molecular biological type of breast cancer between 2015 and 2019. Patients were divided equally into two groups: group 1 - oncoplastic breast resection or mastectomy with regional lymph node dissection at the first stage; group 2 - sentinel lymph node biopsy with urgent cytological examination was performed instead of regional lymph node dissection, and lymph node dissection was performed only in case of verified metastasis. There were regional lymph node metastases in 15 (7.5%) patients. Of these, 10 (66.7%) ones had luminal B, Her2/neu-positive type of breast cancer, 3 (20%) and 2 (13.3%) patients - triple negative and Her2/neu-positive breast cancer, respectively. Metastatic regional lymph node lesion was common in luminal B, Her2/neu-positive type (14.7%), in Her2/neu-positive type - 3.6%, in triple negative type - 3.8%. Analysis of relationship between the incidence of regional lymph node lesion on primary tumor dimension, malignancy grade, BRCA1, BRCA2 and CHEK2 gene mutations, as well as lymphovascular invasion in tumor found no significant differences. Luminal B, Her2/neu-positive breast cancer has the highest aggressiveness regarding regional metastasis (14.7%) among prognostically unfavorable types of breast cancer in stage I-IIA patients.

Measure of Stage Migration Due to Significant Nodes Detected on Imaging in Patients with Uterocervical Cancer Using the FIGO 2018 Staging System

Abstract While the earlier International Federation of Gynecology and Obstetrics (FIGO) staging guidelines for carcinoma cervix were only based on clinical examination findings, the revised guidelines published in 2018 incorporated imaging and pathological assessments to the staging system.This article compares the imaging-based new FIGO staging system with the old clinical staging and assesses the degree of stage migration.In this institutional review board-approved retrospective study, consecutive patients who were diagnosed with uterocervical cancer and underwent imaging (i.e., computed tomography [CT]/magnetic resonance imaging [MRI]/positron emission tomography-CT [PET-CT]/ultrasound [USG]) between 2013 and 2017 were reviewed. Imaging findings were documented, and stage was assigned as per the revised 2018 FIGO staging system for cervical cancer and compared with the previous FIGO staging system. The degree of stage migration was compared between the new and the old FIGO staging systems. The degree of stage migration due to significant lymph nodes detected on different imaging modalities was assessed.274 patients with a mean age of 51 years and a range of 20 to 80 years were reviewed. The distribution as per the FIGO 2009 were: 0.3% (n = 1) in stage IA1 and IA2, 6.2% (n = 17) in stage IB1, 1% (n = 3) in stage IB2, 4% (n = 11) in stage IIA, 44.5% (n = 122) in stage IIB, 0.7% (n = 2) in stage IIIA, 27% (n = 74) in stage IIIB, 5.8% (n = 16) in stage IVA, and 7.2% (n = 20) in stage IVB. Among all these patients, 66.4% (n = 182) patients underwent USG, 53.6% (n = 147) underwent CT, 42.7% (n = 117) had MRI, and 3.6% (n = 10) underwent PET-CT. Only 4% (n = 8) and 0.5% (n = 1) patients who underwent USG at staging were detected to have significant parailiac and para-aortic nodes, respectively. On the other hand, 7.66% (n = 21) had significant para-aortic and 44.16% (n = 121) had significant parailiac nodes on other cross-sectional imaging modalities. There was stage migration in 36.86% of patients, with 23.72% upstaged to stage IIIC1.Fewer lymph nodes were detected on USG than other cross-sectional imaging modalities. Adopting the new FIGO resulted in stage migration in 36.86% of patients, predominantly due to lymph node metastases detected on imaging.

Multidisciplinary tumor boards and surgical intervention improve overall survival in patients with stage iii non-small cell lung cancer: a retrospective cohort study.

Given the poor outcomes and treatment complexities in Stage III NSCLC-especially in challenging subgroups-we aimed to assess whether a multidisciplinary tumour board (MTB) approach combined with surgical intervention could improve overall survival (OS). We retrospectively reviewed 242 patients with Stage III NSCLC treated from January 2018 to September 2023. Patients were managed either via MTB discussions or standard care and were further categorized based on whether they underwent surgical resection. Patients whose cases were discussed in an MTB demonstrated significantly improved overall 1-, 3-, and 5-year survival across the entire Stage III cohort, with particularly pronounced benefits in the stage IIIC subgroup. In addition, surgical intervention was associated with significantly higher overall survival at 1, 3, and 5 years for all Stage III patients, and these benefits were especially evident among those with stage IIIA disease. Our findings suggest that both MTB discussions and surgical resection are associated with higher observed overall survival in Stage III NSCLC. These results support the potential clinical value of integrating multidisciplinary treatment strategies to optimize outcomes in this challenging patient population.

Predictive Factors Aiding in the Estimation of Intraoperative Resources in Gastric Cancer Oncologic Surgery.

Background/Objectives: Operating rooms represent valuable and pivotal units of any hospital. Therefore, their management affects healthcare service delivery through rescheduling, staff shortage/overtime, cost inefficiency, and patient dissatisfaction, among others. To optimize scheduling, we aim to assess preoperative evaluation criteria that influence the prediction of surgery duration for gastric cancer (GC) patients. In GC, radical surgery with curative intent is the ideal treatment. Nevertheless, the intervention sometimes must be palliative if the patient's status and tumor staging prove too advanced. Methods: A 6-year retrospective cohort study was performed in a tertiary care hospital, including all cases diagnosed with GC (ICD-10 code C16), confirmed through histopathology, and undergoing surgical treatment (N = 108). Results: The results of our study confirm male predominance (63.89%) among GC surgery candidates while bringing new perspectives on patient evaluation criteria and choice of surgical intervention (curative-Group 1, palliative-Group 2). Surgery duration, including anesthesiology (175.19 [95% CI (157.60-192.77)] min), shows a direct correlation with the number of lymph nodes dissected (Surgical duration [min] = 10.67 × No. of lymph nodes removed - 32.25). Interestingly, the aggressiveness of the tumor based on histological grade (highly differentiated being generally less aggressive than poorly differentiated) shows differential correlation with surgery duration among curative and palliative surgery candidates. Similarly, TNM staging indicates the need for a longer surgical duration (pTNM stage IIA, IIB, and IIIA) for curative interventions in patients with less advanced stages, as opposed to shorter surgery duration for palliative interventions (pTNM stage IIIC and IV). Conclusions: The study quantitatively presents the resources needed for the optimal surgical treatment of different groups of GC patients, as the disease coding systems in use regard the treatment of each pathology as "standard" in terms of patient management. The results obtained are anchored in the global perspectives of surgical outcomes and aim to improve the management of operating room scheduling, staff, and resources.

Robotic Bilobectomy for Stage IIIA NSCLC With Bulky Nodal Disease After Neoadjuvant Chemoimmunotherapy.

Robotic Bilobectomy for Stage IIIA NSCLC With Bulky Nodal Disease After Neoadjuvant Chemoimmunotherapy.

Methylation aberrations and genomic instability synergistically drive the evolution of intrahepatic cholangiocarcinoma.

DNA methylation and genomic instability are critical drivers of cancer initiation and malignant progression. However, the roles of methylation aberrations and genomic instability in malignant progression have not been thoroughly investigated in intrahepatic cholangiocarcinoma (ICC). To address this, we identified differentially methylated regions (DMRs) and somatic copy number alterations (SCNAs) from 341 ICC samples across various stages. Our findings revealed that stages IAIB, II, IIIA, and IIIB exhibited comparable methylation changes, whereas stage IV ICC showed a pronounced accumulation of stage-specific methylation alterations. Leveraging these findings, we developed a classification model that effectively distinguished stage IV ICC from earlier stages with high accuracy using 15 DMRs. Furthermore, stage IV ICC exhibited slightly higher genomic instability, including an elevated aneuploidy score and a greater proportion of focal amplifications. We also observed a positive correlation between SCNA burden and DNA methylation entropy in the promoter, gene body, and CpG island regions, with the gene body of MDM2 serving as a notable example. These findings highlight the potential of DNA methylation as a biomarker for metastasis diagnosis and the interplay between local genomic instability and aberrant methylation, emphasizing their synergistic roles in driving the evolutionary trajectory of ICC.

Comparative analysis of clinical, morphological and prognostic parameters of non-metastatic skin melanoma

Modern understanding of melanoma carcinogenesis and progression highlights the importance of identifying risk factors and prognosis at early stages.Purpose of the study. Analysis of clinical characteristics in patients with skin melanoma.Patients and methods. A retrospective analysis of the medical records of 142 patients with skin melanoma has been carried out. Data on age, gender, tumor localization, disease stage according to the American Joint Committee on Cancer (8th ed., 2017), histological types according to the WHO classification (2022), as well as treatment methods and disease outcomes have been analyzed.Results. Among the studied patients with skin melanoma, women predominated – 78 cases (54.9 %), men – 64 cases (45.1 %). The average age of patients was 63 ± 5.6 years, ranging from 29 to 88 years. Melanoma was most frequently diagnosed at advanced stages: stages IIIA–IIID were detected in 53 patients (37.3 %), stages IIA–IIC – in 40 (28.2 %), and stages 0 and IA–IB – in 16 (11.3 %) and 33 (23.2 %) patients, respectively. The predominant histological types were nodular melanoma (48.6 %) and superficially spreading melanoma (38.7 %). The most common tumor localizations were the skin of the lower extremities (32.3 %) and the back (30.9 %). In 23 patients (16.2 %) with disease progression, metastases were detected in the brain, lymph nodes, liver, lungs, and bones.Conclusions. The carried-out analysis can help clarify the clinical and morphological features of skin melanoma and improve diagnostic and therapeutic approaches.

A successful control of cardiac amyloidosis by idecabtagene vicleucel in a patient with relapsed and refractory multiple myeloma: a case report and literature review.

A 50-year-old Japanese man with penta-drug refractory multiple myeloma (MM) was found to have stage IIIa cardiac immunoglobulin light-chain amyloidosis before idecabtagene vicleucel (ide-cel) therapy. Ide-cel therapy was started after careful consideration and hospital ethics committee approval. Grade 3 cytokine release syndrome and atrial flutter occurred in the acute phase after ide-cel infusion, but these were well-tolerated with supportive care in the intensive care unit. The patient achieved stringent complete response at day 60 and cardiac response at 9months after ide-cel infusion with the addition of catheter ablation for sustained atrial flutter on day 133. He has maintained both hematological and cardiac remission for over 1year since ide-cel therapy. This case highlights the effectiveness of ide-cel for disease control in heavily pretreated MM with cardiac amyloidosis.

Abstract P1-12-11: Individualized Breast Cancer Treatment Strategies: Real-World Insights from the ROSE Study

Abstract The ROSE study (NCT05377684) is an ongoing observational trial evaluating the Quality of Life (QoL) as the primary endpoint in premenopausal patients with Hormone Receptor (HR)+, HER2-negative early Breast Cancer (BC). The trial focuses on patients treated with a Luteinizing Hormone–Releasing Hormone (LHRH) analogue (triptorelin) combined with oral endocrine therapy, with or without chemotherapy depending on the risk of relapse, as determined by multidisciplinary meetings. Since April 2022 and up to October 2023 (18 months), the trial reached 50% enrollment of its target population. At this milestone, a predetermined interim analysis focused on the evaluation of baseline demographic characteristics, tumor features, and BC treatments. Other secondary objectives (e.g. hormonal levels) were not evaluated at this timepoint. Out of the approximately 200 patients initially enrolled, 195 were deemed eligible for the study. All patients had estrogen receptor-positive early BC and, at baseline, were planned to receive adjuvant endocrine therapy with tamoxifen or aromatase inhibitors combined with triptorelin as ovarian function suppression therapy. The median age at BC diagnosis was 45.5 years, ranging from 30 to 56. Tumor characteristics showed that 97.4% of enrolled patients (n=189) had invasive carcinoma, while 2.6% (n=5) had carcinoma in situ. The grading distribution included 10.8% grade 1 lesions, 69.9% grade 2, and 19.4% grade 3. Staging data according to AJCC 2017 criteria were available for 187/195 patients and revealed the following distribution: 44.9% had stage IA BC (stage IB: 5.3%), 27.7% had stage IIA (stage IIB: 16%), and 5.7% had stage IIIA. The Ki-67 proliferation index was available for 193 patients, with a median value of 17% and a mean value of 22.3%. Regarding therapeutic plans, the monthly triptorelin formulation was prescribed to 92.3% of patients (n=180), while the trimestral was prescribed to 7.7% of patients (n=15). The choice between tamoxifen or aromatase inhibitors depended on the relative risk of recurrence based on the aforementioned prognostic factors, with patients receiving the latter in higher-risk cases. Among the 195 patients, 27.2% (n=53) received adjuvant or neoadjuvant chemotherapy, classifying them as high risk for recurrence. Of these patients, nearly all received aromatase inhibitors and triptorelin (n=48). The remaining 72.8% of patients (n=142) were not considered high-risk enough to warrant chemotherapy, placing them in the intermediate-risk category. These patients were planned to receive triptorelin and either tamoxifen (n=28) or aromatase inhibitors (n=114) in chemotherapy-free treatment plans. The majority of intermediate-risk patients received aromatase inhibitors, indicating a higher risk profile, closer to the high-risk category. The ROSE study highlights an Italian best practice approach that tailors therapeutic plans to the individual needs of each patient, allowing for treatments based on personalized risk assessments. This approach aligns with current national oncology guidelines by minimizing chemotherapy use when possible and instead adopting individualized treatment plans based on specific prognostic factors. However, the observational nature of the ROSE trial provides a realistic snapshot of clinical practices, which may differ from the highly-selected populations typical of randomized controlled trials. This observational study of Italian best practices suggests the potential to redefine relapse risk cutoffs based on prognostic factors, providing more accurate and realistic patient-specific therapeutic approaches based on individual risk. The findings of this study, combined with results from ongoing post hoc analyses which aim to identify these new cutoffs, could potentially support the redefinition of relapse risk to better align with clinical practice, thereby fostering patient-specific therapeutic approaches. Citation Format: Alessandra Fabi, Luisa Carbognin, Alessandro Rossi, Ferdinando Riccardi, Carmen Mocerino, Raffaella Ruocco, Giulia Valeria Bianchi, Giuseppe Fotia, Giuseppe Capri, Antonella Palazzo, Elena Di Monte, Valentina Frescura, Michelino De Laurentis, Vincenzo Di Lauro, Valérie Perrot, Giorgio Mauri, Manuelita Mazza, Nadia Bianco, Elisabetta Munzone. Individualized Breast Cancer Treatment Strategies: Real-World Insights from the ROSE Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-12-11.

Abstract PS3-07: SHR-A1811 as Neoadjuvant Treatment in Patients with HR-Positive, HER2-low Breast Cancer: The first-stage results from an open-label, single-arm, two-stage, phase II clinical trial

Abstract Background: Patients with Hormone receptor (HR)-positive, human epidermal growth factor receptor 2(HER2)-negative breast cancer exhibit lower rates of achieving pathologic complete response (pCR) to neoadjuvant chemotherapy or endocrine therapy, with pCR rates of 10% and 5% respectively. HER2-low breast cancers are enriched in HR-positive breast cancers, but HER2-low patients had significantly lower pCR than those with HER2-0. The anti-HER2 ADC drug T-Dxd has demonstrated anti-tumor activity in HR+/HER2-low advanced breast cancer, based on the DESTINY-Breast 06 study. SHR-A1811, a novel anti-HER2 ADC, has also shown activity in HER2-low advanced breast cancer. Here we conducted this clinical trial to investigate the efficacy and safety of SHR-A1811 as a neoadjuvant treatment in patients with HR+/HER2-low breast cancer. Methods: This was an open-label, single-arm, phase II clinical trial based on Simon's two-stage design. A total of 66 subjects were required for enrollment, with 35 subjects included in the first stage. If 18 or more patients having response, the trial would proceed to the second stage, enrolling an additional 31 subjects. Main inclusion criteria include: aged 18-70 years, treatment-naïve, histologically confirmed invasive breast cancer, cT2-3/N0-2M0, HR+/HER2-low and Ki67&amp;gt;14%. Eligible patients received SHR-A1811 (6.4 mg/kg IV q21 days) for eight cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, residual cancer burden (RCB) 0-1 and pCR. Results: As of June 17, 2024, 34 out of 35 patients in the first stage successfully received the study regimen and finished the operation on schedule. Of all patients, 74.3% (26/35) had node-positive disease, 85.7% (30/35) with stage IIA/IIB, 14.3% (5/35) with stage IIIA at baseline. 74.3% (26/35) patients had baseline HER2 expression of IHC 2+, 25.7% (9/35) were IHC 1+. Our primary endpoint of the first stage was met, with 74.3% (26/35) of patients achieving an ORR, including 26 partial responses and 9 stable diseases. None of the patients achieved pCR. Treatment-related adverse events (TRAEs) were reported in all 35 patients, and the incidence of grade ≥3 TRAEs was 65.7% (23/35), the most common grade ≥3 TRAEs including neutropenia (48.6%,17/35), leukopenia (28.6%,10/35), anemia (22.9%, 8/35), diarrhea and platelet count decreased (11.4%, 4/35). Primary G-CSF prophylaxis was administered to 13 patients, and no grade 3 or higher neutropenia was reported. No interstitial lung disease (ILD) and treatment-related deaths were reported. Conclusions: SHR-A1811 has demonstrated promising anti-tumor activity and an acceptable safety profile as neoadjuvant treatment for patients with HR+/HER2-low breast cancer. The second stage is ongoing, Clinical trial information: NCT05911958. Citation Format: Zhenzhen Liu, Jianghua Qiao, Chengzheng Wang, Xianfu Sun, Min Yan, Lianfang Li, Xiuchun Chen, Jiujun Zhu, Jianfei Wang. SHR-A1811 as Neoadjuvant Treatment in Patients with HR-Positive, HER2-low Breast Cancer: The first-stage results from an open-label, single-arm, two-stage, phase II clinical trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-07.

Abstract P3-06-10: Triple Negative Breast Cancer: The standpoint of Mexican population

Abstract Introduction: Breast cancer is the malignant neoplasm with the highest incidence and mortality rate among Mexican women, accounting for 28% of cancer cases and 16 deaths per 100,000 women over 20 years of age. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that does not express estrogen and progesterone receptors, nor human epidermal growth factor receptor 2 (HER-2). Conventionally it presents with a poor prognosis compared to other subtypes and usually relapses within the first 3 years after diagnosis. Objective: The aim of this study was to describe sociodemographic, epidemiologic, clinical, histopathological and prognostic characteristics of TNBC in a northeast Mexican-based cohort. Methods: Original, retrospective, descriptive and analytical data were analyzed.The study was approved by the Research and Bioethics Committee, 18-year-old patients and older with TNBC diagnosis were included, treated at our University Hospital “Dr. José Eleuterio González” between 2014-2019. Sociodemographic, epidemiologic, histologic, biochemic, diagnosis, treatment and prognosis data were obtained from clinical records. Results: One-hundred thirty-five patients were enrolled. The mean age at diagnosis was 48 ±12.9 years and the most common histological type was invasive ductal adenocarcinoma in 80.7% of cases. Regarding clinical stage, 24.4% were classified as stage IIA, followed by stage IIIA in 21.5% of the patients. Stage IV accounted for 11.9% of the patients. Thirty-four percent of the tumors had a Ki67 index of more than 20% and 11.4% presented BRCA mutations, with BRCA1 being the most prevalent. Platinum based chemotherapy was prescribed in 20.8% of patients. Surgical treatment was performed in 92.4% of patients and 84.9% received radiotherapy. Sixty-two patients reached clinical surveillance and 13 had disease recurrence. Discussion: TNBC represents 23.1 % of breast tumors in México in comparison to USA reports with approximately 15% cases. In our study we observed that the age of diagnosis with a predominance above 40 years was greater than reported in developed countries where TNBC is more commonly diagnosed in premenopausal women; this is probably associated with poor health access and lack of public health education in secondary prevention of breast cancer. Twenty-nine (21.48%) patients had a history of menarche under 12 years. Age of diagnosis, histologic subtype and risk factors tendencies correlate to literature worldwide reports. BRCA mutations in México are estimated at approximately 23% of cases and the incidence of TNBC has been reported substantially in patients with BRCA1 mutations. Reproductive risk factors including early menarche and non-parity regardless of its general relation with breast cancer independently of histologic subtype were frequent among our patients. Unhealthy lifestyles such as sedentarism, overweight, high carbohydrate intake, alcohol consumption and tobacco have been strongly related to breast cancer development and were the predicted lifestyles of our cohort patients. Outlining the epidemiologic and sociodemographic characteristics of patients with TNBC in our population and its influence in the prognosis highlights the importance of reinforcing screening policies and implementing programs that promote healthy lifestyles. Conclusion: The incidence of TNBC in Mexico exceeds the statistics reported in the United States by approximately 8%, with an 8-year greater mean age of diagnosis in comparison to American women. This is due to poor access to healthcare services and the lack of education regarding breast cancer screening, leading to a diagnosis at later stages and, consequently, to a worse prognosis and fatal outcomes. The BRCA prevalence mutations reported in our study was almost 12% lower than reported worldwide, probably due to lack of resources to obtain genetic testing and poor medical follow-up. Citation Format: A. Michelle Barboza-Portillo, Marianela Madrazo-Morales, Alder E. Perales-Mendoza, Ricardo Cerda-Flores, Diana C. Pérez-Ibave, Fernando J. Peña-González, Miranda N. Cardona-Serrato, Marlene A. Luna-Rubio, David Hernández-Barajas, Oscar Vidal-Gutiérrez. Triple Negative Breast Cancer: The standpoint of Mexican population [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-06-10.

Abstract P3-08-11: Clinico-Pathological Features of Breast Cancer Patients Who Recured After Achieving pCR with Neoadjuvant Chemotherapy before Surgery (KBCSG-18)

Abstract Background: Patients who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) before surgery have been reported to have higher long-term survival rates. However, despite a better prognosis, pCR patients have a potential for local and/or distant recurrence. Herein, we report clinico-pathological features of breast cancer patients who recurred after achieving pCR with NAC. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who experienced recurrence after achieving pCR following NAC between January 1999 and April 2022 from 13 cancer hospitals in the Korean Breast Cancer Society Group (KBCSG). The patients were identified in a database that had been managed in each hospital. pCR was defined as no residual invasive cancer in the breast and axillary nodes (ypT0 or ypTis with ypN0). Breast cancers were classified into three subtypes based on hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status. The primary purpose of the study was to identify the clinicopathologic characteristics, recurrence patterns, and overall survival of patients who experienced recurrence after achieving pCR following NAC. This study was approved by an institutional review board in each hospital. Results: A total of 131 patients were identified to have achieved pCR and relapsed thereafter. The median age of the patients was 48 years (range 27-72), with a median follow-up duration of 25.6 months (range 0.5 - 136.7). The median recurrence-free survival (RFS) was 17.0 months (95% CI 13.5-20.5). The distribution of initial clinical TNM stages was as follows: stage IB in 1 (0.8%), stage IIA in 16 (12.2%), stage IIB in 27 (20.6%), stage IIIA in 29 (22.1%), stage IIIB in 11 (8.4%), and stage IIIC in 45 (34.4%) patients. This study included 70 (53.4%) HER2-positive, 50 (38.2%) triple-negative and 8 (6.1%) HR-positive breast cancer patients. Among these populations, 81 (61.8%) had systemic recurrence, 33 (25.2%) experienced local recurrence, and 17 (13.0%) had both local and distant recurrence. Upon reviewing the first presented recurrence patterns of 131 patients, they showed brain (n=45, 34.4%), lung (n=26, 19.8%), liver (n=14, 12.2%), bone (n=14, 10.7%), locoregional lymph node (n=16, 12.2%), ipsilateral breast (n=24, 18.3%), and contralateral breast (n=8, 6.1%) recurrence. After recurrence, median overall survival was 76.7 months (95% CI 41.2-112.2) in the HER2-positive, 45.8 months (95% CI 16.5-75.1) in TNBC, and 40.3 months (95% CI 2.7-77.8) in HR-positive subtypes. Conclusion: Given the limitation of retrospective study, such as selection bias, patients with pCR after NAC followed by relapse showed a high incidence of brain metastasis as the first relapse site and favorable overall survival compared to historical data. Citation Format: Jee Hung Kim, Joon Jeong, Kyung Hae Jung, Jai Min Ryu, Han-Byoel Lee, Hyun-Ah Kim, Jieun Lee, Airi Han, Hee Kyung Ahn, Tae In Yoon, Sung Yong Kim, Eun Young Kim, Ku Sang Kim, Joohyuk Sohn. Clinico-Pathological Features of Breast Cancer Patients Who Recured After Achieving pCR with Neoadjuvant Chemotherapy before Surgery (KBCSG-18) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-08-11.

Abstract P4-09-22: Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2− early breast cancer (EBC)

Abstract Background: In the NATALEE trial, RIB + NSAI has demonstrated invasive disease-free survival and DDFS benefits in patients with stage II and III HR+/HER2− EBC. In an analysis with all patients off RIB, RIB + NSAI reduced the risk of distant disease recurrence vs NSAI alone. Understanding the impact of adjuvant treatments on distant disease recurrences across patient subgroups is critical for clinical decision-making. We present DDFS data from the 4-y landmark analysis of NATALEE across clinically relevant subgroups. Methods: In NATALEE, patients were randomized 1:1 to receive either RIB (400 mg/d, 3 wk on/1 wk off for 3 y) + NSAI (anastrozole 1 mg/d or letrozole 2.5 mg/d for 5 y) or NSAI alone, with men and premenopausal women also receiving goserelin. NATALEE included patients with anatomic stage IIA (either node-negative [N0] with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per AJCC (8th edition). DDFS was a secondary endpoint and was defined as the time from randomization to the first event of distant recurrence, second primary non-breast invasive cancer (except for basal and squamous cell skin carcinomas), or death from any cause. DDFS was assessed across patient subgroups, including anatomic stage and nodal status, using Kaplan–Meier analysis and a Cox proportional hazards model. Results: At the data cutoff of April 29, 2024, with a median duration of follow-up for DDFS of 44.2 months and all patients off RIB, RIB + NSAI demonstrated both a DDFS benefit (HR, 0.715 [95% CI, 0.604-0.847]; nominal P value &amp;lt;.0001) and a distant recurrence-free survival benefit (HR, 0.705 [95% CI, 0.589-0.844]; nominal P value &amp;lt;.0001) in the intent-to-treat population. The DDFS benefit was consistent regardless of anatomic stage (stage IIA [n=1001]: HR, 0.396 [95% CI, 0.218-0.720]; stage IIB [n=1045]: HR, 0.806 [95% CI, 0.524-1.238]; stage IIIA [n=1832]: HR, 0.697 [95% CI, 0.524-0.926]; stage IIIB [n=317]: HR, 0.569 [95% CI, 0.326-0.994]; stage IIIC [n=890]: HR, 0.878 [95% CI, 0.649-1.188]). The absolute DDFS benefit with RIB + NSAI vs NSAI alone increased from 3 y to 4 y for all stage subgroups (stage IIA, 2.3% to 5.1%; IIB, 0.8% to 2.6%; IIIA, 3.1% to 4.6%; IIIB, 6.8% to 11.4%; IIIC, 2.4% to 4.5%). Similarly, a consistent improvement in DDFS was observed regardless of nodal status (N0 [n=613]: HR, 0.696 [95% CI, 0.403-1.204]; node-positive [N+] [n=4480]: HR, 0.726 [95% CI, 0.608-0.867]), and the absolute DDFS benefit increased from 3 y to 4 y across nodal subgroups (N0, 2.7% to 4.2%; N+, 2.4% to 4.6%). The DDFS benefit with RIB + NSAI vs NSAI alone, with increasing benefit up to 4 y, was consistent across other clinically relevant subgroups, including those based on menopausal status and Ki-67 status. Conclusions: With all patients off RIB, RIB + NSAI consistently reduced the risk of distant recurrence across clinically relevant subgroups, including in patients with N0 disease. The DDFS benefit was sustained after the 3-y RIB treatment duration, with increasing absolute benefit up to 4 y. These findings further support adding RIB to adjuvant NSAI in a broad population of patients with HR+/HER2− EBC. Citation Format: Sara Hurvitz, Michal Jarzab, Montserrat Munoz Mateu, Erin Cobain, Jin Zhang, Arielle Medford, Alistair Ring, Priyanka Sharma, Christian Schem, Ionut Temciuc, Zheng Li, Murat Akdere, Juan Pablo Zarate, Denise A. Yardley. Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2− early breast cancer (EBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-09-22.