High-risk Breast Cancer Patients Research Articles

Retrospective evaluation of adjuvant capecitabine dosing patterns in triple negative breast cancer.

The CREATE-X trial demonstrated that adjuvant capecitabine was effective in prolonging survival in high-risk triple-negative breast cancer (TNBC) patients. However, the recommended dose is generally not well tolerated by the US population. The goal of this study is to analyze dosing patterns in an ethnically diverse cohort to better characterize tolerability and inform future dosing guidelines. In our single-center retrospective study, we evaluated safety and tolerability in TNBC patients undergoing adjuvant capecitabine treatment. The primary endpoint, relative dose intensity (RDI) across eight cycles, was examined alongside subgroup analyses based on age, race, BMI, and initial dose. Secondary endpoints include capecitabine-related side effects and survival. 67 patients who completed adjuvant capecitabine at University of Chicago Medicine (UCM) between January 2017 and November 2022 were eligible. The mean RDI across eight cycles of treatment was 60.2% (95% CI: 0.554-0.650). When compared to the CREATE-X trial, the RDI in our population was significantly lower (0.602 vs. 0.787, p < 0.001). There was no statistically significant difference in average RDI across eight cycles for patients stratified by age, BMI, race, or initial starting dose. The most frequently reported adverse events were hand-foot syndrome (73%), diarrhea (27%), and fatigue (22%), consistent with prior studies. Our data demonstrates that a significant portion of patients have a lower tolerated dose of capecitabine in comparison to the recommended adjuvant dose. Acknowledging the limitations of our single-center analysis, RDI was not significantly affected by age, race, BMI, or initial starting dose.

Delays in receipt of neoadjuvant chemotherapy compared to upfront surgery in patients with operable breast cancer.

100 Background: Delays in time from breast cancer (BC) diagnosis to BC treatment initiation (BCTI) including upfront breast surgery (UBS) or neoadjuvant chemotherapy (NACT), can negatively impact BC survival. We evaluated odds of delay in BCTI among patients (pts) who received NACT compared to pts who received UBS. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis of non-metastatic BC between 1/1/2010 – 12/31/2020, who were treated with NACT followed by surgery or UBS followed by adjuvant chemotherapy (AC). Pts who did not receive NACT or UBS within 180 days of diagnosis were excluded. The cohort was stratified by first BC treatment (NACT or UBS), and time to NACT (TTNACT) or time to surgery (TTS) was recorded for each patient in days. Pts were categorized into sub-cohorts by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) lymph node (LN)+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Logistic regression adjusted for demographic, socioeconomic, and tumor characteristics was used to identify delays in BCTI &gt; 60 days. Multiple imputation was used for missing data. Inverse probability treatment weighting (IPTW) was done as a sensitivity analysis. Results: We identified 218,049 eligible pts, 75% were White, 18% were Black, and 8.6% were Hispanic. Median age was 53 years (range 18-90). There were 145,697 (67%) pts who received NACT with median TTNACT of 32days (range 0-180), and 9.8% had a delay &gt; 60 days (Table). There were 72,353 (33.0%) pts who received UBS followed by AC, with a median TTS of 33 days (range 0-180), and 13% with a delay &gt; 60 days. In multivariable analysis, pts who received UBS had higher odds of BCTI delays compared to NACT, with OR 1.50 (95%CI 1.42-1.57) [HR+/HER2-], OR 1.49 (95%CI 1.41-1.58) [HER2+], and OR 1.26 (95%CI 1.18-1.34) [TNBC]. Results from IPTW analysis were similar, groups were well balanced, and pts who received UBS had higher odds of BCTI OR 1.50 (95%CI 1.44-1.57) [HR+/HER2-], OR 1.75 (95%CI 1.67-1.83) [HER2+], and OR 1.46 (95%CI 1.38-1.53) [TNBC]. Conclusions: Among high clinical risk BC patients who received surgery and chemotherapy, those who underwent NACT were less likely to experience delays in BCTI compared to pts who received UBS first. Among eligible pts, use of NACT may reduce delays in BCTI. Patients who received NACT and UBS and associated delays by sub-cohort (n = 218,050). Neoadjuvant Chemotherapy Upfront Surgery N (%) Median TTNACT in Days N (%) Delayed &gt;60 Days N (%) Median TTS in Days N (%) Delayed &gt;60 days Total Cohort 145,697 (67.0) 32 14,221 (9.8) 72,353 (33.0) 33 9,725 (13) HR+/HER2 40,345 (27.7) 34 4,773 (11.8) 29, 676 (41.0) 36 4,754 (16.0) HER+ 56,868 (39.0) 32 5,135 (9.0) 21,759 (30.1) 32 2,771 (12.7) TNBC 48,484 (33.3) 31 4,313 (8.9) 20,917 (28.9) 30 2,200 (10.5)

Development and comprehensive evaluation of a national DBCG consensus-based auto-segmentation model for lymph node levels in breast cancer radiotherapy

Background and purposeThis study aimed at training and validating a multi-institutional deep learning (DL) auto segmentation model for nodal clinical target volume (CTVn) in high-risk breast cancer (BC) patients with both training and validation dataset created with multi-institutional participation, with the overall aim of national clinical implementation in Denmark. Materials and methodsA gold standard (GS) dataset and a high-quality training dataset were created by 21 BC delineation experts from all radiotherapy centres in Denmark. The delineations were created according to ESTRO consensus delineation guidelines. Four models were trained: One per laterality and extension of CTVn internal mammary nodes. The DL models were tested quantitatively in their own test-set and in relation to interobserver variation (IOV) in the GS dataset with geometrical metrics, such as the Dice Similarity Coefficient (DSC). A blinded qualitative evaluation was conducted with a national board, presented to both DL and manual delineations. ResultsA median DSC > 0.7 was found for all, except the CTVn interpectoral node in one of the models. In the qualitative evaluation ‘no corrections needed’ were acquired for 297 (36 %) in the DL structures and 286 (34 %) for manual delineations. A higher rate of ‘major corrections’ and ‘easier to start from scratch’ was found in the manual delineations. The models performed within the IOV of an expert group, with two exceptions. ConclusionDL models were developed on a national consensus cohort and performed on par with the IOV between BC experts and had a comparable or higher clinical acceptance than expert manual delineations.

Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients

PurposeThe aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients. MethodsA total of 195 eligible early BC cases were tested for genomic risk between 2006 – 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics. ResultsMammaPrint identified 118 (60.5%) patients with genomically Low Risk tumors and 77 (39.5%) patients with genomically High Risk tumors. Age, menopausal status, tumor size, receptor status, and nodal status were comparable between MammaPrint Risk categories. The median follow-up was 8.4 years for DMFS and 9.3 years for OS; 8-year follow-up was reported for both endpoints. The 8-year DMFS was 90.4% (95% CI 84.9 – 95.9) in patients with MammaPrint Low Risk tumors compared to 60.8% (95% CI 49.8 – 71.8) for patients with High Risk tumors. Patients with MammaPrint Low Risk tumors exhibited significantly superior 8-year OS (97.3%; 95% CI 94.4 – 100) compared with MammaPrint High Risk tumors (89.5%; 95% CI 82.6 – 96.4; p = 0.028). Multivariate analyses identified MammaPrint as significantly associated with 8-year DMFS and MammaPrint together with Progesterone Receptor positivity with 8-year OS. ConclusionThe prognostic performance of MammaPrint was demonstrated in early-stage clinically intermediate to high-risk BC patients. Moreover, patients with MammaPrint Low Risk tumors had good outcome regardless of treatment regimen, thus supporting personalized treatment choices.

Risk-reducing surgeries for breast cancer in Brazilian patients undergoing multigene germline panel: impact of results on decision making.

To assess the behavior change of high-risk breast cancer patients regarding the intention to undergo risk-reducing mastectomies (RRM) before and after genetic testing results and to identify the main influencing factors in decision-making. Prospective cohort study conducted between November 2021 and October 2022 with women under follow-up at the high-risk outpatient clinic of the State University of Campinas (UNICAMP). Patients were referred for genetic testing, followed by counseling according to the test result. A total of 373 women were included. In the pre-genetic testing analysis, 54.1% of patients intended to undergo RRMs. After testing, 42.2% opted for the procedure. Behavior change occurred in 26.2%, mainly from "yes" to "no/don't know" (72,6%) (p < 0.001). The genetic test result was positive (LPV or PV) in 29.7% of patients. Among the 90 patients with positive results, 62 (68.9%) agreed to RRM, while 22 (24.4%) remained unwilling to accept RRM, regardless of the positive test. Significant influencing factors for behavior change pre- and post-genetic testing (in favor of surgery) in multivariate analysis were: positive genetic test result (OR 2.94, p < 0.001), personal cancer history (OR 2.7, p = 0.008), and ages between 40 and 49years (OR 2.07, p = 0.008) and ≥ 50years (OR 3.47, p < 0.001). In a Brazilian population at high-risk for breast cancer and users of the public health system, it was observed that most desired RRM, however, when genetic testing and counseling were performed, behavior change was observed, especially when the result was positive.

Mutation Spectrum Comparison between Benign Breast Lesion Cohort, Unselected Cancer Cohort and High-Risk Breast Cancer Cohort.

Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n = 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR, n = 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC, n = 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC, n = 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2, CDH1, PALB2, PTEN, and TP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort. ATM, BRIP1, RAD51C, and RAD51D mutations were identified in all cohorts. RAD51C and RAD51D mutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.

3370: Is less axillary surgery safe in irradiated, high-risk breast cancer patients: Results from the SENOMAC trial

3370: Is less axillary surgery safe in irradiated, high-risk breast cancer patients: Results from the SENOMAC trial

3399: DBCG IMN2: Internal mammary node irradiation in 4541 high-risk breast cancer patients treated 2007-2014

3399: DBCG IMN2: Internal mammary node irradiation in 4541 high-risk breast cancer patients treated 2007-2014

3149: The toxicity and value of interstitial brachytherapy boost for high-risk breast cancer patients

3149: The toxicity and value of interstitial brachytherapy boost for high-risk breast cancer patients

Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families.

RAD51C and RAD51D are crucial in homologous recombination (HR) DNA repair. The prevalence of the RAD51C and RAD51D mutations in breast cancer varies across ethnic groups. Associations of RAD51C and RAD51D germline pathogenic variants (GPVs) with breast and ovarian cancer predisposition have been recently reported and are of interest. We performed multi-gene panel sequencing to study the prevalence of RAD51C and RAD51D germline mutations among 3728 patients with hereditary breast and/or ovarian cancer (HBOC). We identified 18 pathogenic RAD51C and RAD51D mutation carriers, with a mutation frequency of 0.13% (5/3728) and 0.35% (13/3728), respectively. The most common recurrent mutation was RAD51D c.270_271dupTA; p.(Lys91Ilefs*13), with a mutation frequency of 0.30% (11/3728), which was also commonly identified in Asians. Only four out of six cases (66.7%) of this common mutation tested positive for homologous recombination deficiency (HRD). Taking the family studies in our registry and tumor molecular pathology together, we concluded that this relatively common RAD51D variant showed incomplete penetrance in our local Chinese community. Personalized genetic counseling emphasizing family history for families with this variant, as suggested at the UK Cancer Genetics Group (UKCGG) Consensus meeting, would also be appropriate in Chinese families.

Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing.

Recently, genes involved in homologous recombination repair (HRR) pathway have been extensively studied. However, the landscapes of HRR gene mutations remain poorly defined in Chinese high-risk breast cancer (BC) patients. Our study aims to identify the status of germline and somatic HRR gene mutations and their association with clinicopathological features in these patients. A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis. Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05). The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008–2016: The DBCG RT Nation study

Background and purposeGuideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data. Materials and methodsThis study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison. ResultsThe study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures. ConclusionNational guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data.

A nomogram for predicting the risk of cancer-related cognitive impairment in breast cancer patients based on a scientific symptom model

Cancer-related cognitive impairment is a significant clinical challenge observed in patients with breast cancer, manifesting during or after treatment. This impairment leads to deteriorations in memory, processing speed, attention, and executive functioning, which profoundly impact patients' occupational performance, daily living activities, and overall quality of life. Grounded in the Symptom Science Model 2.0, this study investigates the contributing factors to Cancer-related cognitive impairment in breast cancer patients and develops a predictive nomogram for this demographic. Employing both univariate and multivariate logistic regression analyses, this investigation delineates the predictive factors influencing outcomes in breast cancer patients. A nomogram was constructed leveraging these identified predictive factors, accompanied by internal validation through bootstrap resampling methodology (1000 bootstrap samples). The efficacy of the predictive model was assessed by employing the Hosmer–Lemeshow goodness-of-fit test and calibration curves. The prevalence of cognitive impairment in breast cancer patients was identified to be 45.83%.Multivariate logistic regression analysis identified the independent predictors of Cancer-related cognitive impairment in breast cancer patients as place of residence, educational level, chemotherapy, benefit finding, post-traumatic growth, anxiety, fear of cancer progression, and fasting blood glucose levels. these factors were integrated into the nomogram. The Hosmer–Lemeshow goodness-of-fit test demonstrated that the prediction model was appropriately calibrated (χ2 = 11.520, P = 0.174). Furthermore, the model exhibited an area under the curve of 0.955 (95% CI 0.939 to 0.971) and a sensitivity of 0.906, evidencing its robust discriminative capacity and accuracy. Utilizing the Symptom Science Model 2.0 as a framework, this study comprehensively examines the multifaceted factors influencing Cancer-related cognitive impairment in breast cancer patients, spanning five critical domains: complex symptoms, phenotypic characterization, biobehavioral factors, social determinants of health, and patient-centered experiences. A predictive nomogram model was established, demonstrating satisfactory predictive accuracy and capability. This model is capable of identifying breast cancer patients with cognitive impairments with high precision. The findings furnish empirical evidence in support of the early detection, diagnosis, and intervention strategies for high-risk breast cancer patients afflicted with Cancer-related cognitive impairment.

Quantitative Analysis of 99mTc-MDP SPECT-CT Data in Diagnosing Bone Metastases in Breast Cancer Patients

Background: In patients with advanced breast cancer (BC), distant metastases happen mainly in the skeleton. This study aimed to investigate the role of 99mTc-MDP SPECT/CT in the differential diagnosis of malignant bone lesions from degenerative benign bone diseases in female BC patients. Methods and Results: The study included 39 female BC patients who underwent a baseline 99mTc-MDP SPECT/CT bone scans. After lesion detection, a quantitative radiotracer uptake analysis was conducted, and the standardized uptake value (SUVmax) was identified in each patient, and the data were then statistically analyzed. SUVmax values were significantly higher in BC patients with malignant metastasis than in patients with degenerative changes (33.04±15.3 vs. 13.25±5.46 g/mL, P&lt;0.05). The SUVmax cut-off value of 22.75 g/mL (25th percentile) obtained through box plot analysis can help to discriminate metastatic from degenerative lesions. The logistic regression analysis indicated that the SUVmax was a significant predictor of metastatic BL (P&lt;0.001, OR = 159.90, B=5.07). Conclusion: Our results suggested that quantitative analysis of the 99mTc-MDP SPECT-CT data can improve diagnostic accuracy in differentiating malignant metastatic bone lesions from degenerative bone lesions in high-risk BC patients.

The efficacy of primary progesterone on survival in early breast cancer: A real world scenario.

e12522 Background: Surgery performed during progestogenic milieu improves survival in breast cancer patients. We previously proved efficacy of pre-operative progesterone in high-risk, operable breast cancer. In another multicenter randomized trial, intra-operative peri-tumoral local anesthetic injection showed 29% reduction in mortality. In this study, several patients had also received progesterone injection since this is adopted as standard of care across some centers including ours. We assessed the effectiveness of pre-operative progesterone in patients who were randomized in the local anesthetic study. Methods: We analyzed 1583 patients randomized on the local anesthetic study during December 2011-October 2018 with respect to receipt of progesterone. All patient who had breast lump of ≥2cm and/or node positive were eligible to receive progesterone injection before surgery. Kaplan Meier curves were plotted along with Cox regression analysis to study factors affecting disease-free and overall survival. Results: Of 1583, 454 patients did not receive, and 1129 patients received progesterone before surgery. The median age of whole cohort was 51 years, median pT size was 3 cm, 45% were node positive, 60% ER/PR+ and 24%TNBC. At median follow-up of 68 (0·5-72) months in surviving patients, there were a total of 292 DFS events (progesterone arm-193, no-progesterone arm-99). The 5-year disease-free survival (DFS) was 86.5% in the progesterone arm and 79.2% in the no-progesterone arm (HR-0.57,0.45-0.73, P&lt;0.001). The 5-year overall survival (OS) was 90.5% in the progesterone arm and 82.8% in the no-progesterone arm (HR-0.47,0.36-0.63,P&lt;0.001). On Cox Regression analysis (Table), administration of progesterone injection was an independent prognostic factor for DFS (HR-0.53,0-41-0.70, p&lt;0.001) and OS (HR-0.44,0-32-0.60, p&lt;0.001) both. Conclusions: The receipt of pre-operative progesterone improved outcomes in the setting of another randomized trial. It should be administered to all high risk (T2/N1) breast cancer patients who are planned for surgery first. [Table: see text]

Delays in receipt of neoadjuvant chemotherapy compared to upfront surgery in patients with operable breast cancer.

e13561 Background: Delays in time from breast cancer (BC) diagnosis to BC treatment initiation (BCTI) including upfront breast surgery (UBS) or neoadjuvant chemotherapy (NACT), can negatively impact BC survival. We evaluated odds of delay in BCTI among patients (pts) who received NACT compared to pts who received UBS. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis of non-metastatic BC between 1/1/2010 – 12/31/2020, who were treated with NACT followed by surgery or UBS followed by adjuvant chemotherapy (AC). Pts who did not receive NACT or UBS within 180 days of diagnosis were excluded. The cohort was stratified by first BC treatment (NACT or UBS), and time to NACT (TTNACT) or time to surgery (TTS) was recorded for each patient in days. Pts were categorized into sub-cohorts by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) lymph node (LN)+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Logistic regression adjusted for demographic, socioeconomic, and tumor characteristics was used to identify delays in BCTI &gt; 60 days. Multiple imputation was used for missing data. Inverse probability treatment weighting (IPTW) was done as a sensitivity analysis. Results: We identified 218,049 eligible pts, 75% were White, 18% were Black, and 8.6% were Hispanic. Median age was 53 years (range 18-90). There were 145,697 (67%) pts who received NACT with median TTNACT of 32 days (range 0-180), and 9.8% had a delay &gt; 60 days (Table). There were 72,353 (33.0%) pts who received UBS followed by AC, with a median TTS of 33 days (range 0-180), and 13% with a delay &gt; 60 days. In multivariable analysis, pts who received UBS had higher odds of BCTI delays compared to NACT, with OR 1.50 (95%CI 1.42-1.57) [HR+/HER2-], OR 1.49 (95%CI 1.41-1.58) [HER2+], and OR 1.26 (95%CI 1.18-1.34) [TNBC]. Results from IPTW analysis were similar, groups were well balanced, and pts who received UBS had higher odds of BCTI OR 1.50 (95%CI 1.44-1.57) [HR+/HER2-], OR 1.75 (95%CI 1.67-1.83) [HER2+], and OR 1.46 (95%CI 1.38-1.53) [TNBC]. Conclusions: Among high clinical risk BC patients who received surgery and chemotherapy, those who underwent NACT were less likely to experience delays in BCTI compared to pts who received UBS first. Among eligible pts, use of NACT may reduce delays in BCTI. [Table: see text]

The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer.

TPS620 Background: Current guidelines limit routine breast cancer (BC) follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Methods: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized BC surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. Eligible patients are adults with confirmed primary invasive intermediate to high-risk early BC, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size (&gt; 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed previously. Patient enrollment during adjuvant endocrine, antibody- or targeted therapy is allowed. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery.Both study arms receive standard follow-up according to national guidelines, and the intensified surveillance arm will be tested for standard tumor markers, CTCs and ctDNA via tumor-informed approach (RaDaR assay). Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Statistics:The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Clinical trial information: NCT05658172 .

Correlation of stress, depression, sleep, and pain with race and body mass index (BMI): Secondary analysis from Alliance A011502.

e23171 Background: A011502 is a phase 3 trial that randomized high-risk nonmetastatic breast cancer (BC) patients (pts) to aspirin 300 mg daily vs. placebo. Obesity and Black race have been shown to be associated with worse clinical outcomes. We studied the association of stress, depression, sleep and pain with each other, and with BMI and race. Methods: At baseline, 2735, 2610, 2720, and 2422 pts completed Perceived Stress Scale (PSS), Center for Epidemiologic Studies Depression Scale Revised (CESD-R), Brief Pain Inventory (BPI), and Pittsburgh Sleep Quality Index (PSQI) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high (27-40). Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5). Associations of measures by race and BMI were analyzed using chi-square test. Results: There was a statistically significant association among stress, depression, pain, and sleep quality (p &lt; 0.01 for all). Compared to pts with BMI &lt; 25, overweight and obese women reported higher stress (2.9%, 2.3% vs. 1.7%, p = 0.04), depression (13.4%, 18% vs. 9.6%, p &lt; 0.01), moderate/severe pain (16.5%, 20.3% vs. 12%, p &lt; 0.01), and poor sleep (64.9%, 71.5% vs. 60.4%, p &lt; 0.01). Black women reported more moderate/severe pain compared to White women or other races (32.9% vs. 14.2% vs. 27.8%, p &lt; 0.01). There was no association of other symptoms with race (Table 1). Conclusions: Obesity was associated with higher stress, depression, poor sleep and pain among BC pts from A011502. Black women reported higher pain compared to other races. Future studies are warranted that determine causal associations, how symptoms may relate to outcome disparities, and develop approaches to address them. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02927249 . [Table: see text]

Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.

11016 Background: A011502 is a phase 3 randomized double-blind clinical trial that enrolled high-risk nonmetastatic breast cancer (BC) patients (pts) and randomized pts to aspirin 300 mg daily vs. placebo. There was no significant difference in invasive disease-free survival (iDFS) between the two arms. A secondary objective was to determine the association of inflammation-affiliated factors (stress, depression, poor sleep quality and pain) with iDFS and overall survival (OS). We hypothesized that these baseline factors are associated with worse clinical outcomes. Methods: At baseline, 2735, 2720, 2422 and 2610 pts completed Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale Revised (CESD-R) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high stress (27-40). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5).Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Associations between the measures of interest and outcomes were performed with multivariable Cox models controlling for age, body mass index, time since diagnosis, race, ethnicity, hormone receptor status and treatment arm. Results: Median follow up was 35 months. The associations from multivariable Cox model are shown in Table 1. Pts who reported high PSS had significantly worse iDFS and (non-significant) worse OS. Moderate/severe average (avg) pain was significantly associated with worse iDFS and OS. Poor sleep quality and depression were associated with worse iDFS and OS but not statistically significant. Conclusions: Pts reporting higher stress and pain at baseline had worse outcomes. We acknowledge that both pain and stress may be related to other non-cancer issues (chronic comorbidities). Our study highlights the need for clinical trials to consider including questionnaires to assess pt-reported outcomes. Future studies are warranted to determine if measures to decrease pain and stress would improve BC outcomes. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . NCT02927249: Clinical trial information: NCT02927249 . [Table: see text]

Profile of breast cancer in patients with Li-Fraumeni syndrome: An institutional experience.

e13042 Background: Li Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome, associated with multisystem cancer predisposition. Considering the rarity of this syndrome, studies are very sparse on survival outcomes of breast cancer with germline TP53 mutation and there exists discrepancy amongst the results. Methods: This retrospective observational study included 17 patients with germline TP53 mutated breast cancer registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st April 2016 to 31st Dec 2023. Among the 577 high-risk breast cancer patients, who underwent germline mutation testing, 231 (40.03%) cases had pathogenic mutation [145(25.12%) were BRCA mutated,15 (2.59%) were TP53 mutated, and the rest were others pathogenic variant]. All the TP53 mutations were crosschecked via the ClinVar mutation database to be classified as pathogenic. Results: The median age of 15 patients was 31 years (23-55) and 12 (80%) cases were premenopausal. All the patients had breast cancer as the index malignancy. The Stage distribution (AJCC-7th edition) Stage I, 1(6.6%); Stage II, 7 (46.6 %); Stage III, 4 (26.6 %); and Stage IV, 3 (20 %). Eight cases (53.3%) were HER2 positive, 4 (26.6%) were hormone receptor-positive, and 3 (20%) were Triple-negative breast carcinoma (TNBC). Ten (10) patients received neoadjuvant chemotherapy and 6 (60%) had a complete pathological response. Eight cases (53.3%) cases had a significant family history with 9 (60%) of them having at least one first-degree relative with cancer and two had more than one first-degree relative with cancer. One patient had a family history of LFS. The most common familial cancer was breast, followed by lung, GI malignancies, brain tumor, and sarcoma. Synchronous breast cancer was seen in 2 patients, synchronous malignancies were seen in 4 cases (one patient: each with lung adenocarcinoma, periampullary carcinoma, carcinoma colon, and synovial sarcoma, along with breast cancer), Four patients (26.6%) had metachronous cancers: lung cancer, ovarian carcinoma, contralateral breast cancer, and high-grade sarcoma respectively. The most common mutations were point mutations ( n = 11, 73.3%) followed by frameshift mutations ( n = 4, 26.6%). The subtypes of point mutations included missense mutations ( n = 9) and nonsense mutations ( n = 2) with the most common aberration being a replacement of arginine with glycine (c.743G&gt;A, p. Arg248Gln) and locus being exon 7. The median disease-free survival was 41 months and progression-free survival was 15 months. Conclusions: The prevalence of TP53 mutation in our breast cancer patients is 2.5%. With standard treatment protocols, the overall survival of LFS-associated breast cancer is similar to the historic cohort of patients without any germline mutation. Active surveillance of the patient and family screening is imperative, for all positive cases.