Low-risk Breast Cancer Patients Research Articles

An Aging-Related lncRNA Signature Establishing for Breast Cancer Prognosis and Immunotherapy Responsiveness Prediction.

Emerging evidence demonstrates the vital role of aging and long non-coding RNAs (lncRNAs) in breast cancer (BC) progression. Our study intended to develop a prognostic risk model based on aging-related lncRNAs (AG-lncs) to foresee BC patients' outcomes. 307 aging-related genes (AGs) were sequenced from the TCGA project. Then, 697 AG-lncs were identified by the co-expression analysis with AGs. Using multivariate and univariate Cox regression analysis, and LASSO, 6 AG-lncs, including al136531.1, mapt-as1, al451085.2, otud6b-as1, tnfrsf14-as1, and linc01871, were validated to compute the risk score and establish a risk signature. Expression levels of al136531.1, mapt-as1, al451085.2, tnfrsf14-as1, and linc01871 were higher in low-risk BC patients, whereas otud6b-as1 expression was higher in high-risk BC patients. In the training and testing set, high-risk patients performed shorter PFI, OS, and DFS than low-risk patients. Our risk signature had the highest concordance index among other established prognostic signatures and displayed ideal predictive ability for 1-, 3- and 5-year patient OS in the nomogram. Additionally, BC patients with different risk score levels showed different immune statuses and responses to immunotherapy via GSEA, ssGSEA, ESTIMATE algorithm, and TIDE algorithm analysis. Of note, the qRT-PCR analysis validated that these 6 AG-lncs expressed quite differentially in BC tissues at various clinical stages. The risk signature of 6 AG-lncs might offer a novel prognostic biomarker and promisingly enhance BC immunotherapy's effectiveness.

Ten-Year Results of Accelerated Partial-Breast Irradiation with Interstitial Multicatheter Brachytherapy after Breast-Conserving Surgery for Low-Risk Early Breast Cancer.

Patients with an early carcinoma of the breast are commonly treated by breast-conserving surgery (BCS) and postoperative radiotherapy. Partial-breast irradiation has gained acceptance in the last few years. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS in the four university hospitals of the province of Las Palmas and treated with APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year IBTR was 1.7% (95%CI: 0.7-2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2-96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients.

Development of lymph node metastasis-related prognostic markers in breast cancer

BackgroundLymph node metastasis (LNM) from Breast cancer (BC) is commonly seen in BC progression. Currently, the identification of genes linked with LNM in BC remains in mystery. MethodsGenes related to BC LNM were screened, and a risk model was constructed based on LASSO-Cox analysis. Combined with the Kaplan-Meier curve, the ability of riskscore to distinguish different baseline characteristics was evaluated, and model was verified by the receiver operating characteristic (ROC) curve. The expression levels of prognostic marker genes were analyzed by qRT-PCR and western blot (WB). ResultsA higher survival rate and longer survival time in low-risk BC patients. The 1, 3 and 5 year AUC values of the training set were 0.79, 0.74, and 0.73, respectively. Results for the validation set was similar to the training set. The differentially expressed genes between the high- and low-risk groups were significantly enriched in immune pathways. In addition, the low-risk group had higher levels of immune infiltration. qRT-PCR and WB results showed that in BC, CDH10, SMR3A, POU3F2, and FABP7 were down-regulated, and LHX1 was up-regulated. ConclusionsWe built a prognostic model of BC based on LNM-related genes, proffering evaluation for prognosis and precise cure of BC. SignificanceAt present, the genes related to lymph node metastasis in BC are still largely unknown and need to be further explored. Searching for potential lymph node metastasis-related genes of BC will provide meaningful biomarkers for BC treatment. Based on TCGA-BRCA data, we established an effective 11-gene prognostic risk model that could predict patient outcomes independently. Our model could classify BC patients and distinguish patients with poor prognosis effectively. Besides, the feature genes we identified might exert a predictive function in immunotherapy. The results of this study provide a new reference for the prognosis and treatment of BC patients with lymph node metastasis.

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre

Purpose Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. Methods we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. Results Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%–100%), and 5-year OS was 96.0% (95%CI: 92.6–99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04–1.42, p = .01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p < .01; p = .02; respectively) and late fibrosis (p < .01; p = .049; respectively). Conclusions ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our ‘real-life’ cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities.

Observed and Predicted Toxicity in Daily Cone-Beam CT-Based Online Adaptive Stereotactic Partial Breast Irradiation with Decreased PTV Margins

Accelerated partial breast irradiation (APBI) delivers smaller radiation volumes over less time compared to whole breast irradiation (WBI), but the organ-at-risk (OAR) sparing allowed by its large (up to 1 cm) planning target volume (PTV) can be improved. PTV can be decreased with daily online adaptive planning, which we hypothesized yields low rates of adverse events observed and predicted by normal tissue complication probability (NTCP) models. Intensity-modulated (IMRT) cone-beam CT (CBCT)-based daily online adaptive stereotactic PBI (A-SPBI) plans with 3-mm PTV from 8 patients were recreated with 1-cm PTV per the Florence APBI IMRT trial planning guideline. Dose statistics with evidence for association with toxicity were compared. Documented toxicities were collected for patients treated with A-SPBI with a minimum follow-up of 3.5 months and Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 grade was assigned. Using α/β = 3 for breast and lung, dose statistics were converted to equivalent doses in 2-Gy fractions (EQD2) for use in NTCP models and for comparison using paired t tests, with differences considered significant if p≤0.05. The table details EQD2 dose statistics for breast, lung, and cosmetic toxicity for A-SPBI plans with 3-mm PTV and their 1-cm PTV re-plans in 8 patients. PTV volume, mean lung dose (MLD), and lung V5, V20, and V30 were significantly lower in 1-cm plans. Acute, subacute (3-6 months), and late toxicities were collected for 30 patients followed for a median of 8 months (range 4-13 months). Radiation dermatitis was the most common acute toxicity (n = 16, 53%), followed by hyperpigmentation (n = 12, 40%), fibrosis (n = 9, 30%), and fatigue (n = 9, 30%). One grade 3 radiation dermatitis was the only grade ≥3 toxicity. Six patients (20%) acutely developed breast or axillary edema: 4 (13.3%) resolved, and 2 (6.7%) developed acutely and persist at last follow-up, >6 months after RT. No patient had a lung V20, V30, or MLD meeting thresholds for radiation-induced lung injury, radiation pneumonitis, or symptomatic or imaging-based pneumonitis models, respectively. The breast V55 model predicted a median risk of unfavorable cosmesis of 33% (range 26-44%) for A-SBPI plans and 35% (range 28-51) for 1-cm PTV plans (p = 0.28). Observed acute toxicities are tolerable and rarely persist in patients treated with A-SPBI with 3-mm PTV margins with daily CBCT-based online adaptation. NTCP modeling predicts similar cosmetic outcome to 1-cm margins. The significant reduction in ipsilateral lung dose with a 3-mm PTV in our first 8 patients especially supports daily adaptation in low-risk breast cancer patients with smoking history and/or lung comorbidity.

Whole Breast Irradiation in Comparison to Endocrine Therapy in Early Stage Breast Cancer-A Direct and Network Meta-Analysis of Published Randomized Trials.

Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42-0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53-1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45-2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59-1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38-1.36; p = 0.305). Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

Risk-Adapted Intraoperative Radiation Therapy (IORT) for Breast Cancer: A Novel Analysis.

Randomized trials have shown that risk-adapted intraoperative radiation therapy (IORT) after breast-conserving surgery for low-risk breast cancer patients is a safe alternative to whole-breast radiation therapy (WBRT). The risk-adapted strategy allows additional WBRT for predefined high-risk pathologic characteristics discovered on final histopathology. The greater the percentage of patients receiving WBRT, the lower the recurrence rate. The risk-adapted strategy, although important and necessary, can make IORT appear better than it actually is. Risk-adapted IORT was used to treat 1600 breast cancers. They were analyzed by the intention-to-treat method and per protocol to better understand the contribution of IORT with and without additional whole-breast treatment. Any ipsilateral breast tumor event was considered a local recurrence. During a median follow-up period of 63 months, local recurrence differed significantly between the patients who received local treatment and those who received whole-breast treatment. For 1393 patients the treatment was local treatment alone. These patients experienced 79 local recurrences and a 5-year local recurrence probability of 5.95 %. For 207 patients with high-risk final histopathology, additional whole-breast treatment was administered. They experienced two local recurrences and a 5-year local recurrence probability of 0.5 % (p = 0.0009). Whole-breast treatment works well at reducing local recurrence, and it is a totally acceptable and necessary addition to IORT as part of a risk-adapted program. However, the more whole-breast treatment that is given, the more it dilutes the original plan of simplifying local treatment and the less we understand exactly what IORT contributes to local control as a stand-alone treatment.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol

BackgroundPartial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients.MethodsThe ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy.DiscussionThis trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients.Trial registrationThe trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

De-Implementation of Axillary Staging and Radiotherapy in Low-Risk Breast Cancer Patients Aged 70-79 Years from Six Italian Cancer Institutes.

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.S.). We assessed the frequency of both procedures in six National Cancer Institutes (IRCCSs) in the North, the Centre, and the South of Italy. Data on tumour characteristics and treatment were obtained from each centre. Patients aged 70-79 years diagnosed with a pT1-pT2, clinically axillary lymph node-negative, oestrogen and/or progesterone receptor-positive, and human epidermal growth factor receptor 2-negative BrC between 2015 and 2020 were eligible for the study. Factors associated with the omission of the two procedures were evaluated using binary penalised logistic regression models. Axillary staging was omitted in 33/1000 (3.3%) women. After simultaneous adjustment for the centre of treatment and all other key variables, axillary staging was omitted more often in 2015-2016 vs. 2017-2020 (odds ratio (OR): 2.7; 95% CI: 1.0-7.5), in women aged 75-79 vs. 70-74 years (OR: 2.3; 95% CI: 1.1-4.9), and in those who had mastectomy vs. breast-conserving surgery (OR: 3.3; 95% CI: 1.2-9.0). The higher the histological grade was, the less frequent were the omissions (OR for grade 3 vs. grade 1: 0.2; 95% CI: 0.0-0.7). Post-lumpectomy radiotherapy was omitted in 56/651 (8.6%) women with no significant association with age, period, tumour stage, and tumour grade. In conclusion, the omission of axillary staging and post-lumpectomy radiotherapy in low-risk older BrC patients was rare in the Italian IRCCSs. Although women included in the study cannot be considered a nationally representative sample of BrC patients in Italy, our findings can serve as a baseline to monitor the impact of future guidelines. To do that, the recording and storage of hospital-based information should be improved.

Abstract P3-05-50: Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer

Abstract Background: Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer. Methods: Pearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Ultimately, a nomogram based on the risk score and several significant clinicopathologic features was established. Results: The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Conclusions: The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies. Citation Format: Hongfei Zhang, Xiafei Yu, Junzhe Yang, Xiaoan Liu, Yanhui Zhu. Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-50.

Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer.

Background: Neutrophil extracellular traps (NETs) are closely associated to tumorigenesis and development. However, the relationship between NETs-related long non-coding RNAs (lncRNAs) and the characteristics of breast tumor remains an enigma. This study aimed to explore the clinical prognostic value of NETs-related lncRNAs, their correlation with the tumor microenvironment (TME) and their predictive ability of drug sensitivity in patients with breast cancer (BC). Methods: The expression profiles of RNA-sequencing and relevant clinical data of BC patients were extracted from TCGA database. The co-expression network analysis, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were employed to construct the NETs-related lncRNAs signature. A nomogram was established and validated to explore the clinical application. Furthermore, the immune microenvironment and drug sensitivity for BC with different prognostic risks were explored. Finally, the expression pattern of lncRNAs was validated using qRT-PCR in BC tissues and their adjacent non-cancerous tissues. Results: Based on NETs-related lncRNAs, a prognostic risk model consisted of 10 lncRNAs (SFTA1P, ACTA2-AS1, AC004816.2, AC000067.1, LINC01235, LINC01010, AL133467.1, AC092919.1, AL591468.1, and MIR200CHG) was established. The Kaplan-Meier analysis showed that the overall survival (OS) was significantly better in low-risk BC patients than in high-risk BC patients (P training cohort < 0.001, P validation cohort = 0.009). The nomogram also showed good predictive accuracy for OS of BC individuals in both training and validation cohorts. The function enrichment analysis revealed that high-risk group was mainly enriched in immune-related functions and pathways, and the tumor mutation burden in this group was markedly higher than that in the low-risk group (p = 0.022). Moreover, significant differences were observed in immune cells, immune functions and immune checkpoint genes among BC patients at different risks (p < 0.05). The response to chemotherapeutic agents and immunotherapy were also closely related with the expression of NETs-related lncRNAs (p < 0.001). The expression of lncRNAs from experimental validation were generally consistent with the bioinformatics analysis results. Conclusion: Our study provided a novel prognostic model for BC and yielded strong scientific rationale for individualized treatment strategies, elucidating immunotherapy in BC patients.

Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients—a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy

PurposeIn the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed.MethodsWomen who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. ‘Low risk’ was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test.ResultsWe identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028).ConclusionMetastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

ASCO 2022 Breast Cancer Updates

"Data presented at ASCO 2022 provide new perspectives of therapy for patients with breast cancer. Starting with the plenary session with DESTINY-Breast04 we are turning a new page in the treatment of metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer patients. The results of the DESTINY-Breast04 trial open a new therapeutic option for half of the patients with metastatic breast cancer, establishing HER2-low metastatic breast cancer as a targetable population with trastuzumab deruxtecan. The indications for antibody drug conjugates are expanding to patients with metastatic hormone receptor positive endocrine resistant disease based on TROPICS-02. From the multitude of clinical trials with antibody drug conjugates, we can envision that this will be likely the new way to deliver chemotherapy in the future. Differences in survival within the three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in upfront metastatic hormone positive breast cancer are emerging. We have data on continuation of ribociclib beyond disease progression on CDK4/6 in the MAINTAIN trial. The FAKTION trial does prove the benefit of the AKT inhibitor capivasertib and does highlight the importance of an extended molecular panel of the phosphatidylinositol3-kinase PI3K pathway. Furthermore, the exploratory analysis of KEYNOTE- 522, examining the correlation of event free survival and residual cancer burden after neoadjuvant treatment in patients with triple negative breast cancer does demonstrate a benefit of pembrolizumab extending to patient which did not achieve pathologic complete response, mainly by a decrease in residual cancer burden. Advances in biomarkers of response to immunotherapy are needed. For early stage breast cancer studies are in support of de-escalation of radiotherapy for low risk breast cancer patients and confirming the lack of benefit of adjuvant chemotherapy for elderly patients, even with high genomic grade index."

145 (PB-058) Poster - Preoperative partial breast irradiation in low-risk breast cancer patients: a systematic review of literature

Background: Since 2017, partial breast irradiation (PBI) is considered standard treatment after breast conserving surgery (BCS) in breast cancer patients with a low risk on recurrence. In order to reduce the irradiated breast tissue volume, toxicity, and the number of radiotherapy sessions, PBI can be performed preoperatively. In this study, we assessed the clinical and oncological outcomes of preoperative PBI.

Construction of prognostic signature of breast cancer based on N7-Methylguanosine-Related LncRNAs and prediction of immune response

Background: Long non-coding RNA (LncRNA) is a prognostic factor for malignancies, and N7-Methylguanosine (m7G) is crucial in the occurrence and progression of tumors. However, it has not been documented how well m7G-related LncRNAs predict the development of breast cancer (BC). This study aims to develop a predictive signature based on long non-coding RNAs (LncRNAs) associated with m7G to predict the prognosis of breast cancer patients. Methods: The Cancer Genome Atlas (TCGA) database provided us with the RNA-seq data and matching clinical information of individuals with breast cancer. To identify the signature of N7-Methylguanosine-Related LncRNAs and create a prognostic model, we employed co-expression network analysis, least absolute shrinkage selection operator (LASSO) regression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. The signature was assessed using the Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve. A nomogram and principal component analysis (PCA) were employed to confirm the predictive signature's usefulness. Then, we examined the drug sensitivity between the two risk groups and utilized single-sample gene set enrichment analysis (ssGSEA) to investigate the association between predictive factors and the tumor immune microenvironment in high-risk and low-risk groups. Results: Nine m7G-related LncRNAs (LINC01871, AP003469.4, Z68871.1, AC245297.3, EGOT, TFAP2A-AS1, AL136531.1, SEMA3B-AS1, AL606834.2) that are independently associated with the overall survival time (OS) of BC patients make up the signature we developed. For predicting 1-, 3-, and 5-year survival rates, the areas under the ROC curve (AUC) were 0.715, 0.724, and 0.726, respectively. The Kaplan-Meier analysis revealed that the prognosis of BC patients in the high-risk group was worse than that of those in the low-risk group. When compared to clinicopathological variables, multiple regression analysis demonstrated that risk score was a significant independent predictive factor for BC patients. The results of the ssGSEA study revealed a substantial correlation between the predictive traits and the BC patients' immunological status, low-risk BC patients had more active immune systems, and they responded better to PD1/L1 immunotherapy. Conclusion: The prognostic signature, which is based on m7G-related LncRNAs, can be utilized to inform patients' customized treatment plans by independently predicting their prognosis and how well they would respond to immunotherapy.

Comprehensive analysis of pyroptotic gene prognostic signatures associated with tumor immune microenvironment and genomic mutation in breast cancer.

BackgroundBreast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer.MethodsPearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Subsequently, a nomogram based on the risk score and several significant clinicopathologic features was established. Ultimately, we further investigated the role of CCL5 in the biological behavior of MDA-MB-231 cell line.ResultsThe low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Additionally, in vitro experiments confirmed that breast cancer cells with high expression of CCL5 had weaker proliferation, invasion and metastasis abilities as well as stronger apoptosis and cell cycle arrest abilities.ConclusionsThe risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies.

Intraoperative radiotherapy versus no radiotherapy for early stage low-risk breast cancer patients undergoing breast-conserving surgery: a propensity score matching study based on the SEER database.

To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). For patients aged 50years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.

Improving the cancer survivorship journey: Developing a survivorship care transition model for rural and underserved low risk breast and gynecologic cancer patients (511)

<b>Objectives:</b> The rapid growth of cancer survivors in the United States, in combination with oncology service workforce shortage, creates an urgent need to develop effective survivorship care models. While survivorship programs are required by the Commission on Cancer and endorsed by national cancer organizations, the evidence base supporting specific components and delivery models is still lacking, and novel approaches are especially needed in rural care settings with high concentrations of underrepresented minority populations. Our team is working to create effective and innovative cancer survivorship care models for low-risk breast and gynecologic cancer patients. <b>Methods:</b> We conducted exploratory research among low-risk breast and gynecologic cancer survivors and primary care providers to inform a subsequent intervention of navigated care transitions. We convened a Patient Advisory Board (PAB) to review a structured menu of cancer survivorship issues, including access to primary care services, compliance with screening recommendations, treatment of comorbid conditions and identified the range of desired survivorship resources. We conducted five virtual PAB meetings via ZOOM, and participants completed four surveys. In parallel, we conducted semi-structured qualitative interviews with seven primary care providers (Family Physicians and OB/GYNs) to understand preferences of cancer survivor care transition timing and informational needs. Both PAB and Provider sessions/interviews were transcribed and coded for content and thematic analysis. <b>Results:</b> Participants in the PAB provided insight into survivorship experiences and processes to facilitate earlier care transitions. They emphasized the need to begin survivorship planning at an earlier stage of care and advocated for the creation of tailored documents relevant to the care needs of particular stages (e.g., diagnosis, definitive treatment, care transitions). Lastly, they identified other overlooked care needs, including adverse effects on sexual health. Primary care provider data aligned with PAB findings, including the need to initiate enhanced communication with the oncologists immediately following diagnosis. Additionally, providers expressed confidence in managing survivorship care based on responses to structured vignettes of breast and gynecological cancer patients. <b>Conclusions:</b> This formative research identified key factors with regard to the development of processes and informational resources necessary to support cancer survivorship care transitions among underserved and rural breast and gynecologic cancer patients. In alignment with findings from primary care providers, this model would focus on initiating survivorship support at an early stage of care, include a broad "menu" of potential patient care needs, and ensure provider training and awareness related to surveillance and referral pathways. Further research to test the feasibility of this model is underway.

P22 Improving the cancer survivorship journey: developing a survivorship care transition model for rural and underserved low-risk breast and gynecologic cancer patients

P22 Improving the cancer survivorship journey: developing a survivorship care transition model for rural and underserved low-risk breast and gynecologic cancer patients

Identification and validation of a novel prognostic signature based on transcription factors in breast cancer by bioinformatics analysis.

Breast cancer (BRCA) is the leading cause of cancer mortality among women, and it is associated with many tumor suppressors and oncogenes. There is increasing evidence that transcription factors (TFs) play vital roles in human malignancies, but TFs-based biomarkers for BRCA prognosis were still rare and necessary. This study sought to develop and validate a prognostic model based on TFs for BRCA patients. Differentially expressed TFs were screened from 1,109 BRCA and 113 non-tumor samples downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was used to identify TFs associated with overall survival (OS) of BRCA, and multivariate Cox regression analysis was performed to establish the optimal risk model. The predictive value of the TF model was established using TCGA database and validated using a Gene Expression Omnibus (GEO) data set (GSE20685). A gene set enrichment analysis was conducted to identify the enriched signaling pathways in high-risk and low-risk BRCA patients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the TF target genes were also conducted separately. A total of 394 differentially expressed TFs were screened. A 9-TF prognostic model, comprising PAX7, POU3F2, ZIC2, WT1, ALX4, FOXJ1, SPIB, LEF1 and NFE2, was constructed and validated. Compared to those in the low-risk group, patients in the high-risk group had worse clinical outcomes (P<0.001). The areas under the curve of the prognostic model for 5-year OS were 0.722 in the training cohort and 0.651 in the testing cohort. Additionally, the risk score was an independent prediction indicator for BRCA patients both in the training cohort (HR =1.757, P<0.001) and testing cohort (HR =1.401, P=0.001). It was associated with various cancer signaling pathways. Ultimately, 9 overlapping target genes were predicted by 3 prediction nomograms. The GO and KEGG enrichment analyses of these target genes suggested that the TFs in the model may regulate the activation of some classical tumor signaling pathways to control the progression of BRCA through these target genes. Our study developed and validated a novel prognostic TF model that can effectively predict 5-year OS for BRCA patients.