Breast Cancer Treatment Outcome Research Articles

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Multi-omic profiling of breast tumor microenvironment uncovers a role of mitochondrial calcium gatekeepers.

In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach. Unlike previous research, we utilized a novel web application tailored for whole tumor tissue, single-cell, and spatial transcriptomics analysis to investigate the association between MiCU1/2 and the tumor immune microenvironment (TIME). Our gene set enrichment analysis (GSEA) provided insights into the primary biological effects of MiCU1/2, while our CRISPR-based drug screening repository identified potential effective drugs. Our study revealed that high MiCU1/2 expression serves as an independent diagnostic biomarker, correlating with advanced clinical status and indicating poorer recurrence-free survival (RFS) rates in BRCA patients. Additionally, spatial transcriptome analysis highlighted the heightened expression of MiCU1/2 in tumors and its relevance in surrounding immune cells. Furthermore, using the CIBERSORT algorithm, we discovered a positive correlation between MiCU1/2 levels and macrophage infiltration, underscoring their potential impact on immune infiltration. We also identified expression patterns of immune-related genes associated with responses against various immune cell types, including CXCL, MIF, GDF, SPP1, and IL16. Finally, our pharmacogenomic screening identified potential small molecule drugs capable of effectively targeting breast cancer cells with elevated MiCU1/2 expression. Overall, our study establishes MiCU1/2 as a promising novel biomarker for BRCA diagnosis and prognostic prediction, as well as a potential therapeutic target, highlighting the importance of exploring these pathways to advance patient care and outcomes in BRCA treatment.

Investigating the impact of STING pathway activation on breast cancer treatment outcomes: development and validation of a prognostic model.

Breast cancer (BRCA) is a significant cause of cancer-associated mortality across the globe. Current therapeutic approaches face challenges such as drug resistance and metastasis. Immune signaling is triggered by chromosomal instability (CIN) generates misplaced DNA structures that activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, triggering. Studies have linked STING activation to BRCA treatment. The bulk RNA-seq data for patients with BRCA were collected from the TCGA-BRCA cohort, GSE20685, and GSE96058 cohorts. STING pathway-related genes (SRGs) were obtained from the Reactome database. Differentially expressed genes were analyzed using the limma package. Immune cell infiltration was analyzed using the IOBR package. Gene Ontology biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, and cancer hallmark pathways were analyzed using the MSigDB database. Prognostic models were prepared using the least absolute shrinkage and selection operator and multiple-factor Cox regression analysis. Single-cell analysis was performed using the Seurat and SCP pipeline. The expression patterns and clinical relevance of SRGs were analyzed in patients with BRCA. Transcriptional differences in the SRGs were observed between normal and tumorous tissues, with global down-regulated STING1 and up-regulated TBK1 in BRCA tissue. Tumor tissues were classified through consensus clustering analysis into two distinct groups, with differences in clinical characteristics and immune infiltration. A prognostic model related to the differences in STING pathway activity-high prognostic stratification potency-was developed and validated. Correlation analysis revealed suppressed overall immune activation in patients with BRCA having higher risk scores. Gemcitabine had a more favorable outcome in the low-risk group. The activity of the prognostic model at the single-cell level was confirmed through single-cell analysis, particularly in CD8 T cells and intratumor natural killer cells. A STING pathway-related prognostic model developed and validated and the model could accurately predict BRCA patient outcomes. These findings have important implications for the personalized treatment and management of patients with BRCA.

Clinicopathological Features and Treatment Outcomes of Male Breast Cancer in Pakistani Population: A 10-Year Retrospective Cross-Sectional Study.

Male breast cancer (MBC) accounts for 1% of global breast cancer cases. On account of its rarity, very few prospective clinical trials have been carried out on MBC. Pakistan has the highest incidence of breast cancer in Asia, but very limited data are available on MBC. The objective is to determine the clinicopathological characteristics and treatment patterns of MBC in Pakistani population. This is a retrospective cross-sectional study. A retrospective cross-sectional study carried out using the cancer database of Shaukat Khanum Memorial Cancer Hospital & Research Center. Men with a histologically proven breast cancer, stage 0 to III disease and requiring surgical intervention were included. The Kaplan-Meier curve and log-rank test were used for survival analysis. Sixty-eight patients with MBC were included with a median age at diagnosis of 55 years. Most patients were stage II (47.1%). Invasive ductal carcinoma (IDC) was the commonest type (89.7%). Estrogen receptor (ER), progesterone receptor (PR), and Her-2 receptor positivity were 92.6%, 86.8%, and 32.4%, respectively. Mastectomy was performed in 95.6% of the cases. Neoadjuvant and adjuvant chemotherapy was administered in 25 (36.8%) and 26 (38.2%) patients, respectively. Fifty-five (80.9%) patients received adjuvant radiotherapy. Most of the patients (89.7%) received tamoxifen. The 5-year overall and disease-free survival was 88.2% and 80.9%, respectively. Patients receiving neoadjuvant chemotherapy had a better overall and disease-free survival (P = .025). Male breast cancer occurs at a relatively earlier age in Pakistani population as compared with Western men. Mastectomy is the preferred surgical option for MBC on account of the advanced disease and delayed presentation. Neoadjuvant chemotherapy has a statistically significant effect on overall and disease-free survival, but in spite of these benefits, it remains underutilized.

A Multioutput Classifier Model for Breast Cancer Treatment Prediction

A growing number of new cases and fatalities occur each year due to breast cancer, making it the most frequent malignancy globally. Utilizing a multioutput classifier technique with algorithms such as CatBoost, XGBoost, NN, and NN Binary, this work presents a new model for predicting breast cancer treatments: surgery, radiotherapy, and chemotherapy. We tackle the pressing need for accurate medical treatments by developing a model to enhance the predicted accuracy of breast cancer treatment outcomes. The model accomplishes impressive results in predicting surgical outcomes; in particular, Neural Networks (NN and NN Binary) perform exceptionally well in terms of recall and precision, reaching 97% accuracy and 98% F1-scores. While the model's accuracy is only about 63% for radiotherapy, it shows a promising recall of up to 84%. Accuracy and precision in chemotherapy predictions remain stable at 82%, with AUC-ROC values of up to 89%, suggesting excellent discrimination ability. By combining multioutput classifiers with sophisticated algorithms, we hope to make treatment prediction models more tailored to individual breast cancer patient profiles, which might usher in a new era of tailored treatment plans and meet the rising demand for precision medicine in cancer care.

Social inequalities in the use of physiotherapy in women diagnosed with breast cancer in Barcelona: DAMA cohort

PurposeThis study aimed to analyze social inequalities in the use and access of physiotherapy service and its clinical and socio-economic determinants in women diagnosed with breast cancer in the hospital network of Barcelona.MethodsData from 2235 women belonging to the mixed (prospective and retrospective) DAMA Cohort were analyzed, including demographic, socio-economic, clinical, and breast cancer treatment outcomes. To determine the influence of such variables on access to physiotherapy, different Poisson regression models with robust variance (obtaining Prevalence Ratios and confidence intervals) were estimated.ResultsAlthough when experiencing different chronic and acute symptoms, only between 20 and 35% of women visited physiotherapist. Two out of 3 women reported to have received insufficient information about medical care and rehabilitation. Age of women, job occupation, education level, having a mutual or private insurance, as well as outcomes related to breast cancer, appear to be factors influencing the access to physiotherapy.ConclusionsSocial and economic inequalities exist on the access to physiotherapy by women diagnosed with breast cancer, which is generally low, and may clearly impact on their functional recovery. Promoting strategies to reduce social bias, as well as improve communication and patient information regarding physiotherapy may be of interest for a better health care in breast cancer diagnosed women.

Abstract A127: Comparing outcomes in breast cancer treatment between fee-for-service and Medicare Advantage patients

Abstract Introduction: Relative to Medicare beneficiaries receiving care through the traditional fee-for-service system (FFS), the percentage of Americans covered by Medicare Advantage (MA) plans has increased over the last decade. As more patients enroll in MA plans, the comparison of outcomes between FFS and MA groups has gained renewed importance. Ohio has a high penetration of MA plans, but differences in outcomes between FFS and MA plans in Ohio is under-studied. Breast cancer is the second most common type of cancer among women, therefore understanding nuances in breast cancer treatment outcomes has broad applicability. In this study, we compare receipt of standard care, time to treatment initiation (TTI), and overall survival (OS) between FFS and MA women diagnosed with incident breast cancer. Methods: We used the Ohio Cancer Incidence Surveillance System (OCISS) cancer registry data linked with Medicare enrollment files and identified patients diagnosed with local and regionally staged breast cancer between 2011-2016. All variables except for FFS and MA enrollment were derived from the OCISS. We developed logistic regression (for analysis of receipt of standard treatment) and Cox regression models (for analysis of TTI and OS) to evaluate the independent association between FFS/MA status and our outcomes of interest, adjusting for age, race, marital status, type of county of residence, neighborhood poverty level, stage at diagnosis, hormone receptor status, and Medicaid dual enrollment. Standard care was defined as receipt of breast-conserving surgery (BCS) or mastectomy, radiotherapy if BCS was received; chemotherapy if regionally staged; and hormone therapy if hormone receptor positive. Results: 12,349 patients were identified that met our inclusion criteria, with 6,801 and 5,548 patients in the FFS and MA groups at the time of diagnosis, respectively. A slightly higher percentage of MA patients were identified as Black (10.3 vs 8.0% on FFS plans). FFS Medicare patients were found to have similar odds of receiving standard care as patients on MA plans (adjusted odds ratio 0.95 [95% CI: 0.88, 1.03]). We detected no difference in TTI between FFS and MA patients, (adjusted hazard ratio (aHR) 0.98 [95% confidence interval (CI): 0.94, 1.01]), or in OS (aHR 1.06 [95% CI: 0.95, 1.18]). No difference was found in receipt of standard care between Black and White patients (aOR 0.88 [95% CI: 0.76, 1.03]). An interaction term with race found that FFS Black patients had significantly lower odds of receiving standard care than their MA counterparts (aOR 0.70 [95% CI: 0.54, 0.92]). We did not find any significant interaction between MA status and race for OS or TTI. Conclusions: MA plans were not associated with any difference in TTI, OS, nor odds of receiving standard treatment for breast cancer compared to FFS Medicare plans. These findings are reassuring given the growing market share of privately administered MA plans, but raise questions with the notable disparity in receipt of standard care between Black FFS enrollees versus Black MA enrollees. Citation Format: Galen Shearn-Nance, Rishi Sachdev, Long Vu, Weichuan Dong, Johnie Rose, Siran Koroukian. Comparing outcomes in breast cancer treatment between fee-for-service and Medicare Advantage patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A127.

Patient-Reported Outcomes of Omission of Breast Surgery Following Neoadjuvant Systemic Therapy

Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials. To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST). Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer with no pathologic evidence of residual disease following standard NST enrolled from March 6, 2017, to November 9, 2021. Validated PRO measures were administered at baseline and 6, 12, and 36 months post-radiotherapy. Data were analyzed from January to February 2023. PRO measures included the Decision Regret Scale (DRS), Functional Assessment of Cancer Therapy-Lymphedema (FACT-B+4), and Breast Cancer Treatment Outcomes Scale (BCTOS). Changes in PRO measure scores and subscores over time. Among 31 patients, the median (IQR) age was 61 (56-66) years, 26 (84%) were White, and 26 (84%) were non-Hispanic. A total of 15 (48%) had triple-negative disease and 16 (52%) had ERBB2-positive disease. Decisional comfort was high at baseline (median [IQR] DRS score 10 [0-25] on a 0-100 scale, with higher scores indicating higher decisional regret) and significantly increased over time (median [IQR] DRS score at 36 months, 0 [0-20]; P < .001). HRQOL was relatively high at baseline (median [IQR] FACT-B composite score 121 [111-134] on a 0-148 scale, with higher scores indicating higher HRQOL) and significantly increased over time (median [IQR] FACT-B score at 36 months, 128 [116-137]; P = .04). Perceived differences between the affected breast and contralateral breast were minimal at baseline (median [IQR] BCTOS score 1.05 [1.00-1.23] on a 1-4 scale, with higher scores indicating greater differences) and increased significantly over time (median [IQR] BCTOS score at 36 months, 1.36 [1.18-1.64]; P < .001). At 36 months postradiotherapy, the cosmetic subscore was 0.45 points higher than baseline (95% CI, 0.16-0.74; P = .001), whereas function, pain, and edema subscores were not significantly different than baseline. In this nonrandomized phase 2 clinical trial, analysis of PROs demonstrated an overall positive experience for trial participants, with longitudinal improvements in decisional comfort and overall HRQOL over time and minimal lasting adverse effects of therapy. ClinicalTrials.gov Identifier: NCT02945579.

9-OR - Exploring the Relationship Between Obesity and Breast Cancer Treatment Outcomes

9-OR - Exploring the Relationship Between Obesity and Breast Cancer Treatment Outcomes

Association of body composition and surgical outcomes in patients with early-stage breast cancer.

Breast cancer is a disease that requires multimodality treatment, and surgical resection of the tumor is a critical component of curative intent treatment. Obesity, defined as a body mass index (BMI) > 30, has been associated with increased surgical complications. Additionally, sarcopenia, a condition of gradual loss of muscle mass, has been associated with worse breast cancer treatment outcomes. Sarcopenia occurs with increased age, inactivity, and poor diet leading to patient frailty, which can increase medical treatment complications. Even patients with high BMI can have sarcopenia (termed sarcopenic obesity). We investigated the association of sarcopenia with surgical complications for breast cancer. A retrospective review was performed of patients diagnosed with breast cancer who received bioelectrical impedance spectrometry analysis of skeletal muscle mass and had surgery at our institution. Patient characteristics, treatment data, surgical type and complications were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status and BMI with surgical complications, adjusted for other patient characteristics. We analyzed 682 patients with stage I to III breast cancer. On multivariable logistic regression controlling for age, BMI, comorbidities, and types of surgeries (lumpectomy, mastectomy with or without reconstruction), sarcopenia (p = 0.66) was not associated with surgical complications. Obesity was associated with a higher rate of surgical complications in patients who received mastectomy with reconstruction (p = 0.01). More complex surgical approaches were associated with a higher risk of surgical complications in our series. Compared with those undergoing lumpectomy or mastectomy without reconstruction, patients undergoing mastectomy with reconstruction were more likely to experience postoperative complications and obesity was associated with higher risk of complication in the latter group. We did not identify a correlation between sarcopenia and rate of adverse surgical outcomes.

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigenetic activity may inform the therapeutic response. We conclude by providing perspectives on the future of therapeutic targeting of epigenetic enzymes, an approach that holds untapped potential to improve breast cancer patient outcomes.

Natural killer cell-related prognostic risk model predicts prognosis and treatment outcomes in triple-negative breast cancer.

Natural killer (NK) cells are crucial to the emergence, identification, and prognosis of cancers. The roles of NK cell-related genes in the tumor immune microenvironment (TIME) and immunotherapy treatment are unclear. Triple-negative breast cancer (TNBC) is a highly aggressive malignant tumor. Hence, this study was conducted to develop a reliable risk model related to NK cells and provide a novel system for predicting the prognosis of TNBC. NK cell-related genes were collected from previous studies. Based on TCGA and GEO database, univariate and LASSO cox regression analysis were used to establish the NK cell-related gene signature. The patients with TNBC were separated to high-risk and low-risk groups. After that, survival analysis was conducted and the responses to immunotherapies were evaluated on the basis of the signature. Moreover, the drug sensitivity of some traditional chemotherapeutic drugs was assessed by using the "oncoPredict" R package. In addition, the expression levels of the genes involved in the signature were validated by using qRT-PCR in TNBC cell lines. The patients with TNBC were divided into high- and low-risk groups according to the median risk score of the 5-NK cell-related gene signature. The low-risk group was associated with a better clinical outcome. Besides, the differentially expressed genes between the different risk groups were enriched in the biological activities associated with immunity. The tumor immune cells were found to be highly infiltrated in the low-risk groups. In accordance with the TIDE score and immune checkpoint-related gene expression analysis, TNBC patients in the low-risk groups were suggested to have better responses to immunotherapies. Eventually, some classical anti-tumor drugs were shown to be less effective in high-risk groups than in low-risk groups. The 5-NK cell-related gene signature exhibit outstanding predictive performance and provide fresh viewpoints for evaluating the success of immunotherapy. It will provide new insights to achieve precision and integrated treatment for TNBC in the future.

Plasma cell-free tumor DNA, PIK3CA and TP53 mutations predicted inferior endocrine-based treatment outcome in endocrine receptor-positive metastatic breast cancer

PurposeHow to factor both tumor burden and oncogenic genomic mutations as variables to predict the outcome of endocrine-based therapy (ET) in ER-positive/HER2-negative metastatic breast cancer patients (MBC) remains to be explored.MethodBlood samples prospectively collected from 163 ER-positive/HER2-negative female MBC patients, before ET, were used for cell-free tumor DNA (cfDNA) analysis. cfDNA was subjected to next-generation sequencing (NGS) to interrogate oncogenic PIK3CA hotspot and TP53 DNA-binding domain (DBD) mutations, including single nucleotide variants (SNVs) or small insertions and deletions (InDels). The variant calling threshold was set at 0.5%. Progression-free survival (PFS) was measured from the start of the ET treatment to the time of disease progression of the same treatment regimen.ResultsOverall, the median PFS was 8.3 months (95% CI 5.7–11.1 months). The median cfDNA was 38.5 ng (range 4.4–1935 ng). The proportion of patients with PIK3CA and TP53 alterations were 25.1 and 15.3%, respectively. Patients with high total cfDNA (HR 1.74, p = 0.003), PIK3CA mutation (HR 1.74, p = 0.007), and TP53 mutation (HR 1.64, p = 0.047) in liquid biopsy conferred worse outcome after ET. Even for patients with low tumor burden, the detrimental effect of PIK3CA or TP53 mutation remained significant (p < 0.001). For patients with either PIK3CA (p < 0.001) or TP53 mutation (p = 0.004), there was significant positive correlation between allele frequency (AF) and total cfDNA.ConclusionAfter adjustment of cfDNA level, PIK3CA and TP53 mutations observed in liquid biopsy exerted detrimental effects on the outcome of ET-based regimens. The AF of PIK3CA or TP53 may be a surrogate marker for PFS.

The role of tumor-infiltrating lymphocytes in triple-negative breast cancer and the research progress of adoptive cell therapy.

The treatment outcome of breast cancer is closely related to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Triple-negative breast cancer (TNBC) lacking ER, PR, and HER2 expression has limited treatment options and a poor prognosis. Tumor-infiltrating lymphocytes (TILs) play a role in promoting or resisting tumors by affecting the tumor microenvironment and are known as key regulators in breast cancer progression. However, treatments for TNBC (e.g., surgery, chemotherapy and radiotherapy) have non-satisfaction's curative effect so far. This article reviews the role of different types of TILs in TNBC and the research progress of adoptive cell therapy, aiming to provide new therapeutic approaches for TNBC.

Breast Cancer Treatment Outcomes for Sex &amp; Gender Minority Patients

Breast Cancer Treatment Outcomes for Sex &amp; Gender Minority Patients

Abstract 2247: Evaluation of multidrug resistant genes among breast cancer patients in Ghana

Abstract Background: Breast cancer (BC) is a leading cause of cancer death in Ghana and around the world. Ghanaian women are diagnosed at younger ages with the more aggressive Triple Negative BC (TNBC) subtype where West African ancestry is associated with advanced BC diagnosis and higher mortality rates compared to age-matched women of European ancestry. Genomic comparisons of BC tumors from women of African and European ancestry show differences in frequencies of single nucleotide polymorphisms (SNP) and copy number variations. These differences may contribute to disparities in disease and treatment outcomes observed in women of African ancestry. Chemotherapy plays a major role in treatment of recurrent and metastatic BC. Long-term BC survival remains poor especially in Africa due to multidrug resistance (MDR). MDR has been associated with binding cassette (ABC) protein transporters. ABCB1, ABCC1 and ABCG2 are ABC transporter genes that code for proteins involved in drug efflux. We hypothesize that SNPs in ABC transporter genes may alter their physiological protective role and increase risk of MDR, treatment failure and death among BC patients. Preliminary dataWe explored gene expression profiles of ABCB1, ABCC1 and ABCG2 in an African ancestry-enriched subset of women with TNBC (ICSBCS cohort: Ghanaian n = 6, African American (AA) n = 9, Ethiopian n = 11). Preliminary data showed significantly higher expression of ABCC1 among Ghanaian and AA patients compared to Ethiopians, and a significant positive correlation with African ancestry. ABCB1 and ABCG2 showed lower expression in all three groups (ns).To study the relationship between ABC transporter gene SNPs and MDR, we have collected data over a 3-year period (2019-2021) from the Oncology Department of the Komfo Anokye Teaching Hospital in Ghana. The overall prevalence of BC recurrence was 3.4% (CI = 2.5 - 4.7%), and prevalence of metastatic BC was 47.6% (CI = 44.6 - 50.6%). Methodology: SNPs in ABC transporter genes will be obtained from 150 consented female BC patients who have undergone chemotherapy. We will compare genotype frequencies among patients with disease recurrence and/or metastasis (n = 100) to those with no disease recurrence or metastasis (n = 50). Single-plex genotyping of the ABC gene SNPs will be completed using a real-time PCR allelic discrimination assay. Conclusion: ABCC1 has been established to be associated with African ancestry. Determining the association of ABC gene SNPs and MDR among Ghanaian BC patients will provide further information on allelic variants and their effects on BC treatment outcomes. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Melissa B. Davis, Lisa Newman, Brian Stonaker, Linda Ahenkorah Fondjo, Christian Obirikorang, Ernest Osei Bonsu, Ernest Adjei, Ishmael Kyei, Mavis Bobie Ansah, Mahteme Bekele, Timothy Chu, Nicolas Robine. Evaluation of multidrug resistant genes among breast cancer patients in Ghana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2247.

Цифрлық және аналогтық рентген-маммографиялық аппараттарды қолдану кезіндегі сәулелік жүктемені салыстырмалы бағалау

In medical practice, X-ray examinations play an important role in making an accurate diagnosis and monitoring the treatment quality. X-ray examination is the use of X-ray radiation to examine a patient in order to diagnose and prevent diseases consisting of one or more radiological procedures. Target radiography is a method of X-ray examination that allows obtaining a flat image of a limited part of the organ under study. Mammography is the most extensive method to diagnose breast cancer. With its help, it is possible to identify pathological changes in tissues and formations at any stage. The average age of patients diagnosed with breast cancer is 61.5 years. The outcome of breast cancer treatment directly depends on the identified stage of tumor, therefore early diagnosis of breast cancer has become one of the most urgent problems. Before the age of 40, mammography is not recommended as a screening, because breast cancer happens rarely at this age. Mammography is carried out for preventive purposes once in 2 years starting from the age of 40, and annually between the age of 50 to 60, and after that – once in 2 years. The purpose of this article is to make a comparative assessment of radiation load when using digital and analog X-ray mammography devices. The article compared and evaluated the possibility of reducing radiation exposure during analog and digital mammography.

Abstract P1-04-01: High HER2/CEP17 ratio is associated with better treatment outcomes in advanced HER2-positive breast cancer treated with pertuzumab, trastuzumab, and docetaxel regardless of HER2 2+ or 3+ results

Abstract Background: Dual HER2 blockade with trastuzumab and pertuzumab combined with docetaxel (DHP) is the standard first-line treatment option for patients with HER2-positive metastatic breast cancer. However, HER2 positivity alone often fails to predict treatment outcome of HER2 targeted therapy. The magnitude of HER2 immunohistochemical staining (IHC) and HER2/CEP17 ratio from in situ hybridization (ISH) is a well-known predictive biomarker for HER2 targeted therapy. In the neo-adjuvant setting, patients with HER2 IHC 3+ have higher pathologic complete response (pCR) rate compared to HER2 IHC&amp;lt; 3+ with HER2 ISH positive. In addition, higher HER2/CEP17 ratio is associated with higher pCR rate in HER2-positive breast cancer patients treated with dual HER2 blockade regimens. However, there is no data whether there is an association between HER2/CEP17 ratio and treatment outcome of DHP regimen in patients with advanced of metastatic breast cancer especially among those with HER2 IHC 3+. Methods: We performed a retrospective cohort study with patients with locally advanced or metastatic HER2-positive breast cancer who were treated with first-line palliative DHP regimen between August 2008 and January 2021 at Seoul National University Hospital. In the clinical setting, HER2 IHC 3+ is defined as HER2 positive and no further ISH testing is required. Additional ISH was performed in patients with HER2 IHC 3+ without archival HER2 ISH results. The association between HER2/CEP17 ratio and treatment outcome was assessed. Results: In total, 165 patients were included with a median follow-up duration of 28.0 months. Among the 165 patients, 35 patients had archival ISH result and additional ISH was performed in 53 patients. The correlation between HER2/CEP17 ratio and treatment outcome was assessed in 88 patients. Cox proportional hazard analysis revealed that HER2/CEP17 ratio is correlated with PFS (HR 0.23, 95% CI 0.11-0.49, p &amp;lt; 0.001). When dichotomized by the median HER2/CEP17 ratio of 4.17, patients with higher HER2/CEP17 ratio had significantly longer PFS (37.5 vs. 17.4 months, p = 0.003) and numerically higher ORR (54.5% vs. 34.1%, p = 0.085). Multivariate analysis revealed that HER2/CEP17 ratio is an independent prognostic factor for PFS (HR 0.72, p = 0.001). Of 88 patients with ISH results, 25 had HER2 IHC 1+ or 2+ and 63 had HER2 IHC 3+. HER2/CEP17 ratio was associated with PFS in both HER2 IHC 1+/2+ patients (HR 0.12, 95% CI 0.02-0.88, p = 0.037) and HER2 IHC 3+ patients (HR 0.18, 95% CI 0.07-0.49, p = 0.001). Patients with higher HER2/CEP17 ratio had longer PFS in both HER2 IHC 1+/2+ patients (28.6 vs. 12.9 months, p = 0.003) and HER2 IHC 3+ patients (Not reached vs. 18.3 months, p = 0.005) when dichotomized by the median HER2/CEP17 of 2.95 and 4.75, respectively. Conclusion: This is the first study to report that higher HER2/CEP17 ratio is associated with longer PFS in HER2-positive advanced breast cancer patients treated with palliative first-line DHP. The strength of this study is that we identified prognostic role of ISH even in patients with HER2 IHC 3+. It would be helpful to perform ISH not only in patients whose HER2 IHC is ambiguous, but also in patients with HER2 IHC 3+ to make better prediction of treatment outcome. Table 1. Patient characteristics. Citation Format: Jeongmin Seo, Jiwon Koh, Dae-Won Lee, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im. High HER2/CEP17 ratio is associated with better treatment outcomes in advanced HER2-positive breast cancer treated with pertuzumab, trastuzumab, and docetaxel regardless of HER2 2+ or 3+ results [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 P1-04-01.

Factors Affecting Treatment Outcome of Metastatic Breast Cancer: Single Institution Study

BACKGROUND: Metastatic breast cancer (MBC) is an incurable disease. AIM: The goal of therapy is to prolong survival and amelioration of quality of life. However, the benefit of later systemic treatment lines is not clear. METHODS: This was a retrospective study of 345 MBC patient., assessment of progression free survival (PFS) survival with first line of treatment and second, third, fourth, fifth, and sixth lines of therapy, and analysis of different prognostic factors. RESULTS: The median overall survival (OS) was 31.7 month. The median PFS was 8.1 versus 3 month for first line of treatment and beyond. Where median PFS1, PFS 2, PFS 3, PFS 4, PFS 5, and PFS 6 were 8.1, 5.8, 3.8, 4.8, 3.4, and 2.6, respectively. PFS of first line was significantly prolonged in hormone positive luminal subtype, bone only metastasis, age above 35, ECOG I-II, and oligometastatic (p = 0.041, 0.038, 0.023, 0.034, 0.0001, and 0.001, respectively). Post-progression survival was 23.4 months and it was significantly prolonged in hormone positive luminal subtype, bone only metastasis, age above 35, ECOG I-II and PFS more than 6 months with first line. CONCLUSION: PFS is reduced with using more treatment lines in MBC. Patients with luminal subtype, bone only metastasis, age above 35, ECOG I-II, and PFS more than 6 months with first line may have the best benefit from later lines.

PI3K inhibitor promotes tumor vessel normalization and improves treatment outcomes of breast cancer with doxorubicin

HS-173 is a specific inhibitor of the Phosphoinositide 3-Kinase α (PI3Kα) subtype. Although it was shown to potentially inhibit tumor angiogenesis, experimental validation studies are still needed. This study provides an experimental basis for the role of HS-173 in breast cancer. A mouse model of subcutaneous transplantation breast cancer was constructed. The mice were treated with different concentrations of HS-173. Immunohistochemical staining was used to detect tumor microvessel density, and the appropriate concentration was determined. Immunofluorescence was used to detect the morphology integrity of tumor vessels’ lumen, transmission electron microscopy to detect tight junctions between endothelial cells and the integrity of the basement membrane, Doppler ultrasound to detect tumor blood perfusion, and small animal live imaging to detect the penetration of doxorubicin in the tumor tissues. After HS-173 treatment, the number of tumor interstitial microvessels decreased, the lack of tumor vascular lumen was reduced, and the continuity and integrity of the vascular lumen were increased. Vascular endothelial cells showed complete morphology with good tight junctions. The extracellular matrix was rich in components and tended to form basement membranes. HS-173 also increased the blood perfusion in the tumor tissue compared with the doxorubicin treatment alone. Further, the fluorescence signal intensity of the tumor tissue doxorubicin was significantly enhanced after HS-173 treatment. The PI3K inhibitor HS-173 showed promising potential in inhibiting tumor angiogenesis and improving the structure and function of blood vessels in the tumor microenvironment.