Metastatic Breast Cancer Patients Research Articles

Characteristics of regional lymph node metastasis in breast cancer and construction of a nomogram model based on ultrasonographic analysis: a retrospective study

ObjectiveThe ultrasonographic characteristics of lymph node metastasis in breast cancer patients were retrospectively analyzed, and a predictive nomogram model was constructed to provide an imaging basis for better clinical evaluation.MethodsB-mode ultrasound was used to retrospectively analyze the imaging characteristics of regional lymph nodes and tumors. Pathological examination confirmed the presence of lymph node metastasis in breast cancer patients. Univariable and multivariable logistic regression analyses were performed to analyze the risk factors for lymph node metastasis. LASSO regression analysis was performed to screen noninvasive indicators, and a nomogram prediction model was constructed for breast cancer patients with lymph node metastasis.ResultsA total of 187 breast cancer patients were enrolled, including 74 patients with lymph node metastasis in the positive group and 113 patients without lymph node metastasis in the negative group. Multivariate analysis revealed that pathological type (OR = 4.58, 95% CI: 1.44–14.6, p = 0.01), tumor diameter (OR = 1.37, 95% CI: 1.07–1.74, p = 0.012), spiculated margins (OR = 7.92, 95% CI: 3.03–20.67, p < 0.001), mixed echo of the breast tumor (OR = 37.09, 95% CI: 3.49–394.1, p = 0.003), and unclear lymphatic hilum structure (OR = 16.07, 95% CI: 2.41–107.02, p = 0.004) were independent risk factors for lymph node metastasis. A nomogram model was constructed for predicting breast cancer with lymph node metastasis, incorporating three significantly correlated indicators identified through LASSO regression analysis, namely, tumor spiculated margins, cortical thickness of lymph nodes, and unclear lymphatic hilum structure. The receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.717 (95% CI, 0.614–0.820) for the training set and 0.817 (95% CI, 0.738–0.890) for the validation set. The Hosmer–Lemeshow test results for the training set and the validation set were p = 0.9148 and p = 0.1648, respectively. The prediction nomogram has good diagnostic performance.ConclusionsB-mode ultrasound is helpful in the preoperative assessment of breast cancer patients with lymph node metastasis. The predictive nomogram model, which is based on logistic regression and LASSO regression analysis, is clinically safe, reliable, and highly practical.

PIK3CA mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer

In metastatic breast cancer (MBC), blood is a source of circulating tumor cells (CTCs). CTCs may serve as a ‘‘real-time liquid biopsy” as they represent metastatic tumor genetics better than primary tumor. PIK3CA is one of the most important oncogenes in treatment-unresponsive breast cancers. The aim of this study was to detect PIK3CA mutations and hereditary cancer variants in CTCs from MBC patients. Forty-seven blood samples were obtained from 20 MBC patients from at least 1/3 consecutive time points. CTCs were quantified using the CellSearch system and isolated from 11/20 patients with ≥5/7.5 ml CTCs (14/47 blood samples) using the DEPArray system. DNA was extracted and amplified to perform Sanger sequencing on PIK3CA gene. Sequencing revealed a pathogenic PIK3CA mutation in 2/11 (18 %) cases. Subsequently, we evaluated a 26-target hereditary gene panel by Next Generation Sequencing and identified a concomitant pathogenic mutation in the TP53 gene in a patient with a PIK3CA mutation. No pathogenic germline variants were found. Our data support the conclusion that CTCs analysis may be used to identify mutations in patients to identify those more likely to metastasize.

Status of incremental costs of first-line treatment recommended in Japanese clinical guidelines for metastatic breast cancer patients.

The increasing incidence and prevalence of breast cancer alongside diagnostic and treatment technology advances have produced a debate about the financial burden cancer places on the healthcare system and concerns about access. This study was conducted at 51 hospitals belonging to the Breast Cancer Study Group of the Japan Clinical Oncology Group using a web-based survey. The survey period conducted from July 2021 to June 2022. The study population included patients with metastatic breast cancer who received the related treatment as their first-line therapy. The proportion of patients who selected that regimen as their first-line treatment was tabulated. The total cost increase for each current standard therapy in comparison to conventional treatments was calculated. A total of 702 patients (pts) were surveyed. Of those enrolled, 342 (48.7%) received high-cost treatment [estimated monthly drug costs exceeding ~500 000 Japanese Yen (JPY)]. Of these, 16 pts (4.7%) were receiving very high-cost treatment, amounting to more than 1 000 000 JPY per month. Fifty three (15.5%) of the patients who received high-cost treatment were 75years of age or older. Of these, 1pt (0.3%) were receiving very high-cost treatment. Analyses of incremental costs by current drugs showed that abemaciclib was costly with total additional cost of 6 365 670 JPY per patient. The total additional cost of the regimen per patient that included palbociclib was the second highest at 4011248 JPY, followed by atezolizumab at 3209033 JPY. The findings indicate that evaluating the financial implications of high-cost treatments requires considering not only drug prices but also analysis of total cost increase.

Identification of circulating tumor cells captured by the FDA-cleared Parsortix® PC1 system from the peripheral blood of metastatic breast cancer patients using immunofluorescence and cytopathological evaluations

Circulating Tumor Cells (CTCs) may serve as a non-invasive source of tumor material to investigate an individual’s disease in real-time. The Parsortix® PC1 System, the first FDA-cleared medical device for the capture and harvest of CTCs from peripheral blood of metastatic breast cancer (MBC) patients for use in subsequent user-validated downstream analyses, enables the epitope-independent capture of CTCs with diverse phenotypes based on cell size and deformability. The aim of this study was to determine the proportion of MBC patients and self-declared female healthy volunteers (HVs) that had CTCs identified using immunofluorescence (IF) or Wright-Giemsa (WG) staining. Peripheral blood from 76 HVs and 76 MBC patients was processed on Parsortix® PC1 Systems. Harvested cells were cytospun onto a charged slide and immunofluorescently stained for identification of CTCs expressing epithelial markers. The IF slides were subsequently WG-stained and analyzed for CTC identification based on morphological features of malignant cells. All testing was performed by operators blinded to the clinical status of each subject. CTCs were identified on the IF slides in 45.3% (≥ 1) / 24.0% (≥ 5) of the MBC patients (range = 0 – 125, mean = 7) and in 6.9% (≥ 1) / 2.8% (≥ 5) of the HVs (range = 0 – 28, mean = 1). Among the MBC patients with ≥ 1 CTC, 70.6% had only CK + /EpCAM- CTCs, with none having EpCAM + /CK- CTCs. CTC clusters were identified in 56.0% of the CTC-positive patients. On the WG-stained slides, CTCs were identified in 42.9% (≥ 1) / 21.4% (≥ 5) of the MBC patients (range = 0 – 41, mean = 4) and 4.3% (≥ 1) / 2.9% (≥ 5) of the HVs (range = 0 – 14, mean = 0). This study demonstrated the ability of the Parsortix® PC1 System to capture and harvest CTCs from a significantly larger proportion of MBC patients compared to HVs when coupled with both IF and WG cytomorphological assessment. The presence of epithelial cells in subjects without diagnosed disease has been previously described, with their significance being unclear. Interestingly, a high proportion of the identified CTCs did not express EpCAM, highlighting the limitations of using EpCAM-based approaches.

Effect of HER2-low status on brain metastasis-free survival and survival after brain metastasis in patients with breast cancer.

The discovery of novel human epidermal growth factor receptor 2 (HER2)-directed antibody‒drug conjugates has accelerated the identification of the HER2-low subtype. However, the biological significance of low HER2 expression in breast cancer brain metastasis (BCBM) is unclear. Patients with HER2-negative BC and brain metastasis were retrospectively screened between February 2012 and November 2023. Brain metastasis-free survival (BMFS) and survival after brain metastasis (SABM) were analyzed according to HER2 expression. A total of 201 female patients, 84 of whom were HER2-low and 117 of whom were HER2-zero, were evaluated. The median BMFS in the entire cohort was 35.6months (95% CI 29.8-41.4). Although HER2-low patients had numerically longer median BMFS than HER2-zero patients (43.7m vs. 30.1m, p = 0.025), multivariate analysis revealed that the difference was not significant (p = 0.167). BMFS between the HER2-low and HER2-zero groups was similar in the hormone receptor (HR)-positive (52.8m vs. 47.6m, p = 0.276) and HR-negative (15.3m vs. 19.7m, p = 0.930) cohorts. The median SABM in the entire cohort was 6.0months (95% CI 3.8-8.1). HER2-low and HER2-zero patients had similar median SAMB (5.4m vs. 6.1m, p = 0.816). The SABM between the HER2-low and HER2-zero groups was similar in the HR-positive (6.3m vs. 8.7m, p = 0.375) and HR-negative (3.3m vs. 4.2m, p = 0.783) cohorts. Low HER2 expression does not affect BMFS or SAMB in brain metastatic breast cancer patients in this real-world population.

Enhanced anti-tumor effects by combination of tucatinib and radiation in HER2-overexpressing human cancer cell lines

BackgroundTucatinib (TUC), a HER2-directed tyrosine kinase inhibitor, is the first targeted drug demonstrating intracranial efficacy and significantly prolonged survival in metastatic HER2-positive breast cancer (BC) patients with brain metastases. Current treatments for brain metastases often include radiotherapy, but little is known about the effects of combination treatment with TUC. Therefore, we examined the combined effects of irradiation and TUC in human HER2-overexpressing BC, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) cell lines. For the latter two, a standard therapy successfully targeting HER2 is yet to be established.MethodsNine HER2-overexpressing (BC: BT474, ZR7530, HCC1954; CRC: LS411N, DLD1, COLO201; NSCLC: DV90, NCI-H1781) and three control cell lines (BC: MCF7, HCC38; NSCLC: NCI-H2030) were examined. WST-1 assay (metabolic activity), BrdU ELISA (proliferation), γH2AX assay (DNA double-strand breaks (DSB), Annexin V assay (apoptosis), and clonogenic assay (clonogenicity) were performed after treatment with TUC and/or irradiation (IR). The relevance of the treatment sequence was analyzed exemplarily.ResultsIn BC, combinatorial treatment with TUC and IR significantly decreased metabolic activity, cell proliferation, clonogenicity and enhanced apoptotis compared to IR alone, whereby cell line-specific differences occurred. In the PI3KCA-mutated HCC1954 cell line, addition of alpelisib (ALP) further decreased clonogenicity. TUC delayed the repair of IR-induced DNA damage but did not induce DSB itself. Investigation of treatment sequence indicated a benefit of IR before TUC versus IR after TUC. Also in CRC and NSCLC, the combination led to a stronger inhibition of metabolic activity, proliferation, and clonogenic survival (only in NSCLC) than IR alone, whereby about 10-fold higher concentrations of TUC had to be applied than in BC to induce significant changes.ConclusionOur data indicate that combination of TUC and IR could be more effective than single treatment strategies for BC. Thereby, treatment sequence seems to be an important factor. The lower sensitivity to TUC in NSCLC and particularly in CRC (compared to BC) implicates, that tumor promotion there might be less HER2-related. Combination with inhibitors of other driver mutations may aid in overcoming partial TUC resistance. These findings are of high relevance to improve long-time prognosis especially in brain-metastasized situations given the intracranial activity of TUC.

Development and validation of an artificial intelligence model for predicting de novo distant bone metastasis in breast cancer: a dual-center study

ObjectiveBreast cancer has become the most prevalent malignant tumor in women, and the occurrence of distant metastasis signifies a poor prognosis. Utilizing predictive models to forecast distant metastasis in breast cancer presents a novel approach. This study aims to utilize readily available clinical data and advanced machine learning algorithms to establish an accurate clinical prediction model. The overall objective is to provide effective decision support for clinicians.MethodsData from 239 patients from two centers were analyzed, focusing on clinical blood biomarkers (tumor markers, liver and kidney function, lipid profile, cardiovascular markers). Spearman correlation and the least absolute shrinkage and selection operator regression were employed for feature dimension reduction. A predictive model was built using LightGBM and validated in training, testing, and external validation cohorts. Feature importance correlation analysis was conducted on the clinical model and the comprehensive model, followed by univariate and multivariate regression analysis of these features.ResultsThrough internal and external validation, we constructed a LightGBM model to predict de novo bone metastasis in newly diagnosed breast cancer patients. The area under the receiver operating characteristic curve values of this model in the training, internal validation test, and external validation test1 cohorts were 0.945, 0.892, and 0.908, respectively. Our validation results indicate that the model exhibits high sensitivity, specificity, and accuracy, making it the most accurate model for predicting bone metastasis in breast cancer patients. Carcinoembryonic Antigen, creatine kinase, albumin-globulin ratio, Apolipoprotein B, and Cancer Antigen 153 (CA153) play crucial roles in the model’s predictions. Lipoprotein a, CA153, gamma-glutamyl transferase, α-Hydroxybutyrate dehydrogenase, alkaline phosphatase, and creatine kinase are positively correlated with breast cancer bone metastasis, while white blood cell ratio and total cholesterol are negatively correlated.ConclusionThis study successfully utilized clinical blood biomarkers to construct an artificial intelligence model for predicting distant metastasis in breast cancer, demonstrating high accuracy. This suggests potential clinical utility in predicting and identifying distant metastasis in breast cancer. These findings underscore the potential prospect of developing economically efficient and readily accessible predictive tools in clinical oncology.

Significance of zoledronic acid in the adjuvant therapy in patients with breast cancer

Introduction. Zoledronic acid is a medicine belonging to the bisphosphonate group. Its action is to inhibit the function of osteoclasts, which leads to a reduction in bone resorption. This preparation has a proven effect in the treatment of osteoporosis and Paget’s disease. Bisphosphonates have also found use in the treatment of breast cancer. Studies conducted for many years indicate that zoledronic acid works most favorably in combination with adjuvant therapy. Breast cancer patients who are postmenopausal and being treated with chemotherapy are at risk of bone mass loss and hypercalcemia. Bisphosphonates effectively manage this. In addition, zoledronic acid indirectly exerts anticancer effects by modulating the immune system. All this allows us to conclude that taking this drug reduces the risk of bone metastasis in breast cancer patients. Dosage is also key in all this. There are several regimens offered to osteoporosis and breast cancer patients. So far, the following have been studied: conventional dosing (4 mg IV every 3-4 weeks), maintenance dosing (4 mg IV every 3-6 months) and metronomic dosing (1 mg IV weekly). It cannot be ruled out that each of these regimens may have a different antitumor effect. By reviewing scientific works, we aim to present the treatment options with zoledronic acid for breast cancer patients. We will describe the impact on their results depending on the dosage and we will present the other side of the coin, which are the side effects of taking this preparation. Aim. This review provides an overview of the effects and impact of zoledronic acid in adjuvant therapy in patients with breast cancer. Material and methods. The article presents the current state of knowledge on zoledronic acid as an adjuvant treatment option in breast cancer patients. It is a detailed literature review using Google Scholar, PubMed and Journal of Education Health and Sport platforms. Publications using the following key words were analyzed: bisphosphonates, zoledronic acid, osteoporosis, breast cancer, bone metastases. Conclusion. Women diagnosed with breast cancer should be treated in a multidisciplinary manner. We treat early detected cancers to achieve complete remission. Long-term survival is our primary goal, and in pursuing it we should consider the potential impact of this treatment on the patient’s skeletal system. Clinical studies allow us to conclude that there is a correlation between the initiation of antiresorptive therapy at an early stage of cancer and overall survival. Additionally, zoledronic acid significantly reduced the number of fractures. The collected data allow us to conclude that the addition of zoledronic acid to the established treatment regimens has a potentially positive effect on the group of postmenopausal patients undergoing tamoxifen treatment or with existing bone metastases. Keywords: bisphosphonates, zoledronic acid, breast cancer, osteoporosis, bone metastases.

Medicinal Mushrooms in Metastatic Breast Cancer: What Is Their Therapeutic Potential as Adjuvant in Clinical Settings?

Breast cancer (BC) is the most commonly diagnosed tumor, remaining one of the leading causes of morbidity and mortality in females worldwide, with the highest rates in Western countries. Among metastatic BC (MBC), triple-negative breast cancer (TNBC) is characterized by the lack of expression of specific receptors, and differs from other subgroups of BC for its increased growth and fast spreading, with reduced treatment possibilities and a worse outcome. Actually, MBC patients are extremely prone to metastasis and consequent relapses, which affect distant target organs (e.g., brain, lung, bone and liver). Hence, the comprehension of biological mechanisms underlying the BC metastatization process is a key requirement to conceive/set up innovative medicinal strategies, with the goal to achieve long-lasting therapeutic efficacy, reducing adverse effects, and also ameliorating Quality of Life (QoL). Bioactive metabolites isolated from medicinal mushrooms (MMs) used as a supportive treatment, combined with conventional oncology, have recently gained wide interest. In fact, mounting evidence has revealed their peculiar promising immunomodulatory, anti-inflammatory and anticancer activities, even though these effects have to be further clarified. Among the group of most promising MMs are Lentinula edodes, Grifola frondosa, Ganoderma lucidum, Ophiocordyceps sinensis and Agaricus blazei, which are already employed in conventional cancer protocols in Asia and China. Recently, a growing number of studies have focused on the pharmacology and feasibility of MM-derived bioactive compounds as a novel valuable approach to propose an effective adjuvant therapy for MBC patients' management. In this review, we summarized the current state of knowledge on the abovementioned MM-derived bioactive compounds and their therapeutic potential in clinical settings.

Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study

ObjectivePyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. MethodsFrom September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. ResultsThe ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. ConclusionThis study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.

Exploration of multi-layered nanofiber adjuvant implants of doxorubicin and resveratrol to prevent post-surgery tumor recurrence and invasion

Tumor-free survival post-surgical ablation is not durable due to tumor recurrence and metastasis in breast cancer patients. Studies have reported that trauma-prone sites are most vulnerable to the seeding of disseminated tumor cells (DTC) and ultimately tumor recurrence. We have developed Doxorubicin (DOX) and Resveratrol (RES) loaded nanofibers (NFs) to be used as adjuvant implants after surgical removal of the breast tumor. The electrospinning technique was employed to develop the NFs. Cell line evaluations showed synergistic activity of the drug combination on the MDA-MB-231 metastatic cell line. The cell cycle analysis revealed that the DOX and RES arrested the cell cycle in the G2/M and G0/G1 phases, respectively. The scratch assay exhibited that the co-delivery of RES prevented the invasive potential of the MDA-MB-231 cell line. The sustained nature of drug release from the NFs decreased DOX-induced necrotic cell death. The co-delivery of RES and DOX promoted apoptotic cell death in the MDA-MB-231 cell line. Thus, we conclude that the DOX and RES-loaded NFs can be employed as post-surgery adjuvant implants to check tumor recurrence and metastasis.

Using Trastuzumab Deruxtecan to treat advanced metastatic breast cancer in patients with varying HER2 expression levels: A single-center experience in Taiwan.

To observe the clinical outcomes of patients diagnosed with metastatic breast cancer undergoing Trastuzumab Deruxtecan (T-DXd) therapy in a real-world setting. The study retrospectively reviewed and collected medical data from 13 patients at Shin Kong Wu Ho-Su Memorial Hospital who underwent T-DXd treatment over a period from April 2022 to June 2023. Demographics, pathological characteristics, treatment patterns, and outcomes were descriptively analyzed. Thirteen patients diagnosed with metastatic breast cancer underwent T-DXd treatment between April 2022 and June 2023. This study observed that T-DXd was effective in patients with high human epidermal growth factor receptor 2 (HER2) levels. In patients with low HER2, the majority also experienced favorable responses. Only 2 patients exhibited poor or no response: one was a BRCA2 carrier with unmanageable disease progression, and the other had a HER2 1 + status with multiorgan metastases whose cancer was not controlled by T-DXd. Additionally, 2 patients with no HER2 expression responded well to T-DXd treatment. T-DXd is a valuable treatment alternative for patients with breast cancer, including those with HER2-high, HER2-low, and HER2-negative statuses. In this study, the majority of patients experienced positive therapeutic effects. However, this evaluation relied on a limited sample size and short-term observations. Additional studies involving larger and more diverse patient groups and long follow-up durations are required.

Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors - a biomarker analysis of the ALICE and ICON trials.

Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy. Programmed death-ligand 1 (PD-L1) expression on CTCs was also measured. Patients with ≥ 2 CTCs per 7.5 mL at baseline had gene expression profiles in tumor suggestive of increased T-cell activity, including increased tumor inflammation signature (TIS) in both triple-negative (P = 0.010) and hormone receptor-positive (P = 0.024) disease. Patients with luminal A BC had higher CTC levels. The association between CTC status and outcome was most apparent 4 weeks into therapy. PD-L1 expression in CTCs was observed in 6/17 CTC-positive patients and was associated with inferior survival. In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy.

Cardiac safety of ribociclib evaluated with 24-hour rhythm Holter electrocardiogram

ObjectiveWe aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG.Material and methodForty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation.ResultsThe mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference.ConclusionThis is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.

AI models predicting breast cancer distant metastasis using LightGBM with clinical blood markers and ultrasound maximum diameter

Breast cancer metastasis significantly impacts women's health globally. This study aimed to construct predictive models using clinical blood markers and ultrasound data to predict distant metastasis in breast cancer patients, ensuring clinical applicability, cost-effectiveness, relative non-invasiveness, and accessibility of these models. Analysis was conducted on data from 416 patients across two centers, focusing on clinical blood markers (tumor markers, liver and kidney function indicators, blood lipid markers, cardiovascular biomarkers) and maximum lesion diameter from ultrasound. Feature reduction was performed using Spearman correlation and LASSO regression. Two models were built using LightGBM: a clinical model (using clinical blood markers) and a combined model (incorporating clinical blood markers and ultrasound features), validated in training, internal test, and external validation (test1) cohorts. Feature importance analysis was conducted for both models, followed by univariate and multivariate regression analyses of these features. The AUC values of the clinical model in the training, internal test, and external validation (test1) cohorts were 0.950, 0.795, and 0.883, respectively. The combined model showed AUC values of 0.955, 0.835, and 0.918 in the training, internal test, and external validation (test1) cohorts, respectively. Clinical utility curve analysis indicated the combined model's superior net benefit in identifying breast cancer with distant metastasis across all cohorts. This suggests the combined model's superior discriminatory ability and strong generalization performance. Creatine kinase isoenzyme (CK-MB), CEA, CA153, albumin, creatine kinase, and maximum lesion diameter from ultrasound played significant roles in model prediction. CA153, CK-MB, lipoprotein (a), and maximum lesion diameter from ultrasound positively correlated with breast cancer distant metastasis, while indirect bilirubin and magnesium ions showed negative correlations. This study successfully utilized clinical blood markers and ultrasound data to develop AI models for predicting distant metastasis in breast cancer. The combined model, incorporating clinical blood markers and ultrasound features, exhibited higher accuracy, suggesting its potential clinical utility in predicting and identifying breast cancer distant metastasis. These findings highlight the potential prospects of developing cost-effective and accessible predictive tools in clinical oncology.

Surveillance for Distant Metastasis in Breast Cancer Patients Who Underwent Contemporary Management: A Report from the Korean Breast Cancer Society Survivor Research Group

BackgroundCurrent guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes.Patients and MethodsWe retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician’s decisions.ResultsHigh-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29–2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32–4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS.ConclusionsFrequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.

Trastuzumab-Induced Organising Pneumonia in Breast Cancer Patient

Patients with metastatic breast cancer often have respiratory symptoms due to various causes. Trastuzumab is a drug used in the treatment of HER2/neu over-expressing breast cancer patients. Organising pneumonia is a type of idiopathic interstitial pneumonia that mimics infection or progressive disease and can be difficult to diagnose in the setting of malignancy. Making a correct diagnosis is of extreme importance since any delay in the treatment can result in significant adverse patient outcome. Here, we have described a case of organising pneumonia associated with the use of trastuzumab in metastatic breast cancer patients. On the basis of clinical data, including findings such as a decreased PaO2 level and findings on chest CT scan, these patients were diagnosed with drug-induced organising pneumonia. Although it is a rare adverse event associated with trastuzumab, it may cause rapid deterioration without preceding symptoms; hence, even though it is very rare, with an incidence of less than 2%, it is still crucial to intervene so as to prevent the occurrence of such an unfavourable outcome by means of close observation and early diagnosis along with an early withdrawal of the drug and an immediate commencement of corticosteroid therapy.

B2 Prognostic Index in Determining Prognosis in Metastatic Breast Cancer.

To determine the relationship between the B2 prognostic index (B2PI) scoring method and prognosis in metastatic breast cancer, and to create a formula based on parameters that can be easily accessed in daily practice. Descriptive study. Place and Duration of the Study: Department of Medical Oncology, Dokuz Eylul University, Izmir, Turkiye, between May 2010 and June 2021. The clinicopathological characteristics of the patients were compared between the groups. All female breast cancer patients over the age of 18 years with de novo metastatic and non-metastatic breast cancers who developed metastasis during follow-up, were included in the study. Those with a second solid cancer or haematological malignancy and with a life expectancy of less than 3 months were excluded from the study. Chi-square and Fisher's exact tests were used to compare categorical data between the groups. Overall survival evaluations were made using the Kaplan-Meier analysis method and Log-Rank test. Risk factors for mortality were evaluated in Cox regression analysis. In all statistical tests, p <0.05 was considered statistically significant. There were 176 patients in this study, out of which 111 (63.1%) were de novo metastatic. When the effect of B2PI risk groups on overall survival in intrinsic subtypes was analysed, significant differences were found in the overall survival of B2PI risk groups in all subtypes except HER2+ ER- (HER2 overexpression subtype). According to the B2PI scoring system, the median overall survival was higher for both low-risk and moderate-risk patients compared to those in the high-risk category. For metastatic breast cancer patients, the B2PI can be used to determine prognosis and develop treatment strategies, as it is a clinical decision-making tool based on parameters that are easily accessible in daily practice. Metastatic breast cancer, B2 prognostic index, Prognosis, Survival.

The Effect of C-Reactive Protein/Lymphocyte Ratio (CLR) on PFS in Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitors: A Novel Biomarker.

Hormone positive breast cancer is a tumor with high mortality. Combining antihormonal therapy with cyclin dependent kinase 4/6 inhibitors (CDK4/6i) has resulted in longer survival. The effect of inflammatory parameters such as c-reactive protein and c-reactive protein/lymphocyte ratio (CLR) on efficacy and survival in CDK4/6i treatment is unknown. In our study, we aimed to investigate the role of CLR and some parameters in predicting progression-free survival (PFS) with CDK4/6i. This retrospective cohort study included 78 patients with denovo and recurrent metastatic breast cancer treated with CDK4/6i. Cut off values for the prediction of mortality by various numerical parameter scores were performed by ROC Curve analysis. The effect of clinical variables, inflammatory and histopathological parameters on survival was analyzed by Kaplan-Meier method. Neutrophil/lymphocyte ratio (NLR) and CLR were statistically significant in predicting mortality (p < 0.05). Ki67 and CLR were correlated with PFS. Age and CLR were correlated with OS (p < 0.05). CLR was statistically significant for both PFS (p = 0.022) and OS (p = 0.006). In patients with metastatic hormone-positive breast cancer using CDK4/6i, low CLR and low Ki67 were correlated with longer PFS duration.

Exploring the Relationship between MicroRNAs, Intratumoral Microbiota, and Breast Cancer Progression in Patients with and without Metastasis.

Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.