The overall number of breast cancer patients at risk of developing local-regional disease recurrence has been increasing due to long-term survivorship from improvements in multimodality breast cancer treatment and a steady increase in breast cancer incidence. Many patients receive radiotherapy as part of definitive multidisciplinary breast cancer treatment, and to date, practitioners have approached reirradiation delivery with reticence due to concern for serious toxicities that may be incurred with high cumulative radiation doses. However, a subset of patients with breast cancer recurrence may benefit from reirradiation for improved locoregional tumor control. An emerging body of evidence has demonstrated promising efficacy and safety of breast cancer reirradiation that are gradually redefining the treatment paradigm. In addition, an increase in systemic therapy options has further optimized the opportunity for successful salvage of breast cancer recurrence. In this critical review, we review breast cancer radiation and systemic therapy salvage options, available data, ongoing studies, and treatment delivery considerations.

Receptor conversion following neoadjuvant therapy in breast cancer may influence prognosis and adjuvant treatment decisions. This systematic review and meta-analysis evaluated the prognostic significance of changes in hormone receptor (HR) and HER2 status after neoadjuvant therapy.

This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the prognostic effect of receptor conversion after neoadjuvant treatment in breast cancer. Studies reporting receptor status before and after neoadjuvant therapy, with associated survival outcomes, were included. Pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) were calculated using random-effects models.

Twenty-two studies (n = 5370) were included in this meta-analysis. HR gain demonstrated significantly improved DFS (HR 0.49, 95 % CI 0.25-0.97; p = 0.04), but no OS benefit. HR loss was associated with both significantly worse DFS (HR 3.42, 95 % CI 1.93-6.08; p < 0.001) and OS (HR 1.99, 95 % CI 1.04-3.84; p = 0.04). HER2 gain had a negative impact on DFS (HR 1.89, 95 % CI 1.00-3.58; p = 0.05), with no significant effect on OS. HER2 loss was associated with significantly poorer DFS (HR 1.92, 95 % CI 1.51-2.43; p < 0.001) and OS (HR 2.20, 95 % CI 1.44-3.38; p < 0.001).

This systematic review and meta-analysis demonstrates that receptor conversion following neoadjuvant therapy in breast cancer significantly impacts survival outcomes. Specifically, gaining HR positivity is associated with improved DFS, while losing HR positivity correlates with worse DFS and OS. With regards to HER2, gaining positivity is associated with worse DFS, and losing positivity is associated with worse DFS and OS, compared to patients who maintain their initial status. These findings underscore the potential importance of reassessing receptor status after neoadjuvant therapy to tailor subsequent treatment decisions accurately.

Estrogen receptor (ER)-positive breast cancer is the most common subtype, accounting for approximately 80% of cases, with endocrine therapy as the standard postoperative treatment. However, despite risk-reducing therapies, the risk of recurrence remains substantial. Studies, including the POETIC trial, have demonstrated that low Ki67 levels following short-term neoadjuvant endocrine therapy (sNAET) are associated with a favorable prognosis. The objective of this study is to identify genes associated with the suppression of cell cycle progression by sNAET in postmenopausal patients with ER-positive/human epidermal growth factor receptor 2-negative breast cancer.

Ninety-seven tissue samples were collected and classified into groups based on Ki67 expression levels before and after treatment. RNA sequencing and real-time quantitative reverse transcription PCR were performed to analyze gene expression in tumor samples from patients stratified into High-High (H-H) or High-Low (H-L) groups based on Ki67 levels before and after sNAET.

Among the differentially expressed genes identified, CXCL9 and ABCA12 were significantly upregulated in the H-H group and were associated with a poor response to endocrine therapy. Conversely, NPY1R was significantly upregulated in the H-L group, suggesting greater responsiveness. In multivariate logistic regression analysis, CXCL9 (OR: 0.65, p = 0.024) and NPY1R (OR: 1.61, p = 0.048) were significant predictors of Ki67 reduction.

These findings suggest that CXCL9 and NPY1R could serve as predictive biomarkers for endocrine therapy response. Identifying these biomarkers may facilitate personalized treatment strategies, including the addition of therapies such as chemotherapy for resistant cases.

This review aims to investigate the issue of treatment nonadherence and to present the available strategies to improve adherence to oral treatments in breast cancer. A literature search was conducted to contextualise the issue of nonadherence, investigate the reasons behind nonadherence, and demonstrate strategies to address treatment nonadherence in breast cancer. Findings indicate that adherence rates decrease while discontinuation rates increase with increasing lengths of breast cancer treatment course. Lack of adherence is proven to be detrimental to treatment outcomes. Patients struggle to adhere to treatment due to inadequate relationships with healthcare providers, lack of information, psychological distress, and side effects. Healthcare providers should evaluate patient's experience to provide the necessary support. Following this assessment, healthcare providers may recommend interventions addressing patient knowledge, psychological distress or side effects. Treatment adherence remains an issue for oral therapeutics in breast cancer. After patient assessment, healthcare providers can offer personalised strategies to improve treatment adherence. The most crucial interventions address patient knowledge, psychological distress, and side effects.

Hormone receptor (HR) status may be unstable during breast cancer (BC) progression, and changes occur in approximately 20-30% of BC patients at the time of recurrence. The biologic tumor switch from HR+ to HR- status is associated with worse clinical outcomes and warrants alternative management. We aimed to characterize clinical and pathologic features of a subset of ER+/HER2- breast cancer patients who converted to triple negative phenotype upon recurrence, and investigate the molecular alterations associated with HR loss during BC progression.

We retrospectively identified 112 patients who had primary ER+/HER2- breast cancer and developed local or distant recurrence through our institutional database. Patients were divided into two cohorts based on receptor profile of recurrent tumor: discordant TNBC (n = 20) and concordant ER+/HER2- tumors. The following variables were collected: tumor histology, grade, pT, pN, ER, PR, HER2 expression in primary and recurrent tumors, molecular profiling, and adjuvant treatment history.

The average time for HR+ tumors to recur as TNBC was 148 months. The two cohorts showed similar clinicopathologic characteristics, including patient's age at diagnosis, tumor type, grade, stage, ER expression, and treatment history before tumor recurrence. PTEN inactivating mutations were more frequently identified in the discordant TNBC (6/20, 30%) compared to the concordant ER+/HER2- tumors (6/92, 5.5%) (p = 0.007).

Increased signaling via the PI3K/AKT/PTEN pathway may be a mechanism for the transition to hormone independence in recurrent diseases.

Breast cancer, which arises from the epithelial tissue of the breast, is one of the most common cancers affecting women worldwide. Its incidence and mortality rates have been increasing in both developed and developing countries. As a hormone-dependent cancer, breast cancer is classified into several molecular subtypes based on the expression of key markers: Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER-2), and Ki67. PR loss is associated with endocrine resistance and a poorer prognosis in breast cancer. Despite this, the underlying mechanisms of ER-positive/PR-negative (ER+PR-) breast cancer remain poorly understood. This study aims to review recent advancements in research on ER+PR- breast cancer, analyze its clinical characteristics and molecular mechanisms, and provide recommendations for more targeted therapeutic approaches.

Adherence to adjuvant hormone therapy (AHT) is critical for improving survival in breast cancer patients. This study examines how socioeconomic disparities, osteoarthritis (OA), and OA symptom onset timing influence AHT adherence and survival outcomes.

This retrospective cohort study included 33,142 women with invasive breast cancer (2011-2015) from the Korean National Health Insurance Service. Group-based trajectory modeling (GBTM) identified AHT adherence patterns based on the proportion of days covered (PDC) over five years. Competing risk regression and Cox models assessed the impact of socioeconomic factors, pre-treatment OA, NSAID use, and other variables on AHT discontinuation and survival.

GBTM revealed two adherence patterns: high adherence (83.4 %) and low adherence (16.6 %), with the latter showing a rapid decline in PDC. The low adherence group had a significantly higher risk of treatment discontinuation (SHR: 14.06; 95 % CI: 12.50-14.96; p < 0.001) and mortality (HR: 3.56; 95 % CI: 3.09-4.09; p < 0.001). A longer OA history before AHT (p = 0.001) and pre-AHT NSAID use (p < 0.001) were linked to higher discontinuation risk. Patients with Medical Aid/Veteran insurance (OR: 0.60; 95 % CI: 0.53-0.67; p < 0.001) and those in non-capital regions (OR: 0.74; 95 % CI: 0.69-0.79; p < 0.001) were less likely to show high adherence.

AHT adherence is influenced by socioeconomic factors, pre-existing OA, and OA symptom timing, affecting survival outcomes. Tailored interventions are needed to improve AHT adherence and survival.

Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)-positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear.

Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression.

Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor-negative, human epidermal growth factor receptor 2-negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all P < .001) and those who received neoadjuvant chemotherapy (NAC; P < .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; P = .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; P = .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; P = .048). Among patients treated with NAC (n = 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; P = .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; P = .84).

In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients with ER-low BC should be counseled regarding the potential benefit of ET.

Oral endocrine therapy (OET) is recommended in prevention and treatment of hormone receptor-positive breast cancer (HR+ BC). Despite the reduced incidence, recurrence, and mortality, OET adherence is poor in this patient population. The aim of this study was to review the latest literature to identify effective interventions to improve medication adherence in patients taking OET for prevention or treatment of HR+ BC.

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) framework was used to perform this review. We utilized PubMed, SCOPUS, EMBASE, Cochrane, and Web of Science to acquire articles using search terms including breast cancer, adherence, persistence, and acceptability. Inclusion criteria included publication in peer-reviewed journal, primary data source, longitudinal, patients on OET such as aromatase inhibitors (AIs) or selective estrogen receptor modulators (SERMs), measuring adherence, persistence, or acceptability.

Out of 895 articles identified, 10 articles were included. Majority of patients had early-stage HR+ BC. Two out of two studies incorporating technological intervention, two out of three studies with text communication-based intervention, and three out of five studies with verbal communication-based intervention reported significant improvement in OET adherence and/or persistence.

While the interventions tested so far have shown to improve OET adherence in HR+ BC patients in some studies, there is a need to design combination interventions addressing multiple barriers in this population.

This study showcases effectiveness of novel interventions to improve OET adherence and the need to further develop patient-centered strategies to benefit all patients with HR+ BC.

The assessment of estrogen receptor (ER) expression in breast cancer, has traditionally been performed using ligand-binding assays, followed by immunohistochemistry, and is widely used to predict tumor response to endocrine therapy. ER-low positive breast cancer, formally defined in the 2020 ASCO/CAP testing guidelines, represents a small subset of invasive breast cancers characterized by 1 %-10 % of ER staining. Emerging evidence suggests that ER-low positive tumors constitute a heterogeneous group in terms of clinicopathologic features, molecular profiles, prognosis, and responsiveness to endocrine therapy. These tumors frequently behave more like ER-negative cancers, often displaying a more aggressive clinical course compared to classic ER-positive tumors. The clinical benefit of endocrine therapy in this subset remains uncertain, posing a significant challenge in determining the optimal treatment strategies. This review offers both a historical perspective and a comprehensive, up-to-date analysis of recent advancements in the understanding of ER-low positive breast cancer, with a focus on tumor biology, pathological evaluation, and clinical implications.

Research suggests that systemic immune-inflammation index (SII), neutrophil lymphocyte (NLR), platelet lymphocyte (PLR) and lymphocyte monocyte (LMR) can act as potential prognostic indicators for breast cancer (BC). However, its prognostic value for BC patients undergoing endocrine therapy (ET) remains inconclusive.

We systematically searched Embase, Cochrane Library, PubMed, and Web of Science for studies on the prognostic significance of immune-inflammation indexes for BC patients undergoing ET from inception to May 5, 2024. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were the primary outcomes, and they were statistically analyzed by hazard ratios (HR) with 95% confidence intervals (CI). Sensitivity and subgroup analyses were performed to explore the source of heterogeneity. STATA 15.1 and Review Manager 5.4 were adopted for data analyses.

Fifteen studies with 27 cohorts of 3168 BC patients undergoing ET were included. The results showed that low NLR was associated with prolonged OS (HR = 2.19, 95% CI, 1.67-2.87; P < .00001) and PFS (HR = 1.64, 95% CI, 1.32-2.04; P < .00001) in overall BC patients receiving ET. High LMR was associated with longer OS (HR = 2.67, 95% CI, 1.64-4.33; P < .0001) in the overall BC patients undergoing ET. Low PLR was significantly associated with prolonged PFS (HR = 1.89, 95% CI, 1.40-2.55; P < .0001). Additionally, low PLR was associated with longer OS (HR = 2.16, 95% CI, 1.03-4.52, P = .04), but sensitivity analysis showed that its significance was not robust enough. All subgroup analyses revealed overall roboust results.

Immune-inflammation indexes can potentially act as prognostic biomarkers for BC patients undergoing ET, contributing to wiser decision-making in BC treatment.

Estrogen receptor (ER) expression is critical in breast cancer treatment. While low ER (1-9%) resembles triple-negative cancer with chemotherapy efficacy, the significance of "intermediate expression" (≥ 10%) and the therapeutic efficacy remain unclear. This study explores the differences in staining patterns and molecular characteristics of ER-low to intermediate expression to guide treatment.

A total of 104 breast cancer patients treated between January 2008 and July 2024 with an Allred Proportion Score (PS) of 2-4 were included. PS2 (n = 21) was classified as ER-low, while PS3 (n = 26) and PS4 (n = 57) as ER-intermediate (ER-int). ER-int was further divided by ER staining pattern: "Island" (heterogeneous) and "Scatter," (uniform) subgroups. The prognosis, clinical factors, and gene expression profiles (n = 11) were analyzed.

The Island subgroup was associated with poorest prognosis (p = 0.0116), particularly among the patients treated with endocrine-only treatment patients (p < 0.0001). Elevated tumor-infiltrating lymphocyte (TIL) levels correlated with worse prognosis in endocrine-only treatment patients (p < 0.0043), with TIL levels highest in ER-low, followed by Island and Scatter subgroups. Island tumors were enriched in CD36, GZMB, and type I interferon genes; additionally, 23 "ISLAND" genes showed significant prognostic differences in the TCGA BRCA ER-int (10-69%) cohort.

This study emphasizes the importance of recognizing heterogeneity within the ER-int subtype. Identifying distinct ER staining patterns and prognostic significance of TILs and transcriptome in ER-int tumors suggests the need for individualized treatment strategies for Island subtype.

This study aims to assess the prescribing patterns and combinations of endocrine therapy medications for breast cancer across six cities in China over a six-year period.

Data on outpatient prescriptions were sourced from the China Hospital Prescription Analysis Cooperative Project database. The study analyzed trends in endocrine therapy medications, focusing on the number of prescriptions, total costs, defined daily doses (DDDs), and defined daily costs (DDC). The study also examined the use of two-drug combinations separately for premenopausal and postmenopausal women.

The number of prescriptions increased by 49.6% from 55,339 in 2016 to 82,791 in 2021. During the same period, annual costs ranged from 47.71 million to 88.37 million Chinese Yuan (CNY), marking an 85.2% increase. Tamoxifen, which led in DDDs in 2016, fell to sixth place, while exemestane rose from fifth to first place. Anastrozole's rank dropped from first to fourth, with letrozole consistently holding the second position in DDDs. Fulvestrant and goserelin consistently ranked among the top two in DDC. Conversely, toremifene and tamoxifen consistently occupied the lowest two positions in DDC. The combination of aromatase inhibitors (AI) and ovarian function suppression (OFS) represented the largest proportion among drug combinations, with its usage significantly increasing over the years (P = 0.015).

The use of endocrine therapy drugs has increased, with AI being the most frequently used. Additionally, the combination of AI and OFS has become the most prevalent treatment approach.

Estrogen receptor-positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up.

Secondary analysis of 1242 estrogen receptor-positive and HER2-negative patients that were randomly assigned to 2-5 years of 40 mg adjuvant tamoxifen or no endocrine therapy. Distant recurrence-free interval in tamoxifen-treated vs endocrine untreated patients was assessed by Kaplan-Meier, Cox proportional hazards regression, and time-varying analyses.

In premenopausal patients, a statistically significant tamoxifen benefit was observed for lymph node-negative (adjusted hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.87), progesterone receptor-positive (adjusted HR = 0.61, 95% CI = 0.41 to 0.91), and genomic low-risk tumors (adjusted HR = 0.47, 95% CI = 0.26 to 0.85) but only lasted beyond 10 years for genomic low-risk tumors. Postmenopausal patients showed long-term benefit for all good-prognosis markers including low-grade (adjusted HR = 0.55, 95% CI = 0.41 to 0.73), lymph node-negative (adjusted HR = 0.44, 95% CI = 0.30 to 0.64), progesterone receptor-positive (adjusted HR = 0.60, 95% CI = 0.44 to 0.80), Ki-67 low (adjusted HR = 0.51, 95% CI = 0.38 to 0.68), and genomic low-risk tumors (adjusted HR = 0.53, 95% CI = 0.37 to 0.74), and regardless of tumor size (≤20 mm: adjusted HR = 0.55, 95% CI = 0.39 to 0.77; >20 mm: adjusted HR = 0.64, 95% CI = 0.44 to 0.94). Premenopausal patients with no poor-prognosis tumor characteristics (clinical marker score = 0) showed early benefit and postmenopausal long-term benefit.

Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.

The landscape of molecular testing in solid tumors is rapidly expanding. Understanding testing options and limitations can inform treatment decisions for many patients with metastatic disease to the central nervous system (CNS).

There is limited data on health-related quality of life (HRQoL) in older breast cancer (BC) patients. This study examines patient-reported outcomes (PROs) by type of endocrine therapy (ET) prescribed, aromatase inhibitors (AI), or tamoxifen (Tam) to estrogen receptor-positive BC patients aged ≥70 years.

This retrospective review includes 1052 women diagnosed with early-stage BC from the REQUITE study database, who underwent breast conservation surgery (BCS), and received adjuvant breast radiation therapy (RT), and ET as the only systemic therapy. Among them, 201 women were aged ≥70 years. The PROs were assessed by using EORTC-QLQ-C30, BR23, and Multidimensional Fatigue Inventory measures obtained at baseline after BCS, post-RT, and at 1, 2, and 3 years follow-up. Statistical analysis involves mixed model analysis of variance and propensity score weights.

Among the 201 women, 131 received AI, and 70 received Tam. The overall mean age of this cohort is 75.3 years. Compared with Tam, AI-treated patients experience worse insomnia and general and physical fatigue. Tam-treated patients experienced more physical and cognitive functioning decline than the AI-treated patients. The Tam-treated patients also reported more mental fatigue and reduced sexual enjoyment compared to the AI-treated patients.

This study suggests a differential impact by type of ET on distinct HRQoL domains experienced by older postmenopausal women. Furthermore, larger prospective clinical trials are necessary to inform treatment decisions for older ER-positive BC patients, considering patient preferences and understanding trade-offs between disease outcomes and HRQoL.

Endocrine therapy (ET) is a cornerstone in the management of patients with hormone receptor-positive early breast cancer, which accounts for over 70% of cases worldwide. The efficacy of adjuvant ET for 5 years in reducing the risk of recurrence and improving survival outcomes is well documented. However, the risk for late relapses, occurring >5 years after initial treatment, has prompted exploration of longer treatment durations. Extending ET beyond the traditional 5-year period offers additional benefit in reducing the risk of recurrence and improving long-term outcomes. Nevertheless, determining the optimal duration and identifying suitable candidates for extended therapy is often nuanced. This review aims to comprehensively evaluate the current landscape of extended ET in breast cancer management. It provides an overview of the rationale behind extending endocrine treatment in both premenopausal and postmenopausal women, with a focus on clinical trials and observational studies supporting extended therapy. Furthermore, it emphasizes the significance of considering associated toxicities in patient management. It also explores novel strategies involving the combination of ET with new drugs, leading to an evolution of treatment paradigms that may make the need for extended therapy obsolete.

While existing multi-gene assays aid adjuvant treatment decisions, no gene signature has identified HR+/HER2- early breast cancer (EBC) patients at high recurrence risk post-chemo-endocrine therapy (C-ET).

Clinical data and RNA sequencing information from 1457 HR+/HER2- breast cancer patients were collected from West China Hospital, the GEO database, and the TCGA database. Using univariate Cox regression, gene set enrichment analysis, and LASSO regression, ten key genes associated with recurrence were identified. A comprehensive prognostic model was developed by combining the 10-gene risk score with clinicopathological features, and a nomogram was created to predict 3-, 5-, and 7-year recurrence-free survival (RFS). The model's performance was evaluated using AUC and decision curve analysis (DCA).

The 10-gene risk score was significantly associated with recurrence risk of HR+/HER2- EBC after C-ET and effectively distinguished between high-risk and low-risk patients (training: HR: 6.37, P < 0.001; validation: HR: 4.51, P < 0.001). It maintained consistent stratification efficacy across different treatment regimens, clinical stages, and grades. Compared to existing multi-gene signatures (21-gene, 70-gene, EndoPredict, PAM50, GGI), HR+/HER2- EBC patients identified as high-risk by the 10-gene risk score exhibited a higher 10-year cumulative recurrence rate following C-ET. In multivariate Cox regression analysis, the 10-gene risk score remained an independent prognostic factor in both the training and validation sets. The comprehensive model, integrating the 10-gene score and clinicopathological features, showed high predictive accuracy (AUC: 0.734, 0.778, 0.792 for 3, 5, 7 years in training; 0.691, 0.715, 0.709 in validation).

The 10-gene risk score can serve as a tool to predict recurrence risk in HR+/HER2- EBC patients following C-ET, assisting clinicians in developing personalized treatment plans for high-risk patients and ultimately improving patient prognosis.

This study aims to identify characteristic genes associated with cutaneous squamous cell carcinoma (cSCC).

Differentially expressed genes (DEGs) and hub genes in key module were identified using the limma package and weighted gene co-expression network analysis (WGCNA) in R software, respectively. The intersection of these genes was then subjected to LASSO regression to pinpoint characteristic genes. The correlation between immune cell infiltration and these characteristic genes was further elucidated using single-sample Gene Set Enrichment Analysis and Spearman correlation analysis.

A total of 113 DEGs were identified, along with their associated biological pathways. From this pool, five characteristic genes-ADH1B, CCL27, ID4, LRP4 and S100A9-were selected and validated. Immune infiltration analysis revealed significant correlations between these genes and various immune cell types, particularly with CCL27, ID4, LRP4 and S100A9.

The identification of characteristic genes for cSCC provides valuable insights into its molecular mechanisms. The correlations between these genes and immune cell infiltration suggests their potential roles in tumor immunity.

ESR1 mutations are biomarkers in breast cancer patients who develop metastatic disease after endocrine therapy (ET). Recently, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Elacestrant, a selective estrogen receptor degrader for patients harboring ESR1 mutations. This has necessitated the establishment of reliable and sensitive NGS- or PCR-based assays to detect these ESR1 resistance mutations in liquid biopsy samples.

We evaluated NGS results of a pan-cancer cohort of almost 6000 patients from two major German institutes of pathology, to show that the occurrence of ESR1 mutations is extremely rare (<1%) in ET-naïve patients. This suggests that ESR1 mutations arise almost exclusively under the pressure of ET. Therefore, we designed a breast cancer-specific hybrid capture-based NGS liquid biopsy assay covering 12 breast cancer-related genes, including ESR1, PIK3CA, AKT1, ERBB2, BRCA1/2, and TP53. We validated the HS2-Mamma-LIQ assay extensively using reference material to detect mutations to 0.1% variant allele frequency (VAF) and compared the performance to a commercially available ESR1 ddPCR assay.

We show the results of routine diagnostic analysis of the first consecutive 354 patients with activating ESR1 mutations rate of 43%, with 20% of patients harboring co-mutations in PIK3CA and other genes underlining the relevance of tumor heterogeneity. Our study highlights liquid biopsy as a preferred approach for monitoring ESR1 mutations in breast cancer patients by showing cases where NGS analysis suggests complex tumor heterogeneity with multiple ESR1 as well as PIK3CA mutations at different VAFs.

Our findings not only corroborate prior research concerning the rarity of these mutations in unselected patients but also emphasize the importance of robust and broad molecular assays rather than single gene assays in their detection and characterization in the diagnostic setting. Advantages of different approaches are discussed to address the current clinical need.

The purpose of this study was to evaluate and assess the clinical utility of the integrated multidisciplinary patient-centered information (PCI) written by various healthcare professionals for promoting patient-centered care in the treatment and care of breast cancer patients.

This study employed a convergent mixed methods interventional design in which Control and Intervention were compared by integrating both quantitative and qualitative results obtained from questionnaires and verbatim transcripts. In three breast cancer cases, a multidisciplinary team meeting (MDTM) using a conventional electronic health record (EHR) viewer was designated Control, and a MDTM using a conventional EHR viewer plus the integrated multidisciplinary PCI was designated Intervention. Questionnaires, which consisted of questions about efficiency and patient-centeredness employing a 5-point Likert scale, were analyzed statistically using Wilcoxon rank test and summary statistics. Verbatim transcripts were analyzed using a thematic analysis hybrid approach.

Three surgical oncologists and three nurses (ward, outpatient chemotherapy, and palliative care) participated in the MDTMs for both Control and Intervention. The quantitative data suggested that there were statistically significant differences between Control and Intervention (p<0.05), with Intervention superior to Control from the viewpoints of efficiency and patient-centeredness. The qualitative data suggested that the MDTM for Intervention involved more PCI and promoted shared understanding from early in the meeting. Synthesis of both the quantitative and qualitative results suggested that use of the integrated multidisciplinary PCI in MDTMs may facilitate the utilization of PCI and lead to more efficient and patient-centered discussions and decision-making to promote patient-centered care.

Integrating the PCI obtained from medical records of various healthcare specialists already documented in the hospital information system could prove to be helpful for supporting MDTMs and routine clinical practice without placing an additional burden on busy healthcare professionals while also promoting the digital transformation of healthcare.

Identifying high-risk of late recurrence (beyond 10 years) in patients with hormone receptor-positive HER2-negative early breast cancer (EBC) is crucial. The Clinical Treatment Score post-5 years (CTS5) score assesses recurrence risk after 5 years of endocrine therapy (ET). This study validated CTS5 as a prognostic tool for late recurrence by examining its association with Distant Recurrence-Free Survival using GEICAM study data and evaluating model calibration.

We retrospectively analyzed 5739 hormone receptor-positive HER2-negative EBC patients from the El Álamo IV registry (N = 3509, diagnosed between 2002 and 2005) and 4 adjuvant GEICAM studies (N = 2680, conducted between 1996 and 2006). All patients were distant recurrence-free and alive 5 years after starting adjuvant ET.

The CTS5 classified 43.9% of patients as low-risk, 32.2% as intermediate-risk, and 23.9% as high-risk. Significant differences in DR were observed: hazard ratio (HR) for intermediate- vs. low-risk was 2.55 (95% CI, 1.85-3.51, P < .0001), and HR for high- vs. low-risk was 5.77 (95% CI, 4.28-7.78, P < .0001). Similar results were found across subgroups by menopausal status, duration of adjuvant ET, and prior adjuvant chemotherapy (CT). Calibration showed CTS5 overestimated DR rates in low-risk (P = .0314) and high-risk (P < .0001) patients compared to observed rates.

The CTS5 categorized patients based on late DR risk regardless of menopausal status, ET duration, or CT treatment. However, the model tended to overestimate events, particularly in high-risk groups, especially among those treated with ET for less than 60 months or not receiving CT.

The optimal duration of extended endocrine therapy (ET) for women with hormone receptor-positive (HR-positive) early-stage postmenopausal breast cancer remains uncertain. This meta-analysis systematically evaluated the optimal time to prolong aromatase inhibitors ( AIs) therapy for postmenopausal early stage breast cancer who received initial endocrine therapy.

PubMed, Web of Science, Ovid, Scopus, EmBase, and Cochrane Library were searched for randomized controlled trials (RCTs) using keywords related to breast cancer, HR-positive, AIs, and tamoxifen (TAM). Disease-free survival (DFS) was used as the primary endpoint. Meta-analysis was performed using STATA 16.0 and Revman 5.4 statistical software. Hazard ratio (HR) with its corresponding 95% confidence intervals (CI) was used as an effective indicator to assess DFS, OS, and subgroups of extended ET. Relative ratio (RR) was used to assess adverse events.

The study included four RCTs involving 8,748 patients with HR-positive breast cancer. Pooled data showed an improvement in DFS when extending endocrine therapy from 5 to 7-8 years (HR = 0.82, 95% CI: 0.73 ~ 0.93), especially in patients with tumor size ≥ 2 cm (HR = 0.69, 95% CI: 0.49 ~ 0.98), estrogen receptor (ER) and progesterone receptor (PR) positive (HR = 0.77, 95% CI: 0.67 ~ 0.89), human epidermal growth factor receptor 2 (HER-2) positive or negative (HR = 0.85, 95% CI: 0.74 ~ 0.97; HR = 0.44, 95% CI: 0.22 ~ 0.89) and previous chemotherapy (HR = 0.80, 95% CI: 0.68 ~ 0.95). However, DFS has not improved with the extension from 7-8 to 10 years (HR = 0.97, 95% CI: 0.85 ~ 1.10). Furthermore, we found no significant difference in overall survival (OS), adverse events (AEs) analysis revealed a significant increase in the incidence of arthralgia, osteoporosis, bone fractures and asthenia after extended AIs.

The proportion of patients with breast cancer receiving ET extended beyond 5 years has increased, while the extension of AIs treatment from 5 to 7-8 years may be an option for high-risk patients with well-tolerated tumor size ≥ 2 cm, HR-positive, and previous chemotherapy. However, a variety of adverse events may accompany ET therapy, the identification of factors that may benefit breast cancer patients requires further randomized controlled studies.

CRD42022335497.

There is currently no reliable predictive tool for late recurrence in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study aimed to explore the potential of the clinical treatment score post-5l̥years (CTS5) as a predictive tool for long-term survival beyond 5 years in patients with specifically HR-positive, HER2-positive breast cancer. We collected patient-level data from the HERceptin Adjuvant (HERA) (BIG1-01; ClinicalTrials.gov identifier: NCT00045032) trial. Our investigation focused on assessing the risk of late distant recurrence (DR) and overall survival (OS) according to the CTS5 risk score as continuous value and CTS5 stratification risk groups. A total of 1,818 patients with HR-positive, HER2-positive breast cancer were included in this analysis. The CTS5 score, as a continuous variable, emerged as an independent prognostic factor for both late DR (adjusted HR, 2.05; 95% CI, 1.63-2.58; P < 0.001) and OS (adjusted HR, 2.02; 95% CI, 1.58-2.58; P < 0.001), respectively. In addition, multivariable analysis showed a significant association between the high-risk group and adverse outcomes in late DR (adjusted HR, 2.76; 95% CI, 1.84-4.13; P < 0.001) and OS (adjusted HR, 2.44; 95% CI, 1.59-3.73; P < 0.001) compared to low/intermediate group. Consistent results were observed, regardless of age or administration of HER2-targeted therapy. CTS5 is a useful prognostic tool for predicting late DR and OS in HR-positive, HER2-positive breast cancer patients. Extension of endocrine therapy should be actively considered in patients with CTS5 high-risk group.

Estrogen receptor (ER) expression levels in breast cancer tissue predict the efficacy of endocrine therapy and the prognosis of breast cancer patients. Recently, it was reported that the prognosis of patients with ER-low-positive breast cancer was similar to that of ER-negative patients. This study aimed to investigate how ER expression levels impact the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer undergoing long-term follow-up.

The correlation between ER expression levels and prognosis was retrospectively evaluated in a cohort of 3091 consecutive patients with HER2-negative early breast cancer who were treated at our institute between 1981 and 2022. The median follow-up period was 85.2 (range 0-480) months. The proportion of ER-expressing cells in breast cancer tissues was assessed by immunohistochemistry and used to classify patients into four categories: ER negative (<1%), ER-low positive (1% ≤ ER < 10%), ER-intermediate positive (10% ≤ ER < 2/3), and ER-high positive (≥2/3).

Patients with ER-intermediate-positive breast cancer had a prognosis similar to that of patients with ER-low-positive or ER-negative disease. By contrast, patients with ER-high-positive breast cancer had significantly longer disease-free survival (DFS) and overall survival (OS) times than the other groups. Multivariate analysis demonstrated that ER-intermediate positivity was an independent factor for poor prognosis for both DFS and OS in patients with HER2-negative early breast cancer. The distributions of tumor grades 1, 2, and 3 were nearly equal among the ER-intermediate-positive patients, whereas more than half of patients with ER-high-positive breast cancer had grade 1 tumors. By analyzing changes in prognosis over time, we found that the prognosis of patients with ER-high-positive breast cancer markedly improved over three decades, while that of patients with ER-intermediate-positive disease did not.

Patients with ER-intermediate-positive breast cancer differ from patients with ER-high-positive breast cancer, suggesting that the treatment of ER-positive breast cancer patients should be tailored based on ER expression levels.

Establishing whether women with major depressive disorder who develop breast cancer have poor outcomes is key to optimizing care for this population. To this end, we examined associations between major depressive disorder and breast cancer recurrence and mortality.

Using medical record data from the US Department of Veterans Affairs health-care system, we established a retrospective cohort of women with local or regional stage invasive breast cancer between 2010 and 2019 and followed them through 2022. We used a 2-year window to identify women diagnosed with major depressive disorder before breast cancer diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between major depressive disorder and breast cancer recurrence and mortality while accounting for competing risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics.

We identified 6051 women with breast cancer, of whom 1754 (29%) had major depressive disorder. The mean (SD) age at breast cancer diagnosis was 57 (11) years. In multivariable analyses, women with major depressive disorder had a 37% (hazard ratio = 1.37, 95% CI = 1.19 to 1.57) higher risk of recurrence and a 30% (hazard ratio = 1.30, 95% CI = 1.02 to 1.64) higher risk of breast cancer mortality. The association between major depressive disorder and recurrence was stronger among women with estrogen receptor-positive breast cancer. In secondary analyses, there were statistically significant interactions between major depressive disorder and multiple exposures with respect to recurrence, including current smoking, substance abuse, and nonreceipt of screening mammography.

Women with major depressive disorder had inferior breast cancer outcomes compared with women without a history of major depressive disorder. Research is needed to investigate underlying mechanisms linking depression to breast cancer progression and evaluate interventions to improve outcomes in this high-risk population.

In HR+/HER2- early breast cancer (EBC) patients, approximately one-third of stage II and 50% of stage III patients experience recurrence, with poor outcomes after recurrence. Given that these patients commonly undergo adjuvant chemo-endocrine therapy (C-ET), accurately predicting the recurrence risk is crucial for optimizing treatment strategies and improving patient outcomes.

We collected postoperative histopathological slides from 1095 HR+/HER2- EBC who received C-ET and were followed for more than five years at West China Hospital, Sichuan University. Two deep learning pipelines were developed and validated: ACMIL-based and CLAM-based. Both pipelines, designed to predict recurrence risk post-treatment, were based on pretrained feature encoders and multi-instance learning with attention mechanisms. Model performance was evaluated using a five-fold cross-validation approach and externally validated on HR+/HER2- EBC patients from the TCGA cohort.

Both ACMIL-based and CLAM-based pipelines performed well in predicting recurrence risk, with UNI-ACMIL demonstrating superior performance across multiple metrics. The average area under the curve (AUC) for the UNI-ACMIL pipeline in the five-fold cross-validation test set was 0.86 ± 0.02, and 0.80 ± 0.04 in the TCGA cohort. In the five-fold cross-validation test sets, effectively stratified patients into high-risk and low-risk groups, demonstrating significant prognostic differences. Hazard ratios for recurrence-free survival (RFS) ranged from 5.32 (95% CI 1.86-15.12) to 15.16 (95% CI 3.61-63.56). Moreover, among six different multimodal recurrence risk models, the WSI-based risk score was identified as the most significant contributor.

Our multimodal recurrence risk prediction model is a practical and reliable tool that enhances the predictive power of existing systems relying solely on clinicopathological parameters. It offers improved recurrence risk prediction for HR+/HER2- EBC patients following adjuvant C-ET, supporting personalized treatment and better patient outcomes.

In this literature review, methods for the detection of breast cancer biomarkers and the operation of electrochemical sensors are considered. The work of sensors in the determination of breast cancer biomarkers was systematized, a comparative table with other methods was compiled, as was a classification of sensors depending on their intended use. The various traditional methods for the diagnosis of breast cancer biomarkers are described, including mammography, ultrasound, magnetic resonance imaging, positron emission computed tomography, computed tomography, single-photon emission computed tomography, and biopsy, and their advantages and disadvantages are presented. Key sensor parameters for the detection of breast cancer biomarkers are compared, such as the detection limit, linear detection range, response time, sensitivity, and other characteristics depending on the analyte being analyzed. Based on the reviewed scientific papers, the significance of electrochemical sensors in detecting the biomarkers of breast cancer is demonstrated. The types of tumor biomarkers identified by biosensors were analyzed, with a particular focus on HER2. Studies on HER2 detection using electrochemical methods are compared and systematized, and the features of electrochemical biosensors for determining this biomarker are characterized. Possible interfering agents affecting the accuracy of HER2 determination under experimental conditions are considered, their mechanisms of action are analyzed, and ways to eliminate them are proposed. This report provides a summary of the current aspects of scientific research on electrochemical sensors for the detection of breast cancer biomarkers. The development of electrochemical biosensors opens up new prospects for the early diagnosis and prognosis of breast cancer treatment.

High-grade serous carcinoma (HGSC), the most aggressive subtype of epithelial ovarian cancer, is strongly associated with hereditary breast and ovarian cancer (HBOC) syndrome and is primarily linked to germline BRCA1/2 pathogenic variants (PVs). The cumulative risks of ovarian cancer by the age of 70 years are 40% and 18% for carriers of BRCA1 and BRCA2 PVs, respectively. Risk-reducing salpingo-oophorectomy (RRSO) is a recommended preventive strategy that reduces the risk of ovarian cancer by more than 80% and may improve overall survival. However, surgical menopause after RRSO poses several challenges, including infertility and hormonal deficiency. Although the use of hormone replacement therapy may alleviate symptoms, it requires careful consideration of breast cancer risk. Emerging strategies, such as prophylactic salpingectomy with delayed oophorectomy, are being investigated to balance cancer prevention and patient quality of life. Further research is required to refine personalized prevention and management approaches for HBOC-associated ovarian cancer.

The National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer mathematical models have been increasingly utilized by policymakers to address breast cancer screening policy decisions and influence clinical practice. These well-established and validated models have a successful track record of use in collaborations spanning over 2 decades. While mathematical modeling is a valuable approach to translate short-term screening performance data into long-term breast cancer outcomes, it is inherently complex and requires numerous inputs to approximate the impacts of breast cancer screening. This review article describes the 6 independently developed CISNET breast cancer models, with a particular focus on how they represent breast cancer screening and estimate the contribution of screening to breast cancer mortality reduction and improvements in life expectancy. We also describe differences in structures and assumptions across the models and how variation in model results can highlight areas of uncertainty. Finally, we offer insight into how the results generated by the models can be used to aid decision-making regarding breast cancer screening policy.

Phosphodiesterase 4 (PDE4) is an enzyme that specifically hydrolyzes the second messenger cAMP and has a critical role in the regulation of a variety of cellular functions. In recent years, PDE4 has attracted great interest in cancer research, and its role in tumorigenesis and development has been gradually elucidated. Research indicates that abnormal expression or heightened activity of PDE4 is associated with the initiation and progression of multiple cancers, including lung, colorectal, and hematological cancers, by facilitating cell proliferation, migration, invasion, and anti-apoptosis. Moreover, PDE4 also influences the tumor immune microenvironment, significantly immune evasion by suppressing anti-tumor immune responses, reducing T-cell activation, and promoting the polarization of tumor-associated macrophages toward a pro-tumorigenic phenotype. However, the PDE4 family may have both oncogenic and tumor-suppressive effects, which could depend on the specific type and grade of the tumor. PDE4 inhibitors have garnered substantial interest as potential anti-cancer therapeutics, directly inhibiting tumor cell growth and restoring immune surveillance capabilities to enhance the clearance of tumor cells. Several PDE4 inhibitors are currently under investigation with the aim of exploring their potential in cancer therapy, particularly in combination strategies with immune checkpoint inhibitors, to improve therapeutic efficacy and mitigate the side effects of conventional chemotherapy. This review provides an overview of PDE4 in tumorigenesis, drug resistance, immunotherapy, and the anti-tumor actions of its inhibitors, intending to guide the exploration of PDE4 as a new target in tumor therapy.

Neoadjuvant treatment is increasingly being used in patients with breast cancer. Understanding the effects of neoadjuvant agents in the perioperative setting is crucial as it can affect morbidity. Understanding how these agents should be used to maximize optimal time to surgery is crucial as delays can negatively affective cancer outcomes. This review aims to discuss the perioperative considerations surgeons should be aware of prior to scheduling surgery for patients receiving chemotherapy, endocrine therapy, chemotherapy, targeted therapy, and immunotherapy.

Tamoxifen is essential in treating estrogen receptor-positive (ER+) breast cancer, primarily through its active metabolite, endoxifen. Emerging research suggests potential interactions between tamoxifen and gut microbiota. This study investigates the effects of tamoxifen on gut microbiota composition in postmenopausal ER+ and human epidermal growth factor receptor 2 negative (HER2-) breast cancer patients and explores correlations between gut microbiota and endoxifen plasma levels. This prospective observational study included postmenopausal ER+/HER2- breast cancer patients. Fecal and blood samples were collected before and during 6-12 weeks of tamoxifen therapy. Gut microbiota composition was analyzed using 16S rRNA amplicon sequencing of the hypervariable V4 gene region, and plasma endoxifen levels were measured using liquid chromatography-mass spectrometry. Changes in microbial diversity and composition were assessed, with correlations to endoxifen levels. A total of 62 patients were included. Tamoxifen significantly increased microbial richness (p = 0.019), although overall community structure remained consistent between pre- and during-treatment samples. Notable changes were observed in specific microbial taxa, with significant increases in genera such as Blautia (padjusted = 0.003) and Streptococcus (padjusted = 0.010), and decreases in Prevotella_9 (padjusted = 0.006). No significant correlations between gut microbiota and endoxifen levels were identified after multiple comparisons. Tamoxifen therapy increases gut microbial diversity in postmenopausal ER+/HER2- breast cancer patients, though overall microbial community structure remains stable. The absence of significant correlations with endoxifen levels suggests that while tamoxifen affects the gut microbiota, its role in endoxifen metabolism requires further study. More comprehensive research is needed to understand the relationship between tamoxifen, gut microbiota, and therapeutic outcomes.

IntroductionLetrozole is an aromatase inhibitor (AI), which suppresses plasma estrogen levels by inhibiting the aromatase enzyme, that causes the conversion of androgens to estrogen in peripheral tissues. There is very few information in the literature regarding the development of acute heart failure after AI use. We would like to report a case of a patient who was started letrozole for hormonal treatment and developed acute heart failure due to this.Case reportFifty-seven-year-old woman with hormone positive breast cancer was operated after neoadjuvant chemotherapy and received radiotherapy. Letrozole treatment was initiated after radiotherapy and the patient presented to the emergency department after two weeks with cough and dyspnea. Ejection fraction decreased to 20% and acute heart failure developed.Management and outcomeLetrozole treatment was stopped. Afterwards, improvement in the patient's cardiac functions was observed. Letrozole-induced heart failure was thought to be reversible.DiscussionLetrozole is one of the most commonly used HT in the treatment of hormone positive breast cancer. It may rarely cause cardiac side effects. It is very important to make patients aware of these issues and to be consulted by cardiology in case of possible cardiac symptoms.

Integration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences.

Distinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated.

The results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual's predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.