Search Results (59)

Thyroid hormones (THs) regulate metabolism, proliferation, and genomic stability. Clinical studies have linked levothyroxine therapy with higher Oncotype DX Recurrence Scores in breast cancer (BC), suggesting a potential effect of thyroid hormone signaling on genomic risk. Here, we investigated the impact of triiodothyronine (T3) on DNA damage and repair pathways in estrogen receptor-positive T47D breast cancer and non-tumorigenic MCF10A cells. RNA sequencing revealed significant upregulation of RAD51 and enrichment of DNA repair pathways following 24 h T3 exposure. Consistently, T3 increased γH2AX and 53BP1 nuclear foci, indicating transient activation of the DNA damage response (DDR). These effects were transient, returning to baseline after 48 h, suggesting cellular adaptation. T3 also enhanced proliferation at 10 μM but inhibited growth at higher concentrations. Our findings indicate that acute exposure to T3 induces transient genomic stress, providing a potential mechanistic basis for the observed association between thyroid hormone therapy and increased BC recurrence risk. Full article

Several liquid-, and tissue-based markers are available to guide primary diagnosis-, active surveillance-, and treatment-related decision-making for patients with prostate cancer. Most of these tests can improve the balance of harms and benefits associated with early detection, and aid patient selection for treatment intensification. However, the costs of these tests can make their integration in routine clinical practice challenging. To date, prostate-specific antigen (PSA) is still one of the most well-known and widely utilized tumor markers worldwide, with a unique facility ranging from the diagnosis to the treatment-related follow-up of patients with prostate cancer. Future research efforts are needed to integrate biomarkers and novel imaging techniques, such as prostate magnetic resonance imaging, in the decision-making pathways. Despite the growing body of knowledge and evidence, considerable challenges remain in optimizing risk-stratification, improving patient selection and cost-efficacy in different prostate cancer (PCa)-related settings. Full article

Background/Objectives: To evaluate the ability of radiomics analysis of QUS spectral parametric imaging to non-invasively differentiate intermediate-to-high-risk from low-risk Oncotype DX^TM Recurrence Score (ODXRS). Methods: This prospective study included 31 participants (21 intermediate-to-high-risk ODXRS (median age, 56 years [IQR: 49–68 years]) and 10 low-risk ODXRS (median age, 52 years [IQR: 48–58 years])) presenting with ER+ HER2− invasive breast masses acquired between September 2015 and August 2024. Quantitative ultrasound (QUS) spectroscopy produced five spectral maps, from which radiomics features (including statistical, texture, and morphological measures) were extracted from the tumor core and a 5 mm margin. The ground truth label was determined from thresholding the ODXRS. A multivariate predictive model was developed to differentiate intermediate-to-high-risk ODXRS from low-risk ODXRS, with performance assessed via nested leave-one-out cross-validation (LOOCV). Results: A nested leave-one-out cross-validation (LOOCV) analysis demonstrated the generalization performance of a four-feature model. The support vector machine (SVM-RBF) classifier achieved 86% recall, 100% specificity, 93% balanced accuracy, and an area under the receiver operating characteristic curve (AUROC) of 0.95 (CI = 0.88–1.00) in identifying intermediate-to-high-risk versus low-risk ODXRS. Conclusions: The preliminary results suggest the potential radiomics-based model of ODXRS in predicting the risks of recurrence. The results warrant further investigation on a larger cohort. This framework can be a useful surrogate for participants for whom ODX testing is neither affordable nor available. Full article

(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct biologic behavior—remains unvalidated. This study evaluates whether Oncotype DX offers prognostic information with respect to overall survival (OS) in non-metastatic, early-stage patients with IMPC of the breast. (2) Methods: The National Cancer Database (2004–2020) was queried to select for women with ER+/HER2−, T1-T2N0-N1 IMPC who underwent Oncotype DX testing and received no neoadjuvant therapy. Patients were stratified by RS: low (≤11), intermediate (12–25), and high (>25). Kaplan–Meier survival curves and log-rank tests compared 5-year OS between groups. Multivariable Cox proportional hazards models assessed RS as an independent predictor, adjusting for age, race, comorbidities, grade, radiation, and insurance status. (3) Results: A total of 1325 women met the selection criteria. The cohort demonstrated significant survival disparities by RS (log-rank p = 0.017). Five-year OS rates were 97.5%, 97.5%, and 93.7% for low, intermediate, and high-risk patients, respectively. Adjusted multivariate analysis confirmed RS as an independent prognosticator: low (HR = 0.31, 95% CI: 0.15–0.75) and intermediate (HR = 0.32, 95% CI: 0.15–0.75) scores correlated with reduced mortality versus high RS. Omission of radiation therapy (HR = 2.68, 95% CI: 1.05–6.86) and higher comorbidity burden (0 comorbidities vs. ≥2: HR = 0.25, 95% CI: 0.10–0.61) were significantly associated with worse survival. (4) Conclusions: Oncotype DX is predictive for OS in IMPC, with high RS (>25) portending poorer outcomes. The survival detriment associated with RT omission aligns with prior studies demonstrating RT benefit in higher-risk cohorts. These findings validate RS as a prognostic tool in IMPC and underscore its potential to refine adjuvant therapy, particularly RT utilization. Future studies should explore RS-driven treatment personalization in IMPC, including comorbidity management and adjuvant radiation to improve outcomes in this distinct patient population. Full article

(1) Background: Extended endocrine therapy (EET) beyond five years can reduce distant recurrence in early-stage hormone receptor-positive (HR+) breast cancer. The Breast Cancer Index (BCI) predicts recurrence risk and EET benefits, yet racial/ethnic differences in its results remain unexplored. This study evaluates such differences in a diverse early-stage HR+ breast cancer population. (2) Methods: We retrospectively analyzed demographics, tumor characteristics and BCI scores of 159 women in Hawaii with early-stage HR+ breast cancer, self-identifying as Caucasian, Filipino, Japanese, Native Hawaiian, Other Asian/Pacific Islander, or Other. Tumor characteristics included size, grade, histology, lymph node/receptor status, Oncotype DX score, and laterality. Logistic regression used demographics and tumor features as predictor variables, with BCI’s benefit prediction and recurrence risk as outcome variables. (3) Results: Japanese and other Asian/Pacific Islander patients had significantly lower odds of high recurrence risk compared to Caucasian patients. Higher recurrence risk was associated with greater odds of predicted EET. Racial/ethnic differences in EET benefit prediction were not statistically significant. (4) Conclusions: No racial/ethnic differences in EET benefit prediction suggest BCI’s applicability in racially and ethnically diverse populations. Findings among Japanese and other Asian/Pacific Islanders point to potential biological or socioeconomic variation. Limitations include sample size and underrepresentation of certain groups. Future studies should address these gaps and adjust for known risk factors to further clarify BCI’s racial and ethnic implications. Full article

Prostate cancer (PCa) diagnosis has historically relied on the prostate-specific antigen (PSA) testing. Although the screening significantly reduces mortality rates, PSA has low specificity with risks of overdiagnosis and overtreatment. These limitations highlight the need for a more accurate diagnostic approach. Emerging technologies, such as artificial intelligence (AI), novel biomarkers, and advanced imaging techniques, offer promising avenues to enhance the accuracy and efficiency of PCa diagnosis and risk stratification. This narrative review comprehensively analyzed the current literature, focusing on new tools aiding PCa diagnosis (AI-driven image interpretation, radiomics, genomic classifiers, biomarkers, and multimodal data integration) with consideration for technical, regulatory, and ethical challenges related to clinical implementation of AI-based technologies. A literature search was performed using the PubMed and MEDLINE databases to identify relevant peer-reviewed articles published in English using the search terms “prostate cancer,” “artificial intelligence,” “machine learning,” “deep learning,” “MRI,” “histopathology,” and “diagnosis.” Articles were selected based on their relevance to AI-assisted diagnostic tools, clinical utility, and performance metrics. In addition, a separate section was developed initially to contextualize the limitations of current PSA-based screening approaches. The reviewed studies showed that AI had significant utility in prostate mpMRI interpretation (lesion detection; Gleason grading) with high accuracy and high reproducibility. For the pathologist, AI-driven algorithms improve the diagnostic accuracy of digital slide evaluation for histologic diagnosis of prostate cancer and automated Gleason score grading. Genomic tools such as the Oncotype DX test, combined with AI, could also allow for tailored and individualized risk prediction. Overall, multimodal models integrating clinical, imaging, and molecular data often outperform traditional PSA-based strategies and reduce unnecessary biopsies. Transition from PSA-centered toward AI-driven, biomarker-supported, and image-enhanced diagnosis marks a critical evolution in PCa diagnosis. Full article

Background: Oncotype DX (ODX) is widely used to estimate recurrence risk and guide adjuvant therapy in hormone receptor-positive (HR+), HER2-negative early-stage breast cancer. However, limited accessibility and high costs have prompted the use of alternative clinical models, such as the Tennessee nomogram. This study aimed to validate the predictive performance of the Tennessee nomogram in a Korean breast cancer cohort and identify factors contributing to discrepancies between nomogram predictions and ODX results. Methods: We retrospectively analyzed data on1298 patients with HR+/HER2−, node-negative invasive breast cancer who underwent ODX testing between May 2013 and August 2023. Predictive probabilities were calculated using the Tennessee nomogram and compared with actual ODX recurrence scores. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were determined. Discordant cases were examined for clinicopathologic characteristics contributing to prediction errors. Results: The nomogram demonstrated an overall accuracy of 86.1% (sensitivity 0.130, specificity 0.989, AUC 0.776). Discordant results were observed in 13.9% of cases, primarily in patients with a high histologic grade, PR negativity, and elevated Ki-67 index. Most false negatives clustered within the ODX score range of 25–30, suggesting underestimation of risk in borderline-high cases. Conclusions: The Tennessee nomogram may be a useful surrogate when ODX testing is unavailable, but caution is warranted in patients with aggressive tumor biology. In such cases, ODX testing should be prioritized to guide adjuvant therapy decisions. Full article

Background: Breast cancer is a major health concern in Poland, with significant incidence and mortality rates despite national screening programs. This retrospective study aimed to evaluate critical aspects of breast cancer management, focusing on waiting times, treatment coordination, cancer characteristics, diagnostic testing, and staging. Methods: We retrospectively analyzed 587 medical records of breast cancer patients (585 female, 2 male) collected between March 2023 and June 2024 through a data donation model. Data included tumor characteristics (histological type, grade, stage, biological subtype, receptor status, Ki-67), diagnostic and genetic tests, and timelines of key events in the diagnostic and therapeutic pathways. Results: Although referral to first oncology consult (18 days) and MDT referral/admission to treatment (10 days) met NFZ guidelines, diagnosis to surgery (94 days) and diagnosis to drug treatment (109 days) were significantly delayed. No records showed oncology coordinator assignment or educational material provision. Clinically, invasive carcinoma NST (77%) and early-stage (IA/IIA, 61%) were prevalent, with Luminal B (HER2-negative) being the most common biological subtype. BRCA1/2 testing was common, but Oncotype DX was not. For 314 HR+ HER2- patients, stage IA (44%) was most common, with no BRCA1/2 mutations found. Conclusion: Breast cancer care in the Łódź voivodeship falls short of national guidelines due to long waiting times and poor care coordination, a problem worsened by incomplete data. Improving record-keeping and speeding up diagnostic and treatment pathways are crucial for better breast cancer management in Poland. While patient data donation can help analyze real clinical pathways, data completeness, and consistency remain challenges. Full article

Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization of localized disease. This review critically examines recent advances in urinary biomarkers (e.g., PCA3, SelectMDx), tissue-based genomic assays (Oncotype DX Prostate, Prolaris, Decipher), and imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PET-PSMA). We evaluate their diagnostic performance, prognostic value, and clinical utility in risk stratification and individualized treatment decision-making. Methodological and clinical barriers to their routine implementation are also discussed. Current evidence supports the multidisciplinary integration of these biomarkers to overcome the limitations of PSA, improve biopsy decision-making, better distinguish indolent from aggressive tumors, and optimize therapeutic strategies. Finally, future research directions aimed at validating and incorporating emerging biomarkers into clinical practice are outlined, with the goal of improving outcomes in patients with localized prostate cancer. Full article

The concept of “more is better” has long dominated cancer treatment, emphasizing aggressive therapies despite their toxicity. However, the rise of personalized medicine has fostered treatment de-escalation strategies aimed at minimizing toxicity, improving quality of life, and reducing costs. This position paper highlights key applications of de-escalation in medical oncology, with a primary focus on breast cancer and notable examples in colorectal, head and neck, ovarian, lung, and prostate cancers. Various approaches, including dose reduction, treatment duration shortening, and regimen optimization, have demonstrated efficacy without compromising clinical outcomes. Advances in molecular diagnostics, such as Oncotype Dx in breast cancer and circulating tumor DNA (ctDNA) analysis in colorectal cancer, have facilitated patient selection for de-escalation. While these strategies present promising results, challenges remain, particularly in balancing treatment intensity with oncologic control. The review underscores the need for further prospective trials to refine de-escalation approaches and ensure their safe integration into standard oncologic care. Full article

Background: Women with a lower socioeconomic status (SES) have an increased risk of dying from breast cancer (BC) than those with a higher SES. The association of SES with BC survival may be partially mediated by factors such as Oncotype DX (ODX) testing and stage at diagnosis. This study aims to examine SES disparities in survival among HR+/HER2- BC women and to quantify the mediating effects of the ODX test and stage. Methods: We used data from the Louisiana Tumor Registry to identify women aged 20–90 years diagnosed with stage I–II in 2011–2014 and stage I–III in 2015–2017 HR+/HER2- BC who underwent BC surgery. The follow-up cutoff date was 31 December 2020. Cox proportional hazard regression and generalized mediation analysis were both performed. Results: Of 8931 BC women, 41.4% underwent ODX testing. After adjusting for sociodemographic, tumor characteristic, and treatment variables, low SES women had a higher hazard of overall death (HR = 1.16, 95% CI: 1.02–1.32) and BC-specific death (HR = 1.37; 95% CI: 1.01–1.87) compared to high SES women. The ODX test and stage explained 9.0% and 11.2% SES differences in the hazard of overall death and 4.4% and 13.3% in BC-specific death, respectively. Conclusions: Low SES is associated with higher hazard rates of overall and cause-specific death among women with breast cancer, even after adjustment. Differences in Oncotype DX (ODX) testing and stage at diagnosis explained part of these disparities. Targeted interventions are needed to improve access to genomic testing and early detection to reduce SES-related disparities in breast cancer outcomes. Full article

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting. Full article

Background/Objectives: The Oncotype DX recurrence score (ODXRS) has emerged as an important tool for predicting recurrence risk and guiding treatment decisions in estrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer. This review summarizes the current evidence on the clinical utility of the Oncotype DX RS and explores emerging research on potential imaging-based alternatives. The 21-gene assay provides a recurrence score that stratifies patients into low, intermediate, and high-risk groups, helping to identify patients who may benefit from adjuvant chemotherapy. Multiple validation studies have demonstrated the prognostic and predictive value of the ODXRS. However, the test is costly and requires tumor tissue samples. Methods: This paper systemically reviewed the current literature on the use of radiomic analysis of breast MRI to predict Oncotype DX. The literature search was performed from 2016 to 2024 using PubMed. We compared different image types, methods of analysis, sample size, numbers of high/intermediate and low scores, MRI image types, performance indices, among others. We also discussed lessons learned and suggested future research directions. Results: Recent studies have investigated the potential of radiomics applied to breast MRI to non-invasively predict the Oncotype DX RS. Quantitative imaging features extracted from dynamic contrast-enhanced MRI, diffusion-weighted imaging, and T2-weighted sequences have shown promise for distinguishing between low and high RS groups. Multiparametric MRI-based models integrating multiple sequences have achieved the highest performance. Conclusions: While further validation is needed, MRI radiomics may offer a non-invasive, cost-effective alternative for assessing recurrence risk. Full article

Prostate cancer (PCa) is a common malignancy in men and is among the leading causes of cancer-related death worldwide. Genomic tests assess disease aggressiveness and guide treatment, particularly in low- and intermediate-risk PCa. We reviewed the literature on the use of four genomic tests (Prolaris^®, Promark^®, Oncotype DX^®, and Decipher^®) in assessing the prognosis of PCa and their use in treatment decision-making. Most of the studies showed that Prolaris^® has a strong correlation with biochemical recurrence, metastasis risk, PCa-specific mortality (PCSM), and pathological features. Similarly, three studies on Promark^® indicated a connection between results and pathological features in the subsequent prostatectomy, time to metastasis, and biochemical recurrence. Fourteen studies on Oncotype DX^® showed a clear correlation between high scores, death, and PCSM. One study found that routine biopsy pathology reports, combined with serum PSA levels, provide a risk assessment comparable to Oncotype DX^® testing. Results from 22 studies on Decipher^® were controversial. The test was associated with conservative management, suggesting that patients with a high GC score are more likely to need radiation after surgery. Comparative studies indicated that Oncotype DX^® is preferable for assessing PCSM, Decipher^® for predicting metastasis, and Prolaris^® for predicting recurrence. With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice. Full article