Artificial intelligence-assisted evaluation of cardiac function by oncology staff in chemotherapy patients.

Aims: Left ventricular ejection fraction (LVEF) calculation by echocardiography is pivotal in evaluating cancer patients' cardiac function. Artificial intelligence (AI) can facilitate the acquisition of optimal images and automated LVEF (autoEF) calculation. We sought to evaluate the feasibility and accuracy of LVEF calculation by oncology staff using an AI-enabled handheld ultrasound device (HUD). Methods and results: We studied 115 patients referred for echocardiographic LVEF estimation. All patients were scanned by a cardiologist using standard echocardiography (SE), and biplane Simpson's LVEF was the reference standard. Hands-on training using the Kosmos HUD was provided to the oncology staff before the study. Each patient was scanned by a cardiologist, a senior oncologist, an oncology resident, and a nurse using the TRIO AI and KOSMOS EF deep learning algorithms to obtain autoEF. The correlation between autoEF and SE-ejection fraction (EF) was excellent for the cardiologist (r = 0.90), the junior oncologist (r = 0.82), and the nurse (r = 0.84), and good for the senior oncologist (r = 0.79). The Bland-Altman analysis showed a small underestimation by autoEF compared with SE-EF. Detection of impaired LVEF < 50% was feasible with a sensitivity of 95% and specificity of 94% for the cardiologist; sensitivity of 86% and specificity of 93% for the senior oncologist; sensitivity of 95% and specificity of 91% for the junior oncologist; and sensitivity of 94% and specificity of 87% for the nurse. Conclusion: Automated LVEF calculation by oncology staff was feasible using AI-enabled HUD in a selected patient population. Detection of LVEF < 50% was possible with good accuracy. These findings show the potential to expedite the clinical workflow of cancer patients and speed up a referral when necessary.

Neoadjuvant and Adjuvant Immunotherapy in Resectable NSCLC.

Non-small cell lung cancer, even when diagnosed in early stages, has been linked with poor survival rates and distant recurrence patterns. Novel therapeutic approaches harnessing the immune system have been implemented in early stages, following the designated steps of advanced NSCLC treatment strategies. Immune-checkpoint inhibitor (ICI) regimens as monotherapy, combinational, or alongside chemotherapy have been intensely investigated as adjuvant, neoadjuvant, and, more recently, perioperative therapeutic strategies, representing pivotal milestones in the evolution of early lung cancer management while holding great potential for the future. The subject of current ongoing research is optimizing treatment outcomes for patient subsets with different needs and identifying biomarkers that could be predictive of response while translating the trials' endpoints to survival rates. The aim of this review is to discuss all current treatment options with the pros and cons of each, persistent challenges, and future perspectives on immunotherapy as illuminating the path to a new era for resectable NSCLC.

The Use of CA-125 KELIM to Identify Which Patients Can Achieve Complete Cytoreduction after Neoadjuvant Chemotherapy in High-Grade Serous Advanced Ovarian Cancer.

(1) Background: Neoadjuvant chemotherapy followed by interval debulking surgery is used in the treatment of advanced ovarian cancer. However, no tool can safely predict if complete cytoreduction after 3-4 cycles can be achieved. This study aims to investigate if the KELIM score can be a triage tool in the identification of patients that will be ideal candidates for interval debulking surgery (IDS). (2) Methods: We retrospectively analyzed the records of patients with high-grade serous advanced ovarian cancer that were treated in the 1st Department of Obstetrics-Gynecology, 2012-2022, with neoadjuvant chemotherapy followed by IDS. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcome was the association of the KELIM score with residual disease. (3) Results: 83 patients were categorized into two groups: Group A (51 patients) with favorable (≥1) and Group B (32 patients) with unfavorable (<1) KELIM scores. A statistically significant correlation between KELIM and residual disease (p < 0.05) exists, showing that patients with a favorable KELIM score can achieve a complete IDS. Furthermore, there was a statistically significant difference in overall survival (p = 0.017), but no difference was observed in progression-free survival (p = 0.13); (4) Conclusions: KELIM seems to safely triage patients after neoadjuvant chemotherapy and decide who will benefit from IDS.

Perceptions and experiences of fertility preservation in female patients with cancer in Greece.

BACKGROUND: As advances in oncology have led to remarkable and steady improvements in the survival rates of patients with cancer and anticancer treatment can cause premature ovarian failure in women, fertility preservation (FP) has become a global public health concern and an integral part of the care for women diagnosed with cancer during reproductive age. However, for various reasons, FP remains underutilized for patients with cancer. There are substantial gaps in our knowledge about women's experiences and perceptions of the issue. This study aims to contribute to bridging that gap. METHODS: This prospective qualitative study was conducted from March 2018 to February 2023. A combination of purposive and snowball sampling was used. Data were collected by semistructured interviews with nineteen reproductive-age women who had been recently diagnosed with cancer. Data were classified and analysed with a thematic analysis approach. RESULTS: A variety of distinct themes and subthemes emerged from the analysis of the interview data. The cancer diagnosis emerged as a factor that considerably affects the women's attitudes towards biological parenthood: It can further increase their (strong) previous desire or decrease their previous (weak) desire. Women with a recent cancer diagnosis had not received adequate and multidisciplinary counselling, including clear and sufficient information. However, participants felt satisfied with the information they received because they either received the information they requested or remained in denial about the need to be informed (i.e., because they felt overwhelmed after the cancer diagnosis). Embryo cryopreservation emerged as a less desirable FP option for women with cancer. Participants showed respect for human embryos, not always for religious reasons. Surrogacy emerged as the last resort for most participants. Religious, social or financial factors did play a secondary (if any) role in women's decision-making about FP. Finally, male partners' opinions played a secondary role in most participants' decision-making about FP. If embryo cryopreservation was the selected option, partners would have a say because they were contributing their genetic material. CONCLUSIONS: The findings that emerged from the data analysis were partly consistent with prior studies. However, we identified some interesting nuances that are of clinical importance. The results of this study may serve as a starting point for future research.

The Contribution of Lipidomics in Ovarian Cancer Management: A Systematic Review.

Lipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.

The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking.

Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis.

A retrospective multicentric cohort study of checkpoint inhibitors-induced pruritus with focus on management.

BACKGROUND: Limited data on immune checkpoint inhibitor (ICI)-induced pruritus per se and efficacy of different therapeutic modalities in its management exist. OBJECTIVE: To study the quantitative and qualitative characteristics of ICI-induced pruritus per se and to assess the efficacy of the therapeutic modalities usually applied. METHODS: We retrospectively reviewed the records of 91 patients who were under treatment with ICIs for any kind of neoplasia and developed pruritus during treatment. RESULTS: Twenty out of 91 individuals (22.0%) with ICI-induced pruritus had pruritus as the only symptom, while 71/91 (78.0%) presented with pruritus coexisting with an additional cutaneous toxicity. Pruritus was treated with antihistamines (18/20, 90.0%) and/or topical regimens, as first-line choice. In resistant cases, as a second therapeutic intervention, narrow-band UVB (NBUVB), oral steroids and GABA analogs were added (70.0%). Statistical analysis revealed a significant difference in mean pruritus Numerical Rating Scale (NRS) scores between baseline and sequential visits. Moreover, subgroup analysis revealed a significant reduction in mean NRS scores in those treated with phototherapy. LIMITATIONS: Retrospective design, low number of patients and survivorship bias. CONCLUSION: Pruritus per se was present in a substantial portion of our cohort (22.0%). Our study confirms the efficacy of current treatment strategies and suggests NBUVB as a potential steroid-sparing therapeutic alternative.

Investigating Predictive Factors of Dysphagia and Treatment Prolongation in Patients with Oral Cavity or Oropharyngeal Cancer Receiving Radiation Therapy Concurrently with Chemotherapy.

Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51-20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84-27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021-1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53-10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

Critical evaluation and comparison of nutritional clinical practice guidelines for cancer patients.

BACKGROUND: The growing incidence of cancer globally, and the importance of nutrition support for these patients, emphasize the need for the development of nutritional clinical practice guidelines and consensus papers (CPGs) in the field. Numerous relevant CPGs have been published by several organizations worldwide. The aim of this systematic review was to compare the content of the existing CPGs and evaluate the quality of their development using the AGREE-II tool. METHODS: A systematic literature search in PubMed, Embase and Web of Science databases was conducted for the identification of relevant CPGs and consensus papers. Eligible CPGs was blindly evaluated by four appraisers according to the Appraisal of Guidelines for Research and Evaluation ΙΙ (AGREE-II) tool. RESULTS: In total 15 CPGs were identified and were evaluated. All but one set of CPGs underlined the importance of nutritional screening and assessment, whereas recommendations on nutritional interventions, supplements, management of complications and nutritional follow-up were also reported by several organizations. AGREE-II results showed that two CPGs were characterized as high, eight as moderate and five as low regarding their quality of development. CONCLUSIONS: Variety on recommendations could be observed between CPGs that should be considered when applied into clinical practice. Limitations of the existing CPGs could be the fact that they are non-specific and only a minority of them are focused to specific cancer types. Frequent updates for CPGs and inclusion of more nutritional topics should be considered for some CPGs. Improvement of the quality of the CPGs development should also be pursued in future.

Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients.

INTRODUCTION: Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy. OBJECTIVES: We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management. METHODS: Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The internet was searched for relevant studies. RESULTS: A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation. CONCLUSION: Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients' quality of life.

A Multicenter, Prospective, Observational Study to Assess the Clinical Activity and Impact on Symptom Burden and Patients' Quality of Life in Patients with Advanced Soft Tissue Sarcomas Treated with Trabectedin in a Real-World Setting in Greece.

This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0-6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

Prophylaxis of cancer-associated venous thromboembolism with low-molecular-weight heparin-tinzaparin: Real world evidence.

Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score <2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index >30 kg/m2, a history of smoking and a history of metastatic disease, along with administration of erythropoietin. InterD tinzaparin treatment was found to be potentially more efficacious and without safety concerns. The present study is a registered clinical trial (ClinicalTrials.gov code, NCT03292107; registration date, September 25, 2017).

Real-World Data on Treatment Management and Outcomes of Patients with Newly Diagnosed Advanced Epithelial Ovarian Cancer in Greece (The EpOCa Study).

New treatment modalities have been recently introduced in the management of ovarian cancer (OC). Herein, we sought to investigate their implementation in routine clinical practice and examine the real-world management of OC in Greece. EpOCa was a non-interventional, multicenter, retrospective study in patients with advanced epithelial OC. The primary outcome was to estimate the proportions of the different treatment regimens used per line of therapy, while progression-free survival (PFS) and overall survival (OS) were the key secondary endpoints. A total of 154 patients were enrolled in the study, among whom, 40% were tested for BRCA mutations and 30% were found to be positive. Nearly 90% of patients underwent debulking surgery at diagnosis, with few operations being also recorded upon relapse. Platinum-based chemotherapy (CT) was predominantly used in the first line with half of patients also receiving angiogenesis inhibitor (AI), while non-platinum-based CT was preferred in later lines. The median PFS was 18.2 and 8.8 months in the first- and second-line setting, respectively, whereas the median OS was approximately 50 months. Our study adds to the available, but limited, real world data on the management of ovarian cancer providing evidence regarding the applied treatment strategies and outcomes of patients in Greece.

Real-World Data on Thromboprophylaxis in Active Cancer Patients: Where Are We? Are We Getting There?

Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10-1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastasis and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Management of Cancer-associated Thrombosis (CAT): Symptomatic or Incidental.

BACKGROUND: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. PATIENTS AND METHODS: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. RESULTS: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. CONCLUSION: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.

Opposite Prognostic Impact of Single PTEN-loss and PIK3CA Mutations in Early High-risk Breast Cancer.

BACKGROUND/AIM: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease. MATERIALS AND METHODS: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of "grey zone" tumors with low and very low PTEN protein expression. RESULTS: PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen's kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned "grey zone" tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations,single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance. CONCLUSION: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance.

Correlation of MYC Gene and Protein Status With Breast Cancer Subtypes and Outcome of Patients Treated With Anthracycline-Based Adjuvant Chemotherapy. Pooled Analysis of 2 Hellenic Cooperative Group Phase III Trials.

BACKGROUND: The prognostic/predictive value of aberrant MYC gene copies and protein expression is not clear in breast cancer. PATIENTS AND METHODS: Early breast cancer patients were treated with anthracycline-containing chemotherapy within 2 randomized adjuvant trials. MYC gene and centromere-8 status, as well as Myc protein expression were investigated on 1060 paraffin tumors with fluorescence in situ hybridization and immunohistochemistry, respectively. RESULTS: MYC amplification was present in 45% and polysomy-8 in 23% of the tumors. Cytoplasmic staining was observed in 60% and nuclear staining in 26% of the tumors, strongly correlating with each other but not with MYC gene status. MYC gene amplification in the absence of polysomy-8 was associated with adverse disease-free survival (DFS) and overall survival (OS), and remained as an independent unfavorable prognostic factor in multivariate analysis (Wald P = .022 for DFS; P = .032 for OS), whereas patients with MYC amplification and polysomy-8, with polysomy-8 only, and with normal MYC without polysomy-8 performed significantly better compared with those with MYC gene amplification only. Nuclear Myc protein expression benefitted patients treated with paclitaxel (interaction P = .052 for DFS; P = .049 for OS). This interaction remained independently significant in multivariate analysis for OS (overall P = .028). CONCLUSION: The effect of MYC gene status on breast cancer patient outcome seems to depend on the underlying chromosomal instability and appears unfavorable for tumors with MYC amplification without polysomy. Nuclear Myc protein expression seems predictive for benefit from adjuvant paclitaxel. These data might aid in the interpretation of relevant findings from large clinical trials.

Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy.

BACKGROUND: Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated. PATIENTS AND METHODS: Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We evaluated, by quantitative reverse transcription-polymerase chain reaction, 819 formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of RANK, OPG, and RANKL, as well as their ratios, for potential prognostic significance for the development of bone metastases and also for disease-free survival (DFS) and overall survival. RESULTS: Median age was 52.7years, whereas 54.2% of the patients were postmenopausal and 78.3% estrogen receptor/progesterone receptor positive. After a median follow-up of 119.9months, 226 patients (27.6%) had died and 291 patients (35.5%) had disease progression. Low mRNA expression of RANKL was associated with postmenopausal status and greater number of positive lymph nodes (P=.002 and P<.001, respectively). In the univariate analysis, low RANKL mRNA expression was found to be an unfavorable factor for DFS [hazard ratio (HR)=1.33, 95% confidence interval (CI) 1.05-1.68, Wald's P=.018] and bone metastasis-free survival (HR=1.67, 95% CI 1.09-2.56, P=.018), although it did not retain its significance in the multivariate analysis. CONCLUSIONS: Low RANKL mRNA expression in early breast cancer patients is of prognostic significance for increased risk for relapse and bone metastases and might potentially guide clinical decision-making for the use of anti-RANKL agents in the treatment of early breast cancer patients at high risk for metastatic spread, provided that our findings are validated in independent cohorts.