High tumour-infiltrating lymphocytes correlate with distinct gene expression profile and favourable survival in single hormone receptor-positive breast cancer.

Introduction: This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR-/HER2-, 18.4% as ER+/PgR-/HER2+, 26.2% as ER-/PgR+/HER2-, and 10.7% as ER-/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology. Results: Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0-20%. ER-/PgR+ tumours displayed significantly higher TILs density than ER+/PgR- cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER-/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR- subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER-/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group. Conclusions: The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR- and ER-/PgR+).

Influence of Androgen Deprivation Therapy on the Development of Sarcopenia in Patients with Prostate Cancer: A Systematic Review.

The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as biomarker for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. A significant increase in SATI (Subcutaneous Adipose Tissue Index) of 0.32 (95% CI: 0.13-0.51) p = 0.001, decrease in SMI (Skeletal Muscle Index) of -0.38 (95% CI: -0.57 to -0.19) p < 0.0001, and SMD (Skeletal Muscle Density) of -0.46 (95% CI: -0.69 to -0.24) p < 0.0001 were observed. No statistical association was visible between ADT and changes in BMI (Body Mass Index), 0.05 (95% CI: -0.18-0.28), p = 0.686, and VATI (Visceral Adipose Tissue Index): 0.17 (95% CI: -0.02 to 0.37), p = 0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.

Coping with cancer and a history of health-related events.

Background: Cancer is a source of stress related to the resulting change in lifestyle. The processes which take place when a patient is coping with a disease may be explained in terms of the transactional concept of psychological stress (Lazarus, Folkman) and the critical life events model (Filipp). These two complementary theoretical approaches set the direction and aim of the study which was to determine the role played by earlier events responsible for health loss due to a chronic, serious disease in the course of a stress transaction in cancer patients. Materials and methods: The study involved 121 patients with either breast or colorectal cancer undergoing chemotherapy as part of their treatment. They were asked to complete a purpose-designed set of questionnaires which included Revised Illness Perception Questionnaire (IPQ-R), the Mini-Mental Adjustment to Cancer (Mini-MAC) questionnaire, the Hospital Anxiety and Depression Scale (HADS), Acceptance of Illness Scale (AIS). The interdependencies between variables were determined using difference significance tests (Mann-Whitney, Kruskal-Wallis) and the Dunn's correction test. The significance level (alpha) of 0.05 was assumed appropriate for the study. Results: Patients with previous health-related events were found to expect the struggle with cancer to be a greater and more serious challenge. Those patients had suffered loss of health prior to getting cancer and their emotional reactions were heightened. This finding allowed the identification of patients more prone to creating a negative view of their disease. Conclusions: When planning a psychological treatment of patients with cancer, an account must be taken of their past life events and earlier experiences of being ill, in order to implement appropriate psychological intervention aimed at reducing their emotional stress.

Androgen Deprivation Therapy for Prostate Cancer Influences Body Composition Increasing Risk of Sarcopenia.

Computed tomography (CT) scans used in treatment response assessment in prostate cancer (PCa) patients are a useful tool for nutritional status evaluation. The aim of this study was to assess the nutritional status, including sarcopenia development based on CT scans, in PCa patients and its association with progression-free survival (PFS). Sixty-four PCa patients were included (group 1: 34 patients undergoing androgen deprivation therapy (ADT) with docetaxel due to newly diagnosed, hormone-sensitive, metastatic PCa and group 2: 30 patients with castration-resistant metastatic PCa continuing ADT therapy with enzalutamide or abiraterone acetate). Nutritional status was evaluated with anthropometrical parameters, Nutritional Risk Score (NRS), and CT scans at the L3 vertebrae. Survival analyses were performed. According to NRS, nutritional status was significantly related to PFS. In both groups, there was a significant reduction in muscle tissue (total muscle tissue and skeletal muscle index). A significant increase in the distribution of adipose tissue (subcutaneous fat, visceral fat, subcutaneous adipose tissue index, and visceral adipose tissue index) in group one was observed. Sarcopenia was diagnosed in patients but with no influence on PFS. Significant reduction in muscle mass and increase in fat mass was observed in patients treated for PCa with no impact on PFS. The NRS was related to PFS in PCa patients and associated with body composition, assessed by CT after the castration therapy. Long-term castration combined with abiraterone therapy with prednisone or enzalutamide significantly influenced muscle tissue and may lead to sarcopenia development.

Cardiac Safety and Efficacy of SB3 Trastuzumab Biosimilar for ERBB2-Positive Early Breast Cancer: Secondary Analysis of a Randomized Clinical Trial.

Importance: Trastuzumab has been the standard of care for the treatment of patients with ERBB2-positive breast cancer; however, cardiac events have been reported. This long-term follow-up study provides clinical evidence supporting the similarity of a trastuzumab biosimilar (SB3) to reference trastuzumab (TRZ). Objective: To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up. Design, Setting, and Participants: This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment. Interventions: In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years. Main Outcomes and Measures: The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS). Results: A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02771795.

Follow-up after breast cancer treatment.

Background: Breast cancer (BC) is the most common malignancy in women. Due to improved detectability and modern methods of treatment, the number of breast cancer survivors is estimated at 6 million women globally and is still increasing. The follow-up (FU) visits carried out at the Greater Poland Cancer Centre were assessed for compliance with Polish Society of Clinical Oncology (PTOK) and European Society for Medical Oncology (ESMO) guidelines. Materials and Methods: The database covered 484 women who were treated for breast cancer in the Greater Poland Cancer Centre in 2013. Of these, 233 attended FU visits for 5 years after completion of radical treatment and had no cancer relapse. The number of FU visits and the number and type of additional tests performed were analyzed. Results: The median number of FU visits over 5 years was 14, which is in line with the guidelines. 51.6% women had a mandatory annual mammography. A significant number of women had additional tests that are not recommended in the guidelines. Conclusions: There is a need to educate both physicians and patients on the principles of FU check-ups.

Impact of the COVID-19 Pandemic on Breast Cancer Stage at Diagnosis in a Regional Cancer Center in Poland between 2019 and 2021.

The COVID-19 pandemic had a negative effect on oncology healthcare services in Poland, with a reduction in the national breast cancer (BC) screening program coverage rates. This article analyzes the impact of the pandemic on BC stage at diagnosis in a regional cancer center in Poland. Records from BC multidisciplinary team (MDT) meetings that took place in the years 2019-2021 were gathered. BC clinical staging was compared. Age-related subgroups were additionally analyzed to reflect possible screening program disruptions. The total number of BC cases fell by 8% in 2020 compared with 2019, with a 14% fall in the screening age group. In 2021, a stage shift was observed, with stage II BC becoming most frequently diagnosed (as opposed to stage I BC in 2019 and 2020). A statistically significant increase in the number of stage III BC cases was observed in 2021.

High expression of progesterone receptor may be an adverse prognostic factor in oestrogen receptor-negative/progesterone receptor-positive breast cancer: results of comprehensive re-evaluation of multi-institutional case series.

Oestrogen receptor (ER)-negative (-) progesterone receptor (PgR)-positive (+) is the least common combination of steroid receptor expression observed in breast cancer. There are many controversies regarding the actual existence of ER-/PgR+ phenotype. In the current study, we aimed to perform comprehensive immunohistochemical re-evaluation of ER-/PgR+ breast cancers from multiple institutions. A total of 135 cases of ER-/PgR+ breast cancer were collected from 11 institutions from the period 2006-2020 and subsequently stained with three clinically validated anti-ER antibody clones: SP1 (Roche), 1D5 (Dako), and EP1 (Dako), and two anti-PgR antibody clones: 636 (Dako), and 1E2 (Roche). Clinicopathological characteristics of confirmed and re-categorised cases were analysed. Seventy-six cases retained the original ER-/PgR+ phenotype, including 21 HER2+ and 55 HER2- tumours. Forty-seven cases were ER+ with at least one anti-ER antibody, and 12 cases were re-categorised as double-negatives across all anti-ER and anti-PgR antibodies. No significant differences in survival were observed between groups in the HER2+ category. In the HER2- cohort, confirmed ER-/PgR+, ER+ tumours with discrepant ER staining, and triple negatives had inferior overall survival compared to concordant ER+ cases. Progesterone receptor expression in >20% of cells was identified as an adverse prognostic factor in ER-/PgR+/HER2- breast cancer in a multivariable model adjusted by stage (HR 5.0, 95% CI 1.3-19.2, p=0.019). We performed one of the largest validation studies so far on ER-/PgR+ breast cancer and confirmed the existence of this subgroup. Moreover, we identified high PgR expression as an adverse prognostic factor.

Seasonal influenza vaccination among cancer patients during the COVID-19 pandemic in Poland.

INTRODUCTION: In the era of the COVID-19 pandemic overlapping with the influenza season, the number of infections with the abovementioned viruses may result in overload in the healthcare system, difficulties in the diagnosis of respiratory diseases, poorer access to appropriate therapy, and increased mortality. AIM OF THE STUDY: The aim of this study was to analyze the influence of the COVID-19 pandemic on the decision to be vaccinated against seasonal influenza in cancer patients. MATERIAL AND METHODS: An anonymous survey prepared by the authors was made available to patients at the Chemotherapy Department at the Greater Poland Cancer Center. The survey covered 236 respondents, both female (67.4%, n = 159) and male (32.6%, n =77). A 0-10 point numerical scale was used to assess the fear of coronavirus infection and the influenza. Data were collected from June 8 to September 30, 2020. The survey included 25 questions. The patients were informed by physicians about the voluntary and anonymous nature of the survey, to which they gave their oral consent. IBM SPSS Statistics 26 was used for the analysis. RESULTS: The vast majority of patients (69.5%, n = 164) have never been vaccinated against influenza and 30.5% (n = 72) have been vaccinated at least once in the past. In the face of the COVID-19 pandemic, almost » of the patients (24.6%, n = 58) stated that they wanted to be vaccinated against influenza. Only 33.5% (n = 79) of the respondents believed that the influenza vaccine was effective. CONCLUSIONS: Action is needed to increase the percentage of cancer patients who will be regularly vaccinated against the influenza. The COVID-19 pandemic may raise the interest of cancer patients in influenza vaccination.

Cancer patients and internal medicine patients attitude towards COVID-19 vaccination in Poland.

BACKGROUND: The initial approval of the Pfizer/BioNTech and Moderna vaccines by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) marked a milestone in the fight against the COVID-19 pandemic. The increased public debate about the vaccine development process and vaccine side effects has activated the anti-vaccine community, which has begun to spread conspiracy theories about vaccine safety. OBJECTIVES: Our study is the first to investigate the awareness of Polish patients suffering from various chronic diseases, mainly cancer, about vaccination against SARS-CoV-2. MATERIAL AND METHODS: An anonymous survey was made available from November 2020 to February 2021 to representatives of patient organizations through social media (Facebook) and to patients in the Chemotherapy Department of the Clinical Hospital in Poznan. The survey was completed by 836 patients. The majority of the survey respondents had cancer (77%, n = 644), and almost 1/5 of the respondents indicated hypertension (15.7%, n = 131) as well as depression and/or anxiety disorders (11.1%, n = 93). RESULTS: Less than half of the respondents (43.5%, n = 364) believed that SARS-CoV-2 vaccines were safe (40.4%, n = 260, among cancer patients; 53.9%, n = 104, among patients with other medical conditions). More than half of the respondents (60.5%, n = 506) intended to be vaccinated against SARS-CoV-2 (58.8%, n = 378, among cancer patients; 66.3%, n = 128, among patients with other medical conditions). Fear of vaccine complications and lack of belief in vaccine effectiveness were prevalent among both cancer patients and patients with other medical conditions. CONCLUSIONS: The vast majority of cancer and medical patients wanted to be vaccinated against COVID-19. More than half of the respondents did not believe that the COVID-19 vaccine would be safe for them. Education of cancer and medical patients on the safety and effectiveness of the vaccine, as well as the use of additional protective measures against infection, is an extremely important element of prevention during the COVID-19 pandemic.

Awareness of breast cancer patients in Poland about clinical trials as available treatment options.

BACKGROUND: Breast cancer is the most common cancer in women in Poland and worldwide. Due to growing morbidity and mortality, patients are looking for new therapeutic options. Clinical trials give cancer patients a chance to access innovative treatment often not available in the national healthcare system. Patient awareness of clinical trials is an essential element for the development of the clinical trials market. OBJECTIVE: The purpose of this survey was to obtain information from breast cancer patients about their knowledge of clinical trials. METHODS: One hundred people were invited to take part in the study, and were recruited into two groups: 50 patients diagnosed with breast cancer less than 40 years of age, and 50 patients with the same disease over 40 years of age. The survey was completed by female patients online. RESULTS: Most of the subjects correctly understood the assumptions of the clinical trial; most often, both groups of subjects obtained information about medical experiments from the Internet. According to the respondents, the most important motivating factor to participate in the clinical trial was the proposed study drug and their current state of health. Patients would more frequently decide to participate in a clinical trial at the time of cancer progression compared to immediately after diagnosis. Commuting to the research center made recruitment of older patients more difficult (40% of older patients versus 16% of younger patients, p = 0.008). CONCLUSION: Patients with breast cancer are aware of clinical trials and decide to participate in them based on the proposed study drug and their current state of health. Progression of the disease is a factor that increases the willingness to participate in clinical trials.

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers is Mainly Dependent on HER2 Status-A Pilot Study.

Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student's T-test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(-)/PgR(+) and ER(+)/PgR(-) breast cancers. However, a trend for differing expression (p-value ≤ 0.05; FDR > 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(-) group demonstrated elevated levels of four miRNAs-miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p-while the ER(-)/PgR(+) tumors were enriched in another four miRNAs-miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs-miR-29c-3p-the association with the ER(+)/PgR(-) phenotype was confirmed in the TCGA cohort (p-value = 0.024; T-test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR ≤ 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(-) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(-)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(-)/PgR(+) and ER(+)/PgR(-) tumors.

The Preventive role of Regular Physical Training in Ventricular Remodeling, Serum Cardiac Markers, and Exercise Performance Changes in Breast Cancer in Women Undergoing Trastuzumab Therapy-An REH-HER Study.

Cardiotoxicity is known as a severe clinical problem in oncological practice that reduces the options for cancer therapy. Physical exercise is recognized as a well-established protective measure for many heart and cancer diseases. In our study, we hypothesized that supervised and moderate-intensity exercise training would prevent heart failure and its consequences induced by trastuzumab therapy. The aim of this study was to examine the effect of physical training on ventricular remodeling, serum cardiac markers, and exercise performance in women with human epidermal growth receptor 2 (HER2+) breast cancer (BC) undergoing trastuzumab therapy. This was a prospective, randomized, clinical controlled trial. Forty-six BC women were randomized into either an intervention group (IG) or a control group (CG). An exercise program (IG) was performed after 3-6 months of trastuzumab therapy at 5 d/week (to 80% maximum heart rate (HRmax)) for 9 weeks. We then evaluated their cardiac function using echocardiography, a 6-Minute Walk Test (6MWT), and plasma parameters (C-reactive protein (CRP), myoglobin (MYO), interleukin-6 (IL-6), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK)). After the physical training program, we did not observe any significant changes in the left ventricular (LV) ejection fraction (LVEF) and 6MWT (p > 0.05) in the IG compared to the CG (decrease p < 0.05). The differences in the blood parameters were not significant (p < 0.05). To conclude, moderate-intensity exercise training prevented a decrease in the LVEF and physical capacity during trastuzumab therapy in HER2+ BC. Further research is needed to validate our results.

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series.

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERß1, ERß2, ERß5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer.

Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required. Clin Cancer Res; 23(10); 2575-83. ©2016 AACR.

Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches. PATIENTS AND METHODS: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM. RESULTS: In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B. CONCLUSION: Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays.