A retrospective analysis of nadir-neutropenia directed pegylated granulocyte-colony stimulating factor on febrile neutropenia rates in (neo)adjuvant breast cancer chemotherapy regimens.

BACKGROUND: Pegfilgrastim, a pegylated granulocyte colony-stimulating-factor (GCSF), reduces chemotherapy morbidity and mortality in early stage breast cancer. The optimal approach to individual patient selection for GCSF is unknown, in particular whether secondary GCSF should be given after asymptomatic neutropenia, or only after febrile neutropenia (FN). AIMS: To determine if preplanned nadir blood counts and subsequent nadir-neutropenia directed GCSF was effective to reduce rates of FN associated with (neo)adjuvant breast cancer chemotherapy. We also aimed to describe (neo)adjuvant chemotherapy and GCSF prescribing practices at our institution. METHODS: This was a retrospective electronic medical record review. The rate of FN with secondary GCSF after cycle 1 nadir-neutropenia <1.0 × 109 cells/L was compared with the rate of FN in patients who did not have cycle 1 nadir blood counts or secondary GCSF, and analyzed according to patient and treatment data. RESULTS: Between 11/4/2011 and 22/4/2018, 584 patients received (neo)adjuvant chemotherapy. Over all rates of FN were 17%, compared with 9% in patients who received primary GCSF. Rates of FN were highest in docetaxel/carboplatin/trastuzumab (TCH, 27%) and docetaxel/cyclophosphamide (TC, 27%). There were 268 patients (46%) who received primary GCSF and 238 patients (41%) who received secondary GCSF. Rates of FN did not differ between patients who received nadir-neutropenia directed secondary GCSF (6/125, 5%, 95% CI 1.1-8.6), and those who did not have nadir blood counts or secondary GCSF (0/49, 0%, 95% CI not calculable) (P = .1186). GCSF use was associated with lower rates of non-FN hospital admissions. Patients ≥65 years were more likely to have FN and non-FN admissions. Two of three treatment related deaths occurred due to FN. CONCLUSIONS: In this population, nadir-neutropenia directed secondary GCSF was not associated with reduced rates of FN. Observed rates of FN >20% in TC and TCH in routine clinical practice should guide primary GCSF use in accordance with international guidelines.

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.

PURPOSE: Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. METHODS AND MATERIALS: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis. RESULTS: Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1ß, IL-4, and MIP-1α with tumor response. CONCLUSIONS: Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Prognostic Value of the Neutrophil-Lymphocyte, Platelet-Lymphocyte, and Monocyte-Lymphocyte Ratios in Male Breast Cancer Patients.

BACKGROUND: The aim of the present study was to assess the blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) as prognostic factors in male breast cancer (BC) patients. METHODS: A retrospective analysis of 38 male BC patients who were treated at the Institute of Oncology (Gliwice, Poland) between January 2005 and December 2018 was performed. The prognostic value (in terms of overall survival [OS]) of the pretreatment PLR, NLR, and MLR was assessed by univariate analysis. RESULTS: We observed a tendency towards worse OS among male BC patients with lymph node metastases (N+) (5-year OS: 43.5 vs. 73.9%; p = 0.087), a greater tumor size (T4 vs. T1 + T2) (42.0 vs. 70.5%; p = 0.061), and a negative steroid receptor status (PR-) (28.6 vs. 65.6%; p = 0.109). Patients with a family history of cancer had significantly better 5-year OS than patients without a family history of cancer (86.3 vs. 35.0%; p = 0.001). Younger male BC patients (age ≤56 years) had better 5-year OS than patients >56 years of age (82.5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 103) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 103) (4.5-year OS: 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). CONCLUSIONS: The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS.

Germline investigation in male breast cancer of DNA repair genes by next-generation sequencing.

PURPOSE: In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing. METHODS: Germline DNAs were tested in a custom multi-gene panel focused on all coding exons and exon-intron boundaries of 24 selected genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientific) and MiSeq (Illumina) platforms. All variants were recorded and classified by using a custom pipeline. RESULTS: Clinical pathological data and the family history of 81 Male BC cases were gathered and analysed, revealing the average age of onset to be 61.3 years old and that in 35 cases there was a family history of BC. Our genetic screening allowed us to identify a germline mutation in 22 patients (23%) in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. Moreover, 12 variants of unknown clinical significance (VUS) in 9 genes (BARD1, BRCA1, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1, RAD50) were predicted as potentially pathogenic by in silico analysis bringing the mutation detection rate up to 40%. CONCLUSION: As expected, a positive family history is a strong predictor of germline BRCA2 mutations in male BC. Understanding the potential pathogenicity of VUS represents an extremely urgent need for the management of BC risk in Male BC cases and their own families.

Somatic mosaic truncating mutations of PPM1D in blood can result from expansion of a mutant clone under selective pressure of chemotherapy.

BACKGROUND: PPM1D (Protein phosphatase magnesium-dependent 1δ) is known as a damage response regulator, a part of the p53 negative feedback loop. Truncating mutations of PPM1D, resulting in overexpression, are frequently found in the blood of patients with breast or ovarian cancer. To identify whether the PPM1D mutation predisposes patients to such cancers or if it results from the cancer and therapy, somatic PPM1D mutations in association with previous cancer and chemotherapy need to be explored. METHODS: We performed next-generation sequencing (NGS) analysis of blood samples from patients suspected to have hereditary cancer. We grouped the patients according to their diagnoses and history of chemotherapy. For the patients with PPM1D mutations in blood, tumor tissue specimens were examined for the PPM1D mutation using conventional sequencing. RESULTS: A total of 1,195 patients, including 719 patients with breast cancer and 240 with ovarian cancer, were tested, and four (~0.3%) had the truncating mutation in PPM1D. All truncating mutations were in exon 6, in mosaic form, with a mean allele fraction of 11.15%. While 395 out of the 1,195 patients had undergone chemotherapy, the four with the truncating mutation had a history of cisplatin-based chemotherapy. No corresponding mutations were identified in the tumor tissues. CONCLUSIONS: We investigated the frequency of the somatic mosaic PPM1D mutation, in patients with breast or ovarian cancer, which is suggested to be low and related to a history of cisplatin-based chemotherapy. It may be a marker of previous exposure to selective pressure for cells with an impaired DNA damage response.

Serum Proteomic Signatures of Male Breast Cancer.

BACKGROUND: To date, the elucidation of serum protein alterations in male breast cancer (MBC) has not been extensively studied, due to the rarity of the disease. MATERIALS AND METHODS: In the present work, two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) were employed to detect differences in serum protein expression between patients with MBC and healthy controls. RESULTS: A panel of differentially expressed serum proteins was identified, including proteins involved in the regulation of the cell cycle [e.g. cell division cycle 7-related protein kinase (CDC7)], in mitochondrial function [e.g. mitochondrial aldehyde dehydrogenase (ALDH2) and dimethyladenosine transferase 1 (TFB1M)], in lipid metabolism and transport [e.g. apolipoprotein A-I (APOA1) and E (APOE)], in apoptosis and immune response [e.g. CD5 antigen-like (CD5L), clusterin (CLUS) and C-C motif chemokine 14 (CCL14)], in transcription (e.g. protein SSX3 and signal transducer and activator of transcription 3 (STAT3)], in invasion and metastasis (e.g. alpha-2-HS-glycoprotein (FETUA)], in estrogen synthesis [aromatase (CYP19A1)] and other diverse biological roles [e.g. actin-related protein 2/3 complex subunit 4 (ARPC4), dual specificity mitogen-activated protein kinase kinase 4 (MP2K4), ectoderm-neural cortex protein 1 (ENC1), and matrix metalloproteinase-27 (MMP27)]. CONCLUSION: These findings provide valuable insight into the distinct clinicopathological features of MBC and indicate that select serum proteomic markers may help improve MBC management.

A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC. METHODS: This dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients. RESULTS: Forty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6-32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14-45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations. CONCLUSIONS: Single-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01639248 . Registered on July 12, 2012.

Clinical Associations with ABO Blood Group and Rhesus Blood Group Status in Patients with Breast Cancer: A Nationwide Retrospective Study of 3,944 Breast Cancer Patients in Turkey.

BACKGROUND The aim of this study was to investigate the association between A, B, O, Rhesus (Rh)-positive and Rh-negative blood groups and breast cancer in a nationwide cohort of 3,944 patients in Turkey. MATERIAL AND METHODS A retrospective study included 3,944 patients diagnosed with breast cancer between 2004 and 2015 and with known blood type. Clinical and demographic patient data included age, sex, body mass index (BMI), menopausal status. The breast tumor type, size, grade, TNM stage, and the presence of lymph node and distant metastases were noted. Histopathology of the breast tumors had included routine detection of human epidermal growth factor receptor 2 (HER2) and estrogen receptor (ER) levels. RESULTS The 3,944 patients with breast cancer were blood group, type A, B, O, and Rh-positive or Rh-negative; the median age was 47.9 years (range, 18.2-89.6 years); 99.5% (3923/3,844) were women, and 0.5% (21/3944) were men. Patients with blood type 0 had a significantly smaller tumor size compared with patients with blood types A or B. There were no significant differences between blood groups and patient age, BMI, menopausal status, tumor histology, ER status, HER2 status, lymph node and distant metastasis. However, there was a significant difference in the prevalence of lobular breast cancer, levels of ER-positive tumor cells, and prevalence of cases with tumor metastases in Rh-positive patients compared with Rh-negative patients. CONCLUSIONS The findings of this retrospective study showed that the type, grade, stage, and hormonal status of breast cancer showed no significant associations with ABO blood grouping.

Vitamin D levels and breast cancer characteristics: Findings in patients from Saudi Arabia.

Inverse relationship between vitamin D status and risk of breast cancer has been previously reported in the literature. We conducted this study to determine the association between vitamin D levels and breast cancer characteristics in patients from Saudi Arabia. Newly diagnosed breast cancer patients (N=406) were recruited. Serum levels of 25-hydroxyvitamin D [25 (OH) D] were measured at baseline. A significantly higher percentage of patients with triple negative status (18%) had 25 (OH) D levels ≤25nmol/L, compared to only 8% with 25 (OH) D levels >25nmol/L (p=0.009). Patients with 25 (OH) D levels ≤25nmol/L were 2.54 times more likely to present with triple negative status compared to those with 25 (OH) D levels >25nmol/L (p=0.02). Our findings suggest an association between low 25 (OH) D levels and increased risk of triple negative breast cancer.

Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk.

PURPOSE: Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. PATIENTS AND METHODS: Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. RESULTS: Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. CONCLUSION: Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.

Detection of disseminated tumor cells in bone marrow and circulating tumor cells in blood of patients with early-stage male breast cancer.

BACKGROUND: Male breast cancer (MBC) is a rare malignant disease, accounting for <1% of all breast cancers (BCs). Treatment of men with early-stage BC is based on standards established in female BC. Prognostic or predictive markers to guide therapeutic decisions, in particular in early-stage male BC, are missing. Here, we explored whether disseminated tumor cells (DTC) in bone marrow (BM) and circulating tumor cells (CTC) in blood could be suitable biomarkers in male BC. PATIENTS AND METHODS: Five male patients (pT2-4, pN0-2, M0) with hormone receptor-positive, HER2-negative, and ductal primary BC (median age 70 years, range 51-73) were enrolled in a prospective study of patients with early-stage breast cancer. Here, we analyze the male subgroup. DTC in BM were analyzed before therapy and identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. Blood samples (10 ml) were analyzed for CTC using the AdnaTest BreastCancer (AdnaGen AG, Langenhagen, Germany). RESULTS: DTC were found in three out of five male patients (60%) with two DTC detected in one patient and one DTC detected in each of the other two patients. This is compared to a detection rate of 25-40% in pooled analyses of female patients. CTC were only found in one of five patients. After a median follow-up time of 3 years (range 1-10 years), all patients were still alive and free of relapse. CONCLUSION: The prevalence of DTC and CTC in male BC seems comparable with female BC. No prognostic relevance could be documented in this small population. A prospective study or at least larger cases series will be required to assess the prognostic or predictive value of DTC and CTC in this rare disease.

Significance of ABO-Rh blood groups in response and prognosis in breast cancer patients treated with radiotherapy and chemotherapy.

BACKGROUND: To evaluate whether ABO-Rh blood groups have significance in the treatment response and prognosis in patients with non-metastatic breast cancer. MATERIALS AND METHODS: We retrospectively evaluated files of 335 patients with breast cancer who were treated between 2005 and 2010. Demographic data, clinic- pathological findings, treatments employed, treatment response, and overall and disease-free survivals were reviewed. Relationships between clinic-pathological findings and blood groups were evaluated. RESULTS: 329 women and 6 men were included to the study. Mean age at diagnosis was 55.2 years (range: 26-86). Of the cases, 95% received chemotherapy while 70% were given radiotherapy and 60.9% adjuvant hormone therapy after surgery. Some 63.0% were A blood group, 17.6% O, 14.3% B and 5.1% AB. In addition, 82.0% of the cases were Rh-positive. Mean follow-up was 24.5 months. Median overall and progression-free survival times were 83.9 and 79.5 months, respectively. Overall and disease-free survival times were found to be higher in patients with A and O blood groups (p<0.05). However rates did not differ with the Rh-positive group (p=0.226). In univariate and multivariate analyses, ABO blood groups were identified as factors that had significant effects on overall and disease-survival times (p=0.011 and p=0.002). CONCLUSIONS: It was seen that overall and disease-free survival times were higher in breast cancer patients with A and O blood groups when compared to those with other blood groups. It was seen that A and O blood groups had good prognostic value in patients with breast cancer.

Correlation between cancer antigen 15.3 value and qualitative and semiquantitative parameters of positron emission tomography/computed tomography in breast cancer patients.

BACKGROUND: The association of PET/CT and tumor markers can be considered complementary, since any significant increases of tumor markers can indicate the presence of disease while PET/CT is able to detect and describe the tumor sites. In this retrospective, single-institution study, we determine the correlation between cancer antigen (CA) 15.3 value and qualitative and semi-quantitative PET/CT data in breast cancer (BC) patients. METHODS: 193 BC patients (median age 61 yrs) already treated with primary treatment (surgery and others) were identified through institutional databases. All patients underwent PET/CT for increase in tumor markers, post-therapy evaluation, restaging and doubtful conventional imaging for disease relapse. The CA15.3 values before PET/CT scan were collected for all patients. Clinical outcome was defined as presence or absence of disease recurrence based on follow-up data (histological or imaging findings). CA15.3 quartile values and qualitative and semi-quantitative (maximum Standardized Uptake Value - SUVmax) PET/CT findings were compared with chi-square test and linear regression analysis. RESULTS: The mean value of CA15.3 was significantly higher in patients with positive than negative PET/CT (67.51±120.92 vs. 25.54±17.54, p<0.005). PET/CT was positive in 107 (55%) and negative in 86 (45%) patients; CA15.3 value was considered abnormal (≥ 31 UI/mL) in 85 (44%) patients; 57 of them showed positive PET/CT while 28 a negative scan (67 vs. 33%, p<0.05). In all 193 patients, the disease recurrence was found in 71 (37%), whereas 122 (63%) were disease-free. The diagnostic accuracy of PET/CT in all 193 patients was 74%. Among patients with normal CA15.3 value (n=108), 50 showed positive PET/CT; 24 out of these latter 50 patients (48%) had recurrence of disease. The combination of the highest quartile of CA15.3 (value>45 UI/ml) and FDG PET/CT determined high sensitivity and accuracy (92% and 82%, respectively) but a low specificity (50%) for restaging BC patients. The highest specificity (~ 70%) was found when PET/CT and 2nd quartile of CA15.3 (value: 12.95-25) were associated. No correlation between CA15.3 values and SUVmax was found (p=0.489); whereas a trend in increase of the CA15.3 value and SUVmax in the presence of visceral and no-visceral site of disease (22.4±16.2, 64.9±108 and 6.4±4.2, 8.2±5.1, respectively) was identified. CONCLUSIONS: The value of CA15.3 and PET/CT findings are consistently complementary. About 25% of BC patients with a negative CA15.3 value had a positive PET/CT and disease relapse. SUVmax and CA15.3 values are not correlated.

Prognostic value of geriatric assessment in older patients with advanced breast cancer receiving chemotherapy.

INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.

Circulating tumor cells count and characterization in a male breast cancer patient.

A 64-y-old man presented to Medical Oncology Department a metastatic invasive ductal breast carcinoma, positive for estrogen (ER) and progesterone receptors (PR) and Her2/neu negative. The patient was treated with different lines of therapy, with rapid radiological progression of disease. After four courses of a third-line chemotherapy, a radiological stable disease was maintained. The patient was followed by serial blood drawings for the characterization and count of circulating tumor cells (CTC). This is the first report concerning the predictive and prognostic value of CTC in a male breast cancer patient.

Prognostic significance of cyclooxygenase-2 and response to chemotherapy in invasive ductal breast carcinoma patients by real time surface plasmon resonance analysis.

Cyclooxygenase-2 (COX-2), an inducible enzyme, has been implicated in the progression and angiogenesis of breast cancer. The aim of the study is to quantify the concentration of COX-2 and its association with clinico-pathological parameters and response to treatment in patients with invasive ductal carcinoma receiving both neo-adjuvant and adjuvant chemotherapy. The level of COX-2 was estimated using a novel biosensor-based surface plasmon resonance technique in serum of 84 patients with breast cancer (48 patients of neo-adjuvant chemotherapy and 36 patients of adjuvant chemotherapy) and 40 age- and gender-matched normal individuals. A significant increase in COX-2 level was observed in patients compared with normal individuals (p>0.0001). The COX-2 level in serum was found to be significantly higher in patients with lymph node involvement (p<0.0061). 68% (33/48) of the patients receiving neo-adjuvant chemotherapy showed significantly (p<0.0025) reduced COX-2 levels. This study shows significant decrease of COX-2 level in patients with breast cancer treated with both neo-adjuvant and adjuvant chemotherapy. Estimation of COX-2 level in serum may serve as a tumor biomarker in patients with breast cancer.

Bone metastases detection by circulating biomarkers: OPG and RANK-L.

Osteoprotegerin (OPG) is a decoy receptor of the receptor activator of nuclear factor-κB ligand (RANK-L) and plays an important role in the formation of metastatic bone lesions. We evaluated the usefulness of circulating OPG and RANK-L for the detection of bone metastases. We enrolled 143 individuals in the study: 30 healthy donors (HD) and 113 breast cancer patients. Among patients, 49 had no evidence of disease (NEDP), 54 had bone metastases (BMP) at first diagnosis, and 10 had visceral metastases (VMP). Both transcripts were determined in peripheral blood samples using quantitative PCR. Receiver operating characteristic (ROC) curve analysis was used to calculate the diagnostic accuracy of OPG, RANK-L, CEA and CA15-3. OPG and RANK-L median values were significantly lower in BMP (median 0.5, range 0.1-5.7, p<0.001 and median 0.5, range 0.1-4.5, p=0.024, respectively) compared to NEDP (median 1.7, range 0.4-8.9 and median 0.8, range 0.2-3.8, respectively), regardless of the number and type of bone lesions or the presence of visceral metastases. The area under the ROC curve (NEDP vs. BMP) was higher for OPG (82.5, 95% CI 74.5-90.6) than for RANK-L (69.2, 95% CI 59.0-79.40). Specificity for OPG was 87.7% (95% CI 75.7-94.2) and sensitivity was 74.1% (95% CI 60.4-85.0), both values increasing when considered together with CEA and CA15-3. For VMP, OPG and RANK-L were expressed in only one patient. Our results highlight the potentially important role of circulating OPG in the diagnosis of bone metastases. A confirmatory study on a larger case series is ongoing.

Risk factors and incidence of thromboembolic events (TEEs) in older men and women with breast cancer.

BACKGROUND: The purpose of this study is to evaluate the risk factors and the prevalence of thromboembolic events (TEEs) in breast cancer patients. PATIENTS AND METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Breast cancer patients diagnosed from 1992 to 2005 ≥66 years old were identified. International Classification of Diseases, Ninth Revision, and Healthcare Common Procedure Coding System codes were used to identify TEEs within 1 year of the breast cancer diagnosis. Analyses were conducted using descriptive statistics and logistic regression. RESULTS: A total of 89 841 patients were included, of them 2658 (2.96%) developed a TEE. In the multivariable analysis, males had higher risk of a TEE than women [odd ratio (OR) = 1.57; confidence interval (CI) 1.10-2.25] and blacks had higher risk than whites (OR = 1.20; CI 1.04-1.40). Compared with stage I patients, patients with stage II, III and IV had 22%, 39% and 98% increase, respectively, in risk. Placement of central catheters (OR = 2.71; CI 2.43-3.02), chemotherapy treatment (OR = 1.66; CI 1.48-1.86) or treatment with erythropoiesis-stimulating agents (ESAs) (OR = 1.33; CI 1.33-1.52) increase the risk. Other significant predictors included comorbidities, age, receptor status, marital status and year of diagnosis. Similar estimates were seen for pulmonary embolism, deep vein thromboembolism and other TEEs. CONCLUSIONS: In total, 2.96% of patients in this cohort developed a TEE within 1 year from breast cancer diagnosis. Stage, gender, race, use of chemotherapy and ESAs, comorbidities, receptor status and catheter placement were associated with the development of TEEs.

[Breast cancer in the male]. / Cancerul mamar la barbat.

UNLABELLED: The aim of this study is to point out the late diagnosis and initiation of treatment in male with breast cancer. At the same time, to show the importance of the correlation between different markers in assessing the prognostic, as well as the treatment for the patient. MATERIAL AND METHODS: Retrospective study on a group of 15 males with breast cancer, out of 1043 patients with the disease, in a period of 10 years. Eight patients were stage III of disease, 2 were stage II, one was stage I, and in other 3 cases the evaluation of the tumor and of the axillary lymph nodes was performed only by echography, considered stage II. RESULTS: All patients underwent radically modified Madden mastectomy; 4 patients needed a partial resection of the great pectoralis muscle. Adjuvant chemotherapy was performed in 9 patients, and neoadjuvant chemotherapy in 2 cases. Three patients refused the chemotherapy, and one patient chose an alternative paramedical treatment. The treatment with Tamoxifen was done in 11 patients with high values of Progesterone and Estrogen Receptors (PR, ER). At the date of our study, 8 patients were alive, without clinical signs of disease (free of disease), while in 3 patients, alive, clinical signs of disease were detected (recurrence). Survival rate couldn't be evaluated in 4 patients. CONCLUSIONS: Breast cancer in male is usually discovered in locally advanced stages, although most of the patients are regularly screened for chronic hepatitis. Use of biological markers allows a more accurate evaluation of the aggressiveness of the tumor, as well as a more specific treatment for each patient. Modified radical mastectomy type Madden remains the preferred surgical approach. Surgical approach should be considered even in locally advanced cases, as well as in elder patients.