[Show abstract][Hide abstract] ABSTRACT: Abstract
To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer.
We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity.
The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse.
There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions
[Show abstract][Hide abstract] ABSTRACT: Background:
Plasmablastic lymphoma (PBL) is a rare entity which is often causally related to infection by the Human Immunodeficiency Virus (HIV). Despite its predilection for oral cavity involvement, multiple cases of extra-oral involvement have been reported in the literature, more often among immunocompetent individuals.
Herein we present the first case of primary PBL of the breast in an otherwise immunocompetent 36-year-old woman who was successfully treated with consolidation megatherapy and autologous stem cell transplantation.
PBL carries a particularly poor prognosis and more intensive treatment is usually warranted. However, no treatment guidelines exist and treatment choices are made based on case reports and small retrospective case series.
Anticancer research 09/2014; 34(9):5111-5. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients.
Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials.
HER2-genes CN strongly correlated to each other (Spearman’s rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1–3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS).
TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis.
PLoS ONE 08/2014; 9(8):e103707. DOI:10.1371/journal.pone.0103707 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.
From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation.
At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020).
No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2-positive patients demonstrated comparable 3-year DFS and OS rates with those reported in other similar studies.
Australian New Zealand Clinical Trials Registry
BMC Cancer 07/2014; 14(1):515. DOI:10.1186/1471-2407-14-515 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BackgroundalphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. The purpose of this study was to evaluate alphaB-crystallin with respect to clinicopathological parameters and the outcome of patients with operable high-risk breast cancer.MethodsA total of 940 tumors were examined, derived from an equal number of patients who had participated in two randomized clinical trials (paclitaxel-containing regimen in 793 cases). Immunohistochemistry for ER, PgR, HER2, Ki67, CK5, CK14, CK17, EGFR, alphaB-crystallin, BRCA1 and p53 was performed. BRCA1 mutation data were available in 89 cases.Resultsalphaβ-crystallin was expressed in 170 cases (18.1%) and more frequently in triple-negative breast carcinomas (TNBC) (45% vs. 14.5% non-TNBC, p < 0.001). alphaB-crystallin protein expression was significantly associated with high Ki67 (Pearson chi-square test, p < 0.001), p53 (p = 0.002) and basal cytokeratin protein expression (p < 0.001), BRCA1 mutations (p = 0.045) and negative ER (p < 0.001) and PgR (p < 0.001). Its overexpression, defined as >30% positive neoplastic cells, was associated with adverse overall survival (Wald’s p = 0.046). However, alphaB-crystallin was not an independent prognostic factor upon multivariate analysis. No interaction between taxane-based therapy and aβ-crystallin expression was observed.ConclusionsIn operable high-risk breast cancer, alphaB-crystallin protein expression is associated with poor prognostic features indicating aggressive tumor behavior, but it does not seem to have an independent impact on patient survival or to interfere with taxane-based therapy.Trial registrationsACTRN12611000506998 (HE10/97 trial) and
ACTRN12609001036202 (HE10/00 trial).
[Show abstract][Hide abstract] ABSTRACT: The establishment of high dependency units (HDUs) has been an undoubted advance in the management of patients undergoing major oncological procedures. The aim of this study was to examine the impact of various preoperative and perioperative patients' characteristics on the prolonged HDU stay.
We conducted a retrospective study including all gynecologic oncology patients who underwent surgical management and were admitted postoperatively to our hospitals' HDU from 2006 to 2010.
A total of 1,014 patients were transferred to the HDU and divided into two groups according to the length of HDU stay. Group A consisted of 840 (82.8 %) patients who stayed in the HDU for ≤24 h and Group B included 174 (17.2 %) patients who remained in the HDU under close observation for >24 h. Older age was the only preoperative characteristic that remained significantly associated with HDU prolonged stay. In addition, three intraoperative factors such as use of invasive hemodynamic monitoring, bowel resection and estimated blood loss were proved to be independently associated with prolonged HDU stay.
Certain characteristics could identify those patients who are more likely to benefit most from HDU admission.
Archives of Gynecology 03/2014; 290(2). DOI:10.1007/s00404-014-3180-1 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present review aims at providing an assessment of the clinical significance of Biphosphonates (BPs) in the treatment of patients with cancer.
A systematic literature review was performed based on database search in PubMed/Medline and included articles up to August 2013.
BPs can reduce, delay, and prevent complications related to bone metastases. They improve mobility, functionality, pain, and quality of life. They limit survival of any inactive cancer cells in the microenvironment of the bone marrow, contributing to their death from anti-neoplastic treatments. Moreover, they limit and delay bone morbidity due to osteoporosis related to hormonotherapy in breast and prostate cancer. Finally, benefits can be derived from the combination of BPs with radiotherapy in bone density, recalcification, opioid use, and patient's quality of life and performance status.
The contribution of BPs in the course of certain neoplasms is preventive and synergistic to other treatments.
Anticancer research 01/2014; 34(1):23-37. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a phase II trial. This study evaluated weekly docetaxel, as first-line treatment for metastatic breast cancer. Existing data from in vitro and animal model experiments suggest that docetaxel at low doses has anti-angiogenic activity. DNA was extracted from blood samples of 86 patients participating in the trial. Genotyping was performed for selected single-nucleotide polymorphisms (SNPs; VEGF-2578, -1498, -1154, and +936). Moreover, due to the highly polymorphic nature of the studied areas, we were able to analyze additional registered SNPs. All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate. The VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders (42.9% vs 0.0%, P=0.048). Moreover, the VEGF-2578 AA genotype was associated with longer PFS compared with CC (hazard ratio (HR)=0.40; 95% confidence interval (CI) 0.17-0.98; pairwise P=0.0457). Patients with the VEGF-1190 GG genotype demonstrated shorter PFS compared with those with the alternative genotypes (GA and AA) combined (HR=3.85; 95% CI: 1.20-12.50; P=0.0224). In addition, the VEGF-2551/-2534 homozygous del18bp and VEGF-2430/-2425 homozygous ins1bp genotypes were associated with worse PFS compared with no deletion and no insertion, respectively (HR=2.49; 95% CI: 1.02-6.07; pairwise P=0.0442 and HR=2.57; 95% CI: 1.05-6.27; pairwise P=0.0385, respectively). Furthermore, patients with the VEGF-1498 CC genotype exhibited longer median OS compared with those with the alternatives genotypes (CT and TT) combined (HR=0.27; 95% CI: 0.08-0.89; P=0.0311). In multivariate analysis, the VEGF-2578 AA genotype retained its significance (P=0.0220) for PFS. Our results support the association of specific VEGF genotypes with clinical outcome in patients with metastatic breast cancer treated with a potentially anti-angiogenic regimen, such as weekly docetaxel. However, current results should be validated prospectively in larger cohorts.The Pharmacogenomics Journal advance online publication, 24 September 2013; doi:10.1038/tpj.2013.36.
The Pharmacogenomics Journal 09/2013; 14(3). DOI:10.1038/tpj.2013.36 · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We prospectively evaluated the effect of bortezomib, thalidomide and dexamethasone (VTD) consolidation on bone metabolism of 42 myeloma patients who underwent ASCT. VTD started on day 100 post-ASCT; patients received 4 cycles of VTD (first block), were followed without treatment for 100 days and then received another 4 VTD cycles (2nd block). During this 12-month period, bisphosphonates were not administered. Best response included sCR in 15 (35.7%) patients, CR in 13 (30.9%), vgPR in 7 (16.6%), PR in 4 (9.5%) patients, while 3 (7.1%) patients developed progressive disease (PD). Importantly 33.3% and 47.6% of patients improved their status of response after the 1st and 2nd VTD block, respectively. VTD consolidation resulted in a significant reduction of circulating CTX, sRANKL and osteocalcin, while bALP remained stable compared to pre-VTD values. During the study period, only one patient with PD developed a skeletal-related event (i.e. radiation to bone). The median TTP after ASCT was 34 months and the median time to next treatment was 40 months. We conclude that VTD consolidation post-ASCT reduces bone resorption and is associated with a very low incidence of SREs despite the absence of bisphosphonates; the later do not appear to be necessary in this context.Leukemia accepted article preview online, 18 September 2013. doi:10.1038/leu.2013.267.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2013; 28(4). DOI:10.1038/leu.2013.267 · 10.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44(+)/CD24(-/low)].
Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells. Cytoplasmic YB1 was detected more often in carcinomas of ductal type (p = 0.002), of higher nuclear grade (p < 0.001), with lack of ER expression (p = 0.002), positive expression of p53 and Ki67 (p = 0.002 and p = 022, respectively), and with present CD44(+)/CD24(-/low) breast cancer stem cells (p = 0.001), while its association with bcl-2 was found to be inverse (p = 0.042). Nuclear YB1 was found to exert unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and the patients having been subjected to adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively).
Cytoplasmic YB1 is associated with an aggressive and "stem cell-like" tumor phenotype, while nuclear localization discriminates patients at high risk for recurrence, especially those who are subjected to chemo- and radiotherapy.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 09/2013; 40(3). DOI:10.1016/j.ejso.2013.09.008 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs). Whereas the incidence of the disease appears to increase during last decades and the prognosis remains dramatically poor, so far no standard treatment has been established. High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) has been proven effective in relapsed PTCL, while retrospective studies have shown a survival benefit as first-line treatment in some subsets of PTCL patients. However, given disease rarity, there is a paucity of randomized trials in both upfront and relapse setting. Here, we critically evaluated eligible prospective and retrospective studies that address the role of ASCT in treatment of PTCL, with respect to quality of design and performance. Additionally, the role of allogeneic transplantation has been reviewed. The comparison of ASCT with novel agents that emerge or the combination of both, are to be ascertained via prospective randomized trials in this field.
[Show abstract][Hide abstract] ABSTRACT: To explore the activity and safety of two schedules of ixabepilone, as first line chemotherapy, in patients with metastatic breast cancer previously treated with adjuvant chemotherapy, a randomized non-comparative phase II study was conducted. From November 2008 until December 2010, 64 patients were treated with either ixabepilone 40 mg/m(2) every 3 weeks (Group A, 32 patients) or ixabepilone 20 mg/m(2) on days 1, 8 and 15 every 4 weeks (Group B, 32 patients). Overall response rate (the primary end point) was 47% in Group A and 50% in Group B. The most frequent severe adverse events were neutropenia (32% vs. 23%), metabolic disturbances (29% vs. 27%) and sensory neuropathy (12% vs. 27%). Two patients in Group A and 3 in Group B developed febrile neutropenia. After a median follow-up of 22.7 months, median progression-free survival (PFS) was 9 months in Group A and 12 months in Group B. Median survival was 26 months in Group A, whereas it was not reached in Group B. Multiple genetic and molecular markers were examined in tumor and peripheral blood DNA, but none of them was associated with ORR or drug toxicity. Favorable prognostic markers included: the T-variants of ABCB1 SNPs c.2677G/A/T, c.1236C/T and c.3435C/T, as well as high MAPT mRNA and Tau protein expression, which were all associated with the ER/PgR-positive phenotype; absence of TopoIIa; and, an interaction between low TUBB3 mRNA expression and Group B. Upon multivariate analysis, tumor ER-positivity was a favorable (p = 0.0092) and TopoIIa an unfavorable (p = 0.002) prognostic factor for PFS; PgR-positivity was favorable (p = 0.028) for survival. In conclusion, ixabepilone had a manageable safety profile in both the 3-weekly and weekly schedules. A number of markers identified in the present trial appear to deserve further evaluation for their prognostic and/or predictive value in larger multi-arm studies.
ClinicalTrials.gov NCT 00790894.
PLoS ONE 07/2013; 8(7):e69256. DOI:10.1371/journal.pone.0069256 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharmacological inhibition of Hsp90 shows great promise in breast cancer treatment. This is the first systematic review to synthesize all available data and to evaluate the efficacy and safety of Hsp90 inhibitors in breast cancer.
This study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms "breast", "cancer", "Hsp90", "inhibitors".
Overall, 19 articles (190 patients) were eligible. The greatest clinical activity has been observed on the field of HER2-positive metastatic breast cancer. However, accumulating data suggest that Hsp90 inhibitors may play a significant role in the treatment of triple negative and aromatase inhibitor-resistant breast cancer.
In the last decade, the development of Hsp90 inhibitors has moved forward rapidly; however, no phase III trials have been conducted and none agent has been approved for use in the clinical practice.
Breast (Edinburgh, Scotland) 07/2013; 22(5). DOI:10.1016/j.breast.2013.06.003 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable.
[Show abstract][Hide abstract] ABSTRACT: Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis.
39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed.
Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival.
Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer.
Breast Care 06/2013; 8(3):203-7. DOI:10.1159/000352093 · 0.63 Impact Factor