-
The lancet oncology 06/2013; · 14.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: This study was designed to assess the clinical outcomes of patients treated by vertebral augmentation with nitinol endoprosthesis (VNE) to treat painful vertebral compression fractures. METHODS: Forty patients with one or more painful osteoporotic VCF, confirmed by MRI and accompanied by back-pain unresponsive to a minimum 2 months of conservative medical treatment, underwent VNE at 42 levels. Preoperative and postoperative pain measured with Visual Analog Scale (VAS), disability measured by Oswestry Disability Index (ODI), and vertebral height restoration (measured with 2-dimensional reconstruction CT) were compared at last follow-up (average follow-up 15 months). Cement extravasation, subsequent fractures, and implant migration were recorded. RESULTS: Long-term follow-up was obtained in 38 of 40 patients. Both VAS and ODI significantly improved from a median of 8.0 (range 5-10) and 66 % (range 44-88 %) to 0.5 (range 0-8) and 6 % (range 6-66 %), respectively, at 1 year (p < 0.0001). Vertebral height measurements comparing time points increased in a statistically significant manner (ANOVA, p < 0.001). Overall cement extravasation rate was 9.5 %. Discal and venous leakage rates were 7.1 and 0 % respectively. No symptomatic extravasations occurred. Five of 38 (13.1 %) patients experienced new spontaneous, osteoporotic fractures. No device change or migration was observed. CONCLUSIONS: VNE is a safe and effective procedure that is able to provide long-lasting pain relief and durable vertebral height gain with a low rate of new fractures and cement leakages.
CardioVascular and Interventional Radiology 05/2013; · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: Endocrine therapy is a fundamental component of the therapeutic repertoire for treatment of metastatic, hormone receptor-positive breast cancer. Inevitably, however, tumors develop resistance to these compounds, and overcoming this phenomenon is a key motivator of research in this field. Areas covered: This review summarizes the current status of endocrine therapy for the treatment of metastatic disease, with a main focus on postmenopausal patients. Furthermore, strategies that could potentially sustain endocrine resistance and future perspectives in this direction are also to be described. Relevant references were identified by PubMed searches and from the abstract books of the annual meetings of The European Society of Clinical Oncology (ESMO), The American Society of Clinical Oncology (ASCO) and from the San Antonio Breast Cancer Symposia. Expert opinion: Combinations of endocrine therapy with HER2 targeting agents, as well as with compounds that can interfere with PI3K/Akt/mTOR signaling, are two promising strategies for delaying or overcoming endocrine resistance, mediated by these relevant biological pathways. Due to increased costs and the burden of toxicity associated with these combination therapies, compared to endocrine therapy alone, it is imperative to concentrate efforts on establishing biomarkers that can predict efficacy.
Expert Opinion on Pharmacotherapy 10/2012; 13(15):2143-56. · 3.20 Impact Factor
-
Valentina Rossi,
Ivana Sarotto,
Furio Maggiorotto,
Paola Berchialla,
Franziska Kubatzki,
Nicoletta Tomasi,
Stefania Redana,
Rossella Martinello,
Giorgio Valabrega,
Massimo Aglietta,
Riccardo Ponzone, Filippo Montemurro
[show abstract]
[hide abstract]
ABSTRACT: Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2(-)" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm.Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis.Results. Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2(-) by FISH, and HER-2(+) (3+ or HER-2(+) by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2+/HER-2(-) by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2(+) status, a HER-2 2+/HER-2(-) status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649.Conclusion. A HER-2 2+/HER-2(-) status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2(+) tumors, patients with a HER-2 2+/HER-2(-) status are ideal candidates for studies testing this hypothesis.
The Oncologist 09/2012; · 3.91 Impact Factor
-
Filippo Montemurro,
Furio Maggiorotto,
Giorgio Valabrega,
Franziska Kubatzki,
Valentina Rossi,
Alessandra Magistris,
Francesco Marocco,
Marco Gatti,
Ivana Sarotto,
Massimo Aglietta,
Riccardo Ponzone
[show abstract]
[hide abstract]
ABSTRACT: This study was designed to evaluate how the omission of axillary dissection would have altered the indication for adjuvant chemotherapy (ACT) in patients with early breast cancer submitted to conservative surgery with one or two positive sentinel lymph nodes (SLNs).
We identified 321 women in our institutional database who fulfilled the characteristics. All underwent completion axillary lymph node dissection (AD). Each case was blindly reviewed by our breast team in two rounds, and the total number of positive lymph nodes was disclosed only in the second. At each round, the panel chose between: (1) recommend, (2) discuss, (3) do not recommend ACT. Changes between round 1 and 2 were studied by the marginal homogeneity test. Exploratory logistic regression analyses were performed to study predictors of non-SLN involvement and of changes in the indication for ACT.
AD revealed non-SLNs metastases in 96 patients (30 %). Fifty-two patients (16 %) had their initial indication changed at round 2 (p < 0.001). Most of the changes were toward ACT (83 %), and all except two occurred in patients with immunohistochemically defined luminal A and luminal B/HER2-negative tumors. In these two subgroups, a Ki67 above the median value (21 %) was the only independent predictor of no change in the indication to ACT at round 2.
Omission of AD in patients with one or two positive SLNs may change the indication to ACT in a significant proportion of patients with hormone receptor-positive/HER2-negative tumors. All implications should be taken into account before abandoning AD, including a possible biologically tailored surgical approach.
Annals of Surgical Oncology 07/2012; 19(12):3755-61. · 4.17 Impact Factor
-
Daniele Recupero,
Lorenzo Daniele,
Caterina Marchiò,
Luca Molinaro,
Isabella Castellano,
Paola Cassoni,
Alberto Righi, Filippo Montemurro,
Piero Sismondi,
Nicoletta Biglia,
Giuseppe Viale,
Mauro Risio,
Anna Sapino
[show abstract]
[hide abstract]
ABSTRACT: A subgroup of HER2 overexpressing breast tumours co-expresses p95(HER2) , a truncated HER2 receptor that retains a functional HER2 kinase domain but lacks the extracellular domain, thus impairing trastuzumab binding. We evaluated p95(HER2) expression in 99 frozen breast carcinoma samples by western blot analysis. The HER2-positive cell line BT474 treated with pervanadate or pronase was used as positive control for p95(HER2) expression. Immunohistochemistry was performed on parallel formalin-fixed paraffin-embedded sections of the same case series using antibodies directed against either the intra- or extra-cellular binding domain of HER2. In particular, biotinylated trastuzumab (BiotHER) was used to evaluate the binding capacity of the humanised antibody. To avoid a subjective evaluation of the score values and the percentage of immunostained cells, the slides were scanned and automatically analysed. The number of cases with HER2 overexpression (score 3+) and HER2 gene amplification was higher in the p185(HER2) positive/p95(HER2) positive samples than in the p185(HER2) positive/p95(HER2) negative group. Automated analysis confirmed a significantly higher percentage of 3+ scored cells in p95(HER2) positive cases. Conversely, the percentage of 2+ scored cells was higher in p95(HER2) negative cases. The status of the HER2 extracellular domain was then studied using flow cytometry on BT474 cells after pronase enzymatic digestion using trastuzumab and pertuzumab, while the presence of HER2-HER3 dimers was studied using a proximity-ligation assay. In vitro experiments showed that short-term pronase digestion of BT474 cells produced two HER2 fragments (of 95 and 150 kDa, detectable in tissue specimens as well), increased the binding affinity of trastuzumab, reduced the rate of HER2-HER3 dimers and did not interfere with pertuzumab-binding capacity. In conclusion, the presence of p95(HER2) as detected by western blot analysis does not compromise the immunohistochemical detection of HER2. Our data suggest that a reduction of the receptor steric hindrance as induced by enzymatic shedding may facilitate the binding capacity of trastuzumab. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology 07/2012; · 6.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nipple-areola sparing mastectomy (NSM) is increasingly used in patients with non-locally advanced breast carcinoma. Literature data on the preoperative assessment of the nipple-areola complex (NAC) are inconsistent.
Out of 1359 patients submitted to total mastectomy between 2001 and 2010, we selected 61 patients whose pre-operative mammogram (MX) was available (MX group) and 39 patients who underwent preoperative breast magnetic resonance imaging (magnetic resonance imaging (MRI) group). The rate of NAC involvement, the value of MX and MRI to predict NAC involvement and the performance of the Schecter's and Loewn's algorithms for the prediction of NAC involvement were evaluated.
In the combined MX and MRI groups, NAC involvement was found in 14% of the cases. At univariate analysis, tumour stage (p value: 0.03), central tumour location (p value: 0.004), presence of NAC retraction (p value: 0.001) and tumour-NAC distance (p value: 0.006) were associated with NAC involvement, but only the latter parameter retained statistical significance at multivariate analysis (p value: 0.05). Tumour-NAC distance was a key predictor of NAC involvement, with a negative predictive value of 94% for MX and of 100% for MRI when the cut-off was set at 10mm. Overall, the performance of Schecter's and Loewn's algorithms was respectively lower and similar as compared to the original series.
Occult tumour involvement of the NAC is detected in a minority of breast cancer patients submitted to mastectomy. A tumour-NAC distance ⩾10mm by MRI may help select patients candidate to NSM.
European journal of cancer (Oxford, England: 1990) 05/2012; 48(15):2311-8. · 4.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: [-2]pro-prostate-specific antigen (2pPSA), a proform of PSA, is a new marker in patients at risk of prostate cancer. We explored the potential role of 2pPSA in the identification of patients with metastatic progression following radical prostatectomy for prostate cancer. Seventy-six patients with biochemical (PSA) recurrence following radical prostatectomy were studied retrospectively. Diagnostic imaging performed at the time of biochemical recurrence confirmed metastatic disease in 31 of the 76 patients. Serum samples were collected and stored at the time of imaging-confirmed metastatic progression or at the most recent procedure for patients with negative imaging. Median values of PSA, free PSA (fPSA), %fPSA, 2pPSA and prostate health index (PHI) were compared between metastatic and non-metastatic patients by the Mann-Whitney U test. The results of each test were then correlated with metastatic status by univariate and multivariate logistic regression analysis. PSA, fPSA, %fPSA, 2pPSA serum concentrations and PHI values were statistically significantly higher in patients with metastatic disease. Results of the multivariate analysis revealed that 2pPSA remained a statistically significant predictor of imaging-proven metastatic prostate cancer among patients with biochemical recurrence. At a cut-off value of 12.25 pg/ml, 2pPSA outperformed the other markers in terms of sensitivity and specificity (97 and 80%, respectively) with respect to imaging-confirmed metastatic progression. This is the first study suggesting that 2pPSA predicts diagnostic imaging-proven metastatic disease in previously resected prostate cancer patients with biochemical recurrence. Our results merit validation in a prospective study.
Oncology letters 04/2012; 3(4):819-824. · 0.11 Impact Factor
-
Laura Martincich,
Veronica Deantoni,
Ilaria Bertotto,
Stefania Redana,
Franziska Kubatzki,
Ivana Sarotto,
Valentina Rossi,
Michele Liotti,
Riccardo Ponzone,
Massimo Aglietta,
Daniele Regge, Filippo Montemurro
[show abstract]
[hide abstract]
ABSTRACT: We evaluated whether the apparent diffusion coefficient (ADC) provided by diffusion-weighted imaging (DWI) varies according to biological features in breast cancer.
DWI was performed in 190 patients undergoing dynamic contrast-enhanced magnetic resonance imaging (MRI) for local staging. For each of the 192 index cancers we studied the correlation between ADC and classical histopathological and immunohistochemical breast tumour features (size, histological type, grade, oestrogen receptor [ER] and Ki-67 expression, HER2 status). ADC was compared with immunohistochemical surrogates of the intrinsic subtypes (Luminal A; Luminal B; HER2-enriched; triple-negative). Correlations were analysed using the Mann-Whitney U and Kruskal-Wallis H tests.
A weak, statistically significant correlation was observed between ADC values and the percentage of ER-positive cells (-0.168, P = 0.020). Median ADC values were significantly higher in ER-negative than in ER-positive tumours (1.110 vs 1.050 × 10(-3) mm(2)/s, P = 0.015). HER2-enriched tumours had the highest median ADC value (1.190 × 10(-3) mm(2)/s, range 0.950-2.090). Multiple comparisons showed that this value was significantly higher than that of Luminal A (1.025 × 10(-3) mm(2)/s [0.700-1.340], P = 0.004) and Luminal B/HER2-negative (1.060 × 10(-3) mm(2)/s [0.470-2.420], P = 0.008) tumours. A trend towards statistical significance (P = 0.018) was seen with Luminal B/HER2-positive tumours.
ADC values vary significantly according to biological tumour features, suggesting that cancer heterogeneity influences imaging parameters. KEY POINTS : • DWI may identify biological heterogeneity of breast neoplasms. • ADC values vary significantly according to biological features of breast cancer. • Compared with other types, HER2-enriched tumours show highest median ADC value. • Knowledge of biological heterogeneity of breast neoplasm may improve imaging interpretation.
European Radiology 03/2012; 22(7):1519-28. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess long-term clinical outcome of percutaneous vertebroplasty (PV).
PV was performed in 1,634 patients (1,387 women; median age 73 years ± 9.3) with painful osteoporotic vertebral compression fractures (VCFs). All patients had back pain that persisted for ≥ 2 months with a concordant magnetic resonance imaging study. After PV, medical therapy for osteoporosis was continued, and patients were prospectively evaluated (follow-up 11.8-44.9 months, mean 25.0 months). Visual analog scale (VAS), Oswestry Disability Index (ODI), analgesic drug use, and use of external brace support were recorded at baseline and during follow-up. New occurrences of symptomatic vertebral fractures were recorded.
The mean VAS score of 7.94 significantly improved to 1.12 at the primary endpoint (P < .001). Differences in patterns of analgesic usage compared with baseline values were highly statistically significant (marginal homogeneity test, P < .001). Median ODI values of 82% before treatment significantly decreased to 6% (P < .001). Before intervention, 1,279 patients wore a brace; 1,167 (91.2%) patients did not wear a brace after PV (χ(2) = 31.005, P < .0001). A new painful fracture with a significant higher proportion of contiguous vertebrae (63.6%) occurred in 214 (13.1%) patients (z = 7.59, P = .025).
PV can provide durable pain relief and improvement in ambulation in patients with VCFs.
Journal of vascular and interventional radiology: JVIR 12/2011; 22(12):1714-20. · 1.81 Impact Factor
-
Filippo Montemurro,
Valentina Rossi,
Maria Cossu Rocca,
Rossella Martinello,
Elena Verri,
Stefania Redana,
Laura Adamoli,
Giorgio Valabrega,
Anna Sapino,
Massimo Aglietta,
Giuseppe Viale,
Aron Goldhirsch,
Franco Nolè
[show abstract]
[hide abstract]
ABSTRACT: The relationship between quantitative immunohistochemical hormone receptor expression and response to the combination of trastuzumab with chemotherapy in HER2-positive advanced breast cancer is currently unknown.
Estrogen receptor (ER) and progesterone receptor expression was studied both as a dichotomous variable (positivity set at ≥ 1% of positive cells) and as a continuous variable. The effect of hormone receptor expression on overall response rate and progression-free survival in patients receiving trastuzumab-based treatment was studied by univariate and multivariate analysis.
One hundred eleven of 227 consecutive advanced breast cancer patients treated at 2 Institutions had hormone receptor-positive tumors (49%). High expression of ER (≥ 30% of tumor cells) predicted reduced probability of tumor response to trastuzumab plus chemotherapy (multivariate odds ratio, 0.422; 95% confidence interval [CI], 0.222-0.803; P = .009). In patients with hormone receptor-positive tumors (≥ 1% of tumor cells), maintenance endocrine therapy added to trastuzumab upon the completion of chemotherapy was associated with a significant progression-free survival benefit (hazard ratio, 0.521; 95% CI, 0.3325-0.836; P = .007).
Our results suggest a predictive role of hormone receptor expression in HER2-positive tumors. Further investigation in this patient subset is warranted to optimize the use of HER2-targeting agents, chemotherapy, and endocrine therapy.
Cancer 05/2011; 118(1):17-26. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this article is to assess changes in breast vascular maps on dynamic contrast-enhanced MRI (DCE-MRI) after primary chemotherapy in patients with locally advanced breast cancer (LABC).
Thirty-four patients with unilateral LABC underwent DCE-MRI before and after anthracycline- and taxane-based primary chemotherapy. The number of vessels 30 mm or longer in length and 2 mm or larger in maximum transverse diameter were counted on maximum intensity projections of the first subtracted phase for each of the two breasts. Patients achieving pathologic response or small clusters of residual cancer cells after primary chemotherapy were considered as responders, and those with an inferior pathologic response were considered as nonresponders.
The mean (± SD) number of vessels in the breast harboring the cancer and in the contralateral breast was 2.7 ± 1.3 and 1.1 ± 1.0 (p < 0.001), respectively, before primary chemotherapy and 1.3 ± 1.1 and 1.1 ± 1.1 (p = 0.147), respectively, after primary chemotherapy. Overall, primary chemotherapy was associated with a significant reduction in DCE-MRI vascular maps in the breast harboring the cancer only (p < 0.001). Of the 34 patients, 10 were considered responders and 24 were nonresponders. The mean number of vessels in the breast harboring the cancer changed from 2.7 ± 1.1 to 0.6 ± 0.8 for the 10 responders and from 2.7 ± 1.4 to only 1.6 ± 0.9 for the 24 nonresponders. The mean reduction of vascular map in the breast harboring the cancer was significantly higher in responders compared with nonresponders (p = 0.017).
Before primary chemotherapy, DCE-MRI vascular maps were asymmetrically increased ipsilaterally to the LABC. After primary chemotherapy, vascular maps significantly changed only in the breast harboring the cancer, with significant differences between responders and nonresponders.
American Journal of Roentgenology 05/2011; 196(5):1214-8. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: INTRODUCTION: Pharmacological targeting of the tyrosine kinase receptor HER2 with the monoclonal antibody trastuzumab has dramatically changed the outlook of HER2-positive breast cancer patients. However, HER2 is part of a more complex biological network that, when deregulated, plays a central role in sustaining the cancer phenotype. These interactions account for primary or acquired resistance to drugs that hit a single biological target, like trastuzumab. Several preclinical models suggest that simultaneous targeting of crucial metabolic pathways has the potential to circumvent or delay the onset of resistance phenomena in HER2-positive breast cancer cells. AREAS COVERED: This review describes the rationale and results of clinical trials using biologically targeted agents in HER2-positive breast cancer patients. Single drugs that hit multiple targets and cocktails of biologically targeted agents are considered, whereas combinations with chemotherapy are not addressed. EXPERT OPINION: Most of the studies using biological agents to hit multiple targets in HER2-positive breast cancer patients confirm that resistance to single-agent HER2-targeting can be overcome. Further developments will include combination of multi-targeting strategies with chemotherapy in patients with earlier-stage disease. In addition, it is possible that newer molecular predictive factors may allow a more rationale choice of the most appropriate targeting for each individual patient.
Expert Opinion on Pharmacotherapy 03/2011; 12(4):549-65. · 3.20 Impact Factor
-
The Oncologist 03/2011; 16(4):534-6. · 3.91 Impact Factor
-
Daniele Santini,
Bruno Vincenzi,
Vincenzo Adamo,
Raffaele Addeo,
Vittorio Fusco,
Antonio Russo, Filippo Montemurro,
Ilaria Roato,
Stefania Redana,
Gaetano Lanzetta, [......],
Valentina Leoni,
Sara Galluzzo,
Mauro Antimi,
Giuseppa Ferraro,
Maura Rossi,
Salvatore Del Prete,
Maria Rosaria Valerio,
Monica Marra,
Michele Caraglia,
Giuseppe Tonini
[show abstract]
[hide abstract]
ABSTRACT: Many ErbB2-positive cancers may show intrinsic resistance, and the frequent development of acquired resistance to ErbB-targeted agents represents a substantial clinical problem. The constitutive NF-κB activation in some HER-2/neu positive breast cancer may represent a potential cause of resistance to trastuzumab therapy. Preclinical data revealed that 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine is able to enhance NF-κB DNA binding activity and theoretically to increase the resistance to trastuzumab. Two hundred and forty-eight women with pathologically confirmed, uni- or bidimensionally measurable, HER-2-positive metastatic breast cancer (MBC) treated with trastuzumab-based therapy as first line combination for metastatic disease were considered eligible. For all included patients data on smoking habit were detectable from medical records. We retrospectively analysed the smoking habits of 248 MBC patients and correlated these habits with activity and efficacy of trastuzumab-based therapy. No statistically significant difference in terms of response rate (RR), time to progression (TTP) and overall survival (OS) was identified between smokers (former plus active smokers) and never smokers. Moreover, no statistically significant difference in terms of RR, TTP and OS was identified either comparing active smokers and former smokers. Moreover, we did not observed any significant statistical difference in terms of TTP and OS between smokers ≥10 cigarettes/day and <10 cigarettes/day. This study clearly showed lack of any correlation between cigarette smoking habit and both activity and efficacy of trastuzumab-based first line therapy in metastatic HER2/neu positive breast cancer patients.
Oncology Reports 03/2011; 25(6):1545-8. · 1.84 Impact Factor
-
Giovanni Carlo Anselmetti,
Antonio Manca, Filippo Montemurro,
Joshua Hirsch,
Gabriele Chiara,
Giovanni Grignani,
Fabrizio Carnevale Schianca,
Antonio Capaldi,
Delia Rota Scalabrini,
Elena Sardo,
Felicino Debernardi,
Gabriella Iussich,
Daniele Regge
[show abstract]
[hide abstract]
ABSTRACT: Percutaneous vertebroplasty (PV) is a minimally invasive procedure involving the injection of bone cement within a collapsed vertebral body. Although this procedure was demonstrated to be effective in osteoporosis and metastases, few studies have been reported in cases of multiple myeloma (MM). We prospectively evaluated the safety and efficacy of PV in the treatment of vertebral compression fractures (VCFs) resulting from MM.
PV was performed in 106 consecutive MM patients who had back pain due to VCFs, the treatment of which had failed conservative therapies. Follow-up (28.2 ± 12.1 months) was evaluated at 7 and 15 days as well as at 1, 3, 6, 12, 18, and every 6 months after PV. Visual analog scale (VAS) pain score, opioid use, external brace support, and Oswestry Disability Index (ODI) score were recorded.
The median pretreatment VAS score of 9 (range 4-10) significantly (P < 0.001) decreased to 1 (range 0-9) after PV. Median pre-ODI values of 82% (range 36-89%) significantly improved to 7% (range 0-82%) (P < 0.001). Differences in pretreatment and posttreatment use of analgesic drug were statistically significant (P < 0.001). The majority of patients (70 of 81; 86%) did not use an external brace after PV (P < 0.001).
PV is a safe, effective, and long-lasting procedure for the treatment of vertebral compression pain resulting from MM.
CardioVascular and Interventional Radiology 02/2011; 35(1):139-45. · 2.09 Impact Factor
-
Caterina Peraldo-Neia,
Giorgia Migliardi,
Maurizia Mello-Grand, Filippo Montemurro,
Raffaella Segir,
Ymera Pignochino,
Giuliana Cavalloni,
Bruno Torchio,
Luciano Mosso,
Giovanna Chiorino,
Massimo Aglietta
[show abstract]
[hide abstract]
ABSTRACT: Activating mutations of the epidermal growth factor receptor (EGFR) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.
Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.
EGFR protein overexpression (EGFRhigh) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFRhigh tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow tumours. Conversely, in EGFRhigh tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFRhigh (n=3) and mutated/EGFRlow tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.
Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.
BMC Cancer 01/2011; 11:31. · 3.01 Impact Factor
-
Giorgio Valabrega,
Sonia Capellero,
Giuliana Cavalloni,
Gianluca Zaccarello,
Annalisa Petrelli,
Giorgia Migliardi,
Andrea Milani,
Caterina Peraldo-Neia,
Loretta Gammaitoni,
Anna Sapino,
Carla Pecchioni,
Aldo Moggio,
Silvia Giordano,
Massimo Aglietta, Filippo Montemurro
[show abstract]
[hide abstract]
ABSTRACT: Trastuzumab has changed the prognosis of HER2 positive breast cancers. Despite this progress, resistance to trastuzumab occurs in most patients. Newer anti-HER2 therapies, like the dual tyrosine-kinase inhibitor (TKI) lapatinib, show significant antitumor activity, indicating that HER2 can be still exploited as a target after trastuzumab failure. However, since a high proportion of patients fail to respond to these alternative strategies, it is possible that cell escape from HER2 targeting may rely on HER2 independent pathways. The knowledge of these pathways deserve to be exploited to develop new therapies. We characterized two human HER2 overexpressing breast cancer cell lines resistant to trastuzumab and lapatinib (T100 and JIMT-1) from a molecular and biological point of view. Indeed, we assessed both in vitro and in vivo the activity of the multitarget inhibitor sorafenib. In both cell lines, the previously proposed mechanisms did not explain resistance to HER2 inhibitors. Notably, silencing HER2 by shRNA did not affect the growth of our cells, suggesting loss of reliance upon HER2. Moreover, we identified alterations in two antiapoptotic proteins Mcl-1 and Survivin which are known to be targets of the multikinase inhibitor sorafenib. Moreover, sorafenib, strongly inhibited the in vitro growth of T100 and JIMT-1 cells, through the downregulation of both Mcl-1 and Survivin. Similar results were obtained in JIMT-1 xenografts subcutaneously injected in NOD SCID mice. We provide preclinical evidence that tumor cells resistant to trastuzumab and lapatinib may rely on HER2 independent pathways that can be efficiently inhibited by sorafenib.
Breast Cancer Research and Treatment 12/2010; 130(1):29-40. · 4.43 Impact Factor
-
The Lancet 05/2010; 375(9729):1871; author reply 1871-2. · 38.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Combinations of trastuzumab with either docetaxel or vinorelbine are considered valuable treatment options for HER2-positive metastatic breast cancer patients. We performed a retrospective comparison of the clinical outcomes associated with either one of these combinations.
From a multi-institutional database we retrieved 179 patients treated with either docetaxel or vinorelbine plus trastuzumab as first-line therapy for HER2-positive advanced breast cancer.
Docetaxel-trastuzumab was superior to vinorelbine-trastuzumab in terms of response rate (RR: 77 vs 57%, p = 0.01) and median overall survival (OS: 35 vs 23 months, p = 0.04), but not in median time to progression (TTP: 12 vs 10 months, p = 0.53). At multivariate analysis, type of treatment was not associated with TTP but was an independent predictor of OS, with a significant reduction in the risk of death in favor of docetaxel-trastuzumab (HR 0.474, 95% IC 0,303-0.742, p < 0.01).
Docetaxel or vinorelbine, when combined with trastuzumab, provide excellent rates of tumor control in patients with previously untreated HER2-positive advanced breast cancer. Docetaxel may offer some advantage in terms of response rate and resulted in a significantly prolonged overall survival, which, because of the retrospective design of our study, deserves further investigation in prospective trials.
BMC Cancer 01/2010; 10:28. · 3.01 Impact Factor
