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G Viale

Publications and source records attributed to G Viale.

At least 19 recordsLinked to original sources
PubMed2026

Navigating uncertainties and evidence gaps in adjuvant therapy for premenopausal women with HR+/HER2- breast cancer.

Premenopausal women with hormone receptor-positive (HR+)/HER2-negative early breast cancer represent a clinically distinct population, characterized by more aggressive tumor biology, unique survivorship concerns, and complex treatment decision-making. Although evidence from dedicated trials and subgroup analyses is available, management remains challenging because data are heterogeneous, evolving, and often extrapolated from broader populations that include predominantly postmenopausal women. Adjuvant endocrine therapy, with the addition of CDK4/6 inhibitors in selected higher-risk patients, remains the cornerstone of treatment; however major uncertainties persist regarding the optimal use of ovarian function suppression, the interpretation of genomic assays to inform chemotherapy decisions, the selection of candidates for extended endocrine therapy, and the management of adherence, treatment-related toxicities, pregnancy-related issues, and survivorship concerns. Here, we synthesize current evidence across these domains and propose a pragmatic clinical framework to support individualized treatment strategies and optimize care for this population in the contemporary therapeutic landscape.

HR+/HER2- early breast cancer↗
PubMed2006

A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases.

BACKGROUND: Sentinel node biopsy (SNB) has become a standard treatment in staging axillary lymph nodes in early breast cancer. SNB, however, is an invasive procedure and is time-consuming when the sentinel node is analysed intra-operatively. Breast cancer is frequently characterised by increased 2-fluoro-2-deoxy-D-glucose uptake and many studies have shown encouraging results in detecting axillary lymph node metastases. The aim of this study was to compare SNB and -positron emission tomography (-PET) imaging, to assess their values in detecting occult axillary metastases. PATIENTS AND METHODS: In all, 236 patients with breast cancer and clinically negative axilla were enrolled in the study. 18-FDG-PET was carried out before surgery, using a positron emission tomography (PET)/computed tomography scanner. In all patients, SNB was carried out after identification through lymphoscintigraphy. Patients underwent axillary lymph nodes dissection (ALND) in cases of positive FDG-PET or positive SNB. The results of PET scan were compared with histopathology of SNB and ALND. RESULTS: In all, 103 out of the 236 patients (44%) had metastases in axillary nodes. Sensitivity of FDG-PET scan for detection of axillary lymph node metastases in this series was low (37%); however, specificity and positive predictive values were acceptable (96% and 88%, respectively). CONCLUSIONS: The high specificity of PET imaging indicates that patients who have a PET-positive axilla should have an ALND rather than an SNB for axillary staging. In contrast, FDG-PET showed poor sensitivity in the detection of axillary metastases, confirming the need for SNB in cases where PET is negative in the axilla.

Adult↗
PubMed2006

Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease.

BACKGROUND: There is limited knowledge about prognosis, and treatment effects in young women with node-negative disease. PATIENTS AND METHODS: We evaluated biological features, treatment recommendations and prognosis for 841 premenopausal patients with pT1-3, pN0 and M0, operated from 1997 to 2001. RESULTS: Patients below 35 years (101, 12%) were more likely to have tumors > 2 cm (35.6% versus 24.2%, P = 0.002), grade 3 (48.5% versus 31.9%, P = 0.009) and with elevated Ki-67 expression (62.4% versus 50.7%, P = 0.002). At the multivariate analysis a statistically significant difference in disease-free survival (DFS, HR 4.44; 95% CI 2.53 to 7.78, P < 0.0001), risk of distant metastases (DDFS) (HR 3.23; 95% CI 1.32 to 7.94, P = 0.011) and overall survival (OS) (HR 2.89; 95% CI 1.06 to 7.87, P = 0.038) was observed for younger versus older patients and in the subgroup with endocrine responsive tumors (DFS, HR 5.17, 95% CI 2.72-9.83, P = < 0.0001; DDFS, 3.76, 95% CI 1.33-10.6, P = 0.013; OS, 4.71, 95% CI 1.09-20.4, P = 0.039 ). CONCLUSIONS: Compared with less young, very young patients with endocrine responsive and node-negative breast cancer have a worse prognosis. Tailored treatments should be explored in this cohort of patients.

Adult↗
PubMed2006

Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept.

PURPOSE: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of (99m)Tc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity.

Adult↗
PubMed2006

Partial irradiation of the breast: Old challenges, new solutions.

Breast-conserving treatment, characteristically consisting of surgical removal of the tumor and post-operative whole breast irradiation, is nowadays considered as the standard therapeutic approach for most women with stage I/II, invasive breast cancer. Recently, a number of institutions started investigating the feasibility and safety of novel approaches in radiotherapy, modulating concomitantly treatment time and irradiation volume. Whilst this strategy is still under investigation, recent clinical studies on accelerated partial breast irradiation with intra-operative radiotherapy or high conformality irradiation strongly suggest that the way patients with early breast cancer are irradiated should be revisited.

Algorithms↗
PubMed2006

The prevalence and clinical implications of c-kit expression in plasma cell myeloma.

AIM: To evaluate the clinical implications of c-kit (CD117) expression in plasma cell myeloma (PCM). METHODS AND RESULTS: We first evaluated the reliability of immunohistochemistry in assessing c-kit expression by comparing the results with those obtained by flow cytometry and gene expression arrays in 22 PCM and in 10 PCM cell lines. Immunohistochemical results showed a perfect concordance with those of flow cytometry; likewise, immunohistochemical and gene expression data were also concordant in all but one PCM and cell lines analysed. Then, we investigated the clinical implications of c-kit immunoreactivity in bone marrow biopsies of 85 PCM patients with a mean follow-up of 41 months. C-kit immunoreactivity was detected in 24 (28.2%) of the 85 cases and it was significantly associated with a high microvessel density, but not with traditional clinicopathological characteristics or with survival. CONCLUSIONS: Our findings suggest that immunohistochemistry is a reliable indicator of c-kit gene expression and reinforce the notion that approximately one-third of PCM express high levels of c-kit. The lack of association with traditional clinicopathological parameters and patient survival suggests that c-kit expression may not be an adjunct in predicting the clinical course of the disease.

Adult↗
PubMed2006

Peptide receptors in neuroendocrine tumors of the lung as potential tools for radionuclide diagnosis and therapy.

Neuroendocrine tumors of the lung are carcinomas characterized by different impact on the patients' prognosis, ranging from relatively indolent, low- to intermediate-grade neoplasms with longer life expectation (i.e., typical and atypical carcinoids) to very aggressive and poorly differentiated neoplasms with dismal prognosis (i.e., large cell neuroendocrine carcinoma and small cell lung cancer). The standard treatment of typical or atypical carcinoids is the complete surgical resection, whereas the role of radio-chemotherapy in a multimodality treatment or for palliation remains controversial. Conversely, high-grade neuroendocrine carcinomas are in primis treated by aggressive combination chemotherapy, deserving surgical resection for uncommon low-stage tumors. Since evidence has been accumulated that neuroendocrine tumors of the lung are supplied with a wide array of peptide receptors detectable on cell membranes by immunohistochemical methods, innovative strategies for diagnosis and radiometabolic therapy have been devised to target these molecules for the correct clinical management of the patients. In this paper, the structural and functional aspects and the clinical applications of the detection of several peptide receptors in pulmonary neuroendocrine tumors will be reviewed, including somatostatin receptors, vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide family receptors, cholecystokinin /gastrin receptors, bombesin/gastrin releasing peptide receptors, neurotensin receptors, substance P receptors, neuroepeptide Y receptors, calcitonin/calcitonin gene-related peptide receptors, atrial natriuretic peptide receptors, glucagon-like-peptide-1 receptors, oxytocin receptors and endothelin receptors. Only a detailed knowledge of the peptide receptor distribution in these tumor types, especially in uncommon neoplasms such as atypical carcinoids and large cell neuroendocrine carcinomas, is pivotal for planning the most adequate interventions for the patients' diagnosis and therapy.

Carcinoma, Neuroendocrine↗
PubMed2005

Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.

BACKGROUND: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated. PATIENTS AND METHODS: Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B). RESULTS: The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B. CONCLUSIONS: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.

Administration, Oral↗
PubMed2005

Sentinel lymph node biopsy for localised ductal carcinoma in situ?

Intraductal carcinoma of the breast (DCIS), by definition, cannot give axillary metastases. Axillary dissection is therefore not indicated. The role of the sentinel lymph node (SLN) biopsy in the management of DCIS has not yet been established. A 6-13% risk of SLN involvement is reported in Literature. The aim of the present study is to assess the role of SLN biopsy in patients with pure DCIS and attempt to identify guidelines for routine practice in managing such patients. From March 1996 to December 2003, 508 consecutive patients with pure DCIS of the breast underwent SLN biopsy at the European Institute of Oncology in Milan. Clinical and pathological data were prospectively collected. In all cases of previous surgery or stereotactic biopsy performed elsewhere all pathological slides were reviewed. Cases with microinvasion were excluded from this investigation. Lymphatic mapping was performed using a radiocolloid technique. Most of the patients underwent conservative surgery and removal of the SLN which was sent for conclusive histology. SLN metastases were detected in 9 out of 508 (1.8%) patients. In five patients only micrometastasis (<2 mm) was detected. Eight patients underwent complete axillary dissection. In none of these patients did we find additional positive axillary lymph nodes. In conclusion, due to the low prevalence of metastatic involvement (1.8%), SLNB should not be considered a standard procedure in the treatment of all patients with DCIS. In pure non-comedo DCIS completely excised by radical surgery with free margins of resection SLNB should be avoided since not only it is unnecessary but could also jeopardize a successive re-SLNB in case of invasive recurrence. A very extensive and accurate histological examination of the tumour in DCIS is compulsory to exclude micro-invasive foci and, finally, to decrease the prevalence of unexpected SLN metastases. SLNB should be considered in case of DCIS where there exists a strong doubt of invasion at the definitive histology, such as large solid tumours or diffuse or pluricentric microcalcifications undergoing mastectomy. Moreover, if the trend is statistically confirmed with a wider population, large comedo-DCIS, presenting superior risk of SLNs metastasis, could be scheduled for SLNB. If the SLN is micrometastatic complete axillary dissection is not unavoidable.

Breast Neoplasms↗
PubMed2005

Are all high-grade breast cancers with no steroid receptor hormone expression alike? The special case of the medullary phenotype.

BACKGROUND: Medullary carcinoma (MC) of the breast is associated with favorable prognosis compared with other histological types, despite high nuclear grade, fast proliferation and lack of steroid hormone receptor expression. We retrospectively evaluated the clinical relevance of selected immunohistochemical features of tumors in three cohorts of patients with typical medullary (MC), 'atypical' medullary (AMC) or ductal (DC) breast carcinoma. PATIENTS AND METHODS: Evaluation was performed on node-negative tumor specimens from 40 patients who had either MC (12 patients), AMC (nine patients) or DC (19 patients), treated in a single institution. All had no hormonal receptor, Ki-67 > or =30%, G3, expansive pattern of growth and peritumoral lymphocytic infiltration. In addition, p27, p21 and HER2/neu overexpression, p53, cyclin E and E-cadherin expression, presence of apoptotic cells, stromal tenascin (TN), and type of immune cell infiltration (CD3- and CD68-positive cells) were assessed. RESULTS: No difference in expression of HER2/neu, p21, p27, p53, number of apoptotic cells and CD68-positive cells was detected. Lower levels of stromal TN expression were found in MC compared with DC (P=0.0007), but differences between MC and AMC were not significant (P=0.27). A higher proportion of intratumoral CD3-positive cells was seen in MC than in AMC (P=0.046). No differences were seen between MC and DC (P=0.73). With a median follow-up of 67 months, three patients with DC had relapsed in distant sites, while one patient with AMC had a second primary. Two patients with MC had reappearance of DC in the breast. CONCLUSIONS: The three distinct disease types, selected by having similar high proliferation, had similar expression of cell cycle regulators. The lower expression of TN and massive infiltration of T lymphocytes might both indicate a special interaction between tumor cells and microenvironment, important features for conferring improved prognosis through negligible invasive and metastatic potential to MC. In our series, however, patients with a previous MC are not free from the risk of developing a subsequent DC. Finally, defining AMC as a distinct entity from DC is not justified.

Adult↗
PubMed2005

Breast cancer diagnosed during pregnancy and lactation: biological features and treatment options.

AIM OF THE STUDY: Assessment of biological features and treatment of patients with breast cancer presenting during pregnancy or lactation. PATIENTS AND METHODS: Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR), Ki-67, HER2/neu, prognostic markers, treatment and follow-up of 21 patients with breast cancer during pregnancy (BCdP) and 17 with breast cancer during lactation (BCdL) are presented. RESULTS: Median age was 36 and 33 years, median tumour size was 2.4 and 2.5 cm, axillary lymph nodes were positive in 10 of 21 pregnant patients and 11 of 17 lactating patients, respectively. Both ER and PgR were not expressed in six of 21 pregnant women and nine of 17 lactating patients. All the six women who had concurrent diagnosis of breast cancer and pregnancy (first trimester) preferred termination of pregnancy although an alternative option was discussed. Five patients received anthracycline containing chemotherapy during the second and third trimester with no complications for patient and child. Conservative surgery was performed in 15 of 21 patients during pregnancy with no local reappearance after a median follow-up of 24 months. Three pregnant women underwent lymphoscintigraphy and sentinel lymph node biopsy. CONCLUSIONS: Patients who had concurrent diagnosis of breast cancer and pregnancy (early first trimester) preferred termination of pregnancy to allow easier completion of treatment. Conservative surgery was safe also in women with BCdP. Sentinel node biopsy might be considered for pregnant patients with a clinically negative axilla.

Abortion, Legal↗
PubMed2005

Development of axillary surgery in breast cancer.

Axillary surgery is a critical part of the treatment of breast carcinoma: its importance is related to the staging of disease, prescription of adjuvant therapy and prognosis. For years, complete axillary dissection has remained the standard approach to breast cancer lymphatic staging; its value is still high, but the development of sentinel-node biopsy has significantly changed the indication of the procedure. We discuss the evolution of axillary surgery in breast cancer.

Axilla↗
PubMed2004

Minimal and small size invasive breast cancer with no axillary lymph node involvement: the need for tailored adjuvant therapies.

BACKGROUND: Prognosis of patients with node-negative disease and tumor size <1 cm is a matter of controversy. While data exist to clearly correlate small tumor size to better prognosis, the fact that very small breast cancers may express biological markers of dire prognosis leads many to ignore small tumor size during treatment decision-making. PATIENTS AND METHODS: Data from 425 patients classified as having node-negative pT1mic, pT1a or pT1b after surgery (from April 1997 to December 2001) at the European Institute of Oncology, were analyzed to be described as disease-free according to prognostic variables including: Ki-67 (<20% versus > or =20% of the cells), ER (absent versus positive > or =1% of the cells), PgR (absent versus positive > or =1% of the cells), grade, overexpression or amplification of HER2/neu, presence of peritumoral vascular invasion and age (by decade). The median follow-up for this cohort of patients was 43 months. RESULTS: No local or distant relapse was observed for patients with pT1mic breast cancer; 4-year disease-free survival for pT1a and pT1b was 97.0% and 97.6%, respectively. In both univariate and multivariate analyses the most relevant prognostic factor for this low-risk population was Ki-67 labeling. The 4-year disease-free survival was 99.2% for tumors with low Ki-67 and 93.3% for tumors with high Ki-67 (> or =20%) labeling. The hazard ratio (HR) for patients with high Ki-67 was 12.9 (95% CI 1.5-112.0, P=0.02). CONCLUSIONS: Within the first 4 years, microinvasive breast cancer parallels ductal carcinoma in situ (DCIS) rather than invasive carcinoma. Costs and benefits of adjuvant therapy should be accurately weighted in these patients. Patients with pT1a and pT1b, node-negative disease have a limited but substantial risk of recurrence and therefore adjuvant therapy, according to endocrine responsiveness of the tumor and patient preference, should continue to be offered as a reasonable treatment option.

Adult↗
PubMed2003

Optimised nuclear medicine method for tumour marking and sentinel node detection in occult primary breast lesions.

The aim of this study was to evaluate the feasibility of sentinel node (SN) biopsy in occult breast lesions with different radiopharmaceuticals and to establish the optimal lymphoscintigraphic method to detect both occult lesions and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and twenty-seven consecutive patients suspected to have clinically occult breast carcinoma were enrolled in the study. In addition to the radioguided occult lesion localisation (ROLL) procedure, using macroaggregates of technetium-99m labelled human serum albumin (MAA) injected directly into the lesion, lymphoscintigraphy was performed with nanocolloids (NC) injected in a peritumoral (group I) or a subdermal site (group II). In group III, a sole injection of NC was done into the lesion in order to perform both ROLL and SNOLL. Overall, axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%) patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes were not visualised, whereas SNs were successfully localised in 85 of 86 patients of group II ( P<0.001). Pathological findings revealed breast carcinoma in 148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131 axillary SNs were removed in 118 patients with breast carcinoma; intraoperative examination of the SNs revealed metastatic involvement in 16 out of 96 cases of invasive carcinoma (16.7%). It is concluded that the combination of the ROLL procedure with direct injection of MAA into the lesion and lymphoscintigraphy performed with subdermal injection of radiocolloids represents the method of choice for accurate localisation of both non-palpable lesions and SNs.

Adult↗
PubMed2003

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer.

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

Adult↗
PubMed2003

Preoperative systemic treatment: prediction of responsiveness.

The use of predictive factors allows a more effective use of available therapies by enabling clinicians to distinguish patients likely to obtain substantial benefit from treatment from those for whom the same therapy is less likely to be effective. A most relevant aspect of clinical research is thus to develop alternative therapeutic approaches which are more efficacious for this latter group, particularly important since treatment effects are likely to be small. In the preoperative setting several predictors of response were identified. They include: diameter of the lesion (larger lesions respond less than smaller lesions), MIB-1 increased expression associated with increased response to chemotherapy, and estrogen receptor (ER) and progesterone receptor (PgR) expression in the tumor typically associated with increased response to endocrine therapies. Other factors include HER-2/neu overexpression, which is a target for treatment with the humanized monoclonal antibody against its extracellular domain, is hypothesized to increase response to anthracycline combination chemotherapy and to lead to an improved response to some endocrine agents (e.g. letrozole) rather than to others. Although primary endocrine therapy demonstrated activity and low profile of side effects in selected populations of older patients, it is infrequently used. On the other hand, chemotherapy remains the mainstay of treatment being considered to be a more active and better documented option. Experience at the European Institute of Oncology on 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) treated with primary chemotherapy, indicated that a proper selection of primary treatment should be based on tumor characteristics such as ER and PgR status. In particular, patients with tumors with no ER and PgR expression (endocrine-unresponsive disease) at the baseline core-biopsy had a significantly higher response rate to chemotherapy if compared with tumors with some ER/PgR expression. In fact, the absence of ER and PgR expression was the strongest predictors of pCR at the multivariate analysis (P<0.0001). Information on endocrine responsiveness before primary systemic therapy will lead to better tailoring of treatment modalities, thus avoiding chemotherapy in selected populations where other approaches (e.g. endocrine primary therapy) might be more useful.

Animals↗