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Robin L Jones

Publications and source records attributed to Robin L Jones.

14 recordsLinked to original sources
PubMed2026

Management of Soft Tissue and Visceral Leiomyosarcomas.

IMPORTANCE: Leiomyosarcoma is a rare and heterogeneous malignant mesenchymal neoplasm associated with substantial morbidity and mortality. Given recent advances in biologic understanding and the complexity of leiomyosarcoma, a consensus-driven approach is needed to harmonize management and address remaining clinical and research gaps. OBJECTIVE: To provide an evidence-based synthesis of current diagnostic and therapeutic approaches for leiomyosarcoma by an international panel of physicians, researchers, and patient advocates, focusing on site-specific management, systemic therapy strategies, and key areas of clinical uncertainty, while identifying unmet needs and research priorities. EVIDENCE REVIEW: This review is based on a comprehensive evaluation of the literature, including clinical trials, observational studies, and international consensus guidelines. Sources were identified through MEDLINE (via PubMed) and Embase database searches and reference screening, then supplemented by multidisciplinary expert consensus. Emphasis was placed on studies informing diagnosis, surgical management, radiotherapy, and systemic therapy in leiomyosarcoma. FINDINGS: The rarity and heterogeneity of leiomyosarcoma poses substantial challenges in its management. In localized disease, complete surgical resection remains the cornerstone of treatment, with evidence supporting the use of site-specific perioperative treatment strategies. Prospective data supporting neoadjuvant or adjuvant chemotherapy are lacking, and the role of radiotherapy differs across anatomic disease sites and institutions. In advanced disease, multiple systemic therapies demonstrate activity, including anthracycline-based and gemcitabine-based combinations, trabectedin, and tyrosine kinase inhibitors, although optimal sequencing after first-line therapy remains undefined. Emerging data suggest potential benefit from treatment continuation strategies and selected use of local therapies in oligometastatic settings. Molecular heterogeneity is increasingly recognized but has not yet translated into routine clinical implementation, and integration of molecular profiling into diagnostic pathways for predictive and therapeutic insights remains an unmet need. CONCLUSIONS AND RELEVANCE: This international consensus addresses the diagnosis and management of leiomyosarcoma. Management requires a multidisciplinary, site-specific approach informed by limited but evolving evidence. Key uncertainties persist, particularly regarding perioperative therapy, optimal sequencing and combination of systemic treatments, and integration of molecular data. Continued international collaboration and leiomyosarcoma-specific clinical trials are needed to refine treatment strategies and improve patient outcomes.

Journal Article↗
PubMed2007

Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis.

PURPOSE: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. EXPERIMENTAL DESIGN: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. RESULTS: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with 'basal-like' immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. CONCLUSIONS: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.

Breast↗
PubMed2006

MYC amplification in breast cancer: a chromogenic in situ hybridisation study.

AIMS: To analyse the correlation between MYC amplification and various clinicopathological features and outcome in a cohort of 245 patients with invasive breast carcinoma treated with surgery followed by anthracycline-based chemotherapy. Given the high prevalence of MYC amplification in tumours of BRCA1 mutation carriers and the similarities between these and sporadic "basal-like" carcinomas, the prevalence of MYC amplification in "basal-like" breast carcinomas was investigated. METHODS: MYC gene copy number was assessed on tissue microarrays containing duplicate cores of 245 invasive breast carcinomas by means of chromogenic in situ hybridisation using SpotLight C-MYC amplification probe and chromosome 8 centromeric probe (CEP8). Signals were evaluated at 400x magnification; 30 morphologically unequivocal neoplastic cells in each core were counted for the presence of the gene and CEP8 probes. RESULTS: Amplification was defined as a MYC:CEP8 ratio >2. Signals for both MYC and CEP8 were assessable in 196/245 (80%) tumours. MYC amplification was found in 19/196 cases (9.7%) and was not associated with tumour size, histological grade, positivity for oestrogen receptor, progesterone receptor, HER2, epidermal growth factor, cytokeratins 14, 5/6 and 17, MIB1 or p53. Only 4% of basal-like carcinomas showed MYC amplification, compared to 8.75% and 10.7% of luminal and HER2 tumours respectively. On univariate analysis, MYC amplification displayed a significant association with shorter metastasis-free and overall survival and proved to be an independent prognostic factor on multivariate survival analysis. CONCLUSION: MYC amplification is not associated with "basal-like" phenotype and proved to be an independent prognostic factor for breast cancer patients treated with anthracycline-based chemotherapy.

Anthracyclines↗
PubMed2006

Cyclin D1 protein overexpression and CCND1 amplification in breast carcinomas: an immunohistochemical and chromogenic in situ hybridisation analysis.

Conflicting results on the prevalence of cyclin D1 ovexpression and its correlation with CCND1 amplification and outcome of breast cancer patients have been reported. Owing to limited sensitivity and specificity of most antibodies against cyclin D1, evaluation of cyclin D1 immunoexpression is reported to be problematic. The aims of this study were to assess the prevalence of cyclin D1 expression in breast carcinomas using the SP4 rabbit monoclonal antibody; to correlate cyclin D1 expression with amplification, assessed using chromogenic in situ hybridisation (CISH); and to analyse the relationship between CCND1 amplification and overexpression with clinicopathological parameters and outcome in a tissue microarray containing replicate tumour samples from 245 breast cancer patients. Immunohistochemistry for cyclin D1 was performed using the SP4 and the results were scored according to the Allred scoring system. CISH was carried out using the Zymed CCND1 SpotLight probe. CISH signals were counted in 60 morphologically unequivocal neoplastic cells. Amplification was defined as >5 signals per nucleus in more than 50% of cancer cells, or when large gene copy clusters were seen. Strong cyclin D1 expression and CCND1 amplification were found in 67.4 and 14.5% of the cases, respectively. A strong correlation between cyclin D1 overexpression and CCND1 amplification was demonstrated (P<0.0001). Cyclin D1 expression showed a positive correlation with hormone receptor expression (both ER and PgR, P<0.0001). An inverse correlation was observed between an immunohistochemical panel of 'basal-like' markers and both cyclin D1 overexpression (P<0.0001) and CCND1 amplification (P<0.0001). On univariate analysis cyclin D1 expression showed a correlation with longer overall survival (OS). Neither cyclin D1 nor CCND1 were independent prognostic factors for disease-free survival or OS. The results of this study confirm the association between cyclin D1 overexpression and positivity for hormone receptors and the lack of CCND1 amplification in basal-like breast carcinomas.

Antibodies, Monoclonal↗
PubMed2006

Neoadjuvant treatment for early-stage breast cancer: opportunities to assess tumour response.

Primary, preoperative, or neoadjuvant chemotherapy was introduced in the early 1970s as part of an integrated therapeutic approach to treat inoperable locally advanced breast cancer. The approach resulted in high responses, and sufficient downstaging to allow mastectomy in some patients. In addition, a small number of pathological complete responders were reported. Gradually, the idea of preoperative chemotherapy was extended to include patients with large but operable early-stage breast cancer, with the possibility in some cases of downstaging the primary tumour to avoid mastectomy, and to allow breast-conserving surgery to be done. This approach allows the tumour to be used as a measure of treatment response in vivo. More recently, the possibility has opened up for neoadjuvant chemotherapy to provide information on the use of clinical, pathological, and molecular endpoints, which can be used as surrogate markers to predict long-term outcome in the adjuvant setting. In addition, the anatomical accessibility of the breast provides the potential for serial biopsies to investigate molecular changes during treatment.

Antibodies, Monoclonal↗
PubMed2006

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue.

Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without intrinsic tyrosine kinase activity, whose expression is not restricted to neural cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell growth and proliferation. NGFR expression was immunohistochemically analysed in normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions, in 22 tumours with myoepithelial differentiation and in two cohorts of breast cancer patients: a series of 245 invasive breast carcinomas studied with tissue microarrays and 37 high-grade invasive ductal carcinomas with basal-like immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for NGFR. Scattered NGFR-positive cells were observed in solid areas of six out of nine cases of hyperplasia of usual type, whereas in flat atypia, lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%) metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast carcinomas. NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001). NGFR showed a statistically significant association with longer disease-free (P<0.05) and overall survival (P<0.01) in the cohort of patients with basal-like carcinomas. This study demonstrates the usefulness of NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive lesions and myoepithelial differentiation in breast carcinomas. Furthermore, provisional data in a small number of basal-like breast carcinomas suggest that NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.

Breast↗
PubMed2006

Anthracycline cardiotoxicity.

The use of anthracyclines is limited by dose-dependent cardiotoxicity. Three forms of anthracycline cardiotoxicity are described; an immediate pericarditis-myocarditis syndrome, an early onset chronic progressive CHF developing during or shortly after therapy and late-onset cardiotoxicity presenting years following treatment. A number of risk factors have been reported, including; cumulative dose, administration schedule, mediastinal radiotherapy, old and young age, concurrent cardiovascular disease, combination therapy, gender, ethnicity and chromosomal abnormalities. Evaluation of left ventricular ejection fraction has been widely adopted as a means of monitoring and assessing anthracycline-induced cardiotoxicity. Biochemical markers and other techniques, such as endomyocardial biopsy, metaiodobenzylguanidine and indium-111-antimyosin scintigraphy are not routinely used. Methods employed to prevent cardiotoxicity include cumulative dose limitation, alteration of administration schedule, anthracycline analogues, liposomal formulations and the cardioprotective agent, dexrazoxane. With the growing number of paediatric malignancy survivors and the increasing use of anthracyclines in the adjuvant treatment of breast cancer, the cardiotoxicity associated with these agents will remain a formidable issue for physicians. Further work is required to identify patients at increased risk of cardiotoxicity and to develop novel methods of protecting and treating this adverse effect.

Anthracyclines↗
PubMed2006

Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs.

Anthracyclines are a well-known cause of cardiotoxicity, but a number of other drugs used to treat cancer can also result in cardiac and cardiovascular adverse effects. Cardiotoxicity can result in the alteration of cardiac rhythm, changes in blood pressure and ischemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to catastrophic life-threatening, and sometimes fatal, sequelae. These events may occur acutely or may only become apparent months or years following completion of oncological treatment. Ischemia and rhythm abnormalities are treated symptomatically in most cases. Knowledge of these toxicities can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient.

Anthracyclines↗
PubMed2005

Differential sensitivity of liposarcoma subtypes to chemotherapy.

Liposarcoma is one of the most common soft tissue sarcomas and has a number of different subtypes: well-differentiated; dedifferentiated; myxoid/round cell; and pleomorphic. However, the response of these subgroups to chemotherapy is not well documented. In this study, we have conducted a retrospective analysis of a prospectively maintained database of soft tissue sarcoma patients treated at the Royal Marsden Hospital. Eighty-eight liposarcoma patients who received chemotherapy between August 1989 and June 2004 were identified. The response rates to chemotherapy of the different histological subtypes and overall and progression free survival were investigated. Survival according to histological grade was also assessed. A statistically significant higher response rate to first-line chemotherapy was observed in patients with myxoid liposarcoma compared to de- and well-differentiated tumours, 48% (95%CI; 28-69) and 11% (95%CI; 2-29), P = 0.005. Similarly, those with myxoid liposarcoma had a significantly higher response rate compared to all other liposarcoma patients, 48% (95%CI; 28-69) and 18% (95%CI; 8-31). Patients with lower grade tumours had better overall survival. This retrospective analysis suggests that myxoid liposarcoma is relatively chemosensitive in comparison to a combination of other liposarcomas, and in particular de- and well-differentiated tumours. Further confirmation of these results should be sought by similar analyses of other databases.

Adult↗
PubMed2005

The development and application of imatinib.

The hallmark characteristics of cancer include an unrestrained proliferation involving activation of growth signals, loss of negative regulation and dysfunctional apoptotic pathways. Targeting abnormal cell signalling pathways should provide a more selective approach to cancer treatment than conventional cytotoxic chemotherapy. Tyrosine kinases play an essential role in the signalling pathways involved in the control of cellular proliferation and growth. Imatinib is a small-molecule tyrosine kinase inhibitor of the ABL fusion gene, platelet derived growth factor receptors (PDGFR) and KIT. This agent has demonstrated considerable activity in chronic myeloid leukaemia (CML) by inhibiting the BCR-ABL fusion protein and gastrointestinal stromal tumours (GISTs), which are predominantly driven by activating mutations in KIT. A number of other rare conditions are also responsive, for example, dermatofibrosarcoma protuberans, which is driven by a chromosomal translocation involving PDGF-B and Col1A1, resulting in overexpression of PDGF-B, and hypereosinophillic syndrome, which can be caused by activating PDGFR mutations. The pivotal registration study for newly diagnosed CML was a large randomised trial comparing 400 mg/day of imatinib to a combination of IFN-alpha and cytarabine, which demonstrated a significantly higher complete haematological and cytogenetic response rate in the imatinib arm. In the case of GIST a randomised study in patients with inoperable or metastatic disease explored doses of 400 - 600mg and reported a response rate of > 50% in each arm plus disease stabilisation and an improvement in performance status. Large randomised trials have subsequently been performed, comparing 400 with 800mg/day. The first to report indicates that the larger dose is associated with improved progression-free survival, although it is not yet known whether or not this will translate into a difference in overall survival. The most common KIT mutation involves exon 11 and is associated with a statistically significant better response and prognosis compared with other mutations or no detectable mutations. Mutational analysis is likely to become increasingly important in the selection of patients for neoadjuvant and adjuvant treatment and in helping to understand the nature of acquired resistance.

Antineoplastic Agents↗
PubMed2004

Efficacy and safety of trastuzumab.

The human epidermal growth factor receptor (HER) 2 is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Targeted therapy directed against this receptor has been developed in the form of a humanised monoclonal antibody, trastuzumab. This antibody has shown activity as a single agent in metastatic breast cancer both prior to chemotherapy and in heavily pretreated patients. A pivotal Phase III trial has demonstrated that its use in combination with an anthracycline or paclitaxel results in a significant improvement in survival, time to progression, and response. This has recently been reinforced by another trial with docetaxel. The HER2 status of a tumour is a critical determinant of response to trastuzumab-based treatment. Those that express HER2 at the highest level on immunohistochemistry (IHC), 3+, derive more benefit from treatment with trastuzumab than those with overexpression at the 2+ level. Benefit correlates best with tumours that are positive on fluorescence in situ hybridisation for HER2, regardless of IHC status. Treatment with trastuzumab is generally well tolerated with a low incidence of adverse events. Some patients may experience fever, chills, dyspnoea and pain, particularly with the first administration. Unexpectedly, cardiac toxicity has developed in some patients treated with trastuzumab, and this has a higher incidence in those treated in combination with an anthracycline. 'Cross-talk' between the oestrogen receptor and HER2 pathway has stimulated interest in using trastuzumab in combination with endocrine therapy. Current clinical trials are investigating the role of this agent in the adjuvant setting.

Antibodies, Monoclonal↗