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John F.R. Robertson

Bio: John F.R. Robertson is an academic researcher from University of Nottingham. The author has contributed to research in topics: Breast cancer & Tamoxifen. The author has an hindex of 72, co-authored 283 publications receiving 19786 citations. Previous affiliations of John F.R. Robertson include Royal Derby Hospital & Nottingham City Hospital.


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Journal ArticleDOI
01 Jan 2007-Cancer
TL;DR: Triple‐negative breast cancer (estrogen receptor‐ negative, progesterone receptor‐negative, and HER2‐negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins.
Abstract: BACKGROUND. Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins. METHODS. In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long-term clinical follow-up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER-2, androgen receptor, epidermal growth factor receptor (EGFR), P-cadherin, E-cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior. RESULTS. Of informative cases, 16.3% were of the triple-negative phenotype. The majority of these tumors were grade 3, ductal/no-specific-type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E-cadherin, and positive expression of basal cytokeratins (basal phenotype), P-cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers. In the lymph node-positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node-negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup. Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant. CONCLUSIONS. The authors concluded that assessment of androgen receptor and basal phenotype, in addition to the established pathologic variables, mainly lymph node status and tumor size, can be used to select high-risk and low-risk patients at the time of primary surgery and can provide valuable information on treatment options in these triple-negative tumors. Cancer 2007. © 2006 American Cancer Society

1,211 citations

Journal ArticleDOI
TL;DR: Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.
Abstract: PURPOSE: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women. PATIENTS AND METHODS: This randomized, double-blind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor–positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability. RESULTS: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confiden...

836 citations

Journal ArticleDOI
TL;DR: Fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.
Abstract: PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one × 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P = .84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over ana...

654 citations

Journal ArticleDOI
Bernard Asselain, William E. Barlow, John M. S. Bartlett, Jonas Bergh, Elizabeth Bergsten-Nordström, Judith M Bliss, Francesco Boccardo, Clare Boddington, Jan Bogaerts, Gianni Bonadonna, Rosie Bradley, Etienne Brain, Jeremy P Braybrooke, Philippe Broët, John Bryant, Julie Ann Burrett, David Cameron, Mike Clarke, Alan S. Coates, Robert E. Coleman, Raoul Charles Coombes, C Correa, J. Costantino, Jack Cuzick, David N. Danforth, Nancy E. Davidson, C Davies, Lucy Davies, Angelo Di Leo, David Dodwell, Mitch Dowsett, Fran Duane, Vaughan Evans, Marianne Ewertz, Bernard Fisher1, John F. Forbes1, Leslie G. Ford, Jean-Claude Gazet, Richard D. Gelber, Lucy Gettins, Luca Gianni, Michael Gnant, Jon Godwin, Aron Goldhirsch, Pamela J. Goodwin, Richard Gray, Daniel F. Hayes, Catherine Hill, James N. Ingle, Reshma Jagsi, Raimund Jakesz, Sam James, Wolfgang Janni, Hui Liu, Z Liu, Caroline Lohrisch, Sibylle Loibl, Liz MacKinnon, Andreas Makris, Eleftherios P. Mamounas, Gurdeep S. Mannu, Miguel Martín, Simone Mathoulin, Louis Mauriac, Paul McGale, Theresa McHugh, Philip Morris, Hirofumi Mukai, Larry Norton, Yasuo Ohashi, Ivo A. Olivotto, Soon Paik, Hongchao Pan, Richard Peto, Martine Piccart, Lori J. Pierce, Philip Poortmans, Trevor J. Powles, Kathy Pritchard, Joseph Ragaz, Vinod Raina, Peter M. Ravdin, Simon Read, Meredith M. Regan, John F.R. Robertson, Emiel J. Th. Rutgers, Suzy Scholl, Dennis J. Slamon, Lidija Sölkner, Joseph A. Sparano, Seth M. Steinberg, Rosemary Sutcliffe, Sandra M. Swain, Carolyn W. Taylor, Andrew Tutt, Pinuccia Valagussa, Cornelis J.H. van de Velde, Jos van der Hage, Giuseppe Viale, Gunter von Minckwitz, Yaochen Wang, Zhe Wang, Xiang Wang, Timothy J. Whelan, Nicholas Wilcken, Eric P. Winer, Norman Wolmark, William C. Wood, Milvia Zambetti, Jo Anne Zujewski 
TL;DR: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT.
Abstract: Summary Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Funding Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.

611 citations

Journal ArticleDOI
TL;DR: Findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance, and are associated with good prognosis, ER positivity and older patient age.
Abstract: We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14 Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance

582 citations


Cited by
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Journal ArticleDOI
TL;DR: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.
Abstract: Purpose: To compare the clinical features, natural history, and outcomes for women with “triple-negative” breast cancer with women with other types of breast cancer. Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women9s College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. Results: The median follow-up time of the 1,601 women was 8.1 years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P P Conclusions: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.

3,945 citations

Journal ArticleDOI
01 Jun 2008-Chest
TL;DR: This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

3,944 citations

Journal ArticleDOI
TL;DR: Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer.
Abstract: Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.

3,125 citations

Journal ArticleDOI
TL;DR: This work discusses the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response, and many ERBB inhibitors used in the clinic.
Abstract: ERBB receptor tyrosine kinases have important roles in human cancer. In particular, the expression or activation of epidermal growth factor receptor and ERBB2 are altered in many epithelial tumours, and clinical studies indicate that they have important roles in tumour aetiology and progression. Accordingly, these receptors have been intensely studied to understand their importance in cancer biology and as therapeutic targets, and many ERBB inhibitors are now used in the clinic. We will discuss the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response.

3,083 citations

Journal ArticleDOI
01 Sep 2004-Chest
TL;DR: This article discusses the prevention of venous thromboembolism (VTE) and is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines.

3,064 citations