ORCID Profile
0000-0001-9598-7159
Current Organisations
St George Hospital
,
Saint George Private Hospital
,
Royal Australasian College of Physicians
,
Sutherland Hospital
,
University of New South Wales
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Diverse Presentations of Carcinoma Erysipelatoides from a Teaching Hospital in Australia
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/134938
Abstract: Inflammatory breast carcinoma is a rare form of advanced breast cancer which carries a poor prognosis, even with treatment. Diagnosis is reached on clinical and pathological grounds however, due to its propensity to mimic other conditions, it may often be delayed or missed by attending physicians. This case series describes four patients seen at our institution with a diagnosis of inflammatory breast cancer 3 patients had a history of previously treated breast malignancy. In these cases, the emergence of a new breast lesion evaded initial diagnosis due to incomplete initial physical examination, falsely reassuring imaging results, lack of recognition that a cellulitis picture can resemble metastatic carcinoma, and inconclusive initial biopsy sections. These obstacles to achieve diagnosis serve to further worsen the prognosis by delaying the initiation of multimodality treatment which can improve survival. The purpose of our paper is to increase awareness among breast cancer specialists of the importance of undressing the patient for basic clinical examination of the breasts, recognition of the appearances of this type of local recurrence of breast cancer, and not to rely purely on ultrasound and mammography due to delay in diagnosis in some of our local cases. Sometimes deeper sections and repeat biopsies are needed to make the diagnosis.
Pilot study evaluating the role of cardiac magnetic resonance imaging in monitoring adjuvant trastuzumab therapy for breast cancer
Publisher: Wiley
Date: 12-01-2012
DOI: 10.1111/J.1743-7563.2011.01462.X
Abstract: To explore the incidence of subclinical cardiotoxicity in women treated with adjuvant trastuzumab in the early breast cancer setting using cardiac magnetic resonance imaging (cMRI). The cardiac function and myocardial tissue characteristics of 25 women who had completed adjuvant trastuzumab therapy greater than 6 months previously was evaluated using MRI and comparing this with symptoms and routine echocardiography. Evidence of myocardial tissue damage was seen in two women in the absence of functional change or previous cardiac symptoms. Tissue characterization using cMRI may provide a useful tool in defining trastuzumab induced cardiotoxicity.
CDK4/6 inhibitor plus endocrine therapy for hormone receptor‐positive, HER2‐negative metastatic breast cancer: The new standard of care
Publisher: Wiley
Date: 2021
DOI: 10.1111/AJCO.13555
Extramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancer—a potential diagnostic pitfall
Publisher: Wiley
Date: 04-2009
Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio
Publisher: Elsevier BV
Date: 12-2020
Phase II, double-blind, randomized trial of capecitabine plus enzastaurin versus capecitabine plus placebo in patients with metastatic or recurrent breast cancer after prior anthracycline and taxane t
Publisher: Springer Science and Business Media LLC
Date: 03-09-2010
DOI: 10.1007/S10549-010-1152-0
Abstract: Capecitabine is frequently used in the treatment of recurrent rogressive metastatic breast cancer (MBC) after prior anthracycline and taxane therapy. With the intention of improving the efficacy of single agent capecitabine, we initiated a randomized, double-blind, placebo-controlled Phase II study of the novel serine/threonine kinase inhibitor enzastaurin in combination with capecitabine in a heavily pretreated patient population. Patients received capecitabine 1,250 mg/m(2) twice daily plus enzastaurin 500 mg/day, or capecitabine plus placebo. The capecitabine was administered for the first 14 days of each 21 day cycle. The primary outcome was progression-free survival (PFS) using the log-rank test (1-sided significance level of 0.20). Of 109 patients assessed for eligibility, 85 were enrolled, randomized, and treated (42 and 43 patients in each respective treatment group). The study was terminated early following a preplanned futility analysis. Median PFS (95% CI) was 2.8 (2.1-4.6) months with capecitabine plus enzastaurin versus 4.3 (2.9-6.2) months with capecitabine plus placebo (adjusted hazard ratio: 1.728 [1.00-2.97] P = 0.048). Median overall survival (95% CI) was lower with capecitabine plus enzastaurin than with capecitabine plus placebo (9.9 [7.0-16.6] months vs 14.9 [9.9-19.3] months, P = 0.181). Grade 3/4 adverse events were more frequent with capecitabine plus enzastaurin (42.9% vs 32.6%). Given the lack of PFS benefit, capecitabine plus enzastaurin is unsuitable as therapy for patients with recurrent rogressive MBC after prior anthracycline and taxane therapy. This trial is registered on www.clinicaltrials.gov (identifier: NCT00437294).
Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study
Publisher: Elsevier BV
Date: 2021
Tumour Stroma Ratio Assessment Using Digital Image Analysis Predicts Survival in Triple Negative and Luminal Breast Cancer
Publisher: MDPI AG
Date: 13-12-2020
Abstract: We aimed to determine the clinical significance of tumour stroma ratio (TSR) in luminal and triple negative breast cancer (TNBC) using digital image analysis and machine learning algorithms. Automated image analysis using QuPath software was applied to a cohort of 647 breast cancer patients (403 luminal and 244 TNBC) using digital H& E images of tissue microarrays (TMAs). Kaplan–Meier and Cox proportional hazards were used to ascertain relationships with overall survival (OS) and breast cancer specific survival (BCSS). For TNBC, low TSR (high stroma) was associated with poor prognosis for both OS (HR 1.9, CI 1.1–3.3, p = 0.021) and BCSS (HR 2.6, HR 1.3–5.4, p = 0.007) in multivariate models, independent of age, size, grade, sTILs, lymph nodal status and chemotherapy. However, for luminal tumours, low TSR (high stroma) was associated with a favourable prognosis in MVA for OS (HR 0.6, CI 0.4–0.8, p = 0.001) but not for BCSS. TSR is a prognostic factor of most significance in TNBC, but also in luminal breast cancer, and can be reliably assessed using quantitative image analysis of TMAs. Further investigation into the contribution of tumour subtype stromal phenotype may further refine these findings.
Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JCHF.2019.04.014
Abstract: The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC). Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results. A total of 222 patients with early-stage human epidermal growth factor receptor 2-positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure cardiac death, arrhythmia, or infarction a decrease in LVEF of >15% from baseline or a decrease in LVEF of >10% to <50%. TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a "low-risk TRC score" to identify patients with low TRC incidence. Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS] NCT00858039).
Disseminated intravascular coagulation complicating diagnosis of ROS1‐mutant non‐small cell lung cancer: A case report and literature review
Publisher: Wiley
Date: 22-07-2021
Abstract: Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6–6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene‐addicted lung cancers, especially those containing ROS proto‐oncogene 1 ( ROS1 ) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1 ‐mutant non‐small‐cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of life‐threatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation.
Pegfilgrastim and darbepoetin alfa as haematopoietic support for adjuvant dose dense doxorubicin + cyclophosphamide-paclitaxel in early stage breast cancer patients – results from the ACCELERATE study
Publisher: Elsevier BV
Date: 04-2008
Small HER2-Positive Breast Cancer: Should Size Affect Adjuvant Treatment?
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CLBC.2014.12.012
Abstract: The adjuvant trastuzumab trials largely excluded women with small, node-negative, HER2-positive breast cancers. Accordingly, limited data exist regarding the effect of trastuzumab in the management of these patients. Our aim was to assess the outcomes of, and treatments administered to, women with small (≤ 2 cm), node-negative, HER2-positive breast cancer in 4 Australian cancer centers. A retrospective analysis of data on all women with node-negative, HER2-positive breast cancers ≤ 2 cm diagnosed between 1 January 2001 and 31 December 2011 and treated at 4 cancer centers in Sydney, Australia was undertaken. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). In total, 128 patients with node-negative, HER2-positive breast cancers ≤ 2 cm were identified. Of these, 83 women (65%) received adjuvant trastuzumab which, in 96% of cases, was in addition to adjuvant chemotherapy. At 3-year follow-up, the RFS was 100% and 79.2% and the OS was 100% and 92.6% for women treated with, and without, trastuzumab, respectively. There were 14 recurrence events and 6 deaths in the study population. There were no significant differences in RFS and OS for the 46 women treated with, or without, trastuzumab for those with tumors ≤ 1 cm. There is a growing body of evidence to support the use of adjuvant trastuzumab therapy in the management of small, node-negative, HER2-positive breast cancers. However, future studies with longer follow-up and prospective biomarker analysis might assist in clinical decision-making for this patient group.
Implementing patient question-prompt lists into routine cancer care
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.PEC.2011.04.020
Abstract: To examine the feasibility and acceptability of routine provision of patient question prompt lists (QPLs) to promote patient participation and patient-clinician communication in medical consultations. Four cancer centres across NSW, Australia (two rural, two urban) were invited to participate, involving distribution of QPLs to patients seeing a medical or radiation oncologist, or palliative care clinician. Patients rated their satisfaction after their next consultation. Cancer specialists provided their views at the end of the study. Sixty-four percent (389/606) of patients attending consultations received a QPL. Of patients offered a QPL (426), 91% accepted. Of 139 patients surveyed post-consultation, 89% reported reading the QPL and, of these, 44% referred to the QPL during the consultation at least once. All of 10 cancer specialists providing their views post-implementation reported that QPL implementation in routine practice was feasible and did not strain resources. Cancer patients and cancer specialists showed support for routine dissemination of the QPL. For successful implementation of evidence-based tools we recommend promotion by local clinical ch ions, negotiation with clinic staff about dissemination methods, raised patient awareness through on-site project facilitators, media, consumer and support groups, and availability of resources in hard copy and via online sources.
Survival prediction in triple negative breast cancer using multiple instance learning of histopathological images
Publisher: Springer Science and Business Media LLC
Date: 25-08-2022
DOI: 10.1038/S41598-022-18647-1
Abstract: Computational pathology is a rapidly expanding area for research due to the current global transformation of histopathology through the adoption of digital workflows. Survival prediction of breast cancer patients is an important task that currently depends on histopathology assessment of cancer morphological features, immunohistochemical biomarker expression and patient clinical findings. To facilitate the manual process of survival risk prediction, we developed a computational pathology framework for survival prediction using digitally scanned haematoxylin and eosin-stained tissue microarray images of clinically aggressive triple negative breast cancer. Our results show that the model can produce an average concordance index of 0.616. Our model predictions are analysed for independent prognostic significance in univariate analysis (hazard ratio = 3.12, 95% confidence interval [1.69,5.75], p 0.005) and multivariate analysis using clinicopathological data (hazard ratio = 2.68, 95% confidence interval [1.44,4.99], p 0.005). Through qualitative analysis of heatmaps generated from our model, an expert pathologist is able to associate tissue features highlighted in the attention heatmaps of high-risk predictions with morphological features associated with more aggressive behaviour such as low levels of tumour infiltrating lymphocytes, stroma rich tissues and high-grade invasive carcinoma, providing explainability of our method for triple negative breast cancer.
Abstract P4-15-02: Clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity: Results of CATS
Publisher: American Association for Cancer Research (AACR)
Date: 05-2015
DOI: 10.1158/1538-7445.SABCS14-P4-15-02
Abstract: Background: Adjuvant therapy for HER2-positive breast cancer (HBC) often comprises anthracyclines (A) followed by trastuzumab (T). Trastuzumab-related cardiotoxicity (TRC) is T’s primary toxicity, and led 15% of patients in NSABP-B31 to stop T early. Earlier detection of TRC might enable timely therapeutic intervention, lowering the number of patients ceasing T prematurely. Small, retrospective, unvalidated studies have proposed various markers as predictors for TRC. The Cardiotoxicity of Adjuvant Trastuzumab Study (CATS) aims to assess a panel of clinical, biochemical, and genomic/immunologic markers as predictors for TRC. Methods: HBC patients with a left ventricular ejection fraction (LVEF) ≥ 50% scheduled to receive adjuvant A followed by 12 months’ T were eligible. Serum N-terminal pro-B type natriuretic peptide (NT pro-BNP) and troponin I were measured centrally at baseline (T1), at completion of A (T2), and after 3 and 6 months of T. LVEF was measured at T1, T2, and then 3-monthly until completion of T. Germline SNPs in ERBB2 (V655I), FCGR2A (H131R), and FCGR3A (V158F) were assessed. TRC was defined as: cardiac death, NYHA class 3/4 heart failure, grade 3/4 arrhythmia/ischemia, drop in LVEF & % from baseline, or drop in LVEF of & % to & %. 1 patient with LVEF & % at T2 was excluded. Uni- and multivariate logistic regression were used to determine features associated with TRC. Serum markers were added to the model using forward selection. Results: 17 centers enrolled 222 patients (217 evaluable). Patient characteristics are shown. Baseline characteristicsAge [median (range), yrs]52 (28-77)Baseline LVEF [median (range)]64% (50-82%)Left-sided tumors [n(%)]105 (48%)History of hypertension [n(%)]48 (22%)Doxorubicin [n(%), median total dose]80 (37%), 242mg/m2Epirubicin [n(%), median total dose]137 (63%), 300mg/m2Concurrent taxane with T [n(%)]217 (100%) TRC occurred in 33 patients (15.2%). In multivariate models, lower baseline LVEF (OR 3.23 for a 5% lower LVEF, [95% CI 1.96-5.33], p& .0001) and greater absolute decline in LVEF from T1 to T2 (OR 3.25 for each 5% drop in LVEF, [95%CI 1.83-5.79], p& .0001] were each independent predictors of TRC. NT pro-BNP increased from T1 to T2 (median Δ=1.31pmol/L, p& .0001) and then fell to baseline levels. Troponin I increased from T1 to T2 in 64.5% of patients (p& .0001) and remained above baseline 6 months post-A (p& .0001). NT pro-BNP and troponin I at T1 were not predictive for TRC. There were trends for the absolute increase in NT-pro BNP and troponin I from T1 (pre-A) to T2 (post-A) to be associated with risk of TRC (p=0.08 and 0.09) in univariate analyses. Germline SNPs were not predictive of TRC. Conclusion: This is the largest prospective study analyzing predictors for TRC, and the first studying immune-related SNPs in this context. Consistent with the literature, lower LVEF at baseline increases risk of TRC. Previously unreported, the absolute decrease in LVEF after A is also predictive for TRC. The persistent elevation of troponin I 6 months after completing A demonstrates chronic cardiac stress during therapy. Ongoing modeling analyses (to be presented at the meeting) will determine whether longitudinal changes in serum biomarkers can predict subsequent development of TRC. Citation Format: Shom Goel, Hao Guo, William Barry, Bronwyn Murray, Jodi Lynch, Patricia Bastick, Lorraine Chantrill, Belinda Kiely, Richard Bell, Ehtesham Abdi, Josie Rutovitz, Ray Asghari, Anne Sullivan, Michelle Harrison, Maija Kohonen-Corish, Jane Beith. Clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity: Results of CATS [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13 San Antonio, TX. Philadelphia (PA): AACR Cancer Res 2015 (9 Suppl):Abstract nr P4-15-02.
Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer
Publisher: Springer Science and Business Media LLC
Date: 03-11-2021
DOI: 10.1038/S41598-021-01116-6
Abstract: Triple negative breast cancer (TNBC) comprises 10–15% of all breast cancers and has a poor prognosis with a high risk of recurrence within 5 years. PD-L1 is an important biomarker for patient selection for immunotherapy but its cellular expression and co-localization within the tumour immune microenvironment and associated prognostic value is not well defined. We aimed to characterise the phenotypes of immune cells expressing PD-L1 and determine their association with overall survival (OS) and breast cancer-specific survival (BCSS). Using tissue microarrays from a retrospective cohort of TNBC patients from St George Hospital, Sydney (n = 244), multiplexed immunofluorescence (mIF) was used to assess staining for CD3, CD8, CD20, CD68, PD-1, PD-L1, FOXP3 and pan-cytokeratin on the Vectra Polaris™ platform and analysed using QuPath. Cox multivariate analyses showed high CD68 + PD-L1 + stromal cell counts were associated with improved prognosis for OS (HR 0.56, 95% CI 0.33–0.95, p = 0.030) and BCSS (HR 0.47, 95% CI 0.25–0.88, p = 0.018) in the whole cohort and in patients receiving chemotherapy, improving incrementally upon the predictive value of PD-L1 + alone for BCSS. These data suggest that CD68 + PD-L1 + status can provide clinically useful prognostic information to identify sub-groups of patients with good or poor prognosis and guide treatment decisions in TNBC.
Related Organisations
Related Funding Activities
No related grants have been discovered for Jodi Lynch.