Browsing by Author "Wright, Colleen A."
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- ItemMammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer(Health & Medical Publishing Group, 2013-07-03) Grant, Kathleen A.; Apffelstaedt, Justus P.; Wright, Colleen A.; Myburgh, Ettienne; Pienaar, Rika; De Klerk, Manie; Kotze, Maritha J.Background. Clinical and pathological parameters may overestimate the need for chemotherapy in patients with early-stage breast cancer. More accurate determination of the risk of distant recurrence is now possible with use of genetic tests, such as the 70-gene MammaPrint profile. Objectives. A health technology assessment performed by a medical insurer in 2009 introduced a set of test eligibility criteria – the MammaPrint Pre-screen Algorithm (MPA) – applied in this study to determine the clinical usefulness of a pathology-supported genetic testing strategy, aimed at the reduction of healthcare costs. Methods. An implementation study was designed to take advantage of the fact that the 70-gene profile excludes analysis of hormone receptor and human epidermal growth factor receptor 2 (HER2) status, which form part of the MPA based partly on immunohistochemistry routinely performed in all breast cancer patients. The study population consisted of 104 South African women with early-stage breast carcinoma referred for MammaPrint. For the MammaPrint test, RNA was extracted from 60 fresh tumours (in 58 patients) and 46 formalin-fixed, paraffin-embedded (FFPE) tissue samples. Results. When applying the MPA for selection of patients eligible for MammaPrint testing, 95 of the 104 patients qualified. In this subgroup 62% (59/95) were classified as low risk. Similar distribution patterns for risk classification were obtained for RNA extracted from fresh tumours v. FFPE tissue samples. Conclusions. The 70-gene profile classifies approximately 40% of early-stage breast cancer patients as low-risk compared with 15% using conventional criteria. In comparison, more than 60% were shown to be low risk with use of the MPA validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer.
- ItemReclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis(Academy of Science of South Africa, 2019) Grant, Kathleen A.; Myburgh, Ettienne J.; Murray, Elizabeth; Pienaar, Fredrieka M.; Kidd, Martin; Wright, Colleen A.; Kotze, Maritha J.ENGLISH ABSTRACT: Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (p<0.001) for both receptors (ER: 0.34 and PR: 0.54). Concordance was shown in 61 (82%) cases and discordance in 13 (18%) of the 74 tumours tested. Further stratification by MP/BP identified 49 (66.2%) Luminal A, 21 (28.4%) Luminal B and 4 (5.4%) Basal-like tumours. Neither IHC nor TargetPrint could substitute BP subtyping, which measures the functional integrity of ER and can identify patients with false-positive tumours who are resistant to hormone therapy. These findings support the implementation of a pathology-supported genetic testing approach combining IHC and microarray gene profiling for definitive prognostic and predictive treatment decision-making in patients with early stage breast cancer.
- ItemUltrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis : a randomised pilot trial(BioMed Central, 2016) Franzen, Daniel; Diacon, Andreas H.; Freitag, Lutz; Schubert, Pawel T.; Wright, Colleen A.; Schuurman, Mace M.Background: The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region. Methods: In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard- size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB. Results: We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL ( n = 16; 40 %), tuberculous SPL ( n = 11; 27.5 %) and other benign SPL ( n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively ( p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing ( n = 2), blocked working channel ( n = 2), and arterial hypertension requiring therapeutic intervention ( n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively ( p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively ( p =0.95). Conclusion: UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only. Trial registration: ClinicalTrials.gov (Identifier: NCT02490059).