The role of molecular genetic testing in modern breast heath management

Kotze, Maritha J.; Malan, Jacques; Pienaar, R.; Apffelstaedt, Justus

doi:10.1080/20786204.2005.10873286

Cited by 5 publications

(1 citation statement)

References 14 publications

(11 reference statements)

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“…[14] The first step to incorporate gene expression profiling into clinical management of early-stage breast cancer patients in SA involved a feasibility study of the surgical procedure for specimen collection for the MammaPrint test. [15] The 70-gene MammaPrint test initially required a fresh tumour biopsy taken during surgery for microarray analysis, which was placed into a preservative solution and shipped to the reference laboratory at room temperature. Since the beginning of 2012, the option of using FFPE tumour tissue has also become available for the MammaPrint test.…”

Section: Discussionmentioning

confidence: 99%

MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer

et al. 2013

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Corresponding author: M J Kotze (maritha@sun.ac.za)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.

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Section: Discussionmentioning

confidence: 99%

MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer

et al. 2013

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CYP2D6 genotyping and use of antidepressants in breast cancer patients: test development for clinical application

Merwe

Bouwens

Pienaar³

et al. 2012

Metab Brain Dis

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Approximately 25 % of clinically important drugs and numerous environmental carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and concomitant use of tamoxifen (TAM) with certain antidepressants may increase recurrence risk in breast cancer patients due to reduced enzyme activity. In this study we determined the appropriateness of adding CYP2D6 genotyping to the breast cancer genetic testing options already available in South Africa, which include BRCA mutation screening and transcriptional profiling to assess estrogen receptor (ER) status. A total of 114 South African breast cancer patients, including 52 Caucasian and 62 Coloured (Mixed ancestry), and 63 Caucasian control individuals were genotyped for the most common inactivating allele (CYP2D6*4, rs3892097) previously identified in the CYP2D6 gene. In the initial validation data set consisting of 25 Caucasian and 62 Coloured patients, the CYP2D6*4 allele frequency was significantly higher in Caucasian compared to Coloured patients (24 % vs. 3 %, p < 0.001), similar to previous findings in the general South African population. Extended CYP2D6 genotyping was subsequently performed in an implementation data set of 27 Caucasian breast cancer patients, to determine the prevalence of depression and use of antidepressants in a clinical setting. A medical history of depression and/or use of antidepressants was reported in 37 % (10/27) of these breast cancer patients genotyped for CYP2D6*4. This translational research study has led to increased awareness among clinicians of the potential benefits of CYP2D6 genotyping to facilitate prevention of cumulative risk in a high-risk genetic subgroup of breast cancer patients considered for concomitant treatment of TAM and antidepressants that may reduce enzyme function.

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