Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer

Pohl, Heinrich; Kotze, Maritha J.; Grant, Kathleen A.; Merwe, Lize van der; Pienaar, Fredrieka M.; Apffelstaedt, Justus; Myburgh, Ettienne J.

doi:10.1111/tbj.12605

Cited by 13 publications

(14 citation statements)

References 9 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Published data from South Africa on 109 ER/PR-positive, HER2-negative tumors showed a high risk-to-low risk ratio of 39% versus 61%, 16 whereas 68% of patients in the current series were high risk on MP, indicating that FISH positivity might predict a higher likelihood of a high-risk result but has poor PPV for HER2E.…”

Section: Discussioncontrasting

confidence: 70%

“…On the basis of our findings in this study and the recent evidence from literature of the overestimation of HER2 positivity as determined by clinical guidelines, further evaluation of molecular subtyping in the work up of HER2-positive tumors should be considered, 33 including ER/PR-negative, cHER2-positive tumors < 10 mm. Institutional protocols, such as the MPA applied as a cost-saving strategy in the southern African context, 15 , 16 should be adapted to include patients with ER/PR-positive, cHER2-positive disease with limited nodal involvement to match the demographic characteristics of those reported in the MINDACT trial.…”

Section: Discussionmentioning

confidence: 99%

“…After an initial health economic assessment and the development of an MP pretest algorithm (MPA), 15 this technology was introduced for early-stage ER/PR-positive, HER2-negative tumors in South Africa; to date, 256 tests have been done. In a recent publication, Pohl et al 16 showed that MP altered the treatment decision in 52% of patients in this subgroup. With the recent publication of the results from the EORTC-10041/BIG-3-04 MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) trial, the safety of omitting adjuvant chemotherapy in low-risk tumors, as determined by MP, has been well established.…”

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

Myburgh

Langenhoven

Grant

et al. 2017

JGO

Self Cite

View full text Add to dashboard Cite

PurposeHuman epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping.MethodsClinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor–positive and/or progesterone receptor–positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study.ResultsThe median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal (P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors (P = .0002; 95% CI, 0.40 to 1.06).ConclusionOf the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value.

show abstract

Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

Myburgh

Langenhoven

Grant

et al. 2017

JGO

Self Cite

View full text Add to dashboard Cite

show abstract

“…Integration of these results into treatment decision may lead to a change in therapy in one of every two early-stage breast cancer patients treated in South Africa. 28 In the present study, the molecular subtype based on BP was used as an indicator of the expected response to therapy. The Luminal type of breast cancer is expected to respond to endocrine therapy, whereas the Basal subtype is inherently resistant to endocrine therapy.…”

Section: Discussionmentioning

confidence: 99%

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Grant¹,

Myburgh²,

Murray³

et al. 2019

S. Afr. J. Sci.

Self Cite

View full text Add to dashboard Cite

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 (pless than 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. Significance: Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results. Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping. Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status. Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.

show abstract

“…ER, PR and HER2 status provide useful parameters for selection of patients eligible for transcriptional gene profiling, as evidenced in SA breast cancer patients referred for microarray analysis. Pohl et al [17] demonstrated a change in chemotherapy treatment in 52% of SA patients with early-stage breast cancer by using a newly developed microarray pre-screen algorithm to facilitate risk assessment beyond standard pathology and clinical prediction tools.…”

Section: Single-gene Testing Of Founder Mutations and Snpsmentioning

confidence: 99%

Application of advanced molecular technology in the diagnosis and management of genetic disorders in South Africa

Kotze

2016

S Afr Med J

View full text Add to dashboard Cite

Corresponding author: M J Kotze (maritha@sun.ac.za)Background. Genetic testing has evolved from a niche speciality for diagnosis of rare disorders and carrier screening to subtyping of complex medical conditions for targeted treatment. Genes causing monogenic disorders are well characterised, but risk management of multifactorial and polygenic disorders guided from the genetic background remains a challenge. Objective. This study describes the use of a pathology-supported genetic testing (PSGT) strategy designed to facilitate the move from single-to multi-gene testing and next-generation sequencing (NGS). Methods. In contrast to direct-to-consumer genetic testing, PSGT requires preselection of patients and data integration to determine current and future risk implications. To enable this process, a genomics database resource generated at the interface between the laboratory and clinic is available for clinical interpretation. Results. The PSGT approach led to the development of testing algorithms for improved clinical management of patients with cancer and other complex disorders with a genetic component. Local evidence is presented to demonstrate the application of PSGT for assessment of clinical relevance in patients with rare germline variants and functional polymorphisms underlying shared disease pathways. Conclusion. PSGT is ideally suited to serve as a screening step for microarray analysis and whole genome/exome sequencing as the next frontier in personalised medicine. Use of these advanced molecular technologies to match genotype with phenotype provides a resource for diagnosis and discovery over a lifetime.

show abstract

Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer

Cited by 13 publications

References 9 publications

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

Application of advanced molecular technology in the diagnosis and management of genetic disorders in South Africa

Contact Info

Product

Resources

About