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

Abstract

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.

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

“…Although some studies have demonstrated more high‐risk profiles in grade III infiltrating ductal carcinoma, we could not confirm these findings possibly due to small numbers, but noted this as the only subgroup to have more high than low‐risk MammaPrint results. In view of the excellent 5‐year outcome of low‐risk MammaPrint patients reported in the RASTER trial , our findings support extension of the locally developed MPA to include tumors larger than 4 cm for cost‐effective application microarray‐based gene profiling.…”

“…All patients with early‐stage breast cancer referred for MammaPrint testing between 2007 and 2014 were considered for inclusion in this study. MammaPrint risk scoring and ER, PR and HER2 receptor status were determined as previously described . Patients with incomplete clinical data, those without the option of endocrine therapy (ER/PR negative) or with HER2‐positive tumors or ≥4 nodes involved were excluded.…”

“…MammaPrint was introduced in South Africa in 2007 after FDA approval as supported by significant prognostic and predictive value in both the adjuvant and neo‐adjuvant settings. In conjunction with several health care funders, a MammaPrint Pre‐screen Algorithm (MPA) was formulated in 2009 to ensure cost‐effective use in South Africa . The aim was to identify patients who would be least likely to gain any benefit from chemotherapy limiting the test to untreated ER and/or PR positive, HER2 negative tumors ≤4 cm with <4 lymph nodes involved.…”

Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway

“…The index patient diagnosed with breast cancer at the age of 57 years was referred for the MammaPrint test performed in 2008. She forms part of the cases included in the study of Grant et al [10], who made special mention of this patient due to a low-risk MammaPrint result for both tumours (invasive ductal and lobular carcinoma). Her daughter was diagnosed with invasive ductal carcinoma approximately one year later, at the age of 29 years.…”

“…Grant et al [10] demonstrated the value of a pre-screen algorithm using PSGT to reduce chemotherapy overtreatment in South African breast cancer patients eligible for microarray analysis using the 70-gene MammaPrint test. A similar approach was validated in the Microarray in Node-negative Disease may Avoid ChemoTherapy (MINDACT) trial, which provided level 1A evidence for the clinical utility of MammaPrint.…”