MammaPrint guides treatment decisions in breast Cancer: results of the IMPACt trial

Abstract

Background: Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients. Methods: IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status. Results: The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physicianrecommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status. Conclusions: The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results.

The cost impact of unselective vs selective MammaPrint testing in early-stage breast cancer in Southern Africa

“…This is consistent with recent publication of the IMPACT trial by Soliman et al where the majority (77.5%) of the patients were cLow. 34 Some reasons for this might be the fee-for-service structure or the concern over litigation due to perceived undertreatment but these remain speculative. Currently guideline 1.7, published by ASCO on the use of biomarkers, advises against the use of MP in cLow patients.…”

Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine

“…Multigene tests provide detailed insight into cancer biology with simultaneous information on expression of relevant, prognostic fundamental genes. Some assays are already used in diagnosis, as prognostic panels and for the prediction of treatment effects (mostly adjuvant or neoadjuvant systemic therapy) [ 173 ].…”

Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives

“…Similar results were reported in node-negative [ 113 ] but also node-positive early breast cancer [ 114 , 115 , 116 ]. The Prosigna © PAM50 [ 117 , 118 , 119 , 120 ] and EndoPredict © [ 121 ] assays also demonstrated a 20–35% decreasing of chemotherapy indications in HR+/HER2− early breast cancer.…”

“…Several of the above-mentioned decision-making studies evaluated as secondary objectives the psychological impact of gene expression signatures. They demonstrated an improvement of physicians’ confidence regarding treatment recommendations [ 111 , 113 , 119 , 120 ], as well as a decreasing in patients anxiety and decisional conflict [ 112 , 116 , 117 , 118 , 120 , 121 ]. However, at least two studies showed that an unfavorable genomic result might increase anxiety, especially in a two-step decision making process [ 118 , 121 ].…”