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 physician-recommended 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.

Trial registration: "Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry" (NCT02670577) retrospectively registered on Jan 27, 2016.

Keywords: 70-GS; 80-GS; BluePrint; Breast cancer; Clinical utility; Diagnostic test; MammaPrint; Molecular profiling.

Fig. 1

Consort diagram of IMPACt study. Numbers of patients excluded from the primary objective study population and reasons for exclusion are indicated

Fig. 2

Treatment Plan and Physician Confidence Prior to 70-GS Results. Numbers and percentages of clinically low risk and high risk patients whose physicians planned, prior to receiving 70-GS results, to include or not include chemotherapy as part of their treatment plans are shown (a). There were 176/ 227 clinically low risk patients whose physicians did not include chemotherapy in their treatment plans and 82/131 clinically high risk patients whose physicians included chemotherapy in their treatment plans. Physician confidence in treatment plans, prior to 70-GS result, is shown as a percentage of plans that include chemotherapy or not in each confidence category (complete, high, neutral, and low/very low, p < 0.0001, (b))

Fig. 3

Change in treatment recommendations from pre-70-GS to post-70-GS results and patient agreement with physician recommendations. Numbers of patients in each category (70-GS High Risk, 70-GS Low Risk, pre-70-GS treatment recommendation, and post-70-GS treatment recommendation) are shown for clinically low risk (a, n = 227) and clinically high risk (b, n = 131) patients. Treatment recommendations are indicated as inclusion or exclusion of chemotherapy (CT). Patient agreement/disagreement with physician-recommended treatment plan is shown in (c). Numbers of patients in each category are indicated, as well as the clinical/genomic risk stratification of the patients in each subset

Fig. 4

Physician Change in Confidence in Treatment plans post 70-GS Result. Change in physician confidence in treatment plan shown in a Sankey diagram, with physician-reported confidence (complete, high, neutral, or low/very low) in patient treatment plans prior to receiving 70-GS result on the origins on the left side of the diagram, and the changes in those responses following 70-GS results on the endpoints, shown on the right side of the diagram (a). Numbers in each confidence category prior to 70-GS (left side) and post-70-GS (right side) are given. The width of each flow line is proportional to the number of responses in that category. In b, Post 70-GS confidence categories are shown as a percent of each combined risk category (clinical risk, determined by MINDACT criteria, combined with genomic risk, determined by 70-GS result). Numbers of patients in each category are as follows: 160 C-low/G-low, 64 C-high/G-low, 67 C-low/G-high, 67 C-high/G-high