New genetic test reduces chemotherapy use in patients with early‐stage breast cancer

Abstract

A new genetic test called MammaPrint (Agendia Inc USA, Irvine, Calif.) identified a large group of patients with early-stage breast cancer for whom 5-year distant metastasisfree survival was the same regardless of whether they received adjuvant chemotherapy, according to results from a randomized phase 3 clinical trial. The patients in the study population were considered to be at high risk of disease recurrence based on clinical and biological criteria. Results of the trial, known as MINDACT (Microarray In Node-negative and 1-3 positive lymph node Disease may Avoid ChemoTherapy), were presented at the American Association for Cancer Research Annual Meeting 2016, which was held April 16 to 20, 2016, in New Orleans, Louisiana. Most oncologists currently make recommendations for adjuvant chemotherapy based on common clinical and biological criteria such as patient age and disease stage and grade, as well as hormonal receptor and human epidermal growth factor receptor 2 status. The trial results provide evidence that using MammaPrint could change clinical practice by reducing the use of adjuvant chemotherapy and sparing many patients from an aggressive treatment they will not benefit from, says Martine Piccart, MD, PhD, who presented the data and is head of the medicine department at the Jules Bordet Institute in Brussels, Belgium. For the trial, Dr. Piccart and her colleagues at 111 centers in 9 countries enrolled 6693 women who had undergone surgery for early-stage breast cancer. All patients were categorized as being at low or high risk of disease recurrence in 2 ways: 1) through analysis of tumor tissue using MammaPrint to determine the genetic risk of occurance (G-low or G-high); and 2) using Adjuvant! Online, a tool that calculates the risk of breast cancer recurrence based on common clinical and biological criteria (C-low or C-high). Among the 3356 patients in the MINDACT trial who were categorized as being at high risk of disease recurrence based on common clinical and pathological criteria (C-high), treatment based on MammaPrint results reduced chemotherapy prescriptions by approximately 46%. The 5-year distant metastasis-free survival rate for the discordant G-low/C-high group was reported to be greater than 94% regardless of whether patients received chemotherapy. Of the total number of patients enrolled in the MINDACT trial, approximately 14% were able to avoid chemotherapy by using the test to assess risk when compared with using traditional clinical assessments. Participants were then divided into 4 groups: those with a low risk of disease recurrence by both assessment methods, those with a high risk of disease recurrence by both assessment methods, and patients with a high and low risk of disease recurrence based on MammaPrint and Adjuvant! Online findings. Patients in the low/low group were assigned to no chemotherapy whereas those patients in the high/high group received adjuvant chemotherapy. Patients in the other 2 groups were randomly assigned to receive either chemotherapy or no chemotherapy. In addition to being what to the authors' knowledge is the first prospective, randomized controlled clinical trial of a breast cancer recurrence assay with level 1A clinical evidence and the first prospective translational research study of this size among patients with breast cancer to report the results of a primary objective, the trial has created a huge resource for future research, Dr. Piccart says. She explains that participant tumor samples, blood samples, and clinical outcomes data could be used to gain a substantially better understanding of the biology of breast cancer.