Among patients with early stage breast cancer who were considered at high risk for disease recurrence based on clinical and biological criteria, the MammaPrint genetic test identified a large group of patients for whom 5-year distant metastasis–free survival was equally good whether or not they received adjuvant chemotherapy (chemotherapy given post-surgery), according to results from the randomized, Phase III microarray in node negative disease may avoid chemotherapy (MINDACT) clinical trial to be presented at the AACR Annual Meeting 2016.
“At present, most oncologists make recommendations for adjuvant chemotherapy after considering common clinical and biological criteria such as patient’s age, and the stage and grade, as well as the hormonal receptor and HER2 status of his or her tumour,” said Martine Piccart, MD, PhD, head of the Medicine Department at the Jules Bordet Institute in Brussels, Belgium, and co-founder and chair of the Breast International Group (BIG). “The MINDACT trial results provide level 1A evidence that using MammaPrint could change clinical practice by substantially de-escalating the use of adjuvant chemotherapy and sparing many patients an aggressive treatment they will not benefit from.”
Among the 3356 patients enrolled in the MINDACT trial who were categorized as having a high risk of breast cancer recurrence based on common clinical and pathological criteria (C-high), treatment according to MammaPrint reduced the chemotherapy prescription by 46%. Five-year distant metastasis–free survival for the discordant G-low/C-high group is in excess of 94%, whether patients received CT or not.
Piccart explained that when considering all the patients enrolled in the MINDACT trial, 14% could avoid chemotherapy by using the 70-gene signature MammaPrint genetic test to assess risk compared with using traditional clinical assessments.
From 2007 to 2011, Piccart and colleagues at 111 centres in nine countries enrolled in the trial 6693 women who had undergone surgery for early stage breast cancer (out of 11,288 women screened). All participants were categorized as low or high risk for tumour recurrence in two ways: first, through analysis of tumor tissue using MammaPrint at a central location in Amsterdam; and second, using Adjuvant! Online, a tool that calculates risk of breast cancer recurrence based on common clinical and biological criteria.
The participants were then divided into four groups: 2745 were categorized as having low risk of recurrence by both risk-assessment methods (G-low/C-low), 1806 were categorized as having high risk of recurrence by both risk-assessment methods (G-high/C-high), 592 were categorized as having high risk of recurrence by MammaPrint and low risk of recurrence by Adjuvant! Online (G-high/C-low), and 1550 were categorized as having low risk of recurrence by MammaPrint and high risk of recurrence by Adjuvant! Online (G-low/C-high).
Patients categorized as G-low/C-low were assigned to no adjuvant chemotherapy while those categorized as G-high/C-high were assigned to adjuvant chemotherapy. Patients categorized as G-high/C-low or G-low/C-high were randomly assigned adjuvant chemotherapy or no adjuvant chemotherapy.
According to Piccart, the MINDACT trial is the first prospective randomized controlled clinical trial of a breast cancer recurrence genomic assay with level 1A clinical evidence and the first prospective translational research study of this magnitude in breast cancer to report the results of its primary objective. She added that the trial has also created a huge resource for future research, because research using the participants’ tumor samples, blood samples, and clinical outcomes data could allow us to gain a substantially better understanding of the biology of breast cancer.