Intro text: 

Microarray In Node negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy

A prospective, randomised study comparing the 70-gene signature with the common clinical-pathological criteria in selecting patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes

Applications for access to data and residual biological material from MINDACT may be submitted throughout the year. More information and the application form can be found on http://www.eortc.org/data-sharing/ .

If you have any questions about the use of MINDACT data or residual biological material, please contact the study team at EORTC: mindactRP@eortc.be.

Node-negative and 1-3 lymph node positive breast cancer is a cancer that has not or only minimally spread to the surrounding lymph nodes and has a lower risk of recurrence. Patients with this type of cancer are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment.

The aim of MINDACT was to evaluate the utility of adding the 70-gene signature MammaPrint® to standard clinico-pathological criteria in order to identify those patients with early-stage breast cancer who can be safely spared adjuvant chemotherapy without this significantly affecting their risk of disease recurrence.

The project partners predicted that using MammaPrint® in combination with standard clinico-pathological criteria would result in a more accurate assessment of the risk of recurrence in early breast cancer patients than the usual clinical and pathological assessment. In particular, they predicted that in 10-20% of the women with node-negative and 1-to-3 node positive breast cancer chemotherapy – and the side-effects that come with it – could be safely avoided.

The study proved its main hypothesis and showed that using MammaPrint® had the potential to change the way doctors and patients make decisions about breast cancer. When analysing the data from all 6,693 patients with node negative and =<3 positive lymph nodes enrolled in MINDACT, the trial showed that taking treatment decisions based on MammaPrint® rather than on the basis of the common clinico-pathological factors led to 14% less chemotherapy being prescribed in this study. 

Among the 3,356 patients enrolled in the MINDACT trial who were categorised as having a high risk of breast cancer recurrence based on common clinico-pathological criteria (c-High), MammaPrint® identified 1,550 patients as having a low genomic risk. Not treating this group of patients with chemotherapy would amount to a 46% reduction in chemotherapy prescription. Five-year distant metastasis-free survival for this discordant c-High/g-Low group is in excess of 94%, whether patients received chemotherapy or not. Given the very good outcome without chemotherapy, the added value of chemotherapy in absolute numbers is small in these patients (1.5%), suggesting that chemotherapy could be safely omitted.

In short, MINDACT provides the highest level of evidence to show that using MammaPrint® in combination with clinico-pathological assessment can identify patients who might safely avoid chemotherapy, thereby substantially reducing the prescription of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer.

The primary results of MINDACT were published in 2016 in the New England Journal of Medicine.

The updated results of MINDACT with a median follow-up of 8.7 years support the 2016 findings and confirm the clinical utility of MammaPrint® to identify patients with early breast cancer who may safely avoid post-surgery chemotherapy. While they show a slightly larger distant metastasis-free survival for the discordant c-High/g-Low group, the estimated gain of 2.6% for chemotherapy administration in these patients remains small in light of the harmful side effects of the chemotherapy.

The long term follow-up also includes an exploratory analysis by age. The 70-gene signature test was shown to be particularly useful in decision-making for postmenopausal women within the c-High/g-Low group, for whom chemotherapy added no benefit. In younger women, chemotherapy may still add benefit, but this requires careful discussion between doctor and patient. 

The long term follow-up results were published in March 2021 in the Lancet Oncology.

Microarray analysis is a technology that reveals the individual genes expressed by a tumour and its potential aggressiveness. The MINDACT microarray test –MammaPrint® – examines 70 breast cancer genes that provide essential information to determine how breast cancer tumours are likely to behave (these genes are NOT hereditary breast cancer genes, but only those from the actual tumour). The result of the test is dichotomous; the tumour cells are classified as either low or high genomic risk. When the majority of these genes are inactive, the tumour is considered to represent a low risk of recurrence.

Women aged 18–70 years with operable, invasive breast cancer, with 0 to 3 positive lymph nodes, no distant metastases, and whose frozen tumour sample was collected.

Overall recruitment (completed): 6,693 patients between 2007 and 2011.

The trial is sponsored and run by the European Organisation for Research and Treatment of Cancer (EORTC) under the Breast International Group (BIG) umbrella, and a great many other partners, both from academia and the private sector, and including the breast cancer patient advocacy network Europa Donna. Agendia is the biotechnology company that developed MammaPrint®.

  • A tissue sample from the patient was sent to the laboratory where it was subjected to both clinico-pathological risk assessment using a modified Adjuvant!Online tool, and genomic risk assessment using the MammaPrint® test.
  • If both methods indicated a low risk of recurrence, chemotherapy was not recommended. If both methods suggested a high risk of recurrence, the patient was advised to have chemotherapy.
  • However, in cases where the tests disagreed, patients were randomly assigned to be treated either on the basis of the clinico-pathological assessment or on the basis of the MammaPrint® results.
  • All patients involved in the trial were closely monitored by doctors throughout the process and will be for at least 10 years.
  • The over 52,000 samples derived from these patients, including tissue, blood and serum, are stored in a biorepository for long-term storage, enabling future research.
  • Over 11,000 patients were screened between 2007 and 2011.
  • A “pilot” involving the first 800 patients enrolled was completed in 2010, indicating the viability of the trial despite its complex logistics.
  • Recruitment of 6,693 patients was completed in July 2011.

The primary results were published in 2016 in the New England Journal of Medicine.

112 hospitals in 9 countries are participating in this trial through 7 BIG collaborative groups (EORTC, BOOG, GOIRC, NCRI, SOLTI, Unicancer, WSG).

MINDACT was supported by grants from the European Commission Framework Programme VI (FP6-LSHC-CT-2004-503426, “TRANSBIG Network of Excellence”), the Breast Cancer Research Foundation, Novartis, F. Hoffman La Roche, Sanofi-Aventis, Eli Lilly, Veridex, the U.S. National Cancer Institute, the European Breast Cancer Council-Breast Cancer Working Group (BCWG grant for the MINDACT biobank), the Jacqueline Seroussi Memorial Foundation (2006 JSMF award), Prix Mois du Cancer du Sein (2004 award), Susan G. Komen for the Cure (SG05-0922-02), Fondation Belge Contre le Cancer (SCIE 2005-27), Dutch Cancer Society (KWF), Association Le Cancer du Sein, Parlons-en!, the Brussels Breast Cancer Walk-Run and the American Women’s Club of Brussels, NIF Trust, Deutsche Krebshilfe, the Grant Simpson Trust and Cancer Research UK. This trial was also supported by the EORTC Charitable Trust. Whole genome analysis was provided in kind by Agendia. Total funding: approx. EUR 47 million.

ClinicalTrials.gov identifier: NCT00433589