BIG 3-04


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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

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.

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 study, whose primary results were published in 2016 in the New England Journal of Medicine, 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 was 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 was small in these patients (1.5%), suggesting that chemotherapy could be safely omitted.

Updated results of MINDACT with a median follow-up of 8.7 years presented at ASCO 2020 supported the 2016 findings and confirmed the clinical utility of MammaPrint® to identify patients with early breast cancer who may safely avoid post-surgery chemotherapy. While they showed 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 remained small in light of the harmful side effects of the chemotherapy.

De follow-upanalyse op lange termijn omvatte ook een verkennende analyse naar leeftijd. De 70-genen test bleek bijzonder nuttig te zijn bij de besluitvorming voor postmenopauzale vrouwen in de c-High/g-Low groep, voor wie chemotherapie geen voordeel opleverde. Bij jongere vrouwen kan chemotherapie nog een positief effect hebben, maar dit moet zorgvuldig worden besproken tussen arts en patiënt.  The 9-year long-term follow-up results were published in March 2021 in the Lancet Oncology.

  • 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.

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®.

  • 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.

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

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.

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