Not all small node-negative breast cancers are similar:

Intro text: 

Results of the MINDACT substudy presented at ESMO 2017​

Madrid, 8 September 2017 - Biological characteristics play a significant role in determining the aggressiveness of a tumour, even for small node-negative breast cancers, as confirmed by a substudy of the EORTC10041/ BIG 3-04 MINDACT trial presented today at the 2017 ESMO congress. (1)

“We already knew the importance of tumour biology to potentially indicate a more aggressive tumour behaviour irrespective of favorable clinical or pathological characteristics. In our analysis it was important, however, to see this fact in numbers, as one in four patients with small breast cancers appear to have an aggressive phenotype based on the 70-gene signature [Mammaprint®]”, said Kostantinos Tryfonidis, MD, Clinical Research Physician at the European Organisation for Research and Treatment of Cancer (EORTC), who presented the results on behalf of the TRANSBIG Consortium and MINDACT investigators.

A patient population usually at low-risk of cancer recurrence
Patients with small node-negative (pT1abN0) breast cancer tumours are usually considered to be a population with a low risk of breast cancer recurrence after surgery according to the common clinico-pathological criteria, and the benefit of treating these patients with adjuvant (post-surgery) chemotherapy is still controversial.

A 5-year analysis conducted on a subgroup of patients from the MINDACT study reports that not all small node-negative tumours are the same, some of them carrying cancer cells that are more aggressive according to their biological profile, which could increase the risk of breast cancer returning.

23.7% of the patients included in this analysis, and who were categorised as having a low risk of cancer recurrence based on common clinico-pathological criteria (CL) and a high risk as per genomic assessment (GH), seemed to derive a benefit from adjuvant chemotherapy. These findings confirmed that, for patients with small node-negative (pT1abN0) breast cancer, genomic characteristics represent a determining factor in identifying who might benefit from adjuvant (post-surgery) treatment with chemotherapy.


The study in detail
The study was conducted on a subgroup of 826 patients with small node-negative (pT1abN0) breast cancer who participated in MINDACT and were subjected to both clinico-pathological risk assessment (C) using a modified Adjuvant!Online tool, and genomic risk assessment (G) using the MammaPrint® 70-gene test. 

A majority of the patients (820) were categorised as having a low risk of breast cancer recurrence based on common clinico-pathological criteria (CL). The genomic test identified 624 patients as low-risk (GL) and 201 as high-risk (GH) of cancer returning. There were no cases of patients with a high risk according to clinico-pathological criteria (CH). Among all patients tested, 624 were CL/GL and 196 were CH/GH. Patients categorised as having a low risk of cancer recurrence according to both assessment methods (CL/GL group) were spared adjuvant chemotherapy.

The analysis focused on those patients who had a discordant risk assessment, i.e. CL/GH, and who were randomly assigned to receive chemotherapy based either on the C or G result. The 5-year distant metastases-free survival (DMFS) and overall survival (OS) was compared for this group of patients. Results indicated that 5-year DMFS was 97.3% for patients who received chemotherapy (CT) vs 91.4% for those who did not. 5-year OS was 98.5% for patients treated with CT vs 95.8% for those who were spared CT.

“Looking at these numbers, indeed we get a very strong signal of the benefit of chemotherapy in aggressive small breast tumours. However, we always need to keep in mind that this analysis was not powered to detect a difference in the efficacy of chemotherapy between these two groups of patients, nor was the overall MINDACT study designed to answer this question.”Dr Tryfonidis

MINDACT – a large academic effort towards de-escalating therapies
The MINDACT trial (Microarray INode-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy) is one of the main projects launched by the TRANSBIG Consortium. It involved 6,693 patients from 112 centres in 9 European countries through 7 BIG collaborative academic groups (EORTC, BOOG, GOIRC, NCRI, SOLTI, Unicancer, WSG).

MINDACT was designed to evaluate the utility of adding the 70-gene test (Mammaprint®) to the traditional method of assessing the likelihood of breast cancer recurrence for women with node-negative or 1-to-3 node positive breast cancer. 

The first results of MINDACT were published in 2016 in the New England Journal of Medicine (2) and showed that 46% of the early-stage breast cancer patients identified as high-risk for recurrence based on traditional factors were identified as low-risk when adding the MammaPrint test. The data demonstrated that chemotherapy provided no clinically meaningful benefit for these patients.

The MINDACT results give hope to many women with node-negative or 1-to-3 node positive early breast cancer: in future, it is possible that about half of the patients who would have received adjuvant chemotherapy in the past according to the traditional method of assessing recurrence risk might avoid this treatment and its side-effects.

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®.


Read more about MINDACT


1. Abstract 150O_PR ‘Not all small node negative (pT1abN0) breast cancers are similar: Outcome results from an EORTC 10041/BIG 3-04 (MINDACT) trial substudy‘ will be presented by Dr Konstantinos Tryfonidis during the Profferred Paper session Breast cancer, early on Friday, 8 September 2017, 14:00 to 15:30 (CEST) in the Pamplona Auditorium.

2. Cardoso F, et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. 2016;375(8):717–729. doi: 10.1056/NEJMoa1602253.