LUGANO-MADRID – Even small tumours can be aggressive, according to a study in patients with early stage breast cancer that will be presented at the ESMO 2017 Congress in Madrid. (1) Researchers found that nearly one in four small tumours were aggressive and patients benefited from chemotherapy. Aggressive tumours could be identified by a 70-gene signature.
“Our results challenge the assumption that all small tumours are less serious and do not need adjuvant chemotherapy,” said lead author Dr Konstantinos Tryfonidis, a researcher at the European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
The MINDACT study is managed and sponsored by the EORTC in collaboration with the Breast International Group (BIG) and included 6,693 women with early stage breast cancer (lymph node negative or 1-3 lymph node positive). (2) As previously reported, MINDACT showed that around 46% of patients who were at high clinical risk for recurrence, defined using Adjuvant! might not require chemotherapy. (3) These women had a low genomic risk for recurrence according to MammaPrint, a genomic signature that assists in predicting clinical outcomes in women with early stage breast cancer. (3,4)
The sub analysis presented at ESMO 2017 included the 826 patients in MINDACT with a primary tumour size of less than 1 cm (pT1abpN0). Clinical and genomic risks were assessed and 196 patients (24%) were found to be at clinical low risk and genomic high risk. These patients were randomised to receive, or not receive, chemotherapy.
The researchers found that at five years, very few patients who received chemotherapy experienced disease relapses, showing high rates of distant metastases-free survival, disease-free survival and overall survival, which confirms that they derived benefit from chemotherapy.
“We found that nearly one in four patients with small tumours are at risk of distant metastases and do benefit from chemotherapy,” said Dr Fatima Cardoso, senior author of the study, Co-Principal Investigator of MINDACT and Director of the Breast Unit of the Champalimaud Clinical Centre, Lisbon, Portugal. “This was striking because based on clinical criteria alone you would say that these tumours are not aggressive and therefore patients do not need chemotherapy. But 24% of small tumours had an aggressive biology, which shows that not all small tumours are the same.”
Commenting on the results for ESMO, Dr Evandro de Azambuja, Head of the Medical Support Team, Academic Promoting Team, Jules Bordet Institute, Brussels, Belgium, said: “This study shows that it’s not only tumour size that is important for breast cancer patients but also tumour biology. All tumours in the study were small – less than 1 cm – and the lymph nodes were free of cancer (node negative), which in principle should be a signal of good prognosis. But nearly one in four patients – those identified as genomic high risk – derived benefit from chemotherapy.”
“Small node negative tumours can be very aggressive, even if they are classified as clinical low risk,” said de Azambuja. “Tumour biology needs to be taken into account when deciding adjuvant treatments in this patient population. One cannot forget the patient’s age, performance status, comorbidities and preferences during the discussion.”
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress
- 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 Proffered Paper Session ‘Breast cancer, early stage’ on Friday, 8 September 2017, 14:00 to 15:30 (CEST) in the Pamplona Auditorium.
- The MINDACT study is managed and sponsored by the EORTC in collaboration with the Breast International Group (BIG), Agendia, and many other academic and commercial partners, as well as patient advocates.
- 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.
- van de Vijver MJ, et al. A gene expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002; 347:1999–2009.
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Not all small node negative (pT1abN0) breast cancers are similar: Outcome results from an EORTC 10041/BIG 3-04 (MINDACT) trial substudy
K. Tryfonidis1, C. Poncet1, L. Slaets1, G. Viale2, F. de Snoo3, K. Aalders1, L. Van't Veer4, E. Rutgers5, M. Piccart6, J. Bogaerts1, F. Cardoso7
1Eortc, European Organisation for Research and Treatment of Cancer, Brussels/BELGIUM, 2Pathology, Istituto Europeo di Oncologia, Milan/ITALY, 3Medical, Agendia N.V, Amsterdam/NETHERLANDS, 4University Of California, University of California San Francisco, San Francisco/UNITED STATES OF AMERICA, 5Surgery, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam/NETHERLANDS, 6Medical Oncology, Institute Jules Bordet, Brussels/BELGIUM, 7Breast Unit, Champalimaud Foundation Cancer Center, Lisboa/PORTUGAL
Background: Adjuvant systemic therapy for pT1abN0 breast cancer is controversial, as these tumors overall have a low relapse risk. The best tool to identify a subgroup that would benefit from adjuvant treatment is unknown.
Methods: This subgroup included patients with pT1abN0 tumors enrolled in MINDACT who had both their genomic risk G (per MammaPrint®) & clinical risk C (per a modified version Adjuvant! Online) assessed. Patients characterized as low-risk in both assessments were spared chemotherapy (CT), while in those characterized as C&G high CT was advised. Discordant cases were randomized to receive CT based on the C or the G result. Here, we report the 5-year rates of distant metastasis-free survival (DMFS), distant metastases-free interval (DMFI) & overall survival (OS) for pT1abN0 patients who received or not CT based on their G or C risk result.
Results: 826/6693 (12.3%) patients with pT1abN0 tumors were enrolled in MINDACT. 310/826 (37.5%) were ≥ 60 years & 525/826 (63.6%) postmenopausal. 727/826 samples were reviewed by central pathology; 585/727 (80.5%) were invasive ductal, 662/727 (91.1%) ER positive, 46/727 HER2 positive (6.3%) & 81/727 (11.1%) were grade 3 tumors. IHC subtype classification identified 426/727 (58.6%) as Luminal A; 193/727 (26.5%) Luminal B; 38/727 (5.2%) Luminal B/HER2 positive; 8/727 (1.1%) HER2- positive; 37/727 (5.1%) triple-negative tumors. Almost all patients (820/826; 99.3%) were clinical low-risk (CL). Overall, 624/826 (75.5%) were CL/GL & 196/826 (23.7%) were CL/GH (5 patients were CH/GL, no cases were CH/GH, 1 missing). 5-year DMFS for patients with CL/GH pT1abN0 tumors who received CT was 97.3% (95% CI, 89.4-99.3) vs 91.4% (95% CI, 82.6-95.9) for those who did not. 5-years DMFI & OS for these patients treated with CT were 98.8% (95% CI, 91.9-99.8) & 98.5% (95% CI, 89.6- 99.8) vs 91.4% (95% CI, 82.6- 95.9) & 95.8% (89.1- 98.4%) respectively for those who did not receive CT.
Conclusions: Biological characteristics can be used as determinants of adjuvant CT administration for T1abN0 tumors. An important portion (23.7%) of these small tumors was CL but GH (MammaPrint®) risk and derived a benefit from CT
Clinical trial identification: The numbers below refer to the main MINDACT study: ClinicalTrials.gov number: NCT00433589 EudraCT number:2005-002625-31
Keywords: tumor biology, small breast tumors, MammaPrint, adjuvant chemotherapy
Disclosure: L. Van't Veer: LV reports personal fees and other support from Agendia NV outside the submitted work. Additionally LV is a co- inventor on a patent related to MammaPrint: Diagnosis and prognosis of breast cancer patients (WO2002103320, licensed to Agendia, NV).
M. Piccart: MP has a consulting or advisory role for Astra- Zeneca, MSD, Novartis, Pfizer, Roche- Genentech, Periphagen, Huya, Debiopharm, PharmaMar, Radius, and received funding for the research from most abovementioned companies.
F. Cardoso: Reported consultancy/ research grants from Astellas/ Medivation, Astra Zeneca, Celgene, Daiichi- Sankyo, Eisai, GE Oncology, Genentech, Glaxo Smith Kline (GSK), Macrogenics, Merck- Sharp, Merus BV, Novartis, Pfizer, Pierre- Fabre, Roche, Sanofi and Teva.
All other authors have declared no conflicts of interest.
I declare that some content of the abstract which I am submitting has already been published and /or presented at another event prior to ESMO 2017
The project had two parts. Part one was characterization of small tumours included in MINDACT where genomic per MammaPrint results of these otherwise considered low risk tumours were evaluated. We also validated the subtyping by using BluePrint and TargetPrint and concordance with the classical immunohistochemistry specifically for these tumours. Since the primary analysis of the main MINDACT was not publicly available at that time, this part was submitted and presented as a poster at SABCS 2014. The second and most important part of the project is the one submitted to ESMO 2017, which refers to the outcome results in terms of DMFS, DMFI and OS of these patients with small (below one centimetre) and node negative tumours based on treatment administered per clinical (modified Adjuvant! Online) or genomic (MammaPrint) risk assessment. All results in details of both parts will be presented at ESMO Congress 2017.