Breast Cancer Trials at EORTC

EORTC, the European Organisation for Research and Treatment of Cancer, is a multidisciplinary, pan European organisation that has been organising international trials for over 50 years. Its mission and vision is to improve cancer survival and quality of life of cancer patients. The EORTC, in collaboration with leading breast cancer specialists and radiation oncologists, has conducted major international clinical trials covering all areas of breast cancer care from early to metastatic disease.

Over 50,000 cancer patients have participated in breast cancer trials at EORTC. These include one of the largest EORTC studies (EORTC 10801 ⁽¹⁾), conducted in the 1980’s, comparing mastectomy with breast conserving therapy in operable breast cancer. Results showed that there was no difference between local recurrences in breast cancer conserving therapy compared to mastectomies, however there was a clear benefit to quality of life of the patient. The 20-year follow-up ⁽²⁾ of the EORTC 10801 trial, confirmed that breast conserving therapy could be offered as standard care to patients with early breast cancer, since long-term follow-up in this trial resulted in similar survival to that after mastectomy.

“This was the start of a series of landmark EORTC studies showing that women with early disease could be safely treated without necessarily undergoing drastic surgery such as a mastectomy”, says Saskia Litiere, leading author and statistician at EORTC.

EORTC has pioneered in studies aiming to reduce overtreatment of patients with early breast cancer. After the introduction of breast-conserving therapy, the effect of radiation therapy was studied in several trials including the EORTC 10981-22023 AMAROS⁽³⁾ trial which was practice changing. Patients with clinical T1–2 N0 primary breast cancer were randomly assigned to axillary radiotherapy or axillary lymph node dissection. Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control in 1425 patients.  Axillary radiotherapy resulted in significantly less morbidity including risk of lymphoedema.

EORTC has been an advocator of using molecular biology in clinical research and practice ⁽⁴⁾. It believes better selection of patients through biology leads to better outcomes. In the MINDACT⁽⁵⁾ (Microarray in Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy) study, which was a partnership between EORTC Breast Cancer Group, Breast International Group (BIG) and the transBIG consortium,  showed that around 46% of patients, who were at high clinical risk for recurrence, (defined using a modified version of Adjuvant! Online), may not require chemotherapy as these women had a low genomic risk for recurrence according to the 70-gene signature (MammaPrint). Therefore, chemotherapy with its toxic effects could be avoided in these patients.

“MINDACT was the first study which prospectively used a genomic test to identify those patients who are at a higher risk of relapse”, says Dr Konstantinos Tryfonidis, a clinical research physician at EORTC and author of the study, “thus sparing those patients with truly low risk from not only the short but from the long term toxicity of chemotherapy.”

In the era of precision medicine, EORTC and its investigators continue to strive to change daily practice and improve quality of life and outcomes of breast cancer patients. “EORTC has been instrumental in clinical breast cancer research,” says Dr. Etienne Brain, Chair of the EORTC Breast Cancer Group and a medical oncologist at Institut Curie in Saint-Cloud and Paris. “Multidisciplinary studies like the Breast Conserving Study, AMAROS and MINDACT really showcase EORTC’s excellence in the field.”

 ⁽¹⁾ Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. van Dongen JA, Bartelink H, Fentiman IS, Lerut T, Mignolet F, Olthuis G, van der Schueren E, Sylvester R, Winter J, van Zijl K.; J Natl Cancer Inst Monogr. 1992;(11):15-8.

⁽²⁾ Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial. Litière S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, Van Limbergen E, Baaijens MH, Bogaerts J, Bartelink H. Lancet Oncol. 2012 Apr;13(4):412-9. doi: 10.1016/S1470-2045(12)70042-6. Epub 2012 Feb 27.

⁽³⁾ Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. Epub 2014 Oct 15.

⁽⁴⁾ How can innovative forms of clinical research contribute to deliver affordable cancer care in an evolving health care environment? Burock S, Meunier F, Lacombe D. Eur J Cancer. 2013 Sep;49(13):2777-83. doi: 10.1016/j.ejca.2013.05.016. Epub 2013 Jun 15.

⁽⁵⁾ 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, Glas AM, Golfinopoulos V, Goulioti T Knox S, Matos E, Meulemans B, Neijenhuis PA, Nitz U, Passalacqua R, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Sotiriou C, Stork L, Straehle C, Thomas G, Thompson AM, van der Hoeven JM, Vuylsteke P, Bernards R, Tryfonidis K, Rutgers E, Piccart M; MINDACT Investigators. N Engl J Med. 2016 Aug 25;375(8):717-29. doi: 10.1056/NEJMoa1602253.