BIG’s global de-escalation trials focus on optimising breast cancer treatment

January 28, 2021 0 By FM

The Breast International Group (BIG), a not-for-profit organisation for academic breast cancer research groups from around the world, is paving the way towards more personalised treatment of breast cancer with its large network of over 50 academic breast cancer research groups.

A number of BIG’s de-escalation trials aim to test the possibility to safely reduce the amount and/or the length of some breast cancer treatments or avoid them entirely without increasing the risk of recurrence. The use of cutting-edge genomic tests is closely linked to some of these studies.

BIG’s de-escalation studies contribute to breast cancer treatments being tailored more precisely to individual patient needs. The researches rely on combining resources and multi-disciplinary expertise from around the globe to establish research priorities, improve collaboration, and reduce unnecessary duplication of effort to generate results more quickly.

Currently, four large international long-term breast cancer de-escalation trials are being run or about to be launched under the Breast International Group’s umbrella, which includes: DCIS (BIG 3-07 / TROG 07.01), MINDACT (BIG 3-04 / EORTC 10041), EXPERT (BIG 16-02 / ANZ 1601) and DECRESCENDO (BIG 19-02 / IJB-EBCDecrescendo-2020).

DCIS trial

Results from the ductal carcinoma in situ (DCIS) study, run in 11 countries around the world, showed that individualising radiotherapy for women with DCIS of the breast reduces recurrence after surgery.

DCIS is a condition in which abnormal cells are contained within the milk ducts of the breast. It is not invasive breast cancer but if left untreated, it may turn into invasive breast cancer.

Presented last December at the San Antonio Breast Cancer Symposium, a leading annual international breast cancer congress, the study reported that after breast conserving surgery, higher radiation doses to the part of the breast where the DCIS was found, in addition to radiotherapy of the whole breast, significantly reduced its risk of returning in patients with higher-risk DCIS. Compared to 5 weeks of whole breast radiotherapy, the study also shows that the shorter, more convenient 3 weeks of radiotherapy did not increase recurrence.

Tailoring radiation doses and number of treatments to the recurrence risks in patients undergoing radiotherapy for DCIS after surgery is of intense international interest. These results will likely have a significant impact on how patients with DCIS are best managed worldwide. It could also lead to better use of healthcare resources by minimising over or under-treatment of patients with DCIS.

The DCIS study was activated in Australia and New Zealand in 2007, and internationally in 2009. It is run under the BIG umbrella and Trans-Tasman Radiation Oncology Group (TROG) Cancer Research is the coordinating group and study sponsor.

MINDACT trial

The MINDACT study is carried out by the European Organisation for Research and Treatment of Cancer (EORTC) in close collaboration with BIG in 9 countries throughout Europe. The study showed that up to 46% of high-risk patients with early stage breast cancer could avoid chemotherapy and its likely side effects if a sophisticated tumour genomic test (MammaPrint) showed their cancer was unlikely to recur.

The study, published in 2016 in the New England Journal of Medicine, demonstrated the importance of moving towards using the biological characteristics of a tumour to help safely exclude the need for a treatment which has previously been thought necessary.

In 2020, results of the longer follow-up of patients participating in the MINDACT study confirmed the utility of the MammaPrint test and the possibility to substantially and safely de-escalate the use of post-surgery chemotherapy for some groups of patients, thereby sparing many from an unpleasant treatment and its short and long-term side effects.

EXPERT trial

In the EXPERT trial (BIG radio tuning), BIG, together with Breast Cancer Trials Australia & New Zealand (BCT-ANZ), is studying whether some patients with low risk early breast cancer could be spared radiotherapy after breast conserving surgery. As in MINDACT, a genomic test on breast cancer tumours is being used to determine the risk of the cancer coming back. In patients at low risk of recurrence, the combination of standard radiotherapy and hormone treatment is being compared with hormone treatment alone.

The results of the EXPERT trial, which will be run in 9 countries around the globe, could influence how 2 in 5 women with breast cancer are treated. If the study proves that certain patients do not need radiation therapy, many women affected by this disease may be spared its potential side effects, and healthcare systems could also make significant savings.

DECRESCENDO trial

DECRESCENDO, an international BIG study in collaboration with the Clinical Trials Support Unit of the Jules Bordet Institute (IJB-CTSU, Brussels, Belgium), will shortly start recruiting patients in 12 countries to participate in the study.

While the MINDACT and EXPERT trials base de-escalation decisions on a test of tumour biology performed at study entry, in DECRESCENDO, clinicians will identify patients with lymph node-negative, hormone receptor-negative, HER2-positive breast cancer suitable for chemotherapy de-escalation based on their response to pre-surgical treatment. Those whose tumours show a complete response after surgery will be spared further chemotherapy and receive only anti-HER2 treatment.

Today, breast cancer represents 1 in 4 cancers diagnosed among women globally. About 1 in 8 women will be diagnosed with breast cancer over the course of her lifetime. Because of its high prevalence in low- and middle income countries, female breast cancer has now become the most commonly diagnosed cancer, even surpassing lung cancer.

For men, the lifetime risk of developing breast cancer is about 1 in 800. It has been estimated that by the end of 2020, approximately 2.3 million people, amongst whom about 1% were men, would have been diagnosed with breast cancer across the globe.

Female breast cancer incidence rates are the highest in Australia/New Zealand (about 95%), Western Europe (about 90%), Northern America (about 90%), Northern Europe (about 86%) and Southern Europe (about 80%). These rates far exceed those for other cancers in both developed and developing countries, making it the most commonly diagnosed cancer in women: about one quarter of all new cancer cases worldwide.

It is also the leading cause of cancer death in women (1 in 6), and the fifth-leading cause of cancer mortality worldwide with an estimated 685,000 deaths per year, according to Globocan Report, December 2020.