This year’s theme of World Cancer Day is “Together, all our actions matter”.

The Breast International Group (BIG)’s large global network of over 50 academic breast cancer research groups is at the fore of today’s breast cancer research.

Founded on the idea that working together internationally is essential to making strides towards curing breast cancer, BIG’s clinical trials have led to practice-changing achievements, paving the way towards more personalised treatment of breast cancer.

Together for better treatments

A number of BIG’s 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 the cancer coming back or affecting a patient’s quality of life.

The use of cutting-edge genomic tests is closely linked to some of these “de-escalation” studies.

None of BIG’s achievements would be possible without the willingness to work together.

To test new treatments with enough patients to be confident about the results, clinical research should not be limited to one institution, or even one country.

The single strongest opportunity for success comes from 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.

Therefore, BIG thinks globally and acts locally, helping breast cancer patients from all over the world.

BIG’s de-escalation studies

BIG’s de-escalation studies contribute to breast cancer treatments being tailored more precisely to individual patient needs.

Today, four large international long-term breast cancer de-escalation trials are being run or about to be launched under the BIG umbrella: 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-EBC-Decrescendo-2020).

Important results from the DCIS study (ductal carcinoma in situ), 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 an invasive breast cancer but if left untreated, it may turn into an 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 are 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.

In the MINDACT study, carried out by the European Organisation for Research and Treatment of Cancer (EORTC) in close collaboration with BIG in 9 countries throughout Europe, researchers 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 showed their cancer was unlikely to come back.

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. 

In the EXPERT trial (public name: 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, 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.

Long-term persistence and resilience are needed in academic research

For over 20 years, BIG has been conducting global breast cancer clinical trials and research programmes.

Despite the Covid-19 pandemic and all the challenges it poses, BIG’s network has continued its efforts to advance breast cancer research, demonstrating persistence and resilience, which is needed when conducting large international academic trials. 

BIG trials also follow patients long after the experimental treatment ends, with the aim to detect long-term side effects, improve treatment therapies and patients’ quality of life.

Over 30 clinical trials or research programmes are being run or are under development under the BIG umbrella at any one time. Since 1999, more than 95,000 patients have paticipated in BIG's studies.

Source: BIG