The Danish Breast Cancer Group (DBCG) was established 45 years ago and has a tradition for conducting practice-changing clinical trials. From a radiation therapy (RT) perspective, pivotal trials were initiated in the 1980-ies, and the results have had national and international implications documenting the gains and risks from RT of early breast cancer.
In our millennium, the focus for breast cancer RT trials has been more on fractionation and irradiated volume than on the indication for RT, although the latter is also of increasing interest recently.
There has been a long-standing concern over toxicity from moderate hypofractionation in the DBCG fueled by bad experiences from the days of hypofractionation before the DBCG 82b&c trials. When randomised trials from Canada and the UK demonstrated relatively good results from breast cancer RT based on 40-42.5 Gy / 15-16 fractions for whole breast irradiation, the DBCG decided to reintroduce moderate hypofractionation for early breast cancer through randomised clinical trials. Thus, the DBCG Hypo and DBCG PBI (partial breast irradiation) trials were initiated in 2009, and planned for inclusion of patients in Denmark, however, with a potential for international participation. In addition, the primary endpoints were selected to allow for accrual of patients in very few departments, such that they could be completed even if only the department of the principal investigator participated. Fortunately, the collaboration across Denmark and internationally turned out very fruitful, and accrual was even higher than expected.
Alongside the two mentioned trials, all DBCG departments gradually shifted to CT-based breast cancer RT, leading to a need of CT-based guidelines for target volume delineation. Such guidelines were also of need at the ESTRO courses for multidisciplinary therapy of breast cancer, leading to development of national and international guidelines for target volume delineation of early breast cancer.
When knowing the early results from the DBCG Hypo, the randomised DBCG Skagen trial 1 was launched in 2015 to explore the safety of moderate hypofractionation for loco-regional breast cancer RT in node-positive patients. As part of the Skagen trial 1, the ESTRO consensus for target volume was pivotal to ensure a validation of the usefulness of the ESTRO consensus. In 2018, after knowing the early results from the DBCG PBI trial, the DBCG initiated the DBCG RT Natural trial to test the risk of recurrence in relatively low-risk patients being randomised between PBI versus no RT. Most recently, the DBCG Proton trial was launched in 2020 to investigate the potential of proton therapy for breast cancer patients where standard RT planning leads to high radiation doses to heart and/or lung. In the DBCG Proton trial, the randomisation is between photon versus proton therapy. Together with the DBCG Surgical Committee, the DBCG RT Committee has designed a national trial to introduce immediate reconstruction for selected high-risk breast cancer patients. Unfortunately, the DBCG RT Recon trial is only active in Copenhagen, and in that trial patients with indication for postmastectomy RT are invited to be randomised between immediate reconstruction versus delayed reconstruction.
Currently, the DBCG Hamlet trial is underway: to be irradiated or not to be irradiated, that is the question. The indication for breast cancer RT will be investigated in a randomisation between whole breast irradiation versus no RT for node-negative, hormone receptor positive breast cancer patients ≥55 years who do also accept systemic therapies.
Through these trials, the DBCG explores the limitations of moderate hypofractionation for early breast cancer, the irradiated volume, and the indication for RT in patients operated for early breast cancer. Despite the small size of Denmark, there is a willingness to collaborate in clinical trials, and all RT departments support and participate in most of the DBCG trials.