Norwegian Breast Cancer Group (NBCG) was founded in its present organization in 1988, but the seed was planted already in 1979. At that time a meeting was held at The Norwegian Radium Hospital dealing with multicenter studies in malignant diseases with a special emphasis on breast cancer. A committee consisting of breast surgeons, pathologists, radiologists and oncologists was established to produce the first national guidelines for the treatment of breast cancer, as well as to initiate and run clinical studies. The guidelines were published in 1981 and were named “The blue book” after the color of the cover. In the years to come, several studies testing both chemotherapy and endocrine treatment in adjuvant and metastatic setting were conducted.
In 1988 the NBCG got its present structure with some minor modifications. Breast surgeons and breast oncologists from university clinics in the four health regions of Norway formed the core of the organization. In addition, surgeons and oncologists from each of the 5 health regions were represented, as well as one (later two) pathologist, one (later two) radiologist and one geneticist. In the later years, a plastic surgeon was also included in NBCG. Today, the steering committee consists of 30 members. The members elect an executive committee consisting of 5 persons, which is responsible for preparing topics to and executing the decisions taken by the steering committee, in addition to “day-to-day” management of NBCG.
NBCG revised the clinical guidelines at regular intervals (1988, 1992, 1994, 1998, 2000, 2003) and worked hard to start multicenter studies in breast cancer treatment within Norway. The steering committee of NBCG meets at a minimum biannually, whereas the executive committee has regular meetings in addition to this. Several working groups (surgical-, medical oncology-, radiotherapy-, pathology groups) has been established to draft recommendations and facilitate the work and discussion in NBCG concerning treatment, diagnostics, and research. NBCG has over the last 16 – 17 years adjusted and revised the NBCG guidelines for treating breast cancer every 6 months. This work has ensured a uniform approach to treatment of the individual patient all over Norway. NBCG was instrumental in writing the first National guidelines for breast cancer published by The Norwegian Directorate of Health and is performing revisions one or two times a year. NBCG was also instrumental in writing “The Breast cancer patient care pathway” (“Pakkeforløp for brystkreft”) securing patients the right to be diagnosed and treated within a certain timeframe. The organizational structure of NBCG has in the years after 1988 been blueprinted by most of the tumor groups in Norway (GI-cancer, lung cancer etc.). NBCG has also had a key role in establishing a National Breast Cancer Quality Registry, both as an initiator, planner and creator, – in close collaboration with the Cancer Registry of Norway. This Registry can now be used both to monitor the quality of diagnosis and treatment of breast cancer in Norway, to run decision impact studies and to provide clinicopathological data to clinical and translational studies.
During the years, the group has focused on breast cancer research in several ways. Studies have been initiated where NBCG was the key initiator and executive board for the studies. During the years, more commonly key clinical scientists (many being members of the NBCG) has presented ideas or protocol drafts for studies to NBCG, followed by a collaborative discussion, initiation and execution of the studies. The involvement from NBCG in most of these studies has been instrumental to achieve participation from hospitals all over the country securing both recruitment and study availability for the patients. In the later years, NBCG has also focused on facilitating inclusion in other breast cancer studies in Norway, although outside NBCGs responsibility (including several industry-sponsored trials). An overview (with inclusion/exclusion criteria) of all ongoing studies in Norway (with regular updates) has been established on NBCG’s website, also including an overview based on the clinical situation for the individual patient (see nbcg.no). All new proposed clinical studies (either investigator-initiated or industry-sponsored, irrespective of being suitable as an NBCG study, are presented at the steering committee meeting. Therefore, NBCG has a key role to inform about, discuss, facilitate initiation of and support Norwegian studies of breast cancer in general, as well as being an active part in conducting NBCG studies. In addition, NBCG collaborate with the Scandinavian breast group, Breast International Group (NBCG is a member) as well as other profiled international study groups, in conducting international multicenter trials. Important international multicenter studies could also be strongly supported by NBCG but staying outside the “NBCG umbrella”. These studies are not presented in the following. The list of publications with a significant contribution from NBCG, is presented below. Many of the studies have also produced additional manuscripts not referred in the list. However, as there are translational sub-studies, spin-off sub-studies or updates where the contribution by NBCG as a group is minimal, these have been omitted.
Brief overview of the core study activities:
The first trials (Studies before NBCG-numbering was started) tested chemotherapy and endocrine treatment in metastatic breast cancer. Thereafter, the first NBCG-numbered trials (NBCG 1 – 3) studied the effect of various adjuvant endocrine treatments of breast cancer. Furthermore, NBCG has tested the clinical benefit of adjuvant treatment with aromatase inhibitor (NBCG/Exe 027), the side effects of aromatase inhibitors versus placebo (NBCG/Exe 031). NBCG also participated in the multicenter trial testing estrogen substitution after breast cancer (NBCG/HABITS). The NBCG5 study tested bisfosfonate (clodronate) as part of adjuvant treatment. Several studies of chemotherapy both in the adjuvant and metastatic setting have been conducted through the years. In collaboration with the Scandinavian Breast Group, high dose chemotherapy and autologous stem cell support was tested against dose-escalated FEC chemotherapy as adjuvant treatment in high-risk breast cancer patients (NBCG/SBG9401). In a different study, docetaxel was tested against methotrexate/5FU in anthracycline-resistant metastatic breast cancer (NBCG/SBG9404). In Norway, weekly paclitaxel versus docetaxel three-weekly was studied in advanced breast cancer (NBCG10). As a part of large international studies, NBCG has participated in several trials testing HER2-directed (targeted) adjuvant treatment added to chemotherapy (trastuzumab vs control; trastuzumab vs lapatinib vs trastuzumab/lapatinib)(NBCG/HERA; NBCG12/ALTTO; NBCG13/NeoALTTO). NBCG has had a significant focus on participating in and/or support studies of neoadjuvant treatment, in order to perform in-depth molecular studies of the effect of various systemic treatments on the primary tumor, aiming at identifying tumor signatures/factors associated with resistance or sensitivity to antracyclins, taxans, cyclophosphamide, carboplatin, targeted treatments (HER2-directed, PARP-inhibition, anti-angiogenic treatments)(NBCG6/NeoTAX: recruitment completed, analyses ongoing; NeoAVA: recruitment completed, analyses ongoing; PETREMAC: ongoing; I-BCT: ongoing). Extending the studies of (neo)adjuvant treatment, NBCG has also been importantly involved in conducting a study to test the effect of secondary adjuvant treatment of patients with presence of single disseminated tumor cells in the bone marrow 8-9 months after anthracycline-containing chemotherapy (NBCG9/SATT: recruitment completed, analyses ongoing). Concerning radiotherapy, a study of hypo-fractionated locoregional treatment and integrated boost in breast cancer is conducted by some of the NBCG investigators in collaboration with an international radiotherapy group (SKAGEN1: ongoing). In collaboration with IBCSG, NBCG participates in the POSITIVE trial, testing abruption of endocrine adjuvant treatment to allow pregnancy (NBCG16/IBCSG 48-14: ongoing). Studies of check-point blockade in advanced breast cancer is the focus of two recently launched Norwegian studies, testing immunogenic chemotherapy (liposomal doxorubicin 2qw + oral cyclophosphamide 2/4 weeks) +/- azetolizumab (anti-PD-L1) in triple negative breast cancer (NBCG17/ALICE) and immunogenic chemotherapy +/- nivolumab (anti-PD1) and low dose ipililumab (anti-CTLA4)(NBCG18/ICON). Aiming at primarily reducing overtreatment with adjuvant chemotherapy and establishing molecular breast cancer profiling within all Norwegian health regions, two large NBCG studies will open fall 2018, using Prosigna test for classification of patients into refined prognostic groups, – with participation from 15 hospitals in Norway (NBCG19/EMIT1 for node negative; NBCG20/OPTIMA for node positive in collaboration with the UK OPTIMA study group). In addition, a new NBCG supported neoadjuvant study is planned to be launched early 2019 (PETREMAC2). A list of the studies is provided below.
In conclusion, NBCG has through both its work with national clinical guidelines and its fight for the patients’ right to be treated according to these guidelines, as well as the focus on research and conducting clinical trials, established itself as a beacon in the field of breast cancer in Norway.