Plain English Summary
Background and study aims
Breast cancer accounts for 1/3 of all malignant diagnosis among females world-wide and is often detected in an early stage. The 5-years survival of breast cancer is about 90%, both due to early screening detection and adjuvant therapy. Despite this, breast cancers might develop recurrence throughout the 20 years after diagnosis. For premenopausal women, breast cancer is a leading cause of death and patients are still being under- and over-treated due to imperfect models to predict outcomes. The possibility to de-escalate therapy, without detrimental effect on survival, is warranted. A majority of breast cancer tumours are sensitive to endocrine treatment, and the patients are generally recommended adjuvant endocrine therapy alone or with additional chemotherapy. Tamoxifen is the most recommended oral drug as adjuvant endocrine therapy in premenopausal women.
This study aims to analyse tissue samples taken during an earlier trial and relate their characteristics to the long-term outcomes in the patients who took part in the earlier trial
Who can participate?
Participants from the earlier SBII:2 trial (1986-1991)
What does the study involve?
Tissue samples collected during the original SBII:2 trial will be analysed and their characteristics compared to the long-term outcomes of the patients
What are the possible benefits and risks of participating?
None
Where is the study run from?
Skåne University Hospital, Sweden
When is the study starting and how long is it expected to run for?
May 2018 to December 2024
Who is funding the study?
Governmental funding for clinical research within the Health Care Sector
Who is the main contact?
Prof. Lisa Rydén
lisa.ryden@med.lu.se
Dr Christine Lundgren
christine.lundgren@med.lu.se
Study website
Contact information
Type
Scientific
Contact name
Prof Lisa Rydén
ORCID ID
http://orcid.org/0000-0001-7515-3130
Contact details
Box 177
Lund
SE-221 00
Sweden
+46706720923
lisa.ryden@med.lu.se
Type
Scientific
Contact name
Dr Christine Lundgren
ORCID ID
http://orcid.org/0000-0002-7880-2981
Contact details
Department of Clinical Sciences Lund
Division of Oncology and Pathology
Lund University
Medicon Village
Building 404
Scheelevägen 8
Lund
22363
Sweden
+46 10 24 229 00
christine.lundgren@med.lu.se
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
ClinicalTrials.gov number
Nil known
Secondary identifying numbers
SBII:2 BioLong (1)
Study information
Scientific title
Premenopausal patients randomized to adjuvant tamoxifen versus not: long-term survival in relation to genomic and tumor related factors
Acronym
SBII:2 BioLong
Study hypothesis
Comprehensive genomic and histopathological characterization of primary tumours can improve prediction of long-term prognosis and tamoxifen response in premenopausal patients
Ethics approval(s)
1. Approved 02/02/2017 Lund ethics committee (Box 133, 221 00, Lund; +46 2224180; eva.elvstrand@epn.lu.se), ref: 2015/6
2. Approval for long-term follow-up (Dnr number LU 2015/350) and genomic analyses (Dnr LU 2017/97)
Study design
Prospective-retrospective multicentre interventional randomized trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
No participant information sheet available
Condition
Premenopausal patients with invasive breast cancer
Intervention
The SBII:2 BioLong study is based on a prospective multicenter randomized clinical trial with > 30 years of follow-up of adjuvant tamoxifen
We will collect formalin-fixed archival tissue for gross evaluation of tumour-infiltrating lymphocytes, characterization of them and assessment of lymphovascular invasion in relation to the primary outcome. RNA and DNA will be extracted to enable RNA profiling by PAM50 and additional gene expression analysis with the 360TM panel. Mutational analysis is scheduled to include ESR1, p53, FGFR and PI3K to identify mutations of importance for tamoxifen resistance. The PAM50 and Risk of Recurrence has been thoroughly evaluated on tumors from postmenopausal patients allocated to hormonal therapy and provides additional prognostic information to conventional prognostic markers. Data on prognosis by PAM50 for premenopausal women is sparse and restricted to less than 10 years of follow up. Surrogate subtyping will additionally be compared to the intrinsic subtypes in terms of prognostic capacity
The original SBII:2 trial (1986-1991) is unique as its inclusion was restricted to premenopausal patients and the control arm includes patients without any systemic therapy, the intervention arm received two years of therapy with tamoxifen. The 30 years of follow-up regarding breast cancer mortality, breast cancer-free interval (BCFi) and distant recurrence-free interval (D-RFi) has been published. The SBII:2 BioLong study will add important genomic and histopathological data to improve our knowledge on factors of importance for long-term prognosis in premenopausal patients.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Tamoxifen
Primary outcome measure
BCFi (Breast cancer free interval) over the ~30-year period, measured using patient notes
Secondary outcome measures
1. D-RFi (Distant Recurrence Free interval) over the ~30-year period, measured using patient notes
2. Breast cancer mortality over the ~30-year period, measured using patient notes
3. Overall mortality over the ~30-year period, measured using patient notes
Overall study start date
01/09/2014
Overall study end date
31/12/2024
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients radically operated for invasive breast cancer stage II in the SBII:2 trial
Participant type(s)
Patient
Age group
Adult
Sex
Female
Target number of participants
500
Total final enrolment
564
Participant exclusion criteria
1. Postmenopausal status
2. Metastatic disease
Recruitment start date
01/05/2018
Recruitment end date
31/12/2024
Locations
Countries of recruitment
Sweden
Study participating centre
Skåne University Hospital
Box 177
Lund
SE-221 00
Sweden
Sponsor information
Organisation
Lund University
Sponsor details
Box 177
Lund
SE-221 00
Sweden
+46-46-2220000
mikael.bodelsson@med.lu.se
Sponsor type
Government
Website
ROR
Funders
Funder type
Government
Funder name
Governmental funding for clinical research within the Health Care Sector
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Fre Bertha Kamprad Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Anna och Edwin Bergers Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Gyllenstiernska Krapperup Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Futurum— the Academy for Health and Care
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Clinical Cancer Research Foundation in Jönköping
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The SBII:2 BioLong Study will continuously be presented at international congresses and in publications, we anticipate to publish the first report in 2020
Intention to publish date
31/12/2025
Individual participant data (IPD) Intention to share
No
IPD sharing plan
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 12/05/2019 | 06/12/2019 | No | No | |
| Interim results article | results on predictive value of tumour-infiltrating lymphocytes | 23/12/2020 | 29/12/2020 | Yes | No |
| Interim results article | PAM50 subtyping and ROR score add long-term prognostic information in premenopausal breast cancer patients | 09/05/2022 | 10/05/2022 | Yes | No |
| Interim results article | Relationship between tamoxifen treatment and breast cancer gene expression | 29/09/2023 | 02/10/2023 | Yes | No |
Additional files
- ISRCTN12474687_PROTOCOL_12May19.pdf uploaded 06/12/2019