Long-term outcomes and predictive factors for survival in premenopausal breast cancer treated with tamoxifen
| ISRCTN | ISRCTN12474687 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12474687 |
| Secondary identifying numbers | SBII:2 BioLong (1) |
- Submission date
- 01/11/2019
- Registration date
- 06/12/2019
- Last edited
- 02/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
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
Contact information
Scientific
Box 177
Lund
SE-221 00
Sweden
 ORCID ID |
0000-0001-7515-3130 |
|---|---|
| Phone | +46706720923 |
| lisa.ryden@med.lu.se |
Scientific
Department of Clinical Sciences Lund
Division of Oncology and Pathology
Lund University
Medicon Village
Building 404
Scheelevägen 8
Lund
22363
Sweden
| ORCID ID |
0000-0002-7880-2981 |
|---|---|
| Phone | +46 10 24 229 00 |
| christine.lundgren@med.lu.se |
Study information
| 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 |
| Participant information sheet | No participant information sheet available |
| Scientific title | Premenopausal patients randomized to adjuvant tamoxifen versus not: long-term survival in relation to genomic and tumor related factors |
| Study 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) |
| 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 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 500 |
| Total final enrolment | 564 |
| Participant inclusion criteria | Patients radically operated for invasive breast cancer stage II in the SBII:2 trial |
| 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
Lund
SE-221 00
Sweden
Sponsor information
Government
Box 177
Lund
SE-221 00
Sweden
| Phone | +46-46-2220000 |
|---|---|
| mikael.bodelsson@med.lu.se | |
| Website | https://www.medicine.lu.se/ |
"ROR" |
https://ror.org/012a77v79 |
Funders
Funder type
Government
No information available
No information available
No information available
No information available
No information available
No information available
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| 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 |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
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
Editorial Notes
02/10/2023: Publication reference added.
04/01/2023: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2022 to 31/12/2024.
2. The overall trial end date has been changed from 31/12/2022 to 31/12/2024 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 30/11/2020 to 31/12/2025.
10/05/2022: Publication reference added.
29/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
09/12/2019: Internal review.
06/12/2019: Uploaded protocol (not peer reviewed)
04/11/2019: Trial’s existence confirmed by Lund ethics committee
