Diagnosis of axillary lymph node status in primary breast cancer without a surgical procedure
| ISRCTN | ISRCTN14341750 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14341750 |
| Protocol serial number | NILS 1.0 |
| Sponsor | Lund University |
| Funders | Lunds Universitet, South Swedish Health Care Region, Bröstcancerfonden, Familjen Erling Perssons Stiftelse, Vetenskapsrådet |
- Submission date
- 21/10/2018
- Registration date
- 23/11/2018
- Last edited
- 22/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Today, breast cancer is diagnosed at an early stage due to public screening mammography and increased awareness of the disease in the community. As a consequence of early diagnosis, tumor size at time of diagnosis has decreased and the risk of spread to the lymph nodes now affects less than 30% of all breast cancer patients. Despite this, all breast cancer patients undergo a surgical procedure, sentinel lymph node biopsy, to define if axillary lymph nodes are infiltrated by cancer cells. In more than 70% of these patients, there have no cancer infiltration in their axillary lymph nodes and therefore, the procedure has no benefit. Sentinel lymph node biopsy can lead to side-effects such as pain and swelling.
The aim of the study is to evaluate the capacity of patient related and tumor characteristics to determine whether the cancer has spread to the lymph nodes, so that low-risk groups can avoid sentinel node biopsy.
Who can participate?
Patients diagnosed with invasive breast cancer at any age scheduled for primary surgery and without clinically pathological lymph nodes
What does the study involve?
There is no direct involvement for participants. Instead, their medical records and data will be analysed by the study team and they will receive breast cancer treatment as usual.
What are the possible benefits and risks of participating?
As there is no direct involvement of participants and they will receive routine treatment, there are no known benefits or risks to participants taking part in this study.
Where is the study run from?
Skåne University Hospital (Lund and Malmö) (Sweden)
When is the study starting and how long is it expected to run for?
January 2008 to December 2022
Who is funding the study?
1. Lund Univerisity (Sweden)
2. The Swedish Breast Cancer Fund (Sweden)
3. South Swedish Health Care Region (Sweden)
4. Erling Persson Foundation (Sweden)
5. Vetenskapsrådet [Swedish Research Council] (Sweden)
Who is the main contact?
Professor Lisa Rydén
lisa.ryden@med.lu.se
Contact information
Scientific
Lund University, Medicon Village, Scheleevägen 2
Lund
SE-22381
Sweden
 ORCID ID |
0000-0001-7515-3130 |
|---|---|
| Phone | +46-706720923 |
| lisa.ryden@med.lu.se |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Observational prospective cohort study with retrospective estimation of nodal status |
| Secondary study design | Cohort study |
| Study type | Participant information sheet |
| Scientific title | NILS: Non-Invasive Lymph node Staging |
| Study acronym | NILS |
| Study objectives | Preoperatively available information on clinicopathological characteristics can aid in predicting nodal status in primary breast cancer |
| Ethics approval(s) | 1. Approved 15/08/2012, Lund University, ref: 2012/340 2. Approved 07/07/2019, Swedish Ethical Review Authority, ref: 2019-02139 3. Approved 15/02/2021, Swedish Ethical Review Authority, ref: 2021-00174 |
| Health condition(s) or problem(s) studied | Clinically node-negative primary breast cancer |
| Intervention | Current intervention as of 31/08/2021: Patients in this study are undergoing standard diagnostic work-up within the clinical pathway for breast cancer including a clinical examination, mammogram, ultrasound and core biopsy of the tumor before surgery. At time of surgery, they undergo standard procedure according to the multidisciplinary conference and the tumor and axillary nodes are pathologically examined. No extra diagnostic or interventional procedure is undertaken. Logistic regression and artificial neural network models are applied to predict nodal status from clinicopathological data. No follow-up data is extracted as this is an observational diagnostic trial. Separate cohorts will be used for validation of the nomogram and ANN models. _____ Previous intervention: Patients in this study are undergoing standard diagnostic work-up within the clinical pathway for breast cancer including a clinical examination, mammogram, ultrasound and core biopsy of the tumor before surgery. At time of surgery, they undergo standard procedure according to the multidisciplinary conference and the tumor and axillary nodes are pathologically examined. No extra diagnostic or interventional procedure is undertaken. Logistic regression and artificial neural network models are applied to predict nodal status from clincopathological data. No follow-up data is extracted as this is an observational diagnostic trial. |
| Intervention type | Other |
| Primary outcome measure(s) |
Current primary outcome measure as of 31/08/2021: |
| Key secondary outcome measure(s) |
False negative rate with negative predictive value of NPV max to 10% for prediction of N0, determined from sentinel node biopsy data after surgery |
| Completion date | 21/12/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 23400 |
| Key inclusion criteria | Current inclusion criteria as of 31/08/2021: 1. Invasive breast cancer 2. Clinically and ultrasound node-negative disease 3. Scheduled for primary surgery 4. Female _____ Previous inclusion criteria: 1. Invasive breast cancer 2. Clinically node-negative disease 3. Scheduled for primary surgery 4. Female |
| Key exclusion criteria | 1. Male 2. Previous ipsilateral breast or axillary surgery 3. Previous neoadjuvant therapy 4. Palpable axillary lymphadenopathy 5. No axillary staging |
| Date of first enrolment | 01/01/2009 |
| Date of final enrolment | 21/12/2022 |
Locations
Countries of recruitment
- Sweden
Study participating centre
22185
Sweden
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets analysed during the current study will be available upon request from Lisa Rydén (lisa.ryden@med.lu.se) for baseline characteristics after approval from regulatory authorities responsible of data sharing for Region Skåne. The dataset is kept pseudoanonymised and will be available for any researcher with a documented scientific experience in prediction models of nodal status in order to validate other prediction models generated from their own data. GDPR requires an informed consent to state that data sharing with third party is to be performed and this can be arranged by an opt-out procedure. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Nomogram initial results | 01/10/2017 | Yes | No | |
| Results article | Artificial neural network modeling initial results | 21/06/2019 | 24/06/2019 | Yes | No |
| Results article | Retrospective validation study | 16/01/2024 | 22/01/2024 | Yes | No |
| Basic results | 02/11/2018 | 24/04/2019 | No | No | |
| Other publications | Nomogram validation | 01/05/2021 | 31/08/2021 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN14341750_BasicResults_02Nov2018.pdf
- uploaded 24/04/2019
Editorial Notes
22/01/2024: Publication reference added.
21/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 21/12/2022.
2. The overall end date was changed from 31/12/2022 to 21/12/2022.
31/08/2021: The following changes have been made:
1. The ethics approval has been updated.
2. The overall trial end date has been changed from 31/12/2018 to 31/12/2022 and the plain English summary updated accordingly.
3. The intervention has been changed.
4. The primary outcome measure has been changed.
5. The participant inclusion criteria have been changed.
6. The participant age group has been changed from 'All' to 'Adult'.
7. The target number of participants has been changed from "800" to "800 primary cohort, 600 and 22000 in validation cohort" and the previously added final enrolment number removed.
8. The recruitment end date has been changed from 31/12/2012 to 31/12/2022.
9. Vetenskapsrådet (Swedish Research Council) has been added as a funder and the plain English summary updated accordingly.
10. Publication reference added.
11. The intention to publish date has been changed from 31/03/2019 to 31/03/2023.
24/06/2019: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the results publication.
24/04/2019: The basic results of this trial have been uploaded as an additional file.
