PRECISION: PREvent ductal Carcinoma In Situ Invasive Overtreatment Now

NHS England (NHSE) and Kings College London (KCL) as joint Data Controllers require data form NHS England for the PRECISION: PREvent ductal Carcinoma In Situ Invasive Overtreatment Now study. PRECISION is an international collaboration building on multiple studies conducted in the UK, Europe and the US over the last two decades. It aims to reduce the burden of DCIS overtreatment through the development of tests to support decision-making by clinicians, without compromising the excellent outcomes for DCIS presently achieved.

The following PRECISION project objectives will be addressed in seven work packages (WP)

Ductal Carcinoma in situ (DCIS) and Lobular Carcinoma in situ (LCIS) are types of non-invasive breast cancer. DCIS has always been treated as cancer. It was virtually unknown before breast screening and now accounts for 25% of all ‘breast cancers’ detected. Over 51,000 women are diagnosed with DCIS each year in the USA, over 7,000 in the UK and over 2,300 in the Netherlands. DCIS is usually treated by surgery, radiotherapy and/or endocrine therapy, with the associated ongoing lifelong consequences of treatment. However, there is little evidence that treating low and intermediate grade DCIS is needed to save lives. The risk of developing contralateral breast cancer after DCIS is estimated at around 7% after 10 years in the US. Contralateral prophylactic mastectomies in women with breast cancer have increased over the years, showing that the risk of cancer in the contralateral breast is of increasing concern. However, previous studies have shown that prophylactic mastectomy infers only a small survival benefit in the absence of genetic mutations such as BRCA 1/2 (estimated 5% improvement in survival after 5 years). LCIS is diagnosed mainly as an incidental finding on breast cancer screening. LCIS accounts for 9% of in situ carcinomas, and between 1-2% of all breast cancer diagnoses, and although less common than DCIS, the incidence of LCIS has also increased following the introduction of the screening programme. LCIS is seen more as a risk factor for invasive disease than a precursor, and treatment for LCIS varies but increased surveillance after diagnosis of patients with LCIS is more common than surgical intervention, thus there is the possibility that some patients with LCIS are undertreated.

The data requested under this agreement will address some of work package 1 of the PRECISION Project’s overall objectives (This data is not currently held by the study):

• Improved characterization of DCIS, resulting in less unnecessary treatment of non-invasive DCIS.

• Identify risk factors that predispose to incidence of contralateral DCIS or invasive breast cancer.

• Compare the risk of contralateral breast cancer with the risk of ipsilateral breast cancer.

The aim of the analyses of the two datasets (non-invasive breast cancer primaries from NHSE Screening Sloane Project and invasive breast cancer primaries from NHSE National Disease Registration (NDRS) datasets) is to:

• assess the risk of contralateral breast cancer in patients with screen-detected DCIS compared to screen-detected invasive disease and see how treatment affects the risk of contralateral disease.

• determine whether developing contralateral breast cancer has a detrimental effect on outcome (development of metastatic disease, death from breast cancer).

• understand whether there are any pathological, radiological or other features that predict increased risk of developing contralateral breast cancer.

Contralateral means situated on the opposite side of the body. So in terms of breast cancer it means the opposite side to the side of the original primary tumour/cancer.

Prophylactic means a preventative measure. In terms of breast cancer someone might have prophylactic/preventative treatment to reduce the risk of developing breast cancer.

Prophylactic contralateral mastectomy is when someone has been diagnosed with primary breast cancer on one side and they have their opposite (i.e. contralateral) breast removed (i.e. mastectomy) as a preventative treatment (i.e. prophylactic) to reduce the risk of cancer in that breast.

This aspect of the PRECISION study will take the form of a retrospective cohort study. Data for screen-detected non-invasive breast cancer cases from the Sloane Project and data for screen-detected invasive breast cancer cases from the NDRS datasets with a minimum of 12 months of follow-up from the primary diagnosis date will be requested from NHSE, de-personalised and transferred securely to King’s College London for analysis by the Breast Cancer Genetics research group.

The following NHS England data will be accessed from NDRS:

NDRS Linked Hospital Episode Statistics (HES) Admitted Patient Care (APC)

NDRS Linked Hospital Episode Statistics (HES) Out Patient Care (OPC)

NDRS Systemic Anti-Cancer Therapy (SACT)

NDRS Radio Therapy Data Set (RTDS)

Cancer Registry Dataset

Cancer Waiting Times

The level of the data will be Pseudonymised

The data will be minimised as follows:

Inclusion Criteria

• Female

• Diagnosed with invasive breast cancer

• Age at DIAGNOSIS > 47

• Date of diagnosis is on or after 01 April 2003 up to 31 December 2017

• All ethnicities

• Screen detected

• Resident in England

Exclusion Criteria

• Index tumour with microinvasive morphology

• Previous registration of in situ breast tumours (ICD10 D05x) or invasive breast cancer (ICD10 C50x) – checking back as far as 1988

• Patients with distant spread of disease (metastasis) as part of their primary diagnosis should be excluded (M_BEST = M1 or stagebest = 4.)

• C50x or D05x diagnoses where LATERALITY = B or LATERALITY = L & R at the same time, and DIAGNOSISDATEBEST 6 months before or following DIAGNOSISDATEBEST of the index tumour

• Death Certificate Only cases

NHS England and KCL both rely on Article 6 (1) (e) of the UK GDPR as the lawful basis of processing - "processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller". This is justified through commissioning arrangements which link back to NHS England and other national bodies with statutory responsibilities to improve quality of health care services.

NHS England rely on Article 9(2)(h) of the UK GDPR as the legal basis for processing. "Processing is necessary for the purposes of preventive or occupational medicine, for the assessment of the working capacity of the employee, medical diagnosis, the provision of health or social care or treatment or the management of health or social care systems and services on the basis of Union or Member State law or pursuant to contract with a health professional and subject to the conditions and safeguards referred to in paragraph 3". NHS England are responsible for provision of health and social care, and management of systems and compliance. The processing meets Schedule 1 Part 1 paragraph 2 of the Data Protection Act 2018 as the processing is carried out by KCL, stored on servers at KCL.

KCL rely on UK GDPR Article 9 (2)(j): processing is necessary for scientific research purposes and shall be proportionate to the aim pursued, respect the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This data request is necessary to allow the study team to conduct analysis which supports the research objectives.

KCL is a controller who will also process the Data. There are no other processors involved.

Netherlands are noted in the overarching protocol for the study however for the purposes of this agreement and any data flows from NHSE they are not a Data Controller or Data Processor and will not have access to any data.

In line with the National data opt-out policy, opt-outs are not applied because the data is not Confidential Patient Information as defined in section 251 (10) and section 251 (11) of the National Health Service Act 2006.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data

Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out.

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

The Data is for the invasive breast cancer cases which are sourced from NDRS. The Non-invasive data has been sourced from the SLOANE cohort data held by NHSE Screening team. Both sources of data are meeting different requirements of the study. The two cohorts will not be linked together as part of the research any attempts to do so would be a breach of this DSA.

NHS England will provide the relevant records from the HES, RTDS, SACT, CWT and Cancer Reg datasets to KCL The data will contain no direct identifying data items. The data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient. Researchers from KCL will analyse the data supplied under this agreement for the purposes described above.

The data will be stored on servers at Kings College London.

The data will not leave England/Wales, at any time.

Only Substantive employees of KCL are permitted to access pseudonymised data flowing under this agreement.

All personnel accessing the data have been appropriately trained in data protection and confidentiality.

The data will not be linked with any other data.

There will be no requirement and no attempt to reidentify individuals.

For research articles, the consortium will follow ethical and data protection guidelines and respect the recommendations from the International Committee of Medical Journal Editors on Uniform Requirements for Manuscripts Submitted to Biomedical Journals, the Ethical Considerations in the Conduct and Reporting of Research, Authorship and Contributorship. The consortium will prioritise publications in open access journals to share as early and broadly as possible the research results with the community.

As a minimum requirement the consortium will follow the ‘green’ open access strategy and will ensure that the articles will be freely accessible at least after an embargo period defined by the publishers.

The proposed study results are hoped will increase understanding of in situ breast cancer through characterising the different types of Ductal carcinoma in situ (DCIS) ,identifying markers molecular targets, and producing risk stratification models, all of which can be used in future research.

Ductal carcinoma in situ (DCIS) which means that some cells in the lining of the ducts of the breast tissue have started to turn into cancer cells. These cells are all contained inside the ducts. They have not started to spread into the surrounding breast tissue.

As a substantial proportion of breast cancer diagnoses are of in situ cancers, many patients could potentially benefit from the results of this project. This will be of great value by presenting methods of ascertaining those at higher risk of recurrence, progression, or contralateral incidence of breast cancer, allowing for tailored treatment accordingly and prevention of overtreatment.

Further, this study can provide feasible targets for future development of treatment as well as prophylaxis

Not stated in the register.